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·Controlled Hypotension" in Anesthesia and Surgery

·Publication Number 283
AVERICAN LECTURE SERIES
A Alonograph in
The BANNERSTONE DIVISION of
AMERICAN LECTURES IN ANESTHESIOLOGI
Edited by
JOHN ADRIANI AD
Director Department of Anesthesia
Chanty Hospital
New Orleans Louisiand

·"Controlled Hypotension"
in
Anesthesia and Surgery
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CHARLES C THOMAS
Springfield • Illinois
PUBLISHER
U.S.A

·Publication Number 283
AVERICAN LECTURE SERIEST
A Monograph in
The BANNERSTOVE DIVISION of
AMERICAN LECTURES IN ANESTHESIOLOGY
Edited by
JOHN ADRIANI MD
Director Department of Anesthesia
Charity Hospital
New Orleans Louisiana

·то
MS L.
Whose nommotension has made
this small monograph possible

·CHARLES C THOMAS PUBLISHER
BANNERSTONE HOUSE
301 327 Last Lawrence Avenue, Springfield, Illinois USA
Published simultaneously in the British Commonwealth of Nations by
BLACKWELL SCIENTIFIC PUBLICATIONS LTD OXFORD ENCLAND
Published nmultaneously sa Canada by
THE PYERSOY PRESS TORONTO
This monograph is protected by copyright Na
part of 14 may be reproduced in any manner
without written permission from the publisher
Copyright 1956 by CHARLES C TROVAS
IUBLISHER
Library of Congress Catalog Card Number 55 11242
Pamied 39 the United States of America

·Contents Page 8 5 5 7 11 16 25 30 31 37 Chapter I INTRODUCTION II BLEEDING DURING SURCERY Non anesthetic Factors Anesthetic Factors III THE CONTROL OF BLEEDING DURING SURGERY IV INDUCTION OF HYPOTENSION V POSTURAL ISCHEMIA VI REDUCTION OF CIRCULATING BLOOD VOLUNE Arteriotomy Application of Negative Pressure to the Lower Extremities VII REDUCTION OF PERIPHERAL RESISTANCE CONDUC TION ANESTHESIA Total Spinal Block Epidural Block VIII REDUCTION OF PERIPHERAL RESISTANCE GANGLI ONIC BLOCKADE The Methonium Compounds Arfonad Pendiomide IX PHYSIOLOGICAL CONSIDERATIONS The Level of the Blood Pressure Effects on the Cardiovascular System Effects on the Brain Effects on the Liver Effects on the hidneys The Use of Vasopressor Agents X FATAL AND NON FATAL COMPLICATIONS Complications Mortalities 38 41 46 48 48 55 59 61 61 63 67 70 71 73 75 75 80

·No text on this page.

·"Controlled Hypotension" in Anesthesia and Surgery

·V111
CONTROLLED HYPOTENSION
Chapter
XI CONTRAINDICATIONS
XII INDICATIONS
Surgical Indications
Anesthetic Indications
Medical Indications
XIII REQUIREMENTS
XIV BIBLIOGRAPHY
INDEX
Page
88
94
96
98
99
101
106
137

·I I Introduction THE CONTROL of gross hemorrhage during surgical intervention, and the rapid, adequate replacement of all blood that is lost, constitute fundamental tenets of sound surgical practice Such control is not always accomplished with facility Hemorrhage is occasionally so profuse as to endanger the life of the patient despite the most lieroic remedial measures An even more complex problem is the persistent vascular ooze which often renders operation both tedious and difficult and which may amount to a significant loss of circulating blood volume in the course of a comparatively short period of time Furthermore during certain operative procedures this bleeding need not even be great in quantity to jeopardize surgical success for example, a single drop of blood during the critical stages of the Lempert fenestration operation may obscure the entire operative field and negate a satisfactory result Within the past few years these problems of excessive bleeding during operation have been the subjects of numerous studies both in this country and abroad, and one solution that has been offered consists of the inten tional production of hypotension to achieve a relatively bloodless operative site This concept, while by no means new has recently received widespread notoriety, and is itself sufficiently revolutionary in its character, intriguing in its possibilities, and dangerous in its implications as to warrant detailed consideration It would be clearly premature at this time to attempt the proper evaluation of these techniques or to estimate 3

·Prudence does not go behind nature and ask whence
at is It takes the laws of the world whereby man s being is
conditioned as they are, and keeps these laws that it may
enjoy their proper good It respects space and time climate
want sleep the law of polarity growth and death
the other hand nature punishes any neglect of prudence'
RALPH WALDO EMERSON
on

·II Bleeding During Surgery BLEEDING during surgery occurs only when blood vessels, of whatever type or size, arc cut Normal blood vessels in the absence of pathological processes involving their walls do not ordinarily permit the gross cut of whole blood from their confines Thc parımount cause of bleeding during operation therefore is due to the surgical intervention itself Granted hou ever that this is so, there are nevertheless ccrtun other factors of importance in the causation of bleeding which becomes excessive during the operative period These have been thoroughly reviewed by Gillies who has classified them into two groups accord ing to whether they are anesthetic or non anesthetic in origin (160) Non anesthetic Tactors In the group of non anesthetic factors (Table I) are those specific pathological conditions which prolong coagulation and bleeding times due to vascular deficiency prothrombin deficiency, platelet defi ciency thromboplastin deficiency or fibrinogen defi ciency Such dyscrasias if untreated pre operatively are capable of producing varying degrees of abnormal vascu lar ooze which may become at least troublesome and at times truly dangerous Other pathological processes particularly those involv ing the heart or the lungs may also be a source of in creased bleeding in the incised tissues when accompanied by venous congestion and an increased venous pressure Diseases that produce a high degree of toxicity with con current pyrexia and an increased basal metabolic rate 5 ·CONTROLLED HYPOTENSION" their ultimate position in anesthetic and surgical practice Too much clinical experience has been amassed over too short a period of time to allow the necessary perspective and too little fundamental investigation into the concur rent, profound physiological alterations has been under taken to provide the essential knowledge Furthermore the subject is too charged with emotional tension on both sides of the question concerning the absolute propriety of these techniques On the one hand there can be no doubt that induced hypotension for the production of a relatively bloodless operative field when wisely employed in carefully selected cases for a rational indication, may prove markedly beneficial in the individual patient Brunschwig has stated that, hypotensive anesthesia may prove to be one of the most important developments in the refinement of operative technic for complicated surgical procedures that has been made in recent years (68) On the other hand there is accumulating a body of evidence which indicates that drastic reduction of blood pressure in order to decrease bleeding carries a risk greater than that normally borne by the patient during surgery Armstrong Davison a pioneer in the development of the hypotensive technique has revised his original po sition on the subject and asserts that, the facilitation of the surgical procedure is certainly one of the main duties of the anaesthetist but new measures employed to this end must increase the safety of the patient and not be the means of exposing him to unnecessary hazards (99) Final evaluation of controlled hypotension -be it ac ceptance or rejection and probably somewhere between the two-must await a precise knowledge of the hazards involved in its application to the human organism, and a careful deliberation upon those hazards in relation to the advantages that can be obtained by its utilization in the individual patient ·BLEEDING DURING SURGERY 7 large amounts of blood from the tissues and structures in the operatiscarca and clius icnd 10 dccrcasc thc degree of vascular ooze and hemorrhage Anestheuc Tactors in the group of ancsthetic factors (Table II) that must be considered as influencing the Tacus 11 FACTORS INFLUE,CIVG BLEEDING DURING OPERATION B Anesthetic Factors 1 Agents a Effect on bleeding and clotting times b Effect of depth of anesthesia c. Vasodilatation of direct neric block 2 Techniques a Resistance to respiration b Increased intrapulmonary pressure c. Carbon dioxide accumulation amount of bleeding during surgical procedures, Gillies has directed attention toward both the agents themselves and the techniques by which those agents are administered (160) He has pointed out the fact that although almost all general anesthetic agents have been blamed in the past for excessive bleeding which occurred during operation yet none of those agents in themselves have any great effect upon the bleeding or clotting times of the blood Coagu lation time is prolonged very slightly during nitrous oxide anesthesia reduced somewhat during anesthesia produced by ether chloroform and ethylene and unchanged during anesthesia occasioned by cyclopropane or the intravenous barbiturates On the other hand and of much more importance is the fact that almost all these anesthetic drugs do produce vasodilatation especially of the capıllaries of the skın during light planes of general anesthesia This vaso dilatation has been attributed to an initial inhibition of the hypothalmic centers causing a reduction of constrictor ·6 CONTROLLED HYPOTENSION lead to excessive vascularity and thus to excessive bleeding during surgical intervention Profuse bleeding is most apt to occur in the course of certain specific operatuse procedures both because of the nature of the tissues and structures being operated upon as well as the pathological processes involving those tissues TABLE I FACTORS INFLUENCING BLEEDING DURNG OPERATIOV A on-anesthetic Factors | Defiaenges in the dotting of blood 2. Cardio-pulmonary disease 3 Toxemia Pyrexia 4 Vascularity of tissues 5 Posture and structures Thus both glandular tissues and large bodies of muscles are highly vascular, and operations in volving them may entail significant blood loss certain intracranial inters entions (ligation of congenital aneu sm or very vascular tumors) thyroidectomy intrathoracic operations mastectomy laminectomy, operations on the hip or shoulder joints, and some gynecological proce dures are examples of the types of surgery during which excessive bleeding may be encountered because of the nature of the operative site itself Perhaps the most important non anesthetic factor influ encing the amount of bleeding during operation however is the posture of the patient particularly as regards the site of operation in relationship to the dependent portions of the body If the area of operation is dependent in rela uon to the rest of the body venous engorgement occurs and there is increased vascular oozing into the surgical field. On the other hand when the patient 15 so positioned that the field of operation is maintained superior to the rest of the body gravitational senous drainage will remove ·DITED DURING SURCERS 9 As will be noted subsequently, loucicr, ilic proluchon of an ischemic operilic field is succly 1 pracuicable or justifiable solution to the problem of excessinc bleeding during surgery iſ the price to thic patient must lxc 7 pro found gcncralized cellular intoxication (90) Drugs cmployed as adjutants to incstlicsin for the pur pose of facilitating muscular relation, such as d tubo curarınc dccimcthonium, or succiny Icholine 1171c only scal ellccts upon ginglionc synapses, cxccpt perhaps in truly massic doses As 7 restilt both 150 iletion and active circulatory reflexes combine to cause brish biccding during anesthesia supplemented with muscle relaxants, unless of course the general anesthesia is carried to cry deep levels Even local anesthetic agents will producc izsodilatation with the single cxception that when they are employed for local infiltration and 7 vasoconstrictor is added to prevent toxic absorption vasoconstriction ensues and a decreased amount of bleeding is cncountered When used for direct nerve bloch, however vasodilatation wall occur due to paralysis of the vasoconstrictor fibers of the nerve trunk At least as important as the anesthetic agents employed, and in certain instances of far more importance, are the methods and techniques by which general anesthesia is administered This is most particularly true of the respira tory factors involved in modern methods of anesthetic administration Increased resistance to respiration, whether due to obstruction of the airway or to increased friction within a closed anesthetic circuit causes an increased venous pressure venous congestion and increased vascular ooze ог Similarly the use of assisted controlled respira tions entail the use of increased intrapulmonary pressures which reduce the intrapleural negative pressure or even make the latter positive lift the thoracic wall and force ·8 'CONTROLLED HYPOTENSION tone (160), but it is not a sufficient degree of vasodilata tion to lower the blood pressure Therefore, since the cir culatory reflexes are active in light planes of anesthesia this vasodilatation will lead directly to increased bleeding from the surgical wound Under such circumstances hemorrhage may be brisk except during anesthesia with those agents which produce a relative hypotension from the very outset, such as chloro form and the barbiturates Chloroform reduces the blood pressure from the beginning of its administration by a combination of vagal and dilator effects and it is this immediate hypotension that is a large factor in decreased blood loss associated with anesthesia by that agent so much appreciated by the surgeons of an earlier generation (51) The barbiturates have a marhed depressant action on the hypothalmic centers controlling autonomic activity and thus produce a hypotension albeit a transient one during the induction of anesthesia a bit later in the anesthesia, however the respiratory depressant effects of the barbit urates become more important and offset the decreased tendency toward bleeding attributable to this initial hypo tension (128) A quite different situation pertains during the conduct of deep general anesthesia regardless of which agent may be employed to produce anesthesia (42 517) The vaso dilatation seen during light planes of anesthesia persists but instead of being associated with those factors which serte to increase blood flow and therefore active bleeding (ie, vasodilatation undımınıshed blood pressure normal cardiac output and active circulatory reflexes) the vasodilatation during deep anesthesia is accompanied by a de pression of the pressor reflexes and a fall in blood pressure Excessive bleeding therefore can be prevented by main taining deep levels of general anesthesia the amount of bleeding varying inversely with the depth of anesthesia ·III The Control of Bleeding During Surgery THE PROBLEM of excessive bleeding during surgical interventions is scarcely a new one ind for many years both surgeons and inesthetists have applıcd 1 variety of different methods in an attempt to achieve hemostasis Tor the most part these approaches have been of a local na ture, confined to the operative site itself or to that re stricted portion of the body immediately surrounding the operative area (Table III) The use of tourniquets and Esmarch bandages for operations upon the extremities has been a well known maneuver for a very long time The application of vasoconstrictor substances to the tissues of the operative site has also been employed to provide hemostasis but the utility of this procedure has been somewhat restricted both by the danger of toxic absorption and by the problem of reactive vasodilatation and therefore reactionary hemor rhage Cautery chemical agents of an escharotic nature, and more recently hemostatic sponges have proven ex tremely useful in controlling vascular ooze in fairly lim ited areas of the operative site The local application of both heat and cold have been employed for the achieve ment of hemostasis in the past, and it seems evident from the recent advances in cardiac surgery that hypothermia will gain prominence for the control of hemorrhage in that of surgery although as a generalized rather than as a local measure and for a quite different rationale than 11 type ·10 CONTROLLED HYPOTENSION the diaphragm downward these mineuvers have the tend ency to hinder venous return and cardiac filling rather than to facilitate them as does spontaneous respiration and venous ooze is increased Finally the failure to excrete adequate amounts of the carbon dioxide produced by the patient is a potent cause of increased bleeding during surgery Uncompensated apnea decreased respiratory exchange due to sub apneic doses of respiratory depressant general anesthetic agents or muscle relaxant drugs or inefficient carbon dioxide absorption for numerous technical reasons in closed sys tem methods of inhalational anesthesia all cause a rise in blood pressure and vasodilatation The importance of the impedance of carbon dioxide excretion as a cause of in creased bleeding during surgery has been emphasized recently by the perfection of non rebreathing techniques and the suggestion that they may play a most important role in decreasing vascular ooze during operation (70) ·CONTROL OF DIFFIC 13 stasis on this basis, of course, is due to the attendant pro gressive central depression, which leads to hypotension and thereforc an ischemic opcratic field. The gradual realization of the role played by hypotension in producing a bloodless operative site in chloroform, spinal, and dccp general anesthesias, has led to the intentional reduction of TABLE IV THE HISTORY OF CONTROLLED TYPOTENSION 1946-Gardner Arteniotomy 1918_Gillics. Total Spinal Block 1950_Davison-Pentamethonium Ganglionic Blochade 1930_Enderby-l/examethonium Ganglionic Blochade 19.1_Gusot and Damouscau-Pondomide Ganglionic Blockade 1992-Nicholson Sarnoff and Crchan-Arfonad Ganglionic Blockade blood pressure and the evolution of so-called controlled hypotension during anesthesia and surgery While it is true that hypotension has often provided a relatively bloodless operative field in the past it has only been sought deliberately for that purpose during the last few years (Table IV) In 1946 Gardner (149) introduced the technique of arteriotomy whereby blood is withdrawn from the patient pre operatively via the arterial route and then replaced in part or in toto by the same manner at the end of surgery Such pre operative reduction of the total circulating blood volume by the removal of from 500 to 3000 cc of blood serves to lower the arterial pressure to a level between 50 and 90 mm Hg and at the same time produces peripheral vasoconstriction (196) when com bined with proper positioning of the patient the net result is a reduction of bleeding at the site of surgery Arteriotomy thus approximates a state of hemorrhagic shock and for this reason has been thought to exceed the bounds of physiological rectitude A more physiological approach to the problem was con ·12 "CONTROLLED HYPOTENSION that upon which its earlier use was based Arterial com pression and even temporary ligation, have been used to control hemorrhage in certain instances of vascular sur gery Without question, however, the most important of these TABLE III METHODS OF HEMOSTASIS A Local Methods ! Hemostats ligatures and sutures 2 Tourniquets and Esmarch bandages 3 Vasoconstrictor drugs 4 Cautery escharotic chemical agents and hemostatic sponges 5 Local application of heat or cold 6 Arterial compression or temporary ligation 7 Proper posturing of the patient B General Methods I Chloroform anesthesia 2 Spinal analgesia 3 Deep general anesthesia approaches to the problem of hemostasis has been the meticulous positioning of the patient on the operating table so that the operative site would be superior to the rest of the body This maneuver permits gravitational venous drainage away from the operative site into the dependent portions of the body and thus in large meas ure serves to prevent venous ooze It seems possible, in retrospect that the surgeon s pref erence in the past for chloroform and spinal anesthesia was due as much to the ischemic operative fields which resulted from the hypotension accompanying these forms of anes thesia as it was to the profound muscular relaxation gen erally cited as being the basis for his choice of anesthetic procedure It has also been recognized for some time and even advocated on a few occasions--that excessive bleed ing during surgical intervention could be prevented by recourse to very deep levels of general anesthesia Hemo-

·CONTROL OF DI LFDIN
15
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| Thc deliberate induction of laypotension
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·- 14 CONTROLLED HYPOTENSION tained in Gillies classic studies, in 1948 on total spinal block (175) In this method, the blood pressure is reduced to 70 mm Hg, or below, by the use of spinal anesthesia to achieve paralysis of the entire efferent sympathetic out flow, with lesser degrees of sensory and motor blockade so that the muscles of respiration and the medullary centers remain relatively unaffected Gillies has admitted the phys iological deviations of even this technique (161), but he has assumed that the arteriolar dilatation so produced guarantees normal oxygenation of the tissue cells, and that the decreased cardiac output inherent in the technique is compensated for by the decreased peripheral resistance and therefore the decreased work of the heart Proper posturing of the patient is again an essential feature for the control of bleeding as it is indeed in all methods of con trolled hypotension' The introduction in 1948 of casily injectable gangli onıc blocking agents in the form of the methonium com pounds (32 362) led to the widespread usage of hexame thonium and pentamethonium to lower the blood pressure to systolic levels of 50 to 60 mm Hg and thus control excessive vascular ooze in the operative field (98 120) More recently, arfonad (344), a thiophinium compound and to a lesser extent, pendiomide, (188) a diethylenetri amıne derivative have made possible more readily con trollable forms of ganglionıc blockade for the purpose of reducing excessive bleeding during operation again em ployed in conjunction with proper positioning of the patient A number of other less widely used drugs and tech niques have been applied in similar manner to the prob lem of excessive bleeding during surgery and so-called controlled hypotension is therefore a generic term which includes the total of such diverse clinical ap ·INDUCTION OF IN POTTSIOS 17 Icss fixed entity under normal physiological conditions can be varıcd by artificial mcans as well as by certain pathological processes and therclore may be utilized for the production of controlled hypotension An intentional decrease of the cardiac output has been TABLE FACTORS CONTROLLING BLOOD PRESSURF i Cardiac output 2 Peripheral resistance 3 Circulating blood solume 1 Viscosity of the blood 5 Elastiaty of the arteries sought only by those few workers employing procaine amide (7 311 315 360), a technique of questionable vir tue A decreased cardiac output will of coursc produce TABLE VI FACTORS CONTROLLING CARDIAC OUTPUT I Venous return 2 Force of the heart beat 3 Rate of the heart 4 Arterial pressure hypotension but it is important to realize that the reverse may be true also and to emphasize that all techniques of controlled hypotension are usually associated with a quite unintentional reduction of cardiac output This would appear to be unavoidable inasmuch as the cardiac output is mainly dependent upon the venous return the force of the heart beat the rate of the heart and the arterial pressure itself (Table VI) Obviously any reduc tion of arterial pressure may be expected under most conditions at least to lead to a concomitant decrease of cardiac output (208) Furthermore venous return is also ·IV Induction of Hypotension THE SEVERAL factors which combine to maintain the normal arterial pressure include the cardiac output the total circulating blood volume the peripheral resistance, the viscosity of the blood and the elasticity of the walls of the large arteries (Table V) These various factors are in turn subject to control and influence by an enormous number of other physiological phenomena of nervous hor monal, and physical origin but for the purposes of this discussion the fire basic factors mentioned are of sufficient concern Of these the latter than the viscosity of the blood and the elasticity of the large arteries--are fairly constant and not easily altered for the purpose of inducing hypotension It is true that the viscosity of the blood fluctuates markedly during surgery changing with variations in the chemical composition the gas content the temperature the colloids and the suspended corpuscles but these changes are not amenable to deliberate alterations with any degree of con trol The factors of importance for the reduction of the blood pressure in the techniques of controlled hypoten therefore are the cardiac output, the peripheral re sistance and the total circulating blood volume When the blood volume remains constant arterial pres sure is to a great extent the product of the cardiac output and the peripheral resistance and these particularly the latter can be varied by devious maneuvers for the inten tonal reduction of the arterial pressure The quantity of the total circulating blood volume itself, while a more or 16 sion ·19 INDUCTION OF LOTFUSION Hс. CO2 уис Oz lock RC CA Suprot NUCLE ABS PMR. Adrenalne CURICA Aortle Arch Blood Vesset Heart YA CST Metabolites COM-lons DA. Dz tack TS Other Affcs Pitunteen Histamine Temperature Figure I Regulation of Arterial Tone VMC vasomotor centers HC higher centers cerebral cortex hypothalamus R.C irradia tion from respiratory center CO, central action of CO, O, lack central action of O, lack CB carotid body (chemoreceptors) CS carotid sinus (pressoreceptors) VA venae cavae and right aurice (pressoreceptors) P.A pulmonary artery (pressoreceptors) T.S thoracic-splanchnic arteries (pressoreceptors) A B aortic bodies (chemoreceptors) Aortic aortic arch heart (pressoreceptors) CSF cranial and sacral vasodilator fibres PNR posterior nerve roots vasodilator fibres connector and excitor cells of sym pathetic nervous system Supr gl suprarenal gland (Modified from Samson Wright Applied Physiology 1943 and reprinted from Heymans C Introduction to the Regulation of Blood Pressure and Heart Rate Charles C Thomas Publisher 1950 with the kind per mission of the publishers ) ·18 CONTROLLED HYPOTENSION' reduced in hypotensive states, and becomes a further factor in lowering the cardiac output Hypotension has been induced intentionally, therefore, mainly by creating a disparity between the quantity of the total circulating blood volume and the capacity of the TABLE VII THE PHYSIOLOGICAL BASIS OF THE TECHNIQUES FOR INDUCING HYPOTENSIOV 1 Elasticity of the Arteries relauvely vnalterable 2 | sscosity of the Blood-not amenable to control 3 Decreased Cardiac Output A Pronesty? B Unavoidable with other techniques 4 Reduction of Circulating Blood Volume A Arteriotomy B Vacuum applied to lower extremities 3 Decreased Peripheral Resistance A Conduction anesthesia 10 Total Spinal Block B Ganglionc blockade ie Methoniutn compounds (Modified from Little D M Jr. Induced hypotension in anesthesia y and surgery Anesthesiology 16 320 1955 with the kind permission of the publisher ) vascular bed (Table VII) A reduction of the total circu lating blood volume is embodied in the technique of arteriotomy or arterial bleeding followed by retransfu sion (6) The effective total circulating blood volume is reduced by lowering the peripheral resistance by gangli onic blockade, and then applying a vacuum apparatus to the loner extremities almost an eighth of the total blood volume is trapped in the legs and thighs when suction is exerted on the encased limbs (420) It has been by a reduction in the peripheral resistance however that the arterial pressure has been most easily and therefore most popularly, decreased for the production of controlled hypotension The peripheral resistance resides mainly in the variably contractile arterioles and to a lesser extent, in the capillaries and veins (Figure 1) The ·THE DECREASE OF PERIPHERAL RESISTANCE BY THE INTERRUPTION OF SYMPATHETIC VASOCONSTRICTOR MPULSES 1 DEPRESSION OF AUTONOMIC CENTERS IN MIDBRAIN IE, APRESOLINE 3. STIMULATION OF VASODILATOR CENTER IN MEDULLA 1 E, VERATRUM ALKALOIDS Figure 2 Interruption of sympathetic vasoconstrictor impulses * 2. DEPRESSION OF VASOMOTOR CENTER IN MEDULLA-LE. NARCOTIC AND HYPNOTIC DRUGS, GENERAL ANESTHETIC AGENTS 4 BLOCKADE OF PRE GANGLIONIC SYMPATHETIC FIBERS AS THEY EMERGE FROM THE CORD A TOTAL SPINAL BLOCK B EPIDURAL BLOCK C. PARAVERTEBRAL SYMPATHETIC BLOCK INDUCTION OF HYPOTENSION 6 BLOCKADE OF POST GANGLIONIC SYMPATHETIC NERVE ENDINGS LE, DIBENAMINE, PRISCOL, BENODAINE 7 PARALYSIS OF EFFECTOR CELLS OF VESSEL WALLS-LE, NITRATES, NITRITES, CERTAIN ERGOT PREPARATIONS 5 SYMPATHETIC GANGLIONIC BLOCKADE --IE, METHONIUM COMPOUNDS, PENDIOMODE, ARFONAD PARAVERTEBRAL Symp GANGLIONIC BLOCKADE TEDIOUS 21 ·20 CONTROLLED HYPOTENSION degree of contraction or tone of the arterioles and prob ably also of the small veins, is maintained and controlled by several factors, of prime importance among which is the continuous stream of vasoconstrictor impulses that arise within the brain and pass down the spinal cord and out over the sympathetic fibers of the peripheral vessels The peripheral resistance therefore may be reduced by an interruption of this pathway at any point in its course by suppressing the formation of vasoconstrictor impulses, by blocking their pathway to the peripheral vessels, or by pre venting the response of the effector cells at the termination of the pathway Depression of the autonomic centers which are located in the midbrain will result in 7 decrease in the number and frequency of constrictor impulses arısıng in those centers and this effect has been employed extensively in medicine for the control of hypertension by the adminis tration of hydralazine (Figure 2) This is a drug how ever which has not as yet been found practicable for use during surgical anesthesia Depression of the vasomotor center in the medulla ob longata also will suppress the stream of vasoconstrictor impulses Central vasomotor depression of this type occurs to some degree with most narcotic and hypnotic agents and it is known to occur quite consistently during deep levels of general anesthesia but the deliberate induction of hypotension in this manner has not been considered justifiable because of the generalized cellular intoxication that accompanies such profound central depression Reflex inhibition of the vasomotor centers (or stimula tion of the vasodilator center) will tend to detract from the effect that visoconstrictor impulses have upon the peripheral vessels and so will cause an increase in the cross sectional area of the vascular bed and a fall of blood pressure This is apparently the mode of action of the ·INDUCTION OINARI OTFSION 23 cifically to control the hypertensive crises occurring dur ing the removal of adrenal phcochromocitoma Finally, the responsc at the termination of the pathway can be presented by a direct action of such drugs as the TABLE VIII TECHNIQUES FUPLOYED IV 27 950 CASES TO PRODUC} CONTROLLED HYPOTF\SIO Great Britain and Ireland Anesthetists Cases Grand Total of Cases USA Anesthetists Cases Technique Arteriotomy Total Spinal Block Methonium Compounds Arfonadº Pendiomide Miscellaneous 5 51 166 206 6920 11,979 12 46 115 16 6 208 2 655 3,375 359 63 145 414 9,577 15,354 359 6S 2 163 35 2018 Totals 255 21 125 209 6 805 27 930 Questionnaires were sent to the 602 meinbers of the Assocation of Anaesthetists of Great Britain & Ireland before the general introduction of these compounds into clinical practice (Reprinted from Little D M Jr Induced hypotension in anesthesia and surgery Anesthesiology 16 320 1955 with the lind permission of the publisher) nitrites the nitrates and certain dehydrogenated ergot preparations, upon the effector cells of the vessel walls themselves Again, however, none of these has proven to be sufficiently controllable to be employed extensively during anesthesia and surgery This brief discussion of the physiological basis of the techniques for inducing hypotension would be incomplete without some indication of the relative frequency of their clinical application (Table VIII) Questionnaires were sent to the members of the Association of Anaesthetists of Great Britain and Ireland (197) and to the Diplomates of the American Board of Anesthesiology (198), to ascertain ·22 CONTROLLED HYPOTENSION veratrum alhaloids, although these drugs to date have been used little for controlled hypotension Sympathetic blockade produced by blocking the pre ganglionıc sympathetic fibers as they emerge from the spinal cord, by one of the techniques of conduction anes thesia has proven to be a most useful method of inducing hypotension during anesthesia and surgery Total spinal analgesia, which has long been known to produce sympa thetic paralysis in addition to its effects upon motor and sensory nerves has been employed widely for this purpose Similar results achieved by the same metameric distribu tion of sympathetic paralysis, have been obtained by the use of epidural analgesia Sympathetic blockade also may be effected by blocking the sympathetic ganglia themselves Paravertebral sympa thetic ganglia blockade (which actually blocks the post ganglionic as well as the preganglionic fibers, in some instances) is far too tedious and time-consuming a tech nique for the purposes of controlled hypotension Sym pathetic ganglia blockade however, can be performed with almost indecent ease with the use of such systemi cally acting drugs as tetraethylammonium bromide or duodide pentamethonium or liexamethonium halides arfonad pendiomide and others These dru block the transmission across synapses within the auto nomic ganglia thereby interrupting the stream of vaso constrictor impulses and inducing hypotension Constrictor tone also may be interrupted by blocking the sympathetic nerve endings as they terminate in the walls of the blood vessels by the administration of dibena mine priscol regitine or chlorpromazine These drugs are of uncertain and unpredictable action and have found little use in the techniques of controlled hypotension although they have been employed on rare occasions spe act to ·V con Postural Ischemia Proper positioning of the prtient upon the operating table can often provide remarkablc degrees of hemostasis, and had the techniques of controlled hypotension" con tributed nothing else thicy would have served at least to reemphasize the value of this salutary maneuver to the present generation of surgeons and anesthetists In trolled hypotension, lowered blood pressure is combined with elevation of the operative site to cause the elevated part to become pale and ischemic-a situation which Sır Henry Dale has described most aptly as postural ische mia (127) It is also true, however, that simple elevation of the area of operation above the rest of the body will in itself effectively lessen the amount of bleeding in the wound The promotion of venous drainage is of course the most important factor in this regard If the surgical wound is dependent in relation to all or much of the body, the venous blood in order to leave the wound must oppose the hydrostatic force of the weight of the column of blood in addition to having to exert an anti gravitational force Even when the incision is on a level with the other parts of the body however venous drainage may be impeded by factors which reduce venous return during anesthesia, par ticularly venodilatation, diminution of the pump action of the negative pressure within the thorax secondary to decreased respiratory excursion, and because of general muscular paralysis a failure of the intermittent pressure which is normally brought to bear upon the venous blood 25 ·24 CONTROLLED HYPOTENSION certain facts concerning the clinical practice of controlled hypotension The results of these questionnaires reported some 27 930 cases of controlled hypotension in anesthe sia and surgery 15,354 or roughly 55%, were conducted by the intravenous injection of the methonium com pounds 9,577, or 34% by the induction of total spinal block, which has the advantage of producing surgical anesthesia over much of the body in addition to inducing hypotension 414, or 15% by the institution of the some what cumbersome technique of arteriotomy 359 and 63, respectively by the injection of arfonad and pendıomide which are relatively new drugs and the remaining 2,163 or approximately 8%, by means of a variety of miscellane ous techniques ·POSTURAI ISCHEMIA 27 almost entirely upon the nature and site of the surgical procedure, except that duc consideration must be guen to the dangers of ischemia to vital organs in certain pos tures Craniotomies and other neurosurgical procedures Figure 3 Posture of patient for thoraco-lumbar splanclinicectomy and sympathectomy (Reprinted from Griffiths HW Cand > Gillies J Anaesthesia, 1918 with the kind permission of the authors and the publisher) in the region of the head and neck are performed in a re verse Trendelenburg position, in a head up tilt of up to 30 degrees or even (posterior fossa explorations) in the sitting position Many other forms of head and nech sur gery (fenestration operation radical nech dissection, man dibular resection) have also required reverse Trendelen burg semi Fowler s or a head up tilt position Side tilt of the table and some degree of hyperextension have been employed for radical mastectomy while a true lateral jack knife position has been ideal for intra thoracic opera tions and combined thoraco lumbar splanchnicectomy and sympathectomy (Figure 3) For upper abdominal surgery, ·26 CONTROLLED HYPOTENSION by contraction of the limb muscles (368) When the oper ative site is superior to the rest of the body, however, these factors combine with the effect of gravity to enhance venous drainage away from the area of surgical interven tion and to decrease the amount of bleeding in the wound It is necessary also to consider the effect of posture upon arterial pressure a factor which generally has been disre garded in the past Enderby has attempted to demonstrate that local blood pressure in the wound is reduced 30 mm Hg for every 15 inches of vertical height of the operative site above the level of the heart (125) This is undoubtedly an over simplification of a very complex hemodynamic situation but it brings out the point that, above the level of the heart gravity opposes the hydrodynamic factor in the arteries, while, conversely, below heart level the hydrostatic and hydrodynamic factors are additive in those vessels It has been shown that these effects of posture become exaggerated during controlled hypotension conducted by means of a reduction of peripheral resistance because of the marked increase in the capacity of the vascular bed following upon sympathetic blockade Thus, they may be a source of great danger inasmuch as reflex circulatory activity mediated through receptors in the carotid sinuses aortic arch, and the cardio aortic sinus is obtunded under the circumstances of complete sympathetic blochade and positions which impose a marked anti gravitational factor upon venous return may jeopardize the life of the patient (160) For this same reason however, one can vary the level of the patient s blood pressure by the simple expedi ent of lowering or elevating a leg an arm or even a hand this method of controlling the degree of the hypotension is a most important one in these techniques The position in which the patient is placed for opera tion under controlled hypotension will therefore depend ·TOSTURAL ISCIIEVIA 29 requirements of cercbral metabolism, and there are a number of workers who refuse to employ controlled hy potension with the head aboie tlic level of the horizontal for this very reason. There is the added risk of air em bolism in the head up position lange veins arc cncoun tered in the field of operation and arc inadvertently en tered during conditions of venodilatation and hypoten sion, Other anesthetists have condemned the head-down position because of the possibility that the profound pas site congestion of the cerebral vessels during this posture may predispose to thrombus formation (311), The prone and lateral jach knife positions also have been indicted (274), since when the peripheral vascular bed is fully dı lated and the inferior vena ava is above the level of its contributory veins venous return may be diminished to a point that is incompatible with continued circulation Mention has been made already of the profound reduc tion of venous return and resultant severe hypotension, that may occur with changes in the patient s posture dur ing complete sympathetic blockade and this point applies post-operatively to the same extent that it does during the operation itself since the closure of the skin incision does not necessarily coincide with the termination of sympa thetic blocking activity Shifts in the patients posture must be controlled carefully in the post operative period particularly when the legs are lowered from the lithotomy position, or when the patient is moved from the operating table transported on a stretcher or placed into bed ·28 CONTROLLED HYPOTENSION hyperextension with a raised gallbladder bridge has been used, the hyperextension of the spine in this position prob ably combining with the use of the bridge to compress the inferior vena cava and so to contribute to the degree of hypotension (124) This is true also of the lateral jack knife position, which has been employed for operations upon the kidney, when the highest point has been just below the thoracic cage The supine jack knife, or a 30 degree Trendelenburg position has provided good work ing conditions for radical pelvic or abdominal surgery (58) Operations such as repair of the pelvic floor or com bined abdomino perineal resection have been difficult problems from the point of view of producing a bloodless field but blood loss can be diminished considerably by the use of the lithotomy position in conjunction with a steep head down tilt (391) A steep head down tilt alone has been used for operations upon the lower extremities but because there appears to be a more sensitive (to ganglionic blockade) sympathetic innervation to the lower extremi ties than to the upper part of the body better control of bleeding is possible when the site of operation is above the pelvis and legs (440) These examples suffice to show that in general the posture employed for a specific opera tive intervention conducted under the conditions of 'con trolled hypotension is apt to be closely akin to that which empirical experience had taught many years ago was the mnost practical position for that particular surgical proce dure There are dangers associated with the positioning of the patient in controlled hypotension of which it is necessary to take cognizance Certain postures threaten ischemia to vital organs particularly the brain because induced hypotension and gravity may combine to lower the local blood pressure (as quite distinct from the blood pressure at heart level) below that necessary to fulfill the ·REDUCTION OL BLOOD VOI UNT 31 neurosurgical interventions might lossen liemorrhage and so expedite operation, following which the patient could be reinfused with his own blood to fcestablish normotension Arteriotomy Arteriotomy, as descloped by hohlstacdt and Page (255), appeared to be such 7 tccliniquc, and Gardner therefore induced a relatic hypotension in a patient undergoing cicision of an olfactory groove men ingioma, a large and vascular tumor, to test lus theory A cannula was placed in the dorsalis pedis artery and con nected with a reservoir flash, heparin and sodium citrate being employed to present clot formation within this sys tem The pre-operative withdrawal of 1 600 cc of blood served to lower the systolic pressure from 140 to 100 mm Hg, and at the same time increased the pulse rate to 140 berts per minute It was Gardner s distinct impression that bleeding was greatly reduced during the operative proce dure itself and the removal of the tumor facilitated to that extent At the end of operation prior to the closure of the wound 1,100 cc of the withdrawn blood was rein fused through the arterial cannuli this reinfusion served to raise the systolic pressure from 90 to 120 mm Hg and caused some bleeding from the scalp incision though none from the tumor bed The patients convalescence was un eventful Gardner stressed the fact that the peripheral vasoconstriction which accompanies loss of blood volume was chiefly responsible for the hemostasis and was far more important in this respect than the actual reduction of the arterial pressure The use of the technique of arteriotomy and reinfusion to lessen the extensive bleeding that occurs during craniot omy performed for removal of vascular lesions was ex tended by Hale to include the fenestration operation in which bleeding is not large in amount but rather vexa tious and capable of preventing a successful result should ·VI Reduction of Circulating Blood Volume IN THE COURSE of investigating Secleys suggestion that the intra arterial infusion of blood or plasma might have advantages over the conventional intravenous route in the treatment of shock (255), hohlstaedt and Page de veloped an ingenious method for studying the shock syn drome by means of arterial bleeding and subsequent rein fusion Essentially, this technique consisted of cannulating the femoral artery in a direction toward the heart and then connecting the cannula to a closed reservoir into which the subject might be bled until the blood pressure had been reduced to the desired level The blood was mixed with an anticoagulant during its withdrawal and could be reinfused into the femoral artery in order to restore the blood pressure toward normal through the simple expedient of raising the pressure in the closed reservoir by pumping air into it Gardner adapted this experimental method of arterial bleeding and reinfusion to the clinical problem of brain tumor surgery (149) He had noted that the hazards and difficulties of excısıng certain extremely vascular growths abated considerably as the operation wore on the blood loss increased in amount and the blood pressure fell to hypotensive levels at that point hemostasis was effected more readily and the remainder of the tumor was removed quite easily for a number of years he had pondered a technique whereby the withdrawal of blood prior to 30 ·REDUCTIOY OF BLOOD VOLUNE 99 CRANIOTOMY GIRL - 14 YRS TIME IN MINUTES 15 30 45 60 75 90 105 120 135_150 165 2000 200 1600 160 PULSED 1200 120 SYSTOLIC 800 80 DIASTOLIC BLOOD WITHDRAWN 400 40 1200 co BLOOD WITHDRAWN Figure 5 Arteriotomy for craniotomy The effect of the withdrawal of 1200 cc of blood upon the pulse and blood pressure is shown (Reprinted from Hale D E Anesthesiology 1948 with the kind permission of the author and the publisher) degree of hemostasis was regarded as satisfactory on an average, this required the withdrawal of 1750 cc of blood over the course of half an hour If at any time during the bloodletting or the operation itself there was a further fall in arterial pressure blood was returned immediately to the artery from the reservoir under a pressure of 100 to 200 mm Hg until a systolic level of 80 mm Hg or higher had been regained At the end of the operation, when the need for hemostasis had passed but before the wound had been closed the withdrawn blood was reinfused by both artery and vein (Figure 5) However, since after the re moval of a liter or more of blood from the vascular bed, the blood volume tends to increase from its low initial level due to the entrance of tissue fluids into the circula tion at a rate which will compensate for the loss of 500 cc of blood in an hour the last 500 cc of withdrawn blood ·32 'CONTROLLED HYPOTENSION It occur during the critical maneuver of shaping the fenes tra and preparing the skin flap from the auditory canal (196) He used an apparatus which was a modification of that employed by Gardner (Figure 4) and the radial artery—which he ligated at the termination of the proce dure-as the site of arterial puncture Blood was with drawn rather rapidly at the beginning of surgery until a systolic pressure of 80 mm Hg was reached, or until the TANTI Figure 4 Apparatus for arteriotomy The Y shaped glass canoula is X secured in the radial artery The lower tubing leads directly to the blood collecting flask The upper tubing leads to a manometer for reading the pressure in the radial artery or in the helly flask by means of which the blood may be returned to the patient under pressure The small flask and syringe contain a supply of 001% heparin solution (Reprinted from Hale D E Anesthesiology 1948 with the kind permission of the author and the publisher ) ·REDUCTION OF BLOOD VOLUNF 85 of controllability, both of the arterial pressure as well_75 the total blood volume (48, 150, 163) that is not possible with most other techniques of controlled hypotension When reinfusion is necessary, the intra artcrial route is by far the most cſſicient method for raising thic blood pressure rapidly (165), particularly in the presence of shoch and myocardial ischemi due to decreased hortic pressure (353, 500) Furthermore such reinfusion of the patients own blood instead of replacing the loss with the blood of one or morc donors, not only conserves blood, but also avoids the risks of transfusion reactions or the development of homologous serum jundice. Finally, the reduction of both the total blood volume and the arterial pressure has an important advantage for intracranial surgery the tension of the brain is greatly reduced which facılıtates retraction during difficult expo sures and increases the case with which congenital aneu rysms and other deep seated lesions may be approached (48 295 333) Despite these advantages however there are several dis advantages to the use of arteriotomy The major drawback of this technique of course stems from its modus operandı --vasoconstriction The combination of both a reduced total circulating blood volume and the compensatory vaso constriction which this induces approximates a state of hemorrhagic shock During such hypovolemic hypoten sion the ability of the organism to withstand even a minute blood loss is obtunded and the danger of circula tory depression passing into an irreversible stage is con stant (48) In this connection furthermore it must be emphasized that blood pressure recordings are not an en tirely reliable index of either the state of the peripheral circulation or of the imminence of the phase of irreversi bility (517) Even in the absence of an irreversible phase of circulatory depression however there is still the grave ·34 CONTROLLED HI POTENSION was not administered but was banked and held in reserve for the patient Other workers have added certain refinements to the technique (27, 48, 229, 295 333) but in essence arteriot omy has been employed in the manner just described The apparatus has been modified to provide a closed rather than an open system and the heparın has been admin istered by a slow continuous drip in an attempt to pre vent the formation of small thrombı which occurred when heparin was administered by intermittent injections (333) The use of arteriotomy has been confined almost entirely to neurosurgical procedures (1 e, craniotomy) and the fenestration operation (27 48, 149, 150, 151, 229, 295 333) although recent experimental results indicate that the method may be of great aid in operations upon the open heart and in major hepatic resections (55) Arteriotomy offers certain well defined advantages as compared to other techniques of controlled hypotension' Tirst ind most importantly there is the very obvious hemostatic effect which renders blood loss less severe and thereby facilitates operation to a marked degree This hemostasis is due apparently to the generalized vaso constriction neurogenic in origin which has been shown to be the initial response to bloodletting (255) during the brief stage preceding shoc a specific enzyme is be lieved to be liberated into the plasma which causes this compensatory vasoconstriction (351) Only as the blood volume is reduced further does there result a fall in blood pressure, which then also contributes to the hemostatic effect For this reason it is unnecessary to loner the blood pressure to dangerous levels in order to obtain a definite hemostasis (150) and bloodless operative fields can be achieved by removing only small amounts of blood (6) A second great advantage of arteriotomy is the fact that repeated small bleedings and reinfusions permit a degree ·REDUCTION OF BLOOD VOLUME 37 of controlled hypotension, despite its very rcal advan tages in certain respects Application of Negative Pressure to the Lower Extremi ties It has been recognized for a number of years that the amount of blood going to the lower extremitics can be increased quite markedly by the application of negative pressure to the legs and thighs It has now been shown that this effect is increased considerably during sympa thetic blockade with ganglionic blocking agents (387) Advantage has been taken of this fact to achieve a reduc tion of the effective circulating blood volume by trapping several hundred cc of blood in the legs and thighs during methonium induced hypotension by the use of a negative pressure device which applies pneumatic suction to the loner extremities (Figure 6) This technique has produced controlled hypotension in patients who were resistant to the hypotensive effects of the methonium compounds alone has permitted the use of smaller doses of metho nium compounds and thereby helped to reduce post operative hypotension, and has allowed a better control over the level of the blood pressure which can be raised or lowered promptly by decreasing or increasing the nega tive pressure applied to the legs (420 230) ·36 CONTROLLED HYPOTENSION danger of anoxic tissue damage, since the increased periph eral resistance produced by vasoconstriction necessitates higher arterial pressures, in order to maintain cellular respiration, than the low pressures which may obtain dur ing arteriotomy The fact that this theoretical danger has not materialized during the clinical series that have been MANOMETER METAL CYLINDER RUBBER DIAPHRAGM SPONGE RUBBER PUMP NEGATIVE-PRESSURE DEVICE SHOWING APPLICATION OF CYLINDER TO PATIENT'S LEG Figure 6 Negative pressure device for enhancing methonium induced hypotension (Reprinted from Saunders J W Lancet 1952 with the kind permission of the author and the publisher) reported may be explained in part by the fact that this is the one type of controlled hypotension in which the circulatory reflexes remain active permitting blood to be shunted to vital organs Certain other disadvantages should be mentioned the equipment is cumbersome and the technique itself is difficult and time-consuming to initiate the dangers of infection and air embolism both exist and have been encountered during the clinical performance of the method and the possibility of clot formation within the apparatus is ever present These disadvantages together with the phenomenon of vasoconstriction, have served to make arteriotomy the least popular of all the techniques ·BP WW.HB 120- BP MM. HG 120 B SYSTOLIC PRESSURE B 100- 100 DIASTOLIC PRESSURE 80- 80 60- 60 40- 40 20 20- O O ARTERIES ARTERIOLES CAPILLARIES VEINS ARTERIES ARTERIOLES CAPLLARIES VEINS SYSTEMIC ARTERIAL PRESSURE GRADIENT IN NORMAL SUBJECT AI SITE OF MAXIMAL PERIPHERAL RESISTANCE B3SITE OF TISSUE RESPIRATION SYSTEMIC ARTERIAL PRESSURE GRADIENT IN THE TOTALLY SYMPATHECTOMISED SUBJECT A PERIPHERAL RESISTANCE REDUCED 8NORMAL CAPILLARY PRESSURE SITE OF TISSUE RESPIRATION ·VII Reduction of Peripheral Resistance Conduction Anesthesia PERIPHE ERIPHERAL resistance resides largely in the variably contractile arterioles and is maintained by the continuous stream of vasoconstrictor impulses arısıng from the brain stem and carried via the sympathetic nerves to the vessel walls themselves Interruption of this efferent sympathetic outflow results in arteriolar dilatation and thus effects a reduction of peripheral resistance The capacity of the vascular bed is increased thereby relative to the total circu lating blood volume and this disruption of the finely adjusted balance between the two produces hypotension It has been argued that a reduction of peripheral resist ance is the most nearly physiological method presently available to induce hypotension for the purpose of achiev ing a bloodless operative field during surgical interven tions (175) The pressure within the vascular tree normally is highest in the aorta and falls progressively as the blood flons through the large and small arteries to the arterioles (267) It is in the vast arteriolar network that the truly pronounced fall in pressure occurs (Figure 7) so that by the Figure 7 The effect of arteriolar dilatation on the level of blood pressure necessary for tissue respiration (Reprinted from Grif fiths H W C and Gillies | Anaesthesia 1948 with the kind permissions of the authors and the publisher) 38 ·CONDUCTION AVESTHICSTA 41 hich can be accomplished relaunchy simply, thus have become the methods of choice for the production of con trolled hypotension by means of conduction anesthesia Total Spinal Block Tlie use of total spinal analgesia for surgical interventions has been practised intermittently by bold pioneers since the ezrliest days following Biers initial demonstration of spinal analgesia in 1899 In 1900 Morton employed spinal analgesia to accomplish excision of the superior maxilla (334) and operations upon the head under spinal anilgesia were reported by Payne as early as 1901 (370) Tait and Caglieri injected at sites as high as the cervical region to obtain total spinal analgesia (469) and Jonnesco utilized this method in over 100 opera tions above the level of the diaphragm (233) Le Filliatre also practised massive spinal analgesia, employing barbotage to achieve high levels of block (281) The hypotensive effects achieved by the techniques of these early workers were appreciated rather than understood Pithin has stated In those days (1912) we Inew little or nothing about pressure changes and our only common concern was whether we had anesthesia we used to marvel at the fact that we had such dry wounds (380) koster in the early 1920s was an ardent advocate of total spinal analgesia and employed it intrepidly for such operations as mastoidectomy and thyroidectomy (258 259) He was thoroughly aware of the marked falls in blood pressure which occurred and approved of them because of the dry wounds that they produced in the non dependent portions of the body Bourne and his colleagues have established total spinal analgesia as a valuable method of anesthesia for chest surgery not least because of the great reduction in the amount of bleeding (56 190 191) It is a matter of present day wonder, in view of the drastic nature of the techniques employed not that so ·40 "CONTROLLED HYPOTENSION time that the blood has reached the capillaries the pres sure is only 32 mm Hg This level of pressure is sufficient to maintain tissue oxygenation and cellular respiration The hypothesis has been put forward that, if the periph eral resistance is abolished by arteriolar dilatation, very low arterial pressures 32 mm Hg or above to be exact --should be adequate to maintain the tissue oxygenation and cellular respiration inasmuch as the energy of the blood column need no longer be expended in overcoming the frictional surface resistance of the arteriolar bed In other words the assumption has been made that under conditions of complete arteriolar dilatation and in the presence of a normal blood volume, normovolemic hypotension should be well tolerated by the organism without danger of tissue anoxia (175) The vasoconstrictor fibers which maintain peripheral resistance belong to the thoraco lumbar (sympathetic) di vision of the autonomic nervous system, and arise from preganglionic cell bodies located in the intermediolateral cell column of all twelve thoracic and the upper three or four lumbar segments of the spinal cord The axons of these cells traverse the anterior roots pass to the trunk ganglia as white rami communicantes and are distributed thence to the peripheral vessels either in the outer coats of the large arteries or via the somatic nerve trunks Blockade of these fibers can therefore be effected by local anesthetic agents acting upon the ventral roots upon the rami com municantes or upon the sympathetic chain itself It has been demonstrated that in order to induce a sub stantial fall in blood pressure it is necessary to block almost the entire efferent sympathetic outflow (89 205) Para vertebral and sympathetic chain blocks while theoreti cally feasible would require too many separate injections and would be too tediously time consuming to be prac tical Spinal or epidural (extradural) analgesia both of ·CONDUCTION ANESTIIESIA 43 paralyzed, and it has been shown that motor block re quires the highest and vasomotor block the lowest con centrations of local anesthetic agent, sensory block occu pying a somen hat middle position in this regard (Table IX) Griffiths and Gillies took advantage of these facts to TABLE IX CONCENTRATIONS OF PROCAINE REQUIRED TO BLOCK VARIOUS TI PES OF NERVOUS TISSUE Type of Nervous Tusue % of Procaine Vasomotor Fiber Sensory Fiber Motor Fiber Medullary Centers 0.2 039-0.5 0,5 -075 1.25-1.8 contrive a differential spinal block in wluch there was motor and sensory paralysis to a level appropriate for the proposed operation but which in addition involved the whole sympathetic outflow and so produced a considerable fall in blood pressure (175) Since a concentration of 02% procaine suffices to paralyze preganglionic sympa thetic fibers the phrenic nerves were not affected when the anesthetic solution becoming more and more dilute was allowed to diffuse into the cervical region of the cord They have termed this total spinal block, which they dif ferentiated from total spinal analgesia in that although the blood pressure was reduced to a level of 70 mm Hg or below by blockade of the entire sympathetic outflow, lesser degrees of sensory and motor bloch obtained and therefore the muscles of respiration remained relatively unaffected (160 161, 175) The basic features of total spinal block as evolved by these workers (Figure 8) have consisted of a minimal in jection of pentothal to induce hypnosis, the establishment of high spinal bloch by 150 to 300 mgm of procaine of 15 ·42 'CONTROLLED HYPOTENSION few patients succumbed during these early trials but that any survived at all (175) The surgeon of the era which marked the beginning of the century worked without benefit of the knowledge of the dangers of anoxia or the facilities with which to combat respiratory failure The relatively low mortality that pertained has been ascribed to the fact that anhydrous cocaine was employed and paralyzed the sensory roots but left the motor roots rela tively unaffected by the weaker concentrations which reached the upper spinal segments For it has now been well established that death under spinal analgesia results primarily from peripheral respiratory paralysis (131 482) As the level of anesthesia rises into the choracic regton, the intercostal nerves are paralyzed and respiration becomes entirely diaphragmatic and hence slow and of small am pluude Further ascension of the level of anesthesia into the cervical region paralyzes the phrenic nerves and causes respiratory failure The comportment of the blood pressure during spinal anesthesia has also been the subject of intensive investiga tion (89 205) Vasodilatation sufficient to effect a reduc tion of arterial pressure occurs only after the highest thoracic segments have been paralyzed due to the fact that with lesser degrees of blockade intense compensatory vasoconstriction occurs in those parts of the body to which the sympathetic outflow remains intact (343) It has been recognized for some time that is possible to produce subarachnoid block of sensory fibers that is accompanied by little or no motor paralysis (16) and that when either cocaine (204) or procaine (411) is deposited around 1 mixed nerve blocking of all fibers does not occur simul taneously The technique of differenual spinal block which was developed by Sarnoff and Arrowood (17, 411, 412 413 414) has been employed to investigate the se quence in which the various types of nerve fibers are ·CONDUCTIO ANESTHESIA 45 vis a tergo (already considerably reduced) be incapable of coping with the additional load Venous return could be improved, whenever clinical assessment of the state of thc circulation dictated, by altering the patient's position (particularly by raising the legs, or tilting the table into Trendelenburg or reverse Trendelenburg, as the situation required) or by abolishing the vasodilatation by the use of vasoconstrictor agents which act peripherally As the viso constrictor paralysis passed off normotension was recstab lished if this did not occur prior to closure a vasocon strictor (methedrine) was employed to reveal potential bleeding points The converse problem that of reestab lishment of normotension too early in the course of opera tion may be circumvented by the use of the continuous spinal technique with intermittent injections of the local anesthetic agent being made as required (173 474) Post operative care must be meticulous with particular atten tion being paid to the maintenance of a 20 degree head down position for the first eight hours As compared to other methods for the production of controlled hypotension total spinal block boasts certain well-defined advantages When the technique is conducted properly and the dosage of the local anesthetic agent for intrathecal administration has been estimated correctly, a profound fall in blood pressure and an extremely ischemic field can be produced in almost all instances Furthermore this is achieved by paralysis of the sympathetic outflow only whereas blockade produced by chemical ganglionic blocking agents acts upon both parasympathetic and sym pathetic ganglia and so introduces other complicating factors Finally high spinal block is part of the anesthetic technique itself, and so acquires a double usefulness, in that it produces motor and sensory paralysis in addition to the sympathetic blochade In this connection it must be emphasized that to obtain the fullest benefits from ·44 CONTROLLED HYPOTENSION BO RECORDINGS OF PULSE RATE, RESPIRATION AND BLOOD PRESSURE OF A PATIENT UNDER TOTAL SPINAL ANALGESIA BP RESP PULSE TIME-MINUTES mm Hg DAY MIR per min JO 20 30 40 60 GO 240- 170 230 160- 220 45- 2104 150-s NO BLOOD PRESSURE RECORDABLE 2001 40 1404 190- 180- 130-1 170 35 120- Union OXYGEN LOPROPANE 1607 150-1 30 1104 100 POST. OPERATIVE READINGS 25 90 120 to- 80- 100- NO BLEEDING COLOUR SATISFACTORY 90- 70- 804 154 60- 704 60 BO- 10 50 HEART RATE 40- CONTROLLED RESPIRATION RESPIRATION RATE V SYSTOLIC AND DIASTOLIC BLOOD PAESSURES CODE PULSE RATE Figure 8 Anesthetic record of a patient under total spinal block (Reprinted from Griffiths H W C and Gillies ) Anaesthesia, 1948 with the kind permissions of the authors and the publisher) to 30 mgm of nupercaine administered intrathecally and maintenance of light general anesthesia with nitrous oxide The patient was positioned meticulously to permit the operative site to remain superior so that bleeding was minimal and the patients blood volume remained con stant Since there was generalized arteriolar and post arteriolar dilatation with considerable pooling of blood in the dependent portions of the body emphasis was made of the fact that the anti gravitational resistance to venous return must not be allowed to be too great, lest the arterial ·CONDUCTIO ANESTHESIA 45 vis a tergo (already considerably reduced) be incapable of coping with the additional load Venous return could be improved whenever clinical assessment of the state of the circulation dictated, by altering the patients position (particularly by raising the legs or tilting the table into Trendelenburg or reverse Trendelenburg, as the situation required) or by abolishing the vasodilatation by the use of vasoconstrictor agents which act peripherally As the vaso constrictor paralysis passed off, normotension is recstab Itshed if this did not occur prior to closure, a vasocon strictor (methedrine) was employed to reveal potential bleeding points The converse problem that of reestab lishment of normotension too early in the course of opera tion may be circumvented by the use of the continuous spinal technique, with intermittent injections of the local anesthetic agent being made as required (173, 474) Post operative care must be meticulous, with particular atten tion being paid to the maintenance of a 20 degree head down position for the first eight hours As compared to other methods for the production of controlled hypotension total spinal block boasts certain well-defined advantages When the technique is conducted properly and the dosage of the local anesthetic agent for intrathecal administration has been estimated correctly, a profound fall in blood pressure and an extremely ischemic field can be produced in almost all instances Furthermore this is achieved by paralysis of the sympathetic outflow only whereas blockade produced by chemical ganglionic blocking agents acts upon both parasympathetic and pathetic ganglia, and so introduces other complicating factors Finally high spinal block is part of the anesthetic technique itself, and so acquires a double usefulness in that it produces motor and sensory paralysis in addition to the sympathetic blockade In this connection it must be emphasized that to obtain the fullest benefits from sym ·46 'CONTROLLED HYPOTENSION' spinal block it is necessary to ensure sympathetic paralysis to a high level even if the sensory and motor blocks are restricted to the segments supplying the operative field since otherwise the compensatory vasoconstriction occur ring in the distribution of the unblocked sympathetic fibers may actually increase rather than reduce, bleeding Granted, however, that a low head of arterial pressure associated with vasodilatation and a normal blood volume carries less theoretical danger than illusory higher arterial pressures accompanied by vasoconstriction and a reduced blood volume controlled hypotension produced by spinal anesthesia still carries with it those inherent capac ities for catastrophe which have become the hallmark of these techniques Furthermore, the usual disadvantages associated with spinal analgesia such as headache sepsis, and the lihe still apply The technique lacks the controlla bility that is obviously desirable and found to some degree with certain ganglionıc bloching agents (ie arfonid see Chapter VIII) Finally when a spinal block has been ad ministered to a sufficiently high level to permit upper abdominal or mid abdominal surgery assisted respirations may be necessitated by a diminution of respiratory ex change, and this maneuver by increasing intrapulmonary pressure and therefore venous bach pressure may actually cause an increase in vascular ooze and defeat utterly the objective of the technique Epidural Bloch Epidural analgesia has been advocated for the control of hypertension in eclampsia and the tox emic states of pregnancy on numerous occasions during the past decade but only recently has it been utilized to produce intentional hypotension during surgical proce dures (62, 63 114) Indeed one of the major advantages ascribed to epidural analgesia in the past has been the ab sence of effect upon blood pressure This is of course true only if the block is truly segmental and the number of seg ·CONDUCTION ANESTHESIA 47 ments blocked are few in number However, if tlic block extends over the lumbar outflow and well up into the thoracic segments, sufficient sympathetic fibers are para lyzed to result in a profound fall in arterial pressure (89, 205) Bromage has been a leading exponent of this method for producing controlled hypotension" and has patterned his technique closely after total spinal block as developed by Gillies, extradural block being substituted for the sub arachnoid block (62, 63) The advantages cited include all those attending spinal bloch, but without the inherent dangers of headache meningismus and the like There remain the disadvantages of the greater difficulty in per forming epidural block as compared to the performance of lumbar puncture the admitted inability to prejudge the effective height of an epidural block with the same degree of accuracy as a subarachnoid block, the grave hazard of massive subarachnoid injection the possibility of infection of the epidural space and a failure rate of 14% (even in obviously expert hands) (63) One novel method of controlling bleeding in the oper ative site by the use of epidural analgesia has been the establishment of partial sympathetic blochade, sufficient to induce a mild hypotension, but insufficient to prevent an intense compensatory vasoconstriction in the upper part of the body (343) This combination of generalized hypotension and localized vasoconstriction in the operative site has been exploited particularly in the fenestration operation and other forms of cranial surgery (168) ·VIII Reduction of Peripheral Resistance. Ganglionic Blockade PERIPHERAL resistance can be reduced by interrupt ing the continuous flow of vasoconstrictor impulses to the arterioles at any point in their route Of all the methods for inducing hypotension by the reduction of peripheral resistance the use of ginglionic blocking drugs has proved to be by far the most popular technique in the production of controlled hypotension (see Table VIII), due in large measure no doubt to the fact that the administration of these agents requires merely a simple intravenous injec tion Certain generalızations can be made concerning the use of these drugs They are not anesthetic agents in them selves although clinically the hypotensive state does seem to be associated with a need for less general anesthesia than normal These autonomic ganglionic blocking agents paralyze both parasympathetic and sympathetic ganglia thus introducing undesirable complicating factors in cer tain instances Finally, the failure rate (that is the failure to produce hypotension) is often high when these drugs are employed for that purpose much higher than that encountered in the use of either arteriotomy or the various methods of conduction anesthesia that are utilized to re duce peripheral resistance The Methonium Compounds Pentamethonium and heximethonium are respectively the five and six carbon 48 ·49 GANGLIOVIC BLOCKADE atom homologues of the polymethylene series of metho nium compounds (Figure 9), the pharmacological proper ties of which were described by Piton and Zaimis in 1948 (363) The ten carbon atom homologue, decamethonium, THE METHONIUM COMPOUNDS POLYMETHYLENE BIS TRIMETHYL AMWONIUM COMPOUNDS DECAYETHONIUM (CH₃'3 CH₂ CH₂ CH₂ CH₂ CH₂ CH₂ CH₂-CH₂ CH₂ CH₂ (CH3's BR BR HEXAMETHONIUM (Hylsy CH₂ CH₂ CH ₂ CH ₂ CH ₂ CH 2 N (CHy's DEXTALETHONTUM (CH3'3 Ņ CH₂ CH₂ CH₂ CH₂-CH₂ N (CH3's 1 Figure 9 The methonium compounds I which has a potent myoneural junction blocking activity (350) has achieved widespread use for the production of skeletal muscle relaxation during clinical anesthesia (348) Pentamethonium and hexamethonium on the other hand do not block the myoneural junction to any such signifi cant degree but do inhibit transmission of nervous im pulses through the autonomic ganglia of the sympathetic and parasympathetic nervous systems (364) These potent and specific ganglionic inhibitors apparently act to para lyze ganglionic transmission by raising the threshold of the ganglion cell to acetylcholine released at the pregang Jionic nerve endings (365) It is this blockade or inhibition ·50 CONTROLLED HYPOTENSION of ganglionic transmission which is responsible for the major pharmacological properties of penta and hexa methonium vasodılatation fall in blood pressure, and an increase in blood flow and elevated skin temperatures in the extremities (14 15 71, 177, 423, 472), inhibition of intestinal peristalsis, inhibition of gastric secretion and reduction of gastric motility (108, 237, 238), inhibition of salivary secretion (472) and dilatation of the pupils together with some disturbance of accommodation of the eye Clinical application of these pharmacological properties has been made by the employment of the methonium compounds for the treatment of gastric and duodenal ulcer (237 238 433), peripheral vascular disease (71, 136 137, 146 427) acute ventricular failure (499), intractable hic cup (212, 301 302) toxemias of late pregnancy (330 374 473) and most importantly hypertension (74 93 143 305 307 386, 431 453, 455) The administration of these drugs in the medical therapy of the various hypertensive states has brought to light a number of points of some im portance in connection with their use in the production of controlled hypotension in anesthesia and surgery It is nou generally accepted that although both penta and hexa methonium will produce vasodilatation and a fall in blood pressure the six carbon homologue is prob ably the more predictable and dependable of the two in this regard (74 140 456) however it should be pointed out that not all observers concur in this vien (33) It must be recognized that tolerance may develop to these drugs and for this reason it may become impossible to maintain a satisfactory hypotension (142 252, 473) Indeed, indi vidual resistance may obtain from the very commencement of therapy so that a significant fall in blood pressure is never achieved (30) On the other hand prolonged hypotensive effects may ·GANGLIONIC BLOCKADE 51 follow the use of these agents (495), particularly in the presence of kidney disease and impaired renal function, since these compounds are excrcted almost quantitatively in the urine by both the experimental animal (513) and man (324) The mechanism of the renal cxcretion of the methonium compounds 1175 studied by comparing the clearances of these substances with the simultaneous clearance of inulin, and from the methonium/inulin clearance ratios so obtained it was clearly evident that the renal excretion of methonium compounds is due mainly to glomerular filtration with only minimal tubular excre tion (512) Therefore, even in the absence of renal disease, methonium induced hypotension may decrease glomerular filtration sufficiently to delay excretion of the drug and thus produce a vicious cycle of prolonged activity (306 308) There is also the further danger of bromism or iodism (217, 287, 361 392, 460) if renal function is ab normal or if large doses of either of these salts are em ployed over a prolonged period of time however, this hazard can be circumvented by the use of the bitartrate or chloride preparations (75) Finally there is the every grave problem of dosage, and especially of initial dosage (30) for the individual varia tion in response to a given dose of these substances is im mense (142, 144 289), varying not only between patients but also in the same patient at different times (499) On the one hand this may make a satisfactory therapeutic response to the administration of these drugs difficult or even impossible to attain (252 289 341) and on the other hand a sudden and extreme hypotension may be induced and result in pathological damage to vital organs (213 454), particularly when vascular sclerosis already exists Penta and hexa methonium were employed first in anesthesia as antidotes to the muscle relaxant decametho nium ($50) before the hypotensive effects of these com ·52 CONTROLLED HYT OTENSION pounds were generally appreciated It became apparent immediately that these drugs produced a profound fall in blood pressure when administered to the anesthetized patient (227) and that they should not be employed as antagonists to myoneural blocking agents for this reason However, this hypotensive effect was seized upon immedi ately as the basis for a technique of controlled hypoten sion' (98, 120), and the success achieved thereby led rap idly to the extensive use of the methonium compounds for the medical therapy of hypertension (74 93 143 305 307 386 431, 453, 455) The administration of methonium compounds to induce hypotension for the reduction of bleeding during opera tive interventions has nou become exceedingly wide spread (18 19, 59 78 79 96 110, 123, 124, 126, 127, 211 214 224 231, 239 248 274 279 285 291 303 315, 340 347 349 373 390 399 435 440 465, 479 491 494 502) A number of different techniques have been developed by the many workers who have employed the methonium drugs to induce hypotension but these techniques differ mainly in detuls and minutae The broad general plan of the majority of these techniques is similar to that illus trated in Figure 10: The anesthesia is induced by the administration of intravenous pentothil intubation is per formed (a muscle relaxant usually being employed to facilitate this maneuver) and anesthesia is then main tuned with an inhalation agent (nitrous oxide cyclopro pine ether or trichlorethylene (98 120 127) The metho nium salt is then administered intravenously to produce hypotension hexamethonium consistent achieving this effect and for that reason enjoys a greater vogue than the pentamethonium homologue (19, 59, 79 127 214 231 239 279 303 491 494 502) Two schools of thought have developed regarding dosage one group of workers feels that 1 large (50 to 100 mgm) initial dose is 15 more in ·GANGLIOVIC BLOCHADE 53 necessary to achieve blood pressure levels of from 55 to 65 mm Hg, which will persist for from 40 to 60 minutes, (127) while a second group feels that much smaller doscs (5 to 30 mgm) can be administered every 20 to 30 minutes MEMORIAL HOSPITAL ANESTHESIA RECORD NAVE ROOW_DATETI.PL LA LA LA tim putr 24 AD40100 M surya Anestheid DP 10 ho 120p 02 Phone tion Orol Porte #38 2 00 2010 Alconci 5 ore 4 260 250 240 230 220 200 RECOPERATIVE 100 Taylz 160 ABON 120 Sol SCOPOL Strona! 100 80 SUPALCACATAN 60 40 BU DUCTION Smooth 20 LATERAKE QK ty Fluld Comotion 1 CLOSE Sott factory INCISION SPECIME too of SINGS CH SPOK COUNT Contact to 1000€ € 10 ME turc Bood300 N.S__500 € ME ANOU NP fon 0.7 ms man ..50 m bien Cor! Om of Ponc - Chroni Poner of ne om 293_O THYE Q_$425 c_ente Fem MEW Figure 10 Anesthesia record of hexamethonium hypotension (Re printed from Boyan C P and Brunschwig A Surgery 1952 with the kind permissions of the authors and the publisher ) ·54 CONTROLLED HI POTENSION as the clinical conditions warrant (59, 462) The rationale behind this latter technique has been carried to its logical conclusion by a few who have employed hexamethonium in a dilute intravenous infusion (274, 394) A certain group of patients (about 15%) are resistant to the effects of the methonium compounds it is usually young and robust individuals who fall into this category (126) An other, smaller number of patients develop resistance to repeated doses and it is for this reason that some workers feel that the initial dose must be large enough to achieve the desired fall in pressure, for the required duration of time without recourse to repeated administration (127) Following the initial fall in blood pressure the patient is positioned so that the operative site will be superior to the other portions of the body, and this maneuver usually provides a further reduction of the systolic pressure due to pooling of the blood in the dependent portions of the dilated vascular system (71) Operation is then begun Bleeding is usually minimal, but all the blood that is lost must of course, be replaced in toto Operation generally proceeds with dispatch and the operative time is dimin ished to a considerable extent There is a marked differ ence of opinion concerning the desirability of employing vasoconstrictor agents at the end of operation for the pur pose of raising the pressure and revealing potential bleed ing points prior to closure of the wound (197, 198) the argument against the use of these drugs is that clots and thrombi which have formed in the cut dilated vessels will be retained in situ if the vessels gradually regain tone and contract down about the formed clots whereas sudden increases of intravascular pressure produced by vasopressor drugs will tend to blow out such clots (see Chapter IX) Post operative care must be meticulous perhaps more so with this technique than with other forms of controlled hypotension for the methonium compounds may have ·GANGLIONIC BLOCKADE 55 prolonged effects upon vessels, making changes in the patient's position dangerous for several hours after their admunistration, even though the blood pressure has re turned to normal when the patient is in the horizontal position (71) Arfonad Arfonad, a thiophanium compound with po ARFONAD 00 N.CHCHA GMA CH2 1 HO CH OH-HO сн. CHE сне сна 802-CHOCH CH3 ане- он, 00 OHC 6%,4 (1, DIBENZYL 2' KETOIMIDAZOLIDO 1 * 1,2- TAIMETHYLEME THIOPHANIUM d CAMPHOR SULFONATE Figure 11 Arfonad tent ganglionıc blocking activity (384) has afforded the anesthesiologist a more controllable method of inducing hypotension by means of reduction of the peripheral resistance than can be attained by either conduction anes thesia or the use of the methonium compounds (344) Chemically this drug is d 34 (1 3 dibenzyl 2 ketoimida zolido) 1 2 trimethylene thiophanium d camphor sulpho nate (Figure il) It apparently has direct vasodilator ·56 CONTROLLED HYPOTENSION properties as well as potent ganglionic blochading activity (300) and single intravenous doses of 0 1 or 02 mgm per kgm of body weight will produce a prompt but evanescent depressor response of the arterial pressure (417) Thus it is possible to employ the drug by a continuous intravenous infusion technique to provide graded and rapidly reversi ble falls in arterial pressure It has been administered in this manner in the treatment of acute pulmonary edema in hypertensive crises (95, 410 415 416, 417, 418 419) to control sympathetic overactivity in ulcerative colitis (511), and in the management of hypertensive complications of pregnancy (22) The mechanism responsible for arfonad s very brief action is poorly understood but there is evi dence that at least 30% of the compound is excreted in the urine, apparently unchanged with great rapidity (156) The use of arfonad in controlled hypotension during surgical interventions has been by the continuous infusion technique, and has provided a degree of control over the level of the blood pressure on a minute to minute basis that has not been obtainable with other methods of induced hypotension The anesthetic techniques and man agement have been very similar to those employed when hypotension is achieved by the administration of the me thonium compounds (4 28 76 102, 113 218 251, 286 310 329, 400, 401 402 403 437 489) One innovation made possible by this drug however, has been the development of a modified technique of controlled hypotension (286) This modified concept has been based upon to important facts First that the level of the systolic arterial pressure necessary to produce a relatively bloodless operative field viries tremendously between individual patients and therefore the exact level to which the pressure must be lowered cannot be foretold with any degreee of accuracy prior to actual operation This knowledge can be obtained only after suitable pos ·RADICAL 01 09 MASTECTOMY DATE 1/1/07 O$1 031 110 100 10 00 70 60 DOS 10 A OC VASCULAR IL NO PLZKOING IN 1700 ONINMIDJI ONNOM 01 permission of the publisher ) ton L. ) and Grosskreutz DC Surgery 1954 with the kind induced hypotension (Reprinted from Little D M Jr Hamp Figure 12 Anesthetic chart of modified technique of arfonad GANGLIOVIC BIOCLADF FLOW RATE IN MOM PER 11 MIN ARFONAD ht 180 810 OU 110 MINUTO TIME AIENTO PENTOTHAL-QUOCINYLOHOLINE NITROVI OXIDETRICHLORETHYLENE INTRAVENOUS ENDOTRAONZAL - NOMREINLATKINO METHODS 37 ·58 CONTROLLED HYPOTENSION turing of the patient and direct observation of the bleed ing--or lack of it in the operative field itself Second this level of optimal pressure is often much higher than the dangerously low pressures (50 to 60 mm Hg) often advocated in the past Indeed a significant reduction in PENDIOMIDE CIBA 9295 C2H5 C2H5 (CH3)2 -N-CH2-CH2-- CH2 - CH2 - N-(CH3'2 BR CH3 BR PENTAMETHYL-DIETHYL-3-AZA-PENTANE - 1,5-DIAMMONIUM DIBROMIDE Figure 13 Pendiomide blood loss is frequently noted at pressures of 90 to 100 mm Hg and this may represent only a 10 to 20 mm Hg de crease in pressure from the pre operative normal Under such circumstances the benefits of controlled hypoten sion become available to the patient at less risk of major sequelae In this modified technique (Figure 12) following the completion of anesthetic inducnon and proper posturing of the patient the arfonad infusion in a 0 1% concentra tion is started and run at a sufficiently rapid rate to evoke a substantial fall in arterial pressure As the pressure is being lottered, repeated blood pressure readings are corre lated with the degree of vascular ooze visible in the wound in order to ascertain the all important level of pressure ·GANGLIONIC BLOCKADE 59 which will provide control of excessive bleeding during operation The infusion rate is then regulated to muntain this blood pressure throughout that part of the operation during which it is desirable to control the amount of CRANIOTOMY RESECTION OF ARTERIO VENOUS ANEURYSH 170 110 100 140 100 10 00 60 10 40 10 10 10 16 TIME REMARKO 30 48 50 75 10 109 120 120 180 6 O 198 210 223 240 203 ZTD 2300 3 OTSIKURS 18 DATURATED • MLAD ELEVATED 11 PENDIOMIDE 40 MIN t CRANIOTOMY DUCISION PENDIOMIDE 16 MIN IL PERDIOMIDT 20 MOX 3 BONE FLAP TURNED PENDUOKIDE 80 MON 13 PENDIOMIDE DRIP ON • BLOOD STARTED RY PERDIOMEDE TO MOM 14 PERDIOMIOK DRIP OTP & MENDIONIDE 30 MIN. 10 PIXDIONDE 30 NOW 18 TALLE LLYEL Figure 14 Anesthetic record of hypotension induced with pendio mide (Through the kind courtesy of Dr CR Stephen) bleeding At the end of surgery or in the event of hemor rhage or similar surgical exigency normotension can be restored rapidly by merely discontinuing the infusion Arfonad is not quite the panacea for controlled hypotension however for even this admirable drug has cer tain disadvantages such as the development of tachyphy laxıs the occasional onset of tachycardia under its effect and rarely prolonged hypotensive effects Pendiomide A third method of chemical ganglionic blockade for the purpose of lonering peripheral resistance ·60 CONTROLLED HIPOTENSIOV has been by the administration of the diethylenetramine derivative, pendiomide (188) This drug, chemically is N,N,N',N',3 pentamethyl N N diethyl 3 aza pentane 5 diammonium dibromide (Figure 13) and it has been shown to have marked ability to inhibit the synaptic trans mission of impulses through autonomic ganglia (37 38 44 262, 294, 314) Pendiomide has been employed for the reduction of intra ocular pressure in glaucoma (44) for the treatment of eclampsia (44), for the therapy of herpes zoster (346), for relief of bladder tenesmus during cystos copy (428) for the therapy of acute pulmonary embolism (91 429) and of course, for the production of controlled lıypotension during surgery (24 41 80 106 155 187 188 189 235, 254 407 451 478 516) The anesthetic techniques and management which have been utilized in conjunction with the use of this agent for the production of controlled hypotension have been very similar to those described for methonium or arfonad induced hypotension (Figure 14) A single intravenous injection of pendiomide has an acute effect of five to 10 minutes duration complete recovery occurring in about 30 minutes Pendiomide is therefore somewhat between the methonium compounds and arfonad as far as duration of activity is concerned and the average dose necessary to achieve an optimal hypotensive effect is between 50 and 100 mgm administered at the rate of 10 mgm per min ute Its advantages include high specificity of action and lou toxicity while its major disadvantages are the facts that the dosage is unpredictable and that some patients are resistant to the effects of the drug It appears to be less controllable than arfonad although more controllable than the methonium compounds ·IX Physiological Considerations Gillies Es has referred to the techniques of induced hypotension during anesthesia 75 physiological trespass (161) and there an be no doubt that they frequently do exceed the bounds of physiologicıl rectitude It has been a source of considerable amazement that so many anesthe siologists and surgeons trained to abhor and combat any deviation from normotension, should so suddenly embrace the reactionary philosophy of deliberate hypotension A source of even greater amazement has been the fact that they have done so in the face of a glaring lack of funda mental investigation into the profoundly disturbed physi ology that is inherent in these techniques It would seem imperative that those employing controlled hypotension should understand fully the nature of the physiological derangements so produced particularly as to the state of such vital organs as the heart the brain the liver and the kidneys The Level of the Blood Pressure The levels of the blood pressure sought (but presumably not always at tained) in 27 930 cases conducted under the techniques of controlled hypotension (197 198) are recorded in Table X It is worth noting that these blood pressures low as they may seem in many instances were in all probability even lower in actual fact Woodhall and his associates have demonstrated a significant variation between the pressure readings obtained by the arm cuff method and the actual systemic intravascular pressure as recorded by a Sanborn electromanometer from the cannulated radial 61 ·62 CONTROLLED HYPOTENSION artery during controlled hypotension produced by gang lionic blocking drugs The arm cuff method showed an werage fall of 34 6% in blood pressure under these condi tions, Thereas simultaneous strain gauge recordings indı TABLE Y THE LEVEL OF BLOOD PRESSURE SOUGHT IN 27 930 CASES OF CONTROLLED HYPOTENSIOV Great Britain and Ireland 21,125 Cases US 4 6,805 Cases Grand Total 27,930 Cases Blood Pressure Level 4,571 60 Mm Hg or Less No Fixed Level but Above 60 mm Hg Pre operative Diastolic Level 60-80 Mira Hg 70-80 mm Hg 80 90 Mm Hg 90 Mm Hg 100 Mm Hg Not Stated 6 847 5 727 1 892 666 232 1 690 329 968 50 2,588 166 2 664 3 4 900 968 50 9435 5 893 4056 669 282 1 727 37 (Reprinted from Little D M Ir Induced hypotension in anesthesia and surgery Anesthesiology 16 320 1955 with the kind permission of the publisher ) cated an actual fall of 52 9% in radial arterial pressure (507) Low levels of arterial pressure are undoubtedly seldom physiological when accompanied by vasoconstriction, but a considerable body of evidence has been presented to sup port the contention that hypotension per se, is not neces sarily a dangerous phenomenon if brought about by arte riolar dilatation and without loss of circulating blood volume Phemister and his co-workers have shown that reduction of the systolic blood pressure in rabbits to 25 to 40 mm Hg produced by stimulation of the aortic de pressor nerve could be maintained for a far longer time without lethal outcome than an equal reduction of pres sure produced by hemorrhage (379) Dale and Lardlau ·PAYSIOLOGICAL CO SIDFRATIONS 63 found that a carefully adjusted infusion of acctylcholine could produce dilatation of the cat s arterioles and lower the blood pressure to 30 to 40 mm Hg, although the veins remained well filled and the venous return to the heart was normal, on the other hand when a similar reduction of pressure was produced by a slow infusion of histamine, the venous return failed and the blood was found to be in the engorged capillary bed (94) ? condition which Moon has described as irreversible shock (328) It seems evident from these animil ini estigations, as well as from comparable observations during many thou sands of clinical experiences with the techniques of con trolled hypotension that the mammalian organism can indeed survive prolonged periods of profound hypotension produced by arteriolar dilatation and undoubtedly can do so under such circumstances far more often than it can survive a similır hypotension produced by either capillary dilatation or hemorrhage The interesting question arises however as to the effect of such low pressures upon the organisin itself when it does survive and the role that these hypotensive levels of blood pressure may play in pro ducing mortalities in those who fail to survive Effects on the Cardiovascular System Studies of the pulse rate during operations performed under high spinal analgesia have usually revealed a definite bradycardia (296 297 409) whereas hypotension induced by a ganglionic blocking agent was more likely to be accompanied by a relative (285) or definite (390) tachycardia The discrepancy between these effects of controlled hypotension upon the heart rate may be explained in part by the fact that the sympathetic blockade of high spinal analgesia evokes the Bainbridge reflex the lowered venous pressure within the great veins producing reflexly an increase in vagal tone a bradycardia and a prolonged diastole (175) whereas hypotension induced by ganglionic blocking ·64 CONTROLLED HYPOTENSION agents is accompanied by parasympathetic blockade in addition to the sympathetic blochade and in some indi viduals the former may predominate, with a resultant tachycardia The stroke volume of the heart during operations per formed under high spinal malgesia was reduced from an average control level of 57 3 cc to 28 3 cc and the cardiac output and cardiac index fell to 40% of the basal level (296 297 409) Studies of the cardic output during hypo tension induced by ganglionic bloch zde have shown con flicting results due in large measure to differences in the clinical conditions during the observations, particularly as concerns the degree of hypotension and the posture of the subject during the period of hypotension in the recum bent position cardiac output in the unanesthetized subject was usually well maintained (145 499) When however such patients were tilted from the horizontal to 1 foot down position a significint reduction of cardiac output occurred Cardiac output in surgical patients under condi tions of controlled hypotension' induced by methonium compounds was reduced 53% on the average and as much as 75% in certain patients (445) Investigation of the car diac output by ballistocardiography during arfonad induced hypotension likewise showed a diminished stroke volume although the accompanying compensatory tachy cardia prevented marked alteration of the minute volume (401) Measurements of right auricular pressure during high spinal block demonstrated a profound reduction (296 297 409) which would be expected in view of the fact that the venous pressure is greatly reduced and there is a marked diminution in venous return to the heart both after the induction of high spinal analgesia as well as fol lowing the administration of ganglionic blocking agents (185 427) Pulmonary arterial pressure was decreased ·PHYSIOLOGICAL CONSIDERATIONS 65 markedly also, as much as 34% following high spinal anal gesia (409) and to an even greater extent after the induc tion of hypotension with ganglionic blocking agents (162) The oxygen consumption, in the studies made of high spinal analgesia, decreased an average of 33% but the arteriovenous oxygen difference rose from an average of 407 vol % to 6 79 vol % The oxygen saturation of the arterial blood was not significıntly altered in spite of a slight decrease in the arterial oxygen capacity (tvluch was due to an unexplained fall in hematocrit that amounted to 33%) (296 297, 409) The oxygen consumption in the cat made hypotensive by the administration of either arfonad or hexamethonium was likewise perceptibly re duced (369) The calculated work of the left ventricle was decreased on an average of 85% from the control level (297 409) and led to a marked reduction of coronary flow in the surgical patient undergoing high spinal block (409) A similar decrease in coronary flow has been found in the experi mental animal made hypotensive by either the subdural injection of procaine or the intravenous administration of etamon (115), but more recent studies in anesthetized dogs with renal hypertension (experimental perinephritis) made hypotensive by the intravenous injection of hexa methonium showed that coronary blood flow increased slightly and that coronary vascular resistance decreased during the period of reduced blood pressure (92) A re duction of coronary flow would of course be profoundly significant from the clinical viewpoint and some insight into the matter has been gained from electrocardiographic tracings made during controlled hypotension (72 195 467) Intravenous hexamethonium and pentamethonium are capable of producing changes in the EKG character ized by a vacıllating pulse rate extrasystoles, alteration in the site of the pacemaker and other arrhythmias and de ·66 CONTROLLED IIYPOTENSION pression of the ST segment and T wave, suggestive of coronary insufficiency (127, 179) Similar changes occur during the conduct of controlled hypotension including depression of the ST segment and the T wave, disappear ance of the Pwave and shortening of the PR interval (467) but these changes have been dismissed by the pro ponents of induced hypotension as not indicating myocardial ischemia (230) this is perhaps an unjusufiable assumption The peripheral blood flow as measured in the digits of the hands and feet is increased under high spinal anal gesia despite the hypotension and decre sed cardiac out put (296 297, 409) Ganglionıc blockade with methonium compounds also effected an increase in the mean blood flon of the foot from an average control level of 10 cc/100 cc of foot volume to an average level of 9 8 cc /100 cc of foot volume (427) This increase in peripheral blood flow following the administration of hexamethonium and pentamethonium to the unanesthetized being (14 71 145) however was not demonstrated in the patient under anesthesia (445) Splanchnic blood flow following the administration of hexamethonium to the unanesthetized recumbent human subject fell in proportion to the fall in arterial blood pressure but no change was found in splanchnic vascular resistance (388) This is rather surprising in view of the fact that splanchnic vasodilatation has long been thought to play an important role in the production of the hypotensive state This data on splanchnic blood flow has been confirmed by studies during both low and high spinal analgesia in human beings, no significant changes in splanchnic resistance or oxygen consumption being found (338) The circulation time is greatly prolonged following both spinal analgesia and ganglionic blochade produced supine human ·PITYSIOLOGICAL CONSIDERATIONS 67 by ganglionic blocking agents (162), sometimes to twicc the normal rite (145) and it is obvious that this slowing of the circulation may predispose to thrombosis and cm boli particularly if the sessels arc sclerotic Effects on the Brain Since the brain, of all the tissues of the body is the least tolerant of inoxia, there has been considerablc speculation over the effects of controlled hypotension upon that orgin Trio avenues of investiga tion have been pursued in this regard the nitrous oxide technique developed by hety and Schmidt has been em ployed to measure cerebral blood flow (249) and cerebral function has been measured by both psycho-physical (345) and purely physical (65 425) tests Studies of cerebral hemodynamics during induced hypo tension in the unanesthetized subject have yielded con flicting results and cannot in any event be interpolated directly into the situation that pertains during controlled hypotension inasmuch as general anesthesia becomes a factor that cannot be ignored in the equrtion These in vestigations have been of great interest however for they bring out several facts of importance In the first place it appears that in the supine position cerebral oxygen consumption is maintained near normal whether the induced hypotension is accompanied by a sig nificant decrease in mean cerebral blood flow (331 332 337) or not (92 103) and that the compensatory mecha nism responsible for this maintenance of near normal cerebral metabolism includes both a decrease in cerebral vascular resistance (92103) and a more complete extrac tion of oxygen from the blood flowing through the brain as measured by an increased arteriovenous oxygen differ ence A second important fact that has been revealed is that when a severe head up tilt of 30 to 40 degrees is superim posed upon hexamethonium induced hypotension (464) ·68 CONTROLLED HYPOTENSION in the unanesthetized subject these compensatory mecha nisms no longer suffice to maintain cerebral metabolism and a critical level of cerebral blood flow is reached (be tween 23 9 and 45 8 cc per minute per 100 Gm Brain tis sue with an average value of 35 0 cc per minute per 100 Gm brain tissue) at which the signs and symptoms (ie perspirition, cold clammy skin yawning somnolenice slurring speech nausea and occasionally, convulsions) of cerebral ischemia become manifest (138) Similarly when hypotension is induced acutely by differential spinal bloch, there follows a significant diminution of the mean cerebral blood flow (250) Finally and perhaps very obviously, this critical level of systemic blood pressure at which cerebral ischemia occurs is of course much higher in the hyper tensive subject (100 to 110 mm Hg mean femoral arterial pressure) (138) Investigation of cerebral blood flou under the actual conditions of controlled hypotension during operation has been attempted by measuring the cerebral arterio venous oxygen difference and then calculating the esti mated cerebral blood flow (421) These studies were all made with the patient kept horizontal or nearly so and for this reason the results unfortunately shed no light upon cerebral hemodynamics when Trendelenburg or the re verse Tr lenburg positions are employed during con trolled hypotension Hypotension was produced by the use of hexamethonium and the application of pneumatic suction to the patients legs (230 420) Under these condi tions the arteriovenous oxygen difference was found to be 4 8 vol % (less than normal) and the estimated cerebral blood flow was 46 9 cc blood per minute per 100 Gm brain tissue Since this figure is roughly the equivalent of that found in a healthy adult breathing oxygen it was con cluded that cerebral blood flow was certainly adequate to meet the metabolic demands of the brain in the presence ·PHYSIOLOGICAL CONSIDERATIONS 69 of the decreased cerebral oyigen demand occurring dur ing general anesthesia It was also concluded that sincc the arterial blood pressures of these subjects ranged from 40 to 65 mm Hg during the observations that it may be assumed that controlled hypotension at such blood pres sure levels does not produce deletcrious effects upon the cerebral hemodynamics of the patient remains approxi mately horizontal There is at least suggestne cvidence honcier obtuned both from psycho physical and from purely physical tests of cerebral function that cerebral metabolism is not muin tained at a normal level during controlled hypotension in which the blood pressure is reduced to loss levels and the patient is postured in the head up position Nilsson has adapted the flicher fusion frequency test to the post-operative study of 15 patients who had been operated upon under hexamethonium induced hypoten sion Sıx of these 15 patients showed positive tests indicat ing cerebral injury presumably anoxic in origin and it is most interesting that although the cerebral injuries that were thus demonstrated were not serious five of the six positive tests occurred in patients who had been positioned with the head end of the table raised between 10 to 20 degrees during the operative (and hypotensive) period (345) This indicates that postural ischemia of the brain is 2 very real danger under these circumstances Further evidence in this direction has been supplied by Bromage who employed the electroencephalogram as a measure of cerebral metabolism It has been recognized for some time that the electrical activity of the brain as re corded by the electroencephalogrım becomes abnormal during cellular anoxia the normal alpha rhythm of 10 cycles per second is replaced by slow delta waves of less than four cycles per second and there is a reduction of the total electrical energy of the cortex In three conscious ·70 CONTROLLED HYPOTENSION volunteers who received pentamethonium intravenously and then were postured in a foot down tilt, the severe hypotension so produced was accompanied by coma con vulsions and profound disturbances of cortical rhythm the normal alpha rhythm being replaced by slow delta Haves in irregular combination (65) It is obvious that conclusions drawn from this study must be limited inas much as the surgical patient undergoing controlled hypotension would be under general anesthesia (except during methods based upon conduction anesthesia not supple mented by basal narcosis) under these conditions, cerebral metabolism is reduced almost 30% to 40% and differences between the available oxygen supply and the cerebral oxy gen demand are less likely to occur than in the conscious volunteer Effects on the Liver The anatomy and physiology of the hepatic blood supply are such that a higher critical level of hypotension exists for the liver than for most other tissues The blood supply to the liver is from two sources, the hepatic artery and the portal vein normally the for mer supplies about 20% of the total hepatic inflow at a relatively high oxygen tension (95% saturation) whereas the portal vein supplies the remaining 80% of the blood at a much lower (74%) degree of oxygen saturation When the circulation is slowed as during sympathetic paralysis and hypotension a point may be reached at which such a high degree of oxygen desaturation occurs in the intestinal capıllaries that the oxygen tension of the blood in the por tal vein is nearly as low as that of the blood in the hepatic vein (304) The liver will then depend enurely upon the hepatic artery for its oxygen supply If the flow through the hepatic artery is reduced it may become inadequate for the total needs of the luser and local tissue anoxia will occur This in fact occurs during hypotension The liver ·PHYSIOLOGICAL CONSIDERATIONS 71 which has been subjccicd to moxia becomes unable to form urea from ammonium salts or amino acids (281), loses the power to inactitatc the vasodcpressor material of Shorr (447, 448) and the deterioration of hicpatic function is progressive until a point of irreversiblc clinge is reached (284) This is the scquence of events that may occur under controlled hypotension The estimated hepatic blood flow was decreased 33% from the control value during high spinal analgesia (297) and the hepatic icin oxygen content decreased an average 30% (338) Local anoxia in the liver consequent to the reduced blood flou may then permit the action of VDM it has been observed during a series of laparotomics conducted under epidural blocks which were sufficiently extensive to cause the blood pres sure to fall to 45 to 60 mm Hg that the Invers were dark and cyanotic in appearance and turgid and rubbery in consistency these changes were reversed when the blood pressure was raised by the administration of methedrine or nor adrenaline (64) Occult liver damage may result from this temporary hypoxia (5) Patients with normal pre-operative liver func tions showed abnormal bromsulphalein retention for three to seven days after high spinal analgesia (297) and pathological changes have been shown to occur in the livers of experimental animals after hypotension induced with methonium compounds (432) Indeed hepatic dam age may not necessarily be occult for one fatal case of liver necrosis has been attributed to the use of these techniques (445) Effects on the kidneys Any consideration of the effects of controlled hypotension on the kidneys must distin guish clearly bet een the suppression of urine formation during the period of hypotension and the depression of ·72 CONTROLLED HI POTENSION renal function or the demonstration of morphological changes in the kidney following the restoration of normo tension The formation of urine is by a combination of glomeru lar filtration and tubular reabsorption When the blood pressure is lowered to 70 mm Hg or below in the normal human bemg the hydrostatic pressure in the glomeruli becomes insufficient to maintain filtration and urine for mation may be expected to cease therefore when the arte rial pressure reaches such a level during controlled hypotension Both empirical clinical experience and experimental evidence substantiate this hypothesis Dur ing spinal analgesia in the surgical patient renal function is reduced consistently during periods of hypotension (21 297) The same is true shen the typotension has been induced by ganglionic blockade the lowered systemic arterial pressure in both instances causing a reduction of glomerular filtration effective renal blood flow, and urine formation (253 306 308 321 323 475) The extent of these reductions is dependent upon the intensity of the hypotension a moderate fall in blood pressure will pro duce a decrease in the rate of glomerular filtration for a limuted period of time but after an hour or more there will be a rise in the filtration rate despite the continued presence of hypotension (332 335 337) when the de crease in arterial pressure is profound honever the inulin clearance rate is at a consistently lon level in both man and the experimental inimal (317 432) The suppression of urine formation during the period of hypotension is therefore to be expected if the arterial pressure has been lowered to a significant degree but this fact cannot be construed to mean that renal damage has occurred or will occur in fact it has been argued that even at blood pressures lower than 70 mm Hg the con tinued viability of the renal epithelium is not endangered of effectie ventilation with oxygen is maintained and the ·rii SIOLOGICAL CONSIDERATIONS 73 arteriolar bed is dilnicd by sympathicuc blochadc On the other hand licxamethonium induced hypotension 1175 been shown to causc protcinuria, and the presence of costs and red cells in the urinc post-opcruncly (129) and these findings may (101) be indicatiic of renal dimage (288) At any rate it appears certain the renal dimnge docs in fact occur in view of the lugh incidence of renul complıca tions and their occasional progress to al terminations following the use of the techniques of controlled lypo tension (see Chapter ) The Use of Vasopressor Agents There hasc been marked differences of opinion regarding the adusability of employing vasopressor drugs when it becomes desirable to restore the blood pressure toward normal levels during or at the end of 'controlled hypotension One school of thought has maintained that the blood pressure must be raised prior to closure of the wound in order to permit identification and ligation of all bleeding points since otherwise the danger of reactionary liemorrhage will be great when the pressure finally returns to normal and open Vessels begin to bleed On the other hand there is a second school of thought which feels that to use i vasopressor drug at the end of operation is to defeat the purpose of the tech nique and that to employ one post operatively is to court disaster (440) The reasoning has been as follows during hypotension produced by arteriolar dilatation (1 e, sym pathetic blockade) clots form in the dilated vessels and when the vessels regain their tone following operation they contract down on these formed clots effectively seal ing the vessels however if a vasopressor agent is adminis tered or the blood pressure rises rapidly from any other cause these clots will be expelled and bleeding will ensule There is yet a third group of workers who do not employ vasopressor drugs ordinarily but will do so when the occa sion warrants their use (Table XI) Quite aside from the possibilities of reactionary hemor ·74 'CONTROLLED HYPOTENSION rhage, however, the use of vasopressor drugs also must be considered in the light of recent knowledge of their actions during both anesthesia and hypotension Measurements of the contractile force of the heart have been made with TABLE XI THE USE OF VASOPRESSOR AGENTS IN CO\TROLLED HYPOTENSIOV Anaesthetists in Anesthesiologists Great Britain and Ireland USA Totals Vasopressors not Used Vasopressors Used Vasopressors Sometimes Used 50 38 90 28 63 45 78 101 195 strain gauge arches in intact dogs subjected to hexametho nium induced hypotension and indicate that conditions of hypotension associated with a weakened myocardium should dictate the use of such pressor amines as 1 arterenol methamphetamine or ephedrine, since these drugs will produce an increase in heart force in addition to the well known pressor responses (88) It is also important to re member before employing any vasopressor amines that some of these drugs may precipitate sinister cardiac arrhythmias when administered during anesthesia pro duced by chloroform cyclopropane, or trichlorethylene and even in the absence of those anesthetic agents vasopressor drugs may initiate dangerous arrhythmias if the tissues contain an increased concentration of carbon diox ide (101) Carbon dioxide retention to this extent occurs readily of course as a result of the respiratory depression following the induction of high spinal analgesia or the administration of methonium compounds in the tech niques of controlled hypotension ·X Fatal and Non-Fatal Complications THE PHYSIOLOGICAL derangements inherent in controlled hypotension have resulted in the occurrence of certain fatal and non fatal complications and it has been on the subject of these disasters that the great con troversy over these techniques has arisen As Armstrong Davison has put it, never since the days of the heated controversy about chloroform which divided the anaesthe tists of the United Kingdom has there been a matter which has so raised Emotions end of the see saw with a corresponding depression of the end on which sits Reason It is particularly striking that the adherents of hypotension seem able to discount adverse effects while they presum ably are equally surprised that their opponents see lurk ing dangers in every shadow (101) Complications The complication rate following the use of controlled hypotension is amazingly high The results of questionnaires sent to the members of the Association of Anaesthetists of Great Britain and Ireland revealed this complication rate to be one in every 32 cases the similar questionnaires sent to the Diplomates of the American Board of Anesthesiology reported a complication rate of one in 27 cases and since the total number of complica tions in the 27,930 cases contained in both series was 908 the over all complication rate was one in every 31 cases (Table XII) The most common pertinent complication was reaction 75 ·76 CONTROLLED HYPOTENSION ary hemorrhage, which occurred in 213 cases and thus con stituted 27% of the total number of complications A very great deal of nonsense has been written on the question TABLE XII COVPLICATIONS IN 27 930 CASES OF CONTROLLED HYPOTENSION Great Britain and Ireland 21 123 Cases USA 6,805 Cases Grand Total 27,930 Cases Complication 62 8 24 9 1 Anuria Oliguria Cerebral Thrombosis Retinal Thrombosis Coronary Thrombosis Cardiac Arrest Cardiovascular Collapse Reactionary Hemorrhage Persistent Hypotension Delayed Awakening Blurred Vision Post operatively Others 54 30 20 2 15 7 11 164 3 193 126 28 29 $ 18 22 86 243 78 196 127 45 70 17 Totals Complication Rate 653 1 in 32 255 1 in 27 908 I in 31 (Reprinted from Little D M Jr Induced hypotension in anesthesia and surgery Anesthesiology 16 320 19,5 with the kind permission of the publisher) of reactionary hemorrhage the tendency being to admit the theoretical possibility but to disclaim any knowledge of its actual occurrence It is worth pointing out that in at least eight of these 243 instances reactionary hemorrhage was not just trivial and annoying but sufficiently severe to cause death (see Table XIV) It is unfortunate that there is no data available to indicate whether it is the use or the avoidance of use of vasopressor agents at the cnd of surgery that is most likely to be correlated with the occur rence of reactionary hemorrhage (see Chapter IX) The second most common complication has been a pro ·FATAL AND NO FATAL COMPLICATIONS 77 longed and delayed au akening time after the operation and anesthesia Inic been terminated This phenomenon occurred on 196 occasions and was responsible for 22% of the total number of complications This slow cr recovery following controlled hypotension has becn attributed in the past to either the synergistic effect which ginglionic blocking agents appear to have with general anesthetic drugs or the lowered metabolic rate induced by these drugs and responsible for their sloncr elimination from the body (371) Recent studies suggest that there may be a more important cause in the course of observations on electroencephalographic tracings during induced hypoten sion (65), it was noted that while normal subjects recov ered rapidly and completely when the blood pressure rose above 50 mm Hg an arteriosclerotic volunteer showcd 2 delayed return to consciousness and normal cortical rhythm long after the blood pressure had been restored to a much higher level It is conceivable that the prolonged recovery time seen occasionally in patients who have been subjected to controlled hypotension may be due to cere bral anoxia rather than to the vasodilator drugs them selves Blurred vision in the post operative period was the third most common complication and occurred a total of 127 times It was exhibited exclusively following the use of the methonium preparations and has been attributed to the long lasting action of these drugs upon the eyes power of accommodation While it was surely an inconvenience, it does not appear to have been a complication that carried with it any prolonged deleterious after effects (73 74) Fourth in rank as concerns frequency of complications were disturbances involving the kidneys anuria occurring 62 times and oliguria on 54 occasions Considering the levels of blood pressure sought in the majority of these 27 930 cases of controlled hypotension (see Chapter IX) ·78 CONTROLLED HYPOTENSION' it is rather surprising that there were not more complica tions involving renal function, but these figures do stress the fact that, of all the vital orgins the kidneys are the most liable to damage or dysfunction during induced hypo tension Thrombolic phenomena within essential arterial sup plies occurred a total of 50 times cerebral thrombosis in 29 patients, relinal thrombosis in three patients and coro nary thrombosis in 18 patients There have also been word of mouth reports of mesenteric thromboses, but this complication was not reported on the questionnaires nor has its occurrence been remurled upon in the literature Thrombus formation is an evident danger when the circu lation is slowed to the extent that pertains in controlled hypotension' Cardiac arrest occurred in 22 cases and cardiovascular collapse in 36 cises and in roughly 25% of these cases the morbidity progressed to become a mortality (see Table XIV) Certain other less frequent complications require com ment When the blood is circulating through the periph eral vessels with what amounts to a reduced vis a tergo as is true during normovolemic hypotension the application of external pressure to the walls of those vessels may con stitute a formidable impedance to the flow of blood within the vessel although such pressures would be tolerated well without causing obstruction to circulation under the ordı nary circumstances of normotension What has been termed retractor anemia is an example in point during the conduct of neurosurgical procedures within the cra nium under conditions of controlled hypotension, the retractors employed on the brain substance to provide ade quate operative visualization may so restrict the cerebral circulation in the tissues on which they are exerting pres sure that cerebral anoxia may result (18) This same situa ·FATAL AND NOT TATAL CONrIICATIONS 79 tion can occur in other tissucs thin the brain Pressure necrosis of the laryngcal mucosa luis folloucd the use of an inflated endocriclical cuff in the presence of hypoten sion In another instance, disastrous hortic fcmoral throm bosis followed a difficult ncplirectomy during which large pachs placed in the depths of the wound under consider TarLF VIII CORRELATION OF BLOOD PRESSURF LFVELS WITH THE OCCURRENCF OF COUPLICATIONS IN 6,800 CASES OF "CONTROLLED HIPOTESION Belot 80 Afm 80 mm Hg or Hg abore 3,071 2,661 Cases Cases Complications 7 17 9 1 2 0 5 0 0 Anuria Oliguria Cerebral Thrombosis Retinal Thrombosis Coronary Thrombosis Cardiac Arrest Cardiovascular Collapse Reactionary Hemorrhage Persistent Hypotension 003>p>002 ? significant 002>p>001 significant 25 71 53 0 7 7 001>p>0 001 highly significant 001>p>0001 highly significant 001>p>0 001 highly significant 001>p>0 001 highly significant Reprinted from Hampton L. and Little P M Jr Arch Surg 1953 with the kind permission of the publisher ) able pressure produced compression of the aorta while at the same time the blood pressure had been deliberately reduced to control bleeding Two cases of unilateral blind ness from retinal artery occlusion have occurred appar ently by this same mechanism during controlled hypo pressure on the eyeball by the anesthetic face mask being transmitted through the eye to prevent the flow of blood in the retinal artery (158) Three major generalities may be made concerning these fatal and non fatal complications First it has become very clear that the extent or degree of hypotension is of para mount importance in respect to the occurrence of morbid tension ·80 CONTROLLED HYPOTENSION ities and mortalities Hypotension of the order of 80 mm Hg will be tolerated with far fewer complications than will hypotension below that level of blood pressure (Table XIII) Second it is evident that the duration of hypoten sion is also of significance in respect to the causation of complications 114 hours has been regarded as the upper limit in terms of the length of time that hypotension may be maintained although it is true that induced hypoten $ion has been continued for far longer periods than this without the occurrence of obvious sequelae There is always the possibility, honever, that irreversible shock may follow the use of these techniques and that a method con ceived and begun as controlled hypotension may be come quite literally uncontrolled hypotension (385) Third experimental studies have suggested that, while the extent and duration of hypotension are of obvious impor tance the abruptness of onset of hypotension may be a considerable factor in producing complications (425) The maintenance of the integrity of the cardiovascular system is a delicate and finely adjusted mechanism, and an abruptly induced, acute hypotension appears to be more dangerous than a hypotension of equal proportions that is brought on more slowly Mortalties The deaths which have resulted from the use of the techniques of controlled hypotension have, in general followed the same etiological classifications as the complications and have represented most severe and fatal progressions of those complications In response to ques tionnaires on the subject British anesthetists reported 46 deaths in 21 125 cases or a mortality rate of one in 459 their American colleagues reported 50 deaths in 6 805 cases or a mortality rate of one in 136 cases and the total number of deaths reported in response to both question naires was 96 in 27 930 cases for an over all mortality rate ·81 FATAL AND NO FATAL COMPLICATIONS of one in 291 cases (Table XIV The great disparity be queen the mortality rate in the British Isles and that per taining on the American continent is of interest it may TABLE VIV MORTALITIES IN 27,930 CASES OF "CONTROLLED HYPOTESTOV USA Great Britain and Ireland 21 125 Cases Grand Total 27,930 Cases 6,805 Cases Cause of Death 8 7 9 18 8 8 5 Renal Failure and Anura Cerebral Thrombosis or Anoxia Coronary Thrombosis Cardiac Arrest or Failure Cardiovascular Collapse Reactionary Hemorrhage Following High Spinal Over heparinization (Arteriotomy) Arterial Air Embolisin Aoruc Femoral Thrombosis Pulmonary Infarcts and Edena Persistent Hypotension Neurosurgical Operative Trauma Miscellaneous (Probably not Related) 1 1 1 1 14 7 1 1 14 15 8 Totals Mortality Rate 46 1 in 459 50 1 in 136 96 1 in 291 (Reprinted from Little D M Jr Induced hypotension in anesthesia and surgery Anesthesiology 16 320 1955 with the kind permission of the publisher ) indicate that American anesthesiologists are far less skillful than their British counterparts or it may indicate that the patients subjected to controlled hypotension on this conunent have been selected for indications that have been so urgent that the calculated risks involved are reflected in the mortality rate Renal failure and anuria were the cause of death on nine occasions so that in almost 15% of the cases in which anuria was present as a complication a fatality ensued The ·$ 82 CONTROLLED HYPOTENSION following is a typical case of a mortality resulting from anuria, and also serves to emphasize the dangerous results of hemorrhage during controlled hypotension One death must be attributed to mismanagement of the technique A woman aged 65 years having a combined synchronous abdomino-perineal resection was given 50 mgm hexamethonium bromide Delay occurred in posi tioning her on the table and when the abdomen was opened although the blood pressure was at a satisfactory level of 80 mm Hg and there was no bleeding from the abdominal incision the veins of the pelvis were enor mously dilated and extensive hemorrhage occurred Blood was replaced four pints being given but return to nor mal blood pressure was extremely slow Methedrine was given in repeated doses of 10 mgm and an adrenaline drip was started which kept her blood pressure at 100 mm Hg This was continued intermittently for three days She had complete anuria and died at the end of the third day (Reported on questionnaire sent to the mem bers of the Association of Anaesthetists of Great Britain and Ireland) Cerebral thrombosis and anoxia accounted for the larg est number of deaths 18, and the following case history is illustrative of this sequelae which caused almost 20% of the reported deaths A fit old man with a carcinoma of left pinna for ex cision with block dissection glands of nech Skin flap from occiput and graft from anterior abdominal wall General condition BP 160/85 Electrocardiogram showed slight left ventricular preponderance Anaesthetic Omnopon 1/6 grain scopolamine 1/300 grain Thiopentone 05 gm curare 15 mgm pethidine 50 mgm oxygen cocaine spray cuffed tube Nitrous oxide-oxygen Respiration assisted at first Feet down till 20 degrees Pentamethonium 50 mgm Fifty minute oper ·FATAL AYD VOS FATAI COUPLICATIONS 89 ation during which Icft jugular icin tied Atropinc 1/100 grain Neostigminc 2.5 mgm al cnd Electrocardiograms throughout hypotensive phase showed no change Con sciousness did not return for 41/2 hours post-op Patient then quite normal talling tiling fluid by mouth mox ing all limbs B P 120/80 Next morning 21 hours post operatively found to be scmi-conscious speech slurred left facial palsy Icft arm flacad plantars cxtensor Died 3rd post-operative day PM Very marked atheroma all parts of aorta Leſt internal aroud comnicncement completely occluded by clot and atheroma reduced lumen above clot to pin point Right internal carotid similar plaque of atheroma which had reduced lumen considerably-no dot Right middle cerebral artery recent thrombosis fairly near its origin Recent infarct on right parietal lobe Cerebral arculation was obviously impaired depending mainly on vertebral supply (8-4) Thrombolic mechanisms were the major factor in caus ing death on the eight occasions in which they involved the coronary arteries, as in the next example A fat woman with carcinoma of breast for radical mas tectomy General condition Good BP 172/98 Anaesthetic Omnopon 1/6 grain scopolamıne 1/300 grain Thiopentone 05 gm Nitrous oxide-oxygen tri chlorethylene (does not say whether intubated) Pethi dine 50 mgm BP 130/84 Hexamethonium iodide 20 mgm Taken into theatre Positioned 10 degrees feet down Pethidine 25 mgm BP 98/70 Operation begun Hexamethonium iodide 10 mgm BP 80/58 Remained steady about this les el for 40 minutes when it rose to 90/68 Pulse steady 100-108 Colour good peripheral cir culation satisfactory Further pethidine 25 mgm during this time Just as removal of breast being completed (46 minutes after starting) peripheral circulation noted un ·84 CONTROLLED HYPOTENSION oxygen 95 satisfactory and BP 50/40 Colour of face grey blue Lungs inflated with oxygen Table 10 degrees head down Methedrine 10 mgm iv Pulse imperceptible Fast plasma drip Further methedrine carbon dioxide 5 per cent per cent inflation Operation ended at 64 min utes Condition much improved Colour and breathing satisfactory Pulse 120 B P 92/70 Just under one pint of plasma was given during operation hept in theatre 10 minutes Then as her condition appeared satisfactory patient was transferred on a 10 degree head down trolley to bed which had been blocked Nasal oxygen started Suddenly died 20 minutes post-op PM Both lungs grossly oedematous Air passages not obstructed Small area of infarction in left ventricle An terior descending branch left coronary artery almost en tirely blocked by atheroma (84) Cardiac arrest or failure was the cause of nine of the 96 mortalities reported as in this instance Thirty sıx year old white male undergoing subtotal thyroidectomy for toxic goiter Hexamethonium em ployed at the surgeons request Some signs of toxicity still present in spite of iodine and propylthiouracil treat ment Anesthesia induced with pentothal continued with endotracheal cyclopropane and ether C6 gren with ap parently satisfactory results Thirty minutes later blood pressure fell further and cardiac arrest occurred Cardiac massage performed and later defibrillation Cardiac action was reinstated but the patient failed to recover conscious ness and died four hours later Cause of death not defi nitely determined but presumed to be cerebral and myocardial anoxia (Reported on questionnaire sent to Diplomates of the American Board of Anesthesiology) Cardiovascular collapse was responsible for death in five patients, and may be exemplified in the following case record ·85 FATAL AND NON FATAL COMPLICATIONS A very old man for emergency excision of arcinoma of larynx General condition Very poor risk Docp x ray therapy regarded as no avail BP 110/100 Some canosis duc to obstruction Accessory muscles in usc to some extent Anaesthetic Atropinc 1/75 grain Trcheotomy using I per cent procaine local Some degree of collapse oc curred on inserting cuſſed tube Says thiopentonc and gallamine gien but does not state definitely when Any way lungs infiated with oxygen Recovery in a minute or to Nitrous oxide-oxygen started Blood drip set up Blood pressure then 95/70 Considerablc hemorrhage during tracheotomy so decided to use controlled hypo tension Hexamethonium iodide 30 mgm Blood pressure fell to 50/40 Slope reduced from 25 degrees to 15 degrees feet down tilt Operation started and proceeded rapidly with negligible bleeding After 40 minutes on lifung lar ynx to cut through lower part prior to removal patient coughed and respirations became rapid Thiopentone 01 Gm and gallamine 8 mgm given but response inade quate Thiopentone 005 Gm and gallamine 4 mgm Re sponse satisfactory Few minutes afterwards B P fell from 60/45 to 30/7 and within few minutes patient died PM Small amount of blood in bronchi, and it was thought that this entered during tracheotomy Heart and lungs otherwise in good condition No sign of coronary disease or thrombosis (84) Reactionary hemorrhage, the most frequent complica tion also proved to be a major factor in the production of mortality eight deaths occurred for this reason as in the following instance Middle aged healthy male-hemipelvectomy-ether anesthesia-hexamethonium 225 mgm_head-down posi tion-BP 70 80 mm Hg systolic during greater part of operation-blood loss (measured) about 1000 cc.—re ·86 CONTROLLED HI POTENSION placed during operation–B P returned to normal at end of operation with neosynephrine drip-patient apparently in good condition when he left OR After return to ward B P and pulse disappeared A continuous drip of noradrenaline required to maintain circulation until time of death 48 hours later On the night of operation blood volume studies showed a marked deficit of red cells Hemorrhage was suspected and packed red cells were given since plasma volume was relatively good This was in addition to several transfusions given during the immediate post-operative hours Although no abnormal bleeding could be detected at time of blood volume studies on morning of first post operative day blood had distended the abdomen penis and scrotum in spite of blood replacement and noradrenaline drip, his condition steadily deteriorated and he died on the morn ing of the second post-operative day Autopsy revealed massive hemorrhage into the peri toneal cavity and external genitalia as well as the opera tive site No large vessels could be discovered as the cause of bleeding It appeared to have been due to a general ized capillary ooze In addition there were pulmonary edema and acute passive congestion of the lungs central lobular aschemic necrosis of the liver hemorrhagic in farction of the spleen and kidney and hemoglobinuric nephrosis secondary to shock The question arose as to whether these changes were due to C6 or could in part be attributed to prolonged vasoconstriction (Reported on questionnaire sent to Diplomates of the American Board of Anesthesiology) There were five patients who died following the admin istration of high spinal anesthesia, as in the following case history A healthy man with a prolapsed lumbar disc General condition Operation five years ago for disc Good result until seven weeks ago when twisting spine ·87 FATAL AND TO TATAI COVI LICATIONS caused scicrc rccurrence B P 110/70 Apical systolic inur mur Anaesthetic Morphinc 1/1 grain scopoliminc 1/100 grain Thiopentonc 1 Gm No apnci Intubation casy Put into face-dotin jach Iniſc position Maintenance with nitrous oxide-oxygen trichlorethylenc Spinal with heavy nupercainc 18 ccm Head-down uilt increased Blood pressure fell to unrerdiblc levels Respiration rate fell to 8/min Mathedrine groni1 Apnoca Inflation with oxy gen turned on back heart massage into aortic saline, more mcthcdrine Only momentary response PM nothing significant (81) Finally there were 14 derths in luch thc neurosurgical operative trauma was considered the major ciuse of de mise or at least could not be excluded as a possible factor of major significance To quote one of the replies to the questionnaires Two patients have died 48 hours after operation and one patient has died 72 hours after operation in these neurosurgical patients it has been impossible to determine whether death was due to pre existing disease the sequelae of operative trauma or the induced hypotension This is perhaps an appropriate note upon which to end a discussion of complications and mortalities for there is reason to question the validity of ascribing to induced hypotension the entire burden of guilt in the causation of these complications and deaths herein described It is true that in many instances the techniques of controlled hypo tension would appear to be implicated but until there are comparable series of cases run with and without the use of these techniques it is unfair to attribute all deaths occurring in surgical patients in whom hypotension has been induced as being the direct result of that hypo tension ·XI Contraindications INSIGH into the contraindications to the employment of controlled hypotension follows most naturally upon knowledge of the physiological aberrations produced by these techniques and the morbidities and mortalırıes con sequent to their use The major concern, not unreason ably, has been expressed over the state of the cardiovascu lar system particularly the presence of disease in the various branches of the vascular tree, and over the status of the blood volume and the oxygen carrying capacity of the blood within those vessels In the questionnaires sent to the members of the Association of Anaesthetists of Great Britain and Ireland and to the Diplomates of the Ameri can Board of Anesthesiology each physician was requested to designate his considered contraindications to the use of these techniques (Table XV) The presence of arteriosclerosis, known coronary disease or previous cerebrovascular disease must be considered absolute contraindications to the employment of trolled hypotension since there is great danger that the flow of blood through vessels which are already partially occluded may cease altogether under conditions of hypo tension The risk of coronary thrombosis or occlusion is very real during hypotension, even in the absence of known coronary insufficiency (203) and in spite of the hypothesis that vasodilatation and lowered peripheral re sistance will reduce the work load of the heart (175) Fur thermore since the circulation time is increased almost two fold during induced hypotension thrombus formation 88 con ·CONTRAINDICATIONS 89 is very likely and especially so in the presence of narrowed sessels The fact thi cercuril blood flow, for example, inay be maintained near normal in moderate degrees of hypotension by ? decrcasc in ccrcbral vascular resistance docs Tank TV CONTRAINDICATIONS TO CONTROLLED) 10) TOTF\SIO Anaesthetists in Anesthesiologists Great Britain and Ireland USA 111 Totals 48 Cardiovascular Disease In General Coronary Disease ArterioscleTOSES Cardiac Disease Cerebrovascular Disease Hypertension (Severe) Hepatic Disease Renal Disease Extremes of Age Disturbances of Blood Volume Anemia Hemorrhage Shock Low Blood Volume Polycythemia Uncomplicated Elective Surgery Others 19 57 30 45 22 2. 51 46 32 43 8 48 82 67 119 81 91 54 67 22 88 113 40 31 18 10 40 80 3 54 58 18 7 12 19 4 17 59 36 17 52 49 7 71 117 (Reprinted from Little D M Jc Induced hypotension in anesthesia and surgery Anesthesiology 16 320 1955 with the kind permission of the publisher ) not necessarily mean that there is less likelihood of cere bral thrombosis for if cerebral vascular resistance is reduced by dilatation of the cerebral vessels which is the mechanism that must be assumed unless blood viscosity or intracranial tension are considered to vary the slowing of the linear flow rate and the prolongation of the local circu lation time will enhance the possibility of the develop ment of intravascular thrombosis (103) Cardiac disease in general and particularly cardiac fail ure have been considered contraindications to the use of ·90 'CONTROLLED HYPOTENSION these techniques and in the present state of knonledge this is undoubtedly the correct view It is worth noting in passing, however that the cautious use of ganglionic block ing agents in the therapy of cardiac failure is now under trial, based on the same rationale as the use of phlebotomy or spinal block in the past, and hypotensive techniques may well play an active part in the anesthesia for certain cardiac patients in the future Severe and malignant hypertension must be considered an absolute contraindication to controlled hypotension, but only when excessively severe In all other forms, hyper tension is only a relative contraindication, if the exagger ated effects of hypotension upon cerebral blood flow renal blood flow, and other parts of the cardiovascular mecha nism in the hypertensive subject are kept in mind The presence of hepatic disease must certainly consti tute an absolute contraindication as must the presence of renal disease Liver failure is liable to follow extreme hypotension due to the peculiarities of the hepatic blood supply and a case of acute hepatic necrosis has already been reported following the use of methonium induced hypotension (445) Tests of renal function during and after controlled hypotension demonstrate quite clearly the adverse effects that these techniques may have on the kidneys when the latter are in a diseased state There is a further consideration in connection with kidney function which was mentioned previously and may be extremely important both the methonium compounds and arfonad depend at least in part upon the kidneys for their excre tion In the presence of profound hypotension glomerular filtration is reduced to such an extent that urinary excre tion of these drugs does not occur a vicious cycle is then set up in which failure of the kidneys to excrete these ganglionic blocking agents produces a conunuance of their hypotensive effects As would be expected this is particu ·CONTRAINDICATIONS 91 larly prone to occur when the kidneys themselves are diseased A further absolute contraindication to the use of the techniques of controlled hypotension' is ? disturbance of blood volume and oxygen carrying capacity of the blood such as anemia, hemorrhage, and low blood volume Shock and hypotension are usually part of the clinical pic ture of such disturbances of blood volume and are, of course contraindications in themselves In Addison s Dis ease, hypotension exists already, and although the blood volume may be relatively normal further reduction of the blood pressure must be considered unsafe Extreme in crease in blood volume is also a contraindication because of the markedly slowed circulation the tendency toward thrombotic episodes in patients with polscythemia vera must not be aggravated through further slowing of the circulation by the induction of hypotension There is another absolute contraindication of impor tance If the operating room team, the personnel responsi ble for post operative care or the facilities for either oper ative or post operative care are in any way deficient trolled hypotension should not be employed These are not techniques for the occasional operator or anesthetist they are not techniques for inexperienced or slow sur geons and they are not techniques which can be employed safely when routine post operative care is the only such care available The extremes of age have often been considered as contraindications but it would appear that these are only relative contraindications Patients under sixteen years of age are often resistant to ganglionic blocking drugs par ticularly the methonium compounds and it is therefore occasionally difficult to induce a satisfactory hypotension in such patients This would appear to constitute a fail ure of the technique rather than a contraindication to its con ·92 CONTROLLED HYPOTENSION use, excepting that this failure can on occasion be danger ous of itself for if the ganglionıc blockade produces partial vasodilatation, without a marked fall in blood pressure, operative bleeding may be actually increased (120) The use of these techniques in patsents over 60 years of age has also been considered a contraindication, because of the possibility of unsuspected and latent cardiovascular disease (203) However the absolute chronological age of the patient is far less important than the physiological age of his or her arterial tree Diabetes Mellitus is also a relative contraindication, at least to the use of the methonium compounds for there is a tendency for the blood sugar to fall during the adminis tration of these drugs The hypoglycemia which occurs as a result may become very profound without being recog nized since the usual symptomatology of sweating, palpı tation, restlessness and anxiety, are due to sympathetic and adrenal discharge and hence do not occur in the pres ence of ganglionic blockade The accentuation of the effects of the administration of insulin in the diabetr. patient by the methonium compounds together with the mashing of these effects by general anesthesia, can result in a very dangerous situation (12 176) Without question honever, the most absolute of all contraindications to the use of the techniques of 'con trolled hypotension must be the absence of a rational and urgent indication There can be no justification for the use of induced hypotension merely for convenience during uncomplicated and elective surgery Controlled hypo tension is not a luxury during surgery it is an occasional necessity and must be employed only under conditions of the most compellıng need There are grave dangers associated with its use but there are also on occasion, great advantages to be attained from that use The method must therefore be considered contraindicated in those ·CONTRAINDICATIONS 93 situations in which the advantages do not outweigh the risks involved These contraindications just listed are of immense im portance and failure to respect them can lead to disaster They do not represent merely a list of pathological entities which might conceivably be of theoretical danger they are conditions which bitter empirical experience has taught are incompatible with the successful conduct of 'con trolled hypotension ·XII Indications THE INDICATIONS for which controlled hypoten sion is employed are the crux of the problem concerning these techniques On what basis does one secl to induce hypotension and when does one fight to maintain a nor mal arterial pressure? There is no glib answer to this riddle unless it were to be Sir John Gillies statement to the effect that there is only one true indication for induced hypotension that situation in which its advantages will be of certain benefit to the patient and likely to outweigh the assumed risks In any discussion of the indications for the use of con trolled hypotension therefore it is imperative to make a clear distinction between the specific operative procedures for which these techniques have been employed in the past and the clinical situations for which their use is justi fiably indicated Controlled hypotension has been adro cated for a large variety of operative procedures including such unlikely choices as tonsillectomy dental extractions and caesarean sections Most commonly however it has been employed during extensive surgical interventions in which there could be expected to be a large amount of bleeding sudden or profuse hemorrhage or greatly 37 creased tension within vessels or organs The categorical listing of these procedures as a long one (Table XVI) neurosurgical procedures (18 26 27 80 187 188 189 207 228 318 322 375 376 378 381 394 451 474 491 492 501 515) particularly the removal of highly vascular tumors (4) the ligation of various types of ·INDICATIONS 95 intracranial aneurysms (377, 395, 466, 508), and the re moval of meningiomas (151), head and neck surgery, such as the Lempert fenestration operation (135, 168 200 224, 347, 494) opthalmic surgery (399) in the presence of glau TABLE XVI TYPES OF OPERATIVE PROCEDURES FOR WHICH CONTROLLED HYPOTENSION HAS BEEN EMPLOYED Neurosurgery Vascular Brain Tumor Congenital Aneurysm Meningioma Head and Neck Surgery Lempert Fenestration Operation Ophthalmic Surgery Radical Neck Dissection Thyroidectomy Laryngectomy Surgery of Chest Wall Rádical Mastectomy Thoracoplasty Intra thoraac Surgery Pneumonectomy' Lobectomy Decortication Esophago gastrectomy Cardiovascular Surgery Coarctation of Aorta Patent Ductus Arteriosus Aortic Aneurysm Abdominal Surgery Radical Abdominal Operation Abdomino perineal Resection Gas trectomy Porta caval Shunt Pelvic Surgery Pelvic Evisceration Radical Hysterectomy Pelvic Node Dissection Orthopedic Surgery Spinal Fusion Laminectomy Open Hıp Operation Bone Graft Genito urinary Surgery Prostatectomy Transurethral Resection Nephrectomy Adrenalec tomy Vesico vaginal Fistula Vaginal Plastic Operation Plastic Surgery Skin Graft Skin Flap coma (73 211), a number of otorhinolaryngological pro cedures (155 168, 282, 355 506) thyroidectomy (231 398) radical neck dissection (223 231) and laryngectomy surgery of the chest wall, specifically radical mastectomy (231) and thoracoplasty (398) intra thoracic surgery (105 291 422) such as pneumonectomy (79 96) lobectomy decortication and esophago-gastrectomy (67) cardiovas cular surgery (110 210) particularly that involving large vessels (166) such as coarctation of the aorta patent duc tus arteriosus and aortic aneurysms abdominal surgery (58, 59 60 111) including radical abdominal operations, ·96 CONTROLLED HYPOTENSION gastrectomy abdomino perineal resection thoraco lumbar sympathectomy (175 240) and porta cavıl shunt pelvic surgery (58 59 60 270) particularly pelvic evisceration radical hysterectomy and pelvic node dissection ortho pedic surgery (462) such as spinal fusion, laminectomy (382) open hip operation (242) and bone grafts urologi cal surgery (497) including adrenalectomy nephrectomy prostatectomy (50 85 86 87 325 393) vesico vaginal fistula and vaginal plastic operation and plastic surgery (43 373) particularly shin grafts and skin flaps It must be emphasized that long as thus list is it is by no means com plete for there is scarcely an operative procedure to which the techniques of controlled hypotension have not been applied Yet there are no specific operative procedures for which the use of controlled hypotension is indicated and an enumeration of the surgical interventions for whuch it has been employed must never be confused with the indica tions for its use There are as previously stated a number of well defined clinical situations during operations in which the use of these techniques may become mandatory and without which the operations would be totally unfeas ıble immensely more dangerous or more likely to result in unsuccessful outcomes these are the indications for the use of controlled hypotension (Table XVII) Surgical Indications Foremost among the indications for the use of controlled hypotension must be the con trol of gross hemorrhage during operative procedures for such lesions as intracranial aneurysms Bascular brain tumors and definitive interventions for the excision of other highly vascular lesions which are capable of sudden and profuse hemorrhage An indication of less dramatic but equally important significance has been the control of extensive capillary ooze during operations of considerable magnitude such as abdominal or pelvic es iscerations or ·INDICATIONS 97 radical node dissection The amount of blood lost need not necessarily be great to rcquire thc usc of induced hypotension the Lempert fenestration operation for example, entails very little actual blood loss yet the techniques of TABLE XVII CONTROLLED HYPOTENSIO INDICATIONS FOR Surgical Control of gross hemorrhage_intracranial aneurysm Control of extensive ooze_le abdominal evisceration Bloodless field for visibility-je fenestration Reduction of organ tension-1.2 craniotomy Reduction of intravascular tension-10 cardiac and great vessel surgery Control of hypertensise crises—se pheochromocitoma Avoidance of transfusions-se compatible blood unavailable history transfusion reactions Anesthetic Obtundation of noxious stimuli by ganglionic blockade Artificial hibernation Medical Treatment of pulmonary edema in hypertensie crises Therapy in pulmonary embolisin Pain relief in herpes zoster Relief of venous congestion in cardiac failure Treatment of severe hemorrhages controlled hypotension may be indicated, for the pur pose of increasing visibility in the operative site, by the presence of even a single drop of blood which can obscure the entire operative field during the delicate maneuver of shaping the fenestra and thus negate a successful surgical result The indications for the usage of controlled hypoten sion must also include those situations in which although bleeding may be expected to be minimal, the tensions within the vessels or organs themselves will be of such magnitude as to endanger the life of the patient or to render improbable a satisfactory completion of the surgi cal procedure During the course of craniotomies in pa tients with hugely swollen and edematous brains these ·98 'CONTROLLED HYPOTENSION techniques can be employed to reduce organ tension and so to facilitate surgical exposure, which might otherwise be totally unsatisfactory, and the same may be true of opera tions upon the glaucomatous patient, in whom the reduc tion of arterial pressure leads to a secondary reduction of pressure within the eyeball and permits the performance of operations that would under other circumstances be highly dangerous A similar situation pertains during cer tain instances of cardiac and great vessel surgery, in which, by the reduction of intravascular tension, it may become possible to place clamps upon tense and bulging vessels, which would tear and precipitate massive hemorrhage were the tensions within the lumens not reduced by con trolled hypotension The reduction of vascular tension may be indicated also in certain rarer instances of surgery during which hypertensive crises may threaten to explode quite literally into hemorrhagic accidents a situation en countered in such surgery as the removal of pheochromo cytoma (83) There are certain less frequent indications for the use of controlled hypotension during anesthesia and surgery which should be cited One such indication is the avoid ance of transfusion emergency surgery of an acute nature may be necessary in the absence of compatible whole blood for transfusion, and the use of these techniques can pre vent blood loss to a degree that transfusion may be avoided altogether A similar indication may arise in the rare patient with a history of multiple transfusion reactions who must undergo extensive surgery the use of trolled hypotension in such a patient may circumvent the danger of a major transfusion incompatibility by de creasing blood loss to such an extent that transfusion is not essential (327) These would be most infrequent indica tions under modern operating conditions Anesthetic Indications One interesting outgrowth of con ·INDICATIONS 99 ar the use of controlled hypotension in anesthesia and sur gery has been the use of ganglionıc blockade lo prevent the transmission of noxious impulses This is not, of course a true indication for induced hypotension itself, but it has been suggested that the future may prove that this usage of ganglionıc blochade is the most important and enduring contribution that the techniques of "con trolled hypotension have made to medicine The basis of this use of ganglionic blockade to prevent the transmission of noxious impulses harhs back to the theory of Anoci association pronounced by George Crile, senior some 40 years ago Crile, reasoning along physiological line gued that not only must the brain be protected against destructive psychic strain by the use of general anesthesia, but that local anesthesia must be employed also to exclude the noxious impulses arising from the site of surgical inter vention (90) It is now apparent that many of these nox nous impulses are conveyed by the autonomic nervous system and therefore are susceptible to ganglionıc blockade (57 82 389) The clinical impression has been gained that patients subjected to controlled hypotension de velop surgical shock less frequently than do other surgical patients (510), and that obtundation of noxious impulses by ganglionic blockade is feasible (39 436) The French have made specific utilization of these ideas in their techniques of artificial hibernation in which induced hypotension is one of the several essential factors in a combination that includes hypothermia central ner vous system depression muscle relaxation and that evasive delight déconnexion (484) Medical Indications Finally and similarly an increas ing number of medical therapies have been based upon the use of the ganglionic blocking agents which have achieved prominence through their employment in the techniques of controlled hypotension the treatment of ·100 CONTROLLED }{YPOTENSION pulmonar, edema in hypertensive crises (95, 415 416 417 418, 419) the therapy of pain and neurogenic shock in pulmonary embolism (91, 429) pain relief in herpes zoster (346), the potential relief of venous congestion in cardiac foslure, (505) and the Ireatment of severe hemor Thages (109, 199, 280) and cerebrovascular bleeding (430) a revolutionary but apparently effective therapy The fur ther extension of the use of ganglionic blockade in the therapy of a number of other pathological processes seems assured ·XIII Requirements THE CONDUCT of a surgical intervention performed under the techniques of controlled hypotension de mands meticulous attention to detail and rigid adherence to a set of fundamental tenets Any lapse in the fulfillment of the requirements is a sure invitation to disaster, for these are techniques which are quite capable of either maiming or killing the patient This is not to say that they should be forbidden techniques for most assuredly the results of their use can often be useful sometimes beneficial, and on occasions truly life saving but these are services that are achieved at a price and at times the price may be inordinately high There is a growing tendency throughout medicine but perhaps particularly in anesthe sia and surgery to equate what is new with what is good and to confuse the means with the end—especially where the means are striking and dramatic It therefore devolves upon those who induce hypotension deliberately in the surgical patient to adopt rigid criteria for the execution of the details of controlled hypotension (Table XVIII) for the usefulness of these techniques is entirely dependent upon their successful performance The most unyielding of these requirements without which all the others become meaningless as the absolute necessity for selecting patients to be subjected to these techniques on the basis of the most urgent and rational indications Such indications must be based upon the prob able failure etter of the patient to survive the operation or of the surgery to be compleret succesfully without the ·102 CONTROLLED HYPOTENSION use of controlled hypotension' The use of these tech miques in the absence of a rigidly-defined indication is at best poor judgment and is at worst closely akın to mal practice As a corollary to the requirement that there must be the most scrupulous selection of cases on the basis of inds TABLE (VII THE REQUIREMENTS OF CONTROLLED HYPOTENSION 1 A rational and urgent indication 2 Respect for existing contraindications 3 Restriction of extent and duration of hypotension 4 Normal pre-operative blood volume 5 Drop by drop replacement of blood and Huid loss 6 Adequate oxygenation 7 Due consideration to posturc & Completely competeni anesthesiologist and surgical team 9 Detailed and meticulous post operative care cations that are so urgent that operation could not be per formed successfully in the absence of the employment of these techniques it is mandatory that any existing contra indications be respected in the most assiduous manner These contraindications must be considered to include disease of various branches of the vascular tree hepatic and renal disease, and blood volume disturbances of a number of different types (see Chapter XI) failure to recognize the existence of these pathological entities prior to the induction of hypotension in the surgical patient has been responsible, in the past, for some of the tragic mor bidiues and mortalities which have followed upon the use of controlled hypotension The occasional clinical situa uon does arise in which the need and indication for con trolled hypotension is so overwhelming that the physı cians judgment dictates that an existing contraindication must be sgnored such situations are indeed rare however When a pregnant indication for the use of controlled hypotension does exist and the decision is made to em ·REQUIREMENTS 103 ploy the technique, it is essential that the blood pressure be lowered slowly to the maximal level compatible with the control of bleeding, and that it be maintained at this lowered level the shortest time consistent with the ade quale accomplishment of the surgical intervention It has become very clear that the morbidities and mortalities associated with the use of induced hypotension have been directly related to both the extent and the duration of the reduction of the blood pressure from the pre operative normal From a purely realistic and practical standpoint, It is almost always possible to restrict the period of hypotension to that part of the operative procedure for which its benefits are most necessary, and advantage should be taken of this fact Furthermore since the level of the blood pressure which must obtain in order to provide a relatively bloodless field varies tremendously between individual patients the degree of the hypotension should never be greater than that required in the patient under considera tion These techniques are based upon the production of either a normovolemic or a hypovolemic hypotension and in both instances a point is reached at which the wide spread transgressions of the physiological status quo of the cardiovascular system may progress to irreversible shock This point may be reached with deceiving rapidity when the blood volume is abnormally low at the time of the induction of hypotension or if it is lowered by hemor rhage during the course of the conduct of controlled hypotension For this reason it is a requirement that there be an absolutely normal pre operative total blood volume and red cell mass Furthermore it is necessary to recognize that a low pre operative blood volume often cannot be distinguished on purely clinical grounds or even by the usual laboratory investigations so that the selection of patients should be made on the basis of blood volume determinations This is particularly true of the older ·104 CONTROLLED HYPOTENSION sion cachectic patient with extensive malignant involvement, who represents a state which has been termed chronic shock By the same token hemorrhage or extensive bleeding which occurs during the course of controlled hypoten also will lead rapidly to the point of irreversible shoch, for it has become apparent that patients in whom hypotension has been induced tolerate blood loss poorly A further requirement therefore must be the drop by drop replacement of all blood and fluid that is lost during operation It should be unnecessary to add that an indwell ing cannula into some part of the vascular tree is quite indispensible When hypotension has been induced, the oxygen-carry ing capacity of the blood must be utilized to the fullest extent of tissue oxygenation and cellular respiration are to be maintained near normal The accomplishment of this task of adequate oxygenation requires a completely patent airway at all times high flows of oxygen and adequate (preferably spontaneous) ventilation of the lungs Due consideration to the posture of the patient is ex tremely important in controlled potension This mat ter is of concern not only to promote venous drainage from the wound but also in order to effect the necessary level of hypotension in many instances At the same time It must be remembered that the position of the patient is often the hey to morbidity or mortality in these tech niques Certain postures such as steep Fowler s position, have an undesirable effect upon the blood flow to vital organs particularly the brain Furthermore shifts of pos ture in the presence of a dilated vascular bed carry their own inherent risks since a further and more severe hypo tension can be so induced with a consequent reduction of venous return to a point incompatible with continued cir culatory function These heroic maneuvers of controlled hypotension ·REQUIREMENTS 105 demand the utmost from those cmploying the techniques, which means that therc must bc i completely competent surgical team Not only must the nesthesiologist be highly trained, skilled, and thoroughly conscrsonit with the techniquc cmplo cd, but also tlic openzling surgcon and his assistants must bc dextrous, accomplished, and possessed of a complete understanding of what is licing undertaken In perhaps no ficld of surgical cndcrs our is there greater need for the utmost in cooperation behiscen all members of the operating team Since the dangers to the patient during the immcdirto post-operative period arc at Icast as great as during the operation and the period of hypotcnsion itsell, a final rc quirement is for detailed and meticulous post operative care Posture, airway, oxygenation, determinations of hematocrit and total blood volume, and constant observa tion, are all of concern in the post operative period, for the end of operation does not necessarily signify the end of ganglionic blockade nor the attainment of a normotensive state In a recent survey studying the effects of anesthesia and surgery in 599 548 surgical patients the anesthetic death rate was found to be one in 1560 patients (36) in 27 930 cases of controlled hypotension, the over all mortality rate has been found to be one in 291 patients This is indeed a staggering figure Let there be no doubt that these are gravely dangerous techniques, possessing those inherent capacities for tragedy which always accompany marked deviations from the normal physiological status quo It would be at least convenient merely to dismiss controlled hypotension as a menace to humanity unfor tunately the situation is scarcely that simple For these are techniques which although potentially lethal are capable of immense benefit for the patient when employed for good and sufficient reason by the knowing, the wary, and the skilled ·XIV Bibliography* I ADRIANI J Hypotensie anesthesia I Am A Nurse Anesthetists 22 24 1954 2 Some recent items of interest to laryngologists concern ing anesthesia Ann Otol Rhin & Laryng 62 423 1953 3 ALEXANDER GL Death after anaesthetic with hypotension Lancet 1 299 1953 4 ANDERSOY S and McKISSOCK W Controlled hypotension with arfonad in neurosurgery with special reference to vascular lesions Lancet 2754 1953 5 ANLYAN WG SHINGLETOV W BENSOV WR STEPHEN CR. 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JA. The effect of hexamethonium induced hypotension on water and electrolyte excretion in man Surg Forum 4 584 1953 459 SOFFER A and SWEET R B Effect of position changes of the lower extremities during vasomotor block ).A.M.A 151 1191 1953 460 SOMMERVILLE J and ALIAN J A case of drug eruption induced by hexamethoniura bromide Brit.MJ 1 864 1951 461 STEPHEN CR WOODHALL B ODOV G NOWILL W K and BLOOR B Methods for reduction of surgical blood loss , Ken tucky M.A 52 344 1954 462 STEVEN RJ M and TOVELL, R M Hexamethonium salts as an aid to the orthopedic surgeon J.A.MA 154 402 1954 46% STONE H H Controlled hypotension during surgery Maryland M1 J 3 163 1954 461 MACKRELL, TN and WECHSLER R L The effects of hypotension induced by intravenous hexamethonium and head up tilt upon cerebral hemodynamics in man Am J A Sc 228 112 1954 465 STOYNER J and LINDELL S Controlled hypotension to reduce bleed ing in operative field Nord med 47 206 1952 466 SWANSON HS GALVIN WH and FINCHER E F Total spinal anesthesia in the surgical management of a congenital arterio venous aneurysm Surg Gynec Obst 93 215 1951 467 SWERDLOW M and WADE J W The effects of hexamethonium jodide on the electrocardiograph in anaesthetized subjects Brut I Anaesth 25 284 1953 468 SZUTU C and SCHWEIZER O Use of hexamethonium bromide for the experimental production of controlled hypotension in the anesthetized dog Anesth & Analg 33 18 1954 469 Tait D and CAGLIERI G Experimental and clinical notes on the subarachnoid space JAMIA 35 6 1900 470 TESTA G Lipotensione provocata a scopo antiemorragico in chir urgia Rassegna med sarda 54.261 1952 471 TORRES S R Hipotensao controlada sau utilizacao em 32 casos arurgicos Mied contemp 71 231 1953 ·BIBLIOGRAPID 193 1,2 TURNER R Medical sympathectomy in hypertension a diniai study of methonium compounds Lancet 2 353 1950 473 Mlethonium compounds in hypertension Lancet, 1408 1991 4.4 UNLESY A and LUND J S Continuous spinal anestliesia in intra canal procedures Proc Stop Meet Naso Clin 27 317 1952 415 ULLMANY TD and Dicscort D Elect of hexamethonium (C6) on renal hemodynamics in man AMA Arch Int Med 92-228 19.03 4,6 VALLE C Le sostanze ad allonc bloccante gangliare nel campo Ostetrico e ginecologico I Luso dei ganglioplegia nella media zione preanestetica e nella spotensione controllata Alinerva ginec, 5677 1953 477 VAN BERGEN F H BUCKLEY J J FRENCH LA DOBKIN AD and BROWY I A Physiologic alterations assocated with hexametho. nium induced hypotension Anesthesiology 15 507 1954 4/8 VAY DE WALLE J Quelques considérations sur l'hypotension con trolee pendant la narcose Acta anaesth belg 2 49 1951 479 VAN WIEN W Note préliminaire sur 1 hypotension contrôlée Acta anaesth, belg 2 76 1991 480 Faut il compenser ou prévenir les pertes sanguines en chirurgie thoracque Acla anaesth belg 4-22 1993 481 VEAL, J R RUSSELL A S and ASHBURY F S The reaction of the coronary blood pressure to graded stages of shoch (hemorrhage) Ann Surg 136 485 1952 482 VEHRS GR. Heart beat and respiration in total novocaine anal gesia Northwest Med 30-256 322 1931 483 VENTO RUIZ V Hipotensión controlada en neurocirugla Rev espan oto neuro oftal 13 32 1954 484 VERNEJOUL R Hypotension contrôlée et réfrigération Marseille med 90 420 1953 485 VETTER H GRABYER, G MLCZOCH F and STEINBEREITHNER K Herzkatheter untersuchungen bei massiver blutdrucksenkung durch hexamethonium Alin IVchnschr 32 97 1954 486 VOORHOEVE HC Hemodynamics of controlled hypotension during anesthesia Internat ) Anesth 1 16 1953 487 Kunstmatige bloeddrukverlaging bij synaecologische operaties Nederl tijdschr verlosk 53 329 1903 488 Haemodynamische problemen bu hypotensie Nederl tijdschr geneesk 98 595 1994 489 and DELAHAYE R Un nouvel hypotenseur contrôlable le RO22222 (arfonad) Acta anaesth belg 4 83 1953 ·1 132 CONTROLLED HYPOTENSION and 454 Practical details of the methonium treatment of high blood pressure New Zealand M) 49 637 1950 455 Methonium compounds in high blood pressure Lancet 1 346 1991 456 and ALSTAD KS Treatment of hypertension by penta and hexa methonium salts Bril.M} 1 1217 1951 457 Surh H W The kidney Structure and Function in Health and Disease New York Oxford University Press 1991 458 SYYDEP H B MORRIS G C MOYER J Hand HAYNES B W J. The effect of hexamethonium induced hypotension on water and electrolyte excretion in man Surg Forum 4 584 1953 459 SOFFER A and SWEET RB Effect of position changes of the lower extremities during vasomotor block J.A.M.A 151 1191 1953 460 SOMMERVILLE J and ALLAN J A case of drug eruption induced by hexamethonium bromide Brit.my 1 864 1951 461 STEPHEN C R WOODHALL BODOY G NOWILL, 1 K BLOOR B Methods for reduction of surgical blood loss , ken lucky M.A 52 344 1954 462 STEVEV R J M and TOVELL, RM Hexamethonium salts as an and to the orthopedic surgeon J AMA 154 402 1954 463 STOVE HH Controlled hypotension during surgery Maryland MJ 3 163 1964 461 MachRELL TN and WECIISLER RL. The effects of hypotension induced by intravenous hexamethonium and head up tilt upon cerebral hemodynamics in man Am J M Sc 278 112 1904 465 STOVNER J and LINDELL S Controlled hypotension to reduce bleed ing in operative field Mord med 47-206 1952 466 SWANSON HS CALVIN WH and FINCHER, E F Total spinal anesthesia in the surgical management of a congenital arterio venous aneurysm Surg Gynec & Obst 93 215 1951 467 SWERDLOW M and WADE J W The effects of hexamethonium jodide on the electrocardiograph in anaesthetized subjects Brit , Anaesth 25-284 1993 468 SZUTU C and SCHWEIZER O Use of hexamethonium bromide for the experimental production of controlled hypotension in the anesthetized dog Anesth Analg 37 18 1994 469 Tart D and CAGLIERI G Experimental and dinical notes on the subarachnoid space JAMA 356 1900 470 TESTA G Lipotensione provocata a scopo antiemorragico in chir urgia Rassegria med sarda 34 261 1952 471 TORRES S R Hipotensao controlada sau utilizacao em 32 casos arurgicos Mied contemp 71 231 1953 ·BIBLIOGRAFII 135 507 WOODILALL B Opov G L. Sirin C. R McClur C., and Nel, R.. The use of chemlally induca hypotension in the treatment of intracranial aneunsm lorth Carolina MJ 14 513 1953 508 HOOLSEY R.D and FREIHEIT 11 ) Induced hypotension in surgery of intracranial vascular anomalies report of 2 cases. I Missouri M A 29 916 19,2 509 WRICIT AD Spinat analgesia with special rclerence to operations above the diaphragm 1 Standard 549 1931 510 1 YMAY J B Cox R and Gowts J Discussion on hypotension during anaesthesia Proc Roy Soc Med 46-605 1903 511 TONMAY F F The pharmacology of newcr agents employed in the treatment of gastrointestinal disturbances with special reference to regional leitis and ulceratise colius Bull New York Acad Mfed 28 700 1932 512 YOUNC I M DE WARDENER, H E. and VILES DE Viechanism of the renal excreuon of methonium compounds Brut MJ 2 1500 1951 513 ZA E. J The synthesis of methonium compounds their isolation from urine and their photometric determination Brit Pharma col 5 424 1950 514 ZIMMERMANA Vorteile und gefahren der hypotensionsverfahren bei chirurgischen eingriffen Helvet cher acla 19.293 19.2 515 ZUGLIAVI J A Novos aspectos da neuroarurgia em face da hipo tensão induzida por substanaas ganglioplegicas Rev brasıl cır 25 322 1953 516 ZUKSCHWERDT L Operationen in blutleere durch ganglienblockade (pendiomıd) und lagerung Deutsche med Wchnschr 77 460 1952 517 ZWEIFACH BW HERSHEY SG ROVENSTINE E A LEE RE and CHAMBERS R Anesthetic agents as factors in arculatory reactions induced by hemorrhage Surgery 18 48 1945 ·134 CONTROLLED HYPOTENSION 490 and OKKER J J Onbloedig opereren door middel van hypotensie Nederl tijdschr geneesk 97 1348 1953 491 VOURCHG L hexamethonium en neurochirurgie Anesth et analg 9 376 1952 492 Sur trois cas d hypotension contrôlée par hexamétho nium en neurochirurgie Gaz med France 59 163 1952 493 L hexaméthonium agent hypotenseur en chirurgie Presse med 60 159 1952 494 VYSLONZIL, E Die kontrollierte blutdrucksenkung und ihre bedeu tung fur gehorverbessernde operationen (fenestrationen) Wien klin Ichnschr 64 772 1952 495 WALKER G LEVY L II HYMAN A and ROMNEY R Prolonged hypotensive reaction to hexamethonium J A MA 154 1079 1954 496 WATSCHINGER B KUCHER R STEINBEREITHNER VYSLONZIL E and WIRTINGER W kunstliche blutdrucksenkung und mierenfunk tion Anaesthesist 354 1954 497 WEBER H F Das ganglionblockierende pendiomid (caba) bei urolo gischen erkrankungen und operationen Tien med Wchnschr 103 451 1953 498 WENGER R DONEFF D and VYSLONZIL E Zur kreislaufwirkung ganglienblockierender stoffe praoperative erkennung der durch kontrollierte blutdrucksendung gefahrdeten patienten Deutsche med Ichnschr 78 322 1953 499 WERKO L FRISK ARWADE G and ELIASCH H Effect of hexa methonium bromide in arterial hypertension Lancet 2 470 1951 500 WIGCERS C J Myocardial depression in shock a survey of cardio dynamic studies Am Heart J 33 633 1944 501 WIKLUND PE Controlled hypotension at intracranial operations J Neurosurg 10 617 1953 502 WILFLINCSEDER P Die medikamentose blutdrucksenkung zur ver hutung der operationsblutung Deutsche med Il chnschr 77 619 1952 503 Weitere beobachtungen und erfahrungen mit der medı kamentosen ganglien blockierung wahrend der operation Chirur gta 24 105 1953 504 WILKINS RW HALPERIN M H and LITTER J Effect of dependent position upon blood flow in limb Circulation 2 873 1950 505 Wason V Hand KEELEY K ) The haemodynamic effects of hexamethonium bromide in patients with pulmonary hypertension and heart failure South African J M Sc 18 125 1953 506 WIRTINCER W Erfahrungen mit der kunstlichen blutdrucksenkung in der operativen hals nasen ohrenheilkunde Anaesthesist 2 85 1953 eine

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·Author Index Bclasso E 116 Benks AGO 109 Adnanı J., 106 Bennett 11 S., 8, 108 Alexander GL 106 Bennett 1 A 108 Allan J 51 152 Benson 1 R 71 106 Alstad KS 50 132 Bentel 1152 96 108 119 127 Aluisi C. 116 Berglund E... 56 100 129 Amorth G96 127 Dernsmcic A GO 108 Anderson C. DS4 $5 122 Bertolotto R 108 Anderson S 56 91 106 Boswick FB 65 126 Anduze H, 29 52 54 121 Biaginis 116 Angles C 52 9, 111 Biedermann G 109 Anlyan WG 71 106 Bier 41 Apgar V 106 Bilsland W L 34 35 108 Arden G P 17 29 123 Binet , P. 123 Arnold P50 66 106 Bishop G H 42 117 Arrowood J G 42 106 129 Bizard G 108 Aserman D 52 78 94 107 Ashburn FS 133 Dlakeley C G 96 108 Blalock A 8 108 Asquith E 52 107 Block M A 108 Assal: VS 56 72 107 119 Bloor B 132 Atkinson M., 128 Blum R 109 Bodman R. I 109 B Bonnycastle DD 56 114 Baars J H 107 Borri B L $4 109 Bacher KR 60 107 Boulton T B 56 107 Ballantine RIW 34 56 94 107 Bourne W 41 109 116 Bandiera c 107 Bousquet E 122 Banton AH 50 51 107 Boyan C P 28 52 54 95 96 109 Barbier P 107 Bozza M 109 Barlow RB 14 107 Bradley S E. 116-117 Barnes M 25 52 54 66 112 Brown AS 109 Barnett AJ 50 107 Brown 1 A 183 Bassett D L. 8 108 Brown J M 74 110 Bataille L 52 119 120 Bromage PR 46-47 67 70 71 Beaconsfield P 107 77 109 Beecher H K 8 45 105 107 108 Brunet D Aubiac B 95 109 115 Brunschwig A 4 52 54 95 96 Bein H J 60 99 108 109 Belfrage D 108 Buckley J J 133 137 ·138 CONTROLLED HYPOTENSION' Bucy PC 56 128 Bullough J 9 109 Bunker J P 45 115 Burn RA 77 95 110 Burt CC 50 54 55 66 109 Burstein CL 40 42 47 110 C Caglieri G 41 132 Camerini F 65 109 Cameron A J 77 95 110 Campan L. 29 52 54 121 Campbell A 50 52 77 110 Carbonera D 56 110 Carette L 110 Carravetta M 52 110 Chambers R 835 135 Chapman WP 42 129 Chateaureynaud J 52 95 110 119 Christensen J C 60 94 110 Churchill Davidson HC 72 73 110 111 123 Ciliberti BJ 99 110 Cillo L 126 Cobb CC 98 110 Coers C 80 127 Cole W H J 52 95 125 Costa ) 96 110 Cotten M dev 74 110 Co Tui 40 42 47 110 Coulter R L. 37 66 68 119 Courtin RF 34 35 122 Cox R 99 135 Crehan JP 13 14 55 125 Crile GW 9 99 110 Crosetti J P 60 100 111 Crumpton CW 65 67 111 Culbertson J W 72 120 Cusack AL. J 50 52 111 Cusack P B 50 52 111 Danzig L E 56 100 111 Daumet P 52 95 111 Dauri A 95 111 Davies R. M 111 Davison M H A 4 18 14 25 52 54 66 74 75 98 111 112 de Clive Lowe SG 56 111 Delahaye R 56 133 Dewar H A 67 89 111 de Wardener HE 51 72 73 110 111 123 135 Diengott D72 133 Dobkin AB 133 Docal J C 60 111 Donati GS 111 Doneff D 134 Douglas DM 115 Douglass RA Jr 72 107 Douthwaite AH 50 111 Driver RL 65 112 Drugemoller P 60 100 125 Duboucher H 100 111 Du Bouchet N 52 95 112 du Cailar J 95 112 Dundee J W 56 112 Ebbli C 46 112 Eckenhoff J E 65 112 Eddleman E E Jr 112 Effer DB 116 Eichelberger L 62 127 Eliasch H 50 51 64 184 Emmett J L 112 Enderby GEH 13 14 25 26 28 52 54 66 73 92 112 113 Erlanger J 114 Espinasse J 52 119 120 Esser H 60 108 Etsten B 8 113 Evans B 73 113 D Dale H H 63 111 Damoiseau B 13 14 60 94 116 127 131 Fabrıs F 124 Fanjeux G 113 ·AUTHIOR INDF 139 Fazekas J F 50 113 Ferguson LT42 113 Feruglio F S 113 Fibal J 113 Fincher E. F 9, 132 Fine ) 95 113 Fianetty F A Jr 50 51 95 113 114 Fitzpatrick IF 116 117 Fitzpatrick LJ 47 95 115 Flossdorf T60 100 125 Foltz E. L. 65 112 Fomon S ) 72 107 Ford R. V 113 Foster AD Jr 42 47 125 Fournier J., 52 95 122 Franas I L. 56 112 Frankel E. 50 113 Freeman M 66 127 Freeman NE 113 Freiheit H J 99 135 Freis E D 50 52 64 66 67 93 113 114 180 French L.A 133 Frey R. 114 Frisk AR 50 51 64 134 Furchgott RF 71 131 Clenn " " L. 9, 115 (nuchtel 15 115 Coetz R 1150 G 100 Coflon BS 47 9, 115 Coldicin} 99 110 Coldsmith AJ B 115 Goldstone B 115 Gomet AC 50 100 111 Goodale T 56 100 129 roodman c r 529, 118 Goodyer AS 3) 115 Grace IC GE GO 71 90 131 Crabner G 115 133 Graham AJP 50 51 55 66 109 115 Groenc 45 115 Gregoire V 108 Gricie 11 S 151 122 Griffiths II 1 C. 14 27 38 40 42 44 63 88 96 115 Griffiths J A 92 115 Grob D 50 66 116 Grollman A 131 Grosskreutz DC 8 23 56-57 121 Groves LK 116 Guglielmi F 64 65 109 116 Guidetti B 116 Guiot G 13 14 60 94 95 116 127 131 Gurd F B 41 116 G H Galvin WH 95 132 Gardner WJ 18 30 32 34 35 95 114 Gasser HS 114 Genazzanı E 114 Gerlach H 60 93 114 Gertner SB 56 114 Gili G 114 Gillan J G 79 114 Gillies J 5 7 8 13 14 25 27 38 40 42-44 52 54 61 68 66 88 94 96 99 112 114 115 135 Gilmore HR 60 67 115 Gittelson LA 56 128 Glasser 0 35 115 Gleave G 56 64 128 Habif DV 116 117 Haid B 65 117 Hafkenschiel J H 65 112 Hale DC 32 35 95 114 117 Hall J 98 110 Hall RA 98 110 Halperin MH 134 Hampton LJ 18 23 54 56 57 61 79 115 117 121 Handley CA 72 124 Hankiewicz J 95 128 Harper J K 100 117 Harris H E 95 117 ·138 CONTROLLED HYPOTENSION Bucy P C 56 128 Bullough I 9 209 Bunker } P 45 115 Burn RA 77 95 110 Burt CC 50 54 55 66 309 Burstein CL 40 42 47 110 с Cagliert G 41 132 Cameras P65 109 Cameron A.) 77 9 110 Campan L. 29 52 54 121 Campbell A 50 52 77 110 Carbonera D 56 110 Carette L 110 Carravetta M 52 110 Chambers R 835 185 Chapraan IP 42 129 Chateaureynaud J 52 95 110 119 Christensen J CBO 94 110 Churchill Davidson HC 72 73 110 111 229 Ciliberts B 3 99 110 Culo L. 126 Cobb CC 98 110 Coess C 80 127 Cole W HJ 52 95 125 Costa 96 110 Conen MdeV 74 110 Co Tu, 40 42 47 310 Coulter R L 37 66 68 219 Courtin RF $4 35 122 Cox R 99 ISS Crehan J P IS 14 55 125 Crile GSV 9 99 110 Crosen P 60 100 111 Crumpton CW 65 67 111 Culbertson w 72 120 Cusack AL) 50 52 1! Cusack PB 50 52 111 Danzig L. E 56 100 111 Daumct P52 95 111 Daur A 95 111 Davies R. M Itt Davison MHA 4 18 14 25 52 54 56 74 75 98 1il 112 de Clive Lowe SG 56 111 Delahaye R56 193 Dewar HA 67 89 131 de Wardener HE 51 72 73 110 111 129 135 Diengott D 72 133 Dobkin AB 133 Docal J C 60 111 Donan GS 1 Donefl D 194 Douglas D M 115 Douglass RA jt 72 107 Douthwaite AH 50 131 Driser R L 65 212 Drugemoller P 60 200 125 Duboucher H 100 111 Bu Bouchet N 52 95 112 du Cailar J 95 112 Dundee J W 56 112 E Ebble C 46 112 Eckenhoff J E 65 212 Eddieman EE Jr 112 Ember DB 116 Eichelberger L 62 127 Eliasch H 50 52 64 194 Emmett J L 112 Enderby GEH 13 14 25 26 28 52 54 56 73 92 112 113 Erlanger 114 Espinasse | 52 119 120 Esser H 60 108 Ersten B8 13 Evans B 73 113 D Dale H H 63 111 Damoiseau B 13 14 60 94 516 127 131 Fabris F124 Fanjeux G 113 ·AUTHOR INDEX 141 Landis EM 38 121 Lang H1 121 Langford 11 G 66 116 Langsion W 121 Lassner J 96 119 121 Latscha B1 52 9 112 Lawrence DR 121 Latortha G 29 52 54 121 Leathart GL 121 Learmouth ) 121 Le Brigand J 52 121 Ledru R 100 121 Lee RE 8 35 135 Le Filliatre G41 121 Lehmann G 55 127 Leigh V D 41 109 Le Voyne J 9 121 Leonhardt K0 121 Leveen H H 71 121 Levy L. 51 184 Lewis I 52 69 121 Lindell S 52 132 Lang A 34 9114 Litchfield J W 51 118 Litter J 194 Little DM jr 18 23 54 56 57 61 62 76 79 81 89 114 117 121 Locket 5 51 73 122 Loew F 122 Longtin j 52 95 122 Longtin L 52 95 122 Lorenz W 60 108 Lorhan PH 122 Lottenbach K 60 122 Love J G 34 35 122 Lower WE9 99 110 Lowrance P 116 117 Lundy J S 34 35 94 122 133 Lynn RB 63 66 71 72 122 123 128 129 Vachinnon J 51, 72 123 Mackrell TM 67 132 Magill I W56 123 Vandon GA 17 29 123 Vangiavacchi F OG 121 Mann FC 108 Vanni C. 123 Varland T ) 123 arxer A 123 Vason AA 17 52 60 123 Mathey J 123 McClure C 62 135 McCormick, V 122 McCubbin J W 122 McG:11 R ) 50 122 Vickissock W56 91 106 McLaughlin CR 52 122 McMichael J 65 67 70 115 123 McNally P A 50 52 123 McQueen E. G 50 51 72 123 Meier RGO 99 108 Melrose D G 64 66 71 90 131 Mendelsohn M L 72 123 Menezes LC 94 128 Mennuni R 119 Merle D Aubigne R 123 Méthot JP 122 Metz D B 117 Meyerovitz L 95 113 Miescher K 123 Mignault G52 95 122 Milbled G 108 Miles B E 51 72 73 110 111 123 135 Miller MI 122 Milletti M 94 124 Mills LC 72 124 Mine I G 51 65 67 115 124 Mczoch F 115 133 Molfetta N 96 124 Mondini P 124 Montag 198 124 Moon VH 63 124 Moore FT 111 M Mackey WA 52 123 ·140 CONTROLLED HYPOTENSION Jenkins A R 67 89 111 Johnson RL 50 51 64 66-67 114 130 Joly R 52 9. 122 Jones RR 119 Jonnesco T 41 319 Jungling o 119 Just 60 119 Harvey AM 50 116 Hay EB 117 Haynes B W jr 67 72 117 124 132 Hayward GW 88 92 317 Heckman G 128 Hernbecker P 42 117 Hermann H 40 42 47 117 Hershey SG 8 35 117 195 Heuer AJ 1 94 215 117 118 Heyer HE 112 Heyruang C 17 19 118 Hickam 3 118 Hienert 693 118 Higgins T F 64 66 67 114 Hu!? R 52 95 118 Hills B R 50 218 Homwich H E 8 223 Hirson C51 118 Hoffman T 52 95 228 130 Holle F 118 Holling HE 11% Holt MC 53 118 Hopkın DAB 56 118 Horatz K 118 Horwatz O 125 Howard F 66 327 Howell GR 41 109 Hueber EF 118 Huet PC 95 118 Huggias P A 72 124 Hughes G 52 95 118 Hunter AR 52 94 128 Hyraan A 51 134 kaplan S A 72 107 119 Kasman L. P 41 120 Sattus A A js 66 116 hay AW 50 119 130 heeley h} 100 1344 heller J W 45 315 Kelley RT 64 66 67 114 helly y cc 50 118 Kelsall AR51 118 henny § 52 119 hern E52 96 118 120 123 Kerr WS 45 115 Kety S S 67-68 120 hielbowicz D 113 Kildu& C } 56 120 hilpa rich JA 50 51 120 Kirkendall WM 72 120 Kirsch | 60 120 Kohlstaedt KG 30 31 34 120 Kolbl K 120 hopelman H 65 67 115 Korkis F B 25 52 54 66 212 120 Koster H 41 120 Kronen P 5 74 110 Kucher R 60 95 100 118 120 130 134 Kuhlmann | 120 7 Ing HR 14 507 Inglis AN 41 109 Jackson I 34 56 94 107 119 Jakı ) 130 James A 37 66 68 119 Jenkin PS 52 95 119 Labayle J 95 118 Labont H 120 Laester CH 62 127 Laidlaw PP 63 111 ·AUTHOR INDY 143 Robertazzi RW 09 127 Robertson E 50 52 77 110 Roger V 112 Rollason 1 N 28 52 6S 128 Romano G J 52 95 128 Romeno C 113 Rommcy R 51 134 Rose J C 50 61 66 67 114 Rosenheim 1 L. 50 51 66 106 128 Rosenthal A. 96 128 Rosenthal A I 54 91 128 Roth C. E. 114 Roth F 95 118 Rottgen P 99 128 Rovenstine EA 8 35 42 47 99 100 125 135 Rowlands EN 128 Rowlands S 125 Rycroft BW 52 93 128 Ruggiero WF 40 42 47 110 Ruru P118 Russell AS 133 Russo A 114 Rutkowski ) 95 128 Schachter R 62 127 Schaller 67 80 130 Schecter A. E 115 Scheinberg P 130 Schmidt CF 67-68 120 Schnaper HW 50 51 61 66 67 114 130 Schneider J GO 100 150 Schionbauer L. 100 130 Schroeder H1 A, 50 52 150 Schwartz 12 52 119 120 Schneizc 0 71 72 130 132 Scott L. D 1 50 130 Scott R. W 65 66 71 72 122 129 Scultéty s 130 Scurr CF 25 52 54 56 66 99 112 123 130 Sedzimir CB 56 112 Semeraro D 99 127 Seror J100 111 Shackleton RP W 25 28 50 52 54 66 73 112 127 131 Shackman R 64 66 71 90 122 131 S Sadove M S 56 64 128 Saegado AS 128 Saexinger H 118 Salem M 71 106 Salis S von 128 Samain A 60 128 Sancetta S M 63 66 71 72 122 125 127 129 Sarnoff L C 56 100 129 Sarnoff S J 13 14 42 55 56 100 106 125 129 Saunders J W 18 36 37 66 68 119 129 130 Sauvage Y 52 95 111 130 Saville S 50 130 Savolainen PV 180 Scarborough WR 66 116 Schachter M 131 Shaffer SA 118 Shapiro AP 131 Sherlock S 66 127 Shingleton WW 71 106 Shorr E 71 131 Subaud Y 191 Sicard A 131 Siemons h. 108 Siguier F 60 94 131 Siraeone F A 63 66 71 72 122 128 129 Simpson J A 50 130 Sims J L 131 Smirk FH 37 50 52 120 127 131 132 Smith A N 50 119 Smith H W 132 Smythe CM 116 117 Snyder HB 67 72 117 124 132 Soffer A 132 Sommerville J 51 192 ·142 CONTROLLED HYPOTENSION Moricca G 56 124 Morin G 40 42 47 117 Morris G C Jr 67 72 117 124 192 Morris L E 131 Morris N 50 124 Mortimer P L F 34 35 124 Morton A W 41 124 Moyer J H 67 72 113 117 124 132 Mueller RP 66 71 125 Muklerjee SR 125 Mulder AG 71 121 Muller CA60 100 111 Mundeleer P52 125 Murphy E A 51 125 Murphy Q R 65 67 m Musgrove A H 25 52 54 66 112 Pagliarını G 126 Pallestrini E 95 126 Papper EM 106 116 117 126 Parkhouse J 126 Pasquali E 126 Passaleo J 52 95 112 Paton A 66 127 Paton W DM 14 17 49 51 125 126 Patronicolas P 126 Patury E 126 Payne J P 26 65 126 Payne R 41 126 Pelmore J F 17 52 54 60 77 112 123 126 Penaud C126 Penn J 52 96 108 127 Penny CJ 50 127 Peruzzo L 111 Peterson WG 55 127 Petit Dutaillis D 94 95 127 Pettavel J 60 100 111 Phemister DB 62 127 Pitkın GP 41 127 Pizzioli R 65 109 116 Pokrzywnicki S 95 128 Pooler EH 94 127 Porro A 96 127 Prokop F 71 121 Proot R 52 125 Pryor WW 118 N Natellis F 34 109 Needlernan NL 125 Neill WR 62 135 Neumann C 42 47 125 Nicholson MJ 13 14 55 125 Nieto JC 128 Nilsson E 67 69 125 North J P 42 56 111 113 Norpoth L 60 100 125 Norvill W 132 0 R O Brien D 52 95 12, Odom GL 62 132 135 O Hare M M 50 130 Okker J J 194 O Leary J L 42 117 Olcesky s 51 124 Organe G 49 51 52 125 Orth OS 191 Owen SG 67 89 111 Rakita L 127 Randall LO 55 127 Ranovecchi E 64 116 Reinhold H 80 127 Remouchamps L 52 125 Resegotti E 56 110 Restall PA 97 50 52 127 Reynolds TB 66 127 Ricci C 64 116 Riskın AM 99 127 Rizzi R 52 110 Robelet A 108 Р Page 1 H 30 31 34 35 115 120 122 125 126

·AUTIIOR INDEX
145
York GE. 8 113
Young I M51, 135
Z
1loodhall B62 132 133
Woolsey RD 95 135
Wright AD 135
Wright Samson 19
Tant GM 56 61 128
Wylie W D 72 73 110 111 123
Hyman ) B 25 52 54 56 66 99
112 123 130 135
Wynn Williams D 111
Zaimis EJ 14 49 51 125 126
135
Zimmertaan h. 135
7ugliani ) A 94 155
Zulschucrdt L 60 135
Zweifach BW 8 85 71 117 131
135
Y
Yonkman F F 56 135

·144 CONTROLLED HYPOTENSION Sones F M Jr 116 Soulier J 113 Souza A 126 Spurr CL 113 Stacey RS 121 Stanton J R 114 Stead EAJr 130 Steevers MH 131 Steinbereithner 60 100 115 120 130 133 134 Stellet L 29 52 54 121 Stephen CR 59 62 71 106 132 135 Steven R JM 54 96 132 Stone H H 67 132 Stoneham FJR 17 29 123 Stovner 52 182 Sturtzbecher F 118 Suriani U 94 124 Suyemoto R56 107 Swain PG 51 122 Swanson H S 9 132 Sueet RB 132 Swerdlow M 65 66 132 Szutu C 72 123 192 Valle G 133 Van Bergen FH 133 van de Walle J 60 133 Vanlerenberghe J 108 van Wien W 52 133 Veal J R 133 Vehrs GR 41 133 Vento Ruiz V 139 Vernejoul R 99 133 Vetter H 115 133 Vial J 40 42 47 117 Vineberg A M 41 116 von Felsinger J M 45 115 Voorhoeve HC 56 133 134 Vourch G 52 94 119 134 Vyslonzıl E52 95 134 WV T Tada Y 72 107 Tait D 41 132 Taylor H C 71 106 Testa G 132 Thompson J W 17 126 Thorne M G 50 111 Todd DP 105 107 Torres RP 96 110 Torres SR Tovell RM 54 96 132 Trautmann R 120 Tuohy E B 50 64 66 130 Turner R 50 133 Wade G 50 51 64 66 132 134 Wakım KG 108 Walker G51 134 Walker J 51 126 Walz D 67 80 180 Waters RM 131 Watschinger B 184 Watson J 52 122 Webb J K 117 Weber HF 96 134 Wechsler R L. 67 132 Wenger P 194 Werko L 50 51 64 134 Wiggers C ) 35 134 Wiklund PE 94 134 Wilflingseder P 52 134 Wilkins RW 114 134 Willis K 112 Wilson | H 100 134 Hirtinger W 95 131 Witkın L. 50 113 Wohlraub 118 Wolff H H 128 Wood PM 47 95 115 132 Uihlein A 94 133 Ullmann TD 72 133 ·Subject Index re and renous return 25 Anesthetic indications 98 99 Abdominal eviscerations 96 Aneurysms Abdominal surgery 93 congenital 35 position of patient 27 28 ligation of 6 radical 95 Anhydrous cocaine 42 spinal block 46 Ano association 99 Abdomino-perineal resection 96 Anoxta 42 67 position of patient 28 cellular 69 synchronous 82 cerebral 77 84 Acetylcholine 49 63 liver 70 71 Addisons Disease 91 myocardial 84 Adrenal pheochromocytoma tissue 40 moval of 23 damage arteriotomy 36 Adrenalectomy 96 Anutia 77, 79 82 Age extremes of 89 91 92 Anxiety 92 Air embolism 29 36 81 Aorta Airway 103 atheroma 83 obstruction of 9 coarctation of 95 Alpha rhythm 69 70 compression of 79 Amino acids 71 pressure decreased 35 Ammonium salts 71 Aortic arch 26 Anemia 89 91 Aortic depressor nerve 62 Anesthesia Aortic femoral thrombosis 79 administration of 9 Apnea 10 chloroform 74 Arfonad 14 22 24 46 55 59 90 arculatory reflexes 8 cardiac output 64 conduction 22 70 disadvantages 59 cyclopropane 74 hemorrhage 59 depth of and bleeding 8 oxygen consumption 65 friction within closed anesthetic urinary excretion 56 Circuit 9 Arm elesating and degree of hypo general 70 cension 26 deep 8 12 13 20 Arrhythmias 74 effect on bleeding during sur Arterial air embolism 81 Arterial bleeding and reinfusion hypotensive 4 and shock syndrome 30 spinal 14 Arterial compression 12 trichlorethylene 74 Arterial pressure 13 16 17 62 72 vasodilatation 9 98 147 gery 7 9

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·SUBJECT INDEX 149 vascular 96 Bromism 51 Bromsulphalein retention 71 C Cachectic patient 101 Cacsarean sections 94 Cannula induciling 104 Capıllary dilatation 63 Capıllary ooze 86 control of extensive 96 Carbon dioxide absorption and surgical bleed ing 10 Lempert fenestration operation 3 pressure 8 and carbon dioxide absorp tron 10 arterial 66 69 chloroform 8 in deep general anesthesia 8 level of 61 63 local 28 and height of operative site 26 readings arm cuft method 61 Sanborn electromanometer 61 reduced 14 20 25 30 40 79 103 varying the level of 26 vasopressor agents 73 replacement of during surgery 3 vessels cut dunng surgery 5 Viscosity 17 89 volume arculating 3 16 62 reduction of 30 37 control of an arteriotomy 35 low 89 91 total 103 105 Bone grafts 96 Bradycardia 63 Brain edematous 97 effect of controlled hypotension 67 70 electrical activity of 69 ischemia to 28 postural 69 psychic strain 99 swollen 97 tension 35 tumor surgery 30 retention 74 tissues containing increased con centration of 74 Carcinoma 82 83 85 Cardiac arrest 78 79 81 84 Cardiac arrhythmias 74 Cardiac disease 89 90 Cardiac failure 81 84 89 90 100 Cardiac index 64 Cardiac massage 8t Cardiac output 16 64 factors controlling 17 in deep general anesthesia 8 methonium compounds 64 position of patient 61 Cardiac Sessel surgery 98 Cardio aortic sinus 26 Cardio pulmonary disease 6 Cardiovascular system 63 88 collapse 78 79 81 84 85 disease 92 surgery 95 Carotid sinuses 26 Cautery 11 Cellular intoxication 20 profound generalized 9 Cellular respiration 104 Central nervous system depression 99 Cerebral anoxia 77 78 84 ·148 CONTROLLED HYPOTENSION inhibition of synaptic transmis sion of impulses through 60 Awakening time 76 77 1 B control of in arteriotomy 34 35 decreased 18 effect of posture 26 maintaining normal 16 pulmonary 64 systemic 89 Arterial tone regulation of 19 Arteries elasticity of 17 Arteriolar bed dilated by sympa thetic blockade 73 Arteriolar dilatation 14 62 63 73 Arterioles contraction and tone of 20 Arteriosclerosis 88 Arteriotomy 13 18 24 31 37 81 advantages of 34 35 air ernbolisma 36 anoxic tissue damage 36 apparatus for 32 arculatory depression 35 dot formation 36 craniotomy 38 31 disadvantages 35 36 equipment 36 fenestration operation 34 hemorrhagic shock 35 heparin administration of 34 hepatic resections 34 infection 36 intracranial surgery 35 neurosurgical procedures 34 open heart operations 34 reinfusion 35 vasoconstruction 84 85 Arteriovenous oxygen difference 67 68 Artificial hibernation 99 Atheroma 83 84 Auricular pressure right meas urement of 64 Autonomic activity effect of bar biturates 8 Autonomic ganglia 22 blocking agents 48 Bainbridge reflex 63 Ballistocardiography 64 Barbiturates 51 autonomic activity 8 effect on hypothalmic centers 8 hypotension 8 respiratory depressant effects of 8 Bleeding and depth of anesthesia 8 cerebrovascular 100 control of 11 15 103 during surgery 3 5 10 anesthetic factors 7 10 control of 11 15 103 factors influencing 6 extensive 104 Prevention of 8 9 general anesthetic agents 7 and administration of 9 in wound 25 26 Blindness unilateral 79 Blood clotting of deficiencies in 6 during nitrous oxide anesthe sia 7 general anesthetic agents 7 flow hepatic 71 inaease 50 mean cerebral 67 68 nitrous oxide technique for measuring 67 peripheral 66 splanchnic 66 hepatic 70 71 intra arterial infusion of 30 ·SUBJECT INDEX 149 vascular 96 Bromism 51 Bromsulphalcın retention 71 G Cachectic patient 101 Cacsarean sections 94 Cannula induclling 101 Capillary dilatation 63 Capıllary ooze 86 control of extensive 96 Carbon dioxide absorption and surgical bleed ing 10 Lempert fenestration operation 3 pressure 8 and carbon dioxide absorp tion 10 arterial 66 69 chloroform 8 in deep general anesthesia 8 level of 61 63 local 28 and height of operative site 26 readings arm cuff method 61 Sanborn electromanometer 61 reduced 14 20 25 30 40 79 103 varying the level of 26 vasopressor agents 73 replacement of during surgery 3 Vessels cut during surgery 5 Viscosity 17 89 volutne circulating 3 16 62 reduction of 30 37 control of in arteriotomy 35 low 89 91 total 103 105 Bone grafts 96 Bradycardia 63 Brain edematous 97 effect of controlled hypotension 67 70 electrical activity of 69 ischemia to 28 postural 69 psychic strain 99 swollen 97 tension 85 retention 74 tissues containing increased con centration of 74 Carcinoma 82 83 85 Cardiac arrest 78 79 81 81 Cardiac arrhythmias 74 Cardiac disease 89 90 Cardiac failure 81 84 89 90 100 Cardiac index 64 Cardiac massage 84 Cardiac output 16 64 factors controlling 17 in deep general anesthesia 8 methonium compounds 64 position of patient 64 Cardiac vessel surgery 98 Cardio aortic sinus 26 Cardio pulmonary disease 6 Cardiovascular system 63 88 collapse 78 79 81 84 85 disease 92 surgery 95 Carotid sinuses 26 Cautery ti Cellular intoxication 20 profound generalızed 9 Cellular respiration 104 Central nervous system depression 99 Cerebral anoxia 77 78 84 tumor surgery 30 ·150 CONTROLLED HYPOTENSION Cerebral arterior venous Oxygen difference 68 Cerebral blood flow 89 90 Cerebral circulation 83 Cerebral function measurement of 67 Cerebral hemodynamics 67 69 during induced hypotension 67 Cerebral ischemia 68 Cercbral metabolism 29 67 70 Cerebral oxygen consumption 67 Cerebral thrombosis 78 79 89 and anoxia 81 83 Cerebral vascular resistance 67 89 Cerebral vessels passive congestion of 29 Cerebrovascular bleeding 100 Cerebrovascular disease 88 Chemical agents of escharotic na ture 11 Chemical ganglionic blockade 45 Chest surgery 95 spinal analgesia 41 Chloride preparations 51 Chloroform 12 13 and coagulation 7 blood pressure 8 hypotension 8 Chlorpromazine 11 Circulating blood volume reduc tion of 30 87 Circulation complications to 78 continued 29 obstruction to 78 time 66 67 Circulatory depression arteriotomy 35 Circulatory reflexes effect of muscle relaxants 9 in light planes of anesthesia 8 in deep general anesthesia 8 receptors in aortic arch 26 receptors in cardio-aortic sihus 26 receptors in carotid sinuses 26 Coagulation non anesthetic factors to prolong 57 Cocaine 42 Cold local application of and hemostasis II Colitis ulcerative 56 Coma 70 Complications 75 80 blurred vision 77 cardiac arrest 78 cardiovascular collapse 78 Involving lidneys 77 78 prolonged and delayed awaken ing time 76 77 rate 75 reactionary hemorrhage 76 thrombotic phenomena 78 Conduction anesthesia 22 38-47 Constrictor tone interrupted 22 reduction of 7 Contraindications 88 93 Convulsions 68 70 Coronary arteries 83 Coronary disease 88 Coronary flow 65 Coronary insufficiency 66 Coronary thrombosis 78 79 88 Coronary vascular resistance 65 Cortex electrical energy of 69 Cortical rhythm profound disturb ances of 70 Cranial surgery partial sympathet IC blockade 47 Craniotomy 27 31 97 arteriotomy 33 34 Cyanosis 85 Cydopropane 52 and coagulation 7 Cystoscopy bladder tenesmus dur ing 60 D Dales postural ischemia 15 ·SUBJECT INDEX 151 Decamethonium 49 51 and muscular relaxation 9 Déconnexion 99 Decortication 95 Defibrillation 84 Dehydrogenated cryot prepara tions 29 Delta waics 69 70 Dental extractions 94 Diabetes mellitus 92 Diaphragm moved downward 10 Diastole prolonged 63 Dibenamine 22 Differential spinal block 42 Durodide 22 Diseases cardia pulmonary 6 producing high degree of tox Etamon intra cnous administra tion of 65 Eller 52 and coagulation 7 Ethylene and coagulation 7 Extradural analgesia 40 Extrasystoles 65 Extremities loncr application of negative pres sure to 37 application of vacuum appa ratus 18 elevated skin temperatures in 50 surgery upon 11 Eyeball pressure on 79 F Femoral artery cannulating 30 Fenestration operation $1 arteriotomy 34 partial sympathetic blockade 47 position of patient 27 Fibrinogen deficiency 5 Flicker fusion frequency test 69 Fowler s position 10+ semi 27 city 5 d tubocurarine and muscular re laration 9 Duodenal ulcer 50 G E Edampsia hypertension in 46 pendiomide 60 Edema acute pulmonary 56 Efferent sympathetic outflow pa ralysis of 14 Electrical activity of brain 69 Electrocardiography 65 Electroencephalogram 69 traangs 77 Elimination of drugs from body 77 Emboli 67 Endotracheal cuff inflated 79 Ephedrine 74 Epidural analgesia 22 40 Epidural block 46-47 71 disadvantages 47 Esmarch bandages 11 Esophago gastrectomy 95 Ganglionic blockade 18 28 and transmission of noxious im pulses 99 cardiac output 64 mean blood flow 66 reduction of peripheral resist ance 48 60 Synergistic effect with general anesthesia 77 Ganglionic blocking agents 64 easily injectable 14 medical therapies 99 therapy of cardiac failures 90 Ganglionıc synapses 9 Gastrectomy 96 ·150 CONTROLLED HYPOTENSION Cerebral arterior venous oxygen difference 69 Cerebral blood flow 89 90 Cerebral circulation 83 Cerebral function measurement of 67 Cerebral hemodynamics 67 69 during induced hypotension 67 Cerebral ischemta 68 Cerebral metabolism 29 67 70 Cerebral oxygen consumption 67 Cerebral thrombosis 78 79 89 and anoxia 81 83 Cerebral vascular resistance 67 89 Cerebral vessels passive congestion of 29 Cerebrovascular bleeding 100 Cerebrovascular disease 88 Chemical agents of escharotic na ture 1) Chemical ganglionic blockade 45 Chest surgery 95 spinal analgesia 41 Chloride preparations 51 Chloroform 12 13 and coagulation 7 blood pressure 8 hypotension 8 Chlorpromazine 11 Circulating blood volume reduc tion of 30 37 Circulation complications to 78 continued 29 obstruction to 78 time 66 67 Circulatory depression arteriotomy 35 Circulatory reflexes effect of muscle relaxants 9 in light planes of anesthesia 8 in deep general anesthesia 8 receptors in aortic arch 26 receptors in cardio-aortic sinus 26 receptors in arotid sinuses 25 Coagulation non anesthetic factors to prolong 57 Cocains 42 Cold local application of and hemostasis II Colitis ulcerative 56 Coma 70 Complications 75 80 blurred vision 77 cardiac arrest 78 cardiovascular collapse 78 involving kidneys 77 78 prolonged and delayed awaken ing time 76-77 rate 75 reactionary hemorrhage 76 thrombotic phenomena 78 Conduction anesthesia 22 38-47 Constrictor tone interrupted 22 reduction of 7 Contraindications 88 93 Convulsions 68 70 Coronary arteries 83 Coronary disease 88 Coronary flow 65 Coronary insufficiency 66 Coronary thrombosis 78 79 88 Coronary vascular resistance 65 Cortex elec energy of 69 Cortical rhythm profound disturb ances of 70 Cramal surgery partial sympathet ic blockade 47 Craniotomy 27 31 97 arteriotomy 33 34 Cyanosis 85 Cyclopropane 52 and coagulation 7 Cystoscopy bladder tenesmus dur ing 60 D Dales postural ischemia 15 ·SUBJECT INDFU 158 controlled 4 19 15 25 advantages of arteriatomy 35 and cerebral metabolism 29 anesthetic indications 98 99 dinical practice of 23 24 complications 75 87 conduction anesthesia 58 47 contraindications 88 93 controlling degree of 26 electrocardiographic traangs 65 epidural block 46 ganglionic block 48 history of 13 indications 94 100 medical 99 100 modified technique of 56 58 patients resistant to methonium compounds 37 physiological considerations 61 74 position of patient 26 28 post operative care 105 reduction of peripheral resist ance 26 requirements 101 105 selection of patients 101 102 surgical indications 96 98 techniques employed 23 types of operative procedures 95 degree of 79 80 duration of 80 during complete sympathetic blockade 29 hypovolemic 35 103 induced 4 16 24 arfonad 55 epidural block 46 physiological basis of tech niques for 18 intentional production of 3 thethonium induced 37 normovolemic, 40 103 partial sympathetic blockade 47 persistent 79 91 posture of patient 6! reduction of peripheral resist ance 38-47 uncontrolled 80 TIydralazine 20 Hyperextension 27 28 Flypericnsion 50 89 control of 20 malignant 90 methonium compounds 52 renal 65 sciere 90 Hypnosis 20 43 Hypoglycemia 92 Hypotensive anesthesia 4 Hypothalmic centers inhibition of 7 Hypothermia 11 99 Hypovolemic hypotension 35 Hypoxia 71 Hysterectomy radical 96 I Insulin 92 Intestinal capillaries oxygen de saturation in 70 Intestinal peristalsis inhibition of 50 Intra arterial infusion of blood or plasma 30 Intracranial aneurysins 96 ligation of 91 95 Intracranial interventions 6 Intracranial surgery arteriotomy 35 Intracranial tension 89 Intrapleural negative pressure 9 Intrapulmonary pressure 9 Intra thoraac surgery 6 95 position of patient 27 Intravascular pressure increased 54 Intravascular tension 98 ·152 CONTROLLED HYPOTENSION Gastric motility reduction of 50 Gastric seaetion inhibition of 50 Gastric ulcer 50 Glaucoma 95 98 pendiomide 60 Glomerular filtration 51 72 90 Glomeruli hydrostatic pressure in 72 Goiter toxic subtotal thyroidec during surgery 3 control of gross 3 96 general anesthetic agents 78 reactionary 11 73 76 79 81 85 86 reduction of pressure by 62 replacement of blood 3 severe 100 Hemorrhagic shock 13 arteriotomy 35 Hemostasis 31 position of patient, 12 Hemostatic sponges 11 Hepatic artery 70 Hepatic disease 89 91 102 Hepatic necrosis acute 90 Hepatic resections major artert tomy 84 Gravitational venous drainage 12 Gravity above heart letel 26 below heart level 26 Gynecological surgery 6 H otomy 34 Hand elevating and degree of hypotension 26 Head and neck surgery 95 head down position 28 29 head up position 27 29 operations on spinal analgesia 41 Headache 46-47 spinal analgesia 46 Heart and increased bleeding 5 contractile force of 74 force of beat 17 gravity above level of 26 gravity below level of 26 operations on open arteriotomy 84 rate 17 63 stroke volume 64 Heat local application of and hemostasis 11 Hematocrit 65 determinations of 105 Hemipeliectomy 85 86 Hemoglobinuric nephrosis 86 Hemorrhage 7 59 63 82 85 89 91 94 98 104 Hepatic vein oxygen content 71 Herpes zoster 100 pendiomide 60 Hexamethonium 14 48 50 52 54 68 79 84 anudote to decamethonium 51 bromide 82 coronary blood flow 65 effect on brain 67-68 flicker fusion (requency test 69 halides 22 hypotension anesthesia record 53 intravenous 65 jodide 83 85 oxygen consumption 65 peripheral blood flow 66 splanchnic blood flow 66 Hiccup intractable 50 Hip operations on 6 Histamine 63 Homologous serum jaundice 35 Hypotension abruptness of onset 80 arfonad 55 57 barbiturates 8 chloroforma 8 ·155 SUBJECT INDEX spinal patients resistant to 54 position of patient 54 post-operatiic arc 54 55 renal craction of 51 Inulin dearance ratios 51 Mid abdominal surgery block 46 Mortalities 80-87 rate of 80 81 renal failure and anuria 81 82 Motor blockade 14 Motor paralysis 42 Musde limb contraction of 25 26 paralysis 25 relaxants 10 relaxation 12 99 during surgery 9 skeletal during clinical anes thesia 49 vascular 6 Myocardial anoxia 84 Myocardial ischemia 35 66 Myocardium weakened 74 Myoneural junction 49 position of patient 27 Tetractors employed 78 withdrawal of blood prior to SO 31 Vitrales 23 Nitrites 23 Nitrous oxide 44 52 and coagulation 7 technique for measuring blood flow 67 Mode dissection radical 97 Non rebreathing techniques 10 Nor adrenaline 71 Noxious impulses 99 Nupercaine 44 0 N Narcotic agents 20 Nausea 68 Neck dissection radical 27 Necrosis acute hepatic 90 ischemic 86 liver 71 pressure 79 Negative pressure device 36 Nephrectomy 79 96 Nephrosis hemoglobinuric 86 Nerve block concentrations of procaine re quired 43 direct 9 Neurosurgical procedures 94 arteriotomy 34 operative trauma 81 87 Olfactory groove meningioma ex Cision of 31 Oliguria 77 79 Open hip operation 96 Operative site elevation of 25 29 nature of 6 posture of patient 6 visibility in 97 Opthalmic surgery 95 Organ tension 98 Orthopedic surgery 96 Otorhinolaryngological procedures 95 Over heparinization 81 Oxygen consumption 65 66 Oxygen desaturation in intestinal capillaries 70 Oxygenation 104 105 P Palpitation 92 Parasympathetic blockade 64 Parasympathetic ganglia 48 Paravertebral block 40 Paravertebral sympathetic ganglia blockade 22 Partial sympathetic blockade 47 ·154 'CONTROLLED HYPOTENSION intravascular thrombosis 89 Intravenous barbiturates and co agulation 7 Intubation 52 Inulin clearance at 52 Tate 72 Todısm 51 Irreversibility 35 Ischemia cerebral 68 myocardial 35 66 postural 25 29 of brain 69 to brain 28 vital organs 27 28 Ischemic necrosis 86 Ischemic operative field 9 J Jack knife position 27 Jaundice homologous serum 35 Lempert fenestration operation 3 95 97 Ligation temporary 12 Lithotomy position 28 29 Llier anoria 70 71 blood supply to 70 effect on 70 71 failure 90 level of hypotension 70 necrosis 71 occult damage 71 oxygen supply 70 Lobectomy 95 Lower extremities operations on position of patient 28 Lumbar disc prolapsed 86 87 Lumen 83 Lungs and increased bleeding 5 MI K Kidney complications involving 77 78 disease 51 90 effects on 71 73 excretion of arfonad 90 excretion of methonium com pounds 90 morphological changes 72 position of patient 28 t Mandibular resection 27 Mastectomy 6 radical 27 57 83 95 Mastoidectomy spinal analgesia 41 Medical indications 99 100 Medullary center muscles of 14 Meningiomas removal of 95 Meningisaus 47 Mesenteric thromboses 78 Metabolic rate increased basal 5 lowered 77 Metabolism cerebral 29 Miethedrine 45 71 82 84 Methonium 90 compounds 14 24 48 55 66 91 administration of 52 54 anesthesia 52 blurred vision 77 cardiac output 64 dosage 51 53 effect on liver 71 medical therapy of hyperten son 52 Laminectomy 6 96 Laparotomy 71 Laryngeal mucosa pressure netto sis of 79 Laryngectomy 95 Lateral jack knife position 28 29 Left ventricle calculated work of 65 Leg elevating and degree of hypotension 26 pneumatic suction to 68 ·SUBJECT INDEX 157 hypertension in 16 Pressor reflexos in deep general anesthesia 8 Pressure ncaosus 79 Priscol 22 Trocaine 42 concentrations required for neric block 43 preganglionic sympathetic fibers 43 subdural injection of 65 Prone jack knife position 29 Prostatectomy 96 Protanuria 73 Prothrombin defidency 5 Pulmonary edem, 81 86, 100 Pulmonary embolism 100 acute 60 Pulmonary infarcts 81 Pulse rate 6% vaallating 65 Pupils ce dilatation of 50 Pyrexia 56 depression of 71 Impaired 51 Requirements 101 102 Respiration assisted 9 cellular 3G level of pressure 40 controlled 9 depression 25 74 effect of barbiturates 8 failure 42 inacased resistance to 9 muscles of 14 Restlessness 92 Retinal artery occlusion 79 Retinal thrombosis 78 79 Retractor anemia 78 Retransfusion 18 R Radica) bysterectomy 96 Radical mastectomy 95 position of patient 27 Radical neck dissection 27 9. Radical node dissection 97 Radical pelvic surgery 28 Reactionary hemorrhage 79 81 85 86 Red cell mass 103 Regitine 22 Reinfusion arteriotomy 85 Renal blood flow 90 Renal damage 72 73 Renal disease 89 91 102 Renal epithelium 72 Renat excretion of methonium compounds 51 Renal failure and agura 81 82 Renal function complications involving 77 78 S Salivary secretion oubition of 50 Sanborn electromanomcter 61 Sclerosis vascular 51 Semi Fowler s position 27 Sensory blockade 14 Sepsis spinal analgesia 46 Shock 33 89 91 chronic 104 unteversible 63 80 103 104 surgical 99 syndrome method for studying 30 treatment of 30 Shoulder joints operations on 6 Side tilt of operating table 27 Skin cold cammy 68 flaps 96 grafts 96 Somnolence 68 Speech slurring 68 Spinal analgesia 40 72 bigh 63 64 71 74 arterioyenous oxygen 65 oxygen consumption 69 ·156 'CONTROLLED HYPOTENSION Patent ductus arteriosus 95 Pelvic evisceration 96 Pelvic floor repair of position of patient 28 Pelvic node dissection 96 Pelvic surgery 96 radical position of patient 28 Pendioride 14 22 24 58 60 administration of 60 advantages 60 disadvantages 60 dosage 60 Pentamethonium 14 48 50 70 82 antidote to decamethonium 51 halides 22 intravenous 65 peripheral blood floty 66 Pentothal 43 intravenous 52 Perinephritis experimental 65 Peripheral arculation 83 Peripheral resistance 16 18 20 88 reduction of 26 38-47 by Interruption of sympathetic vasoconstrictor impulses 21 ganglionic blockade 48 60 Peripheral respiratory paralysis spinal analgesia 42 Peripheral vascular disease 50 Perspiration 68 Pheochromocytoma removal of 98 Phlebotomy 90 Physiological considerations 61 74 Plasma intra arterial infusion of 30 Plastic surgery 96 Platelet deficiency 5 Pneumatic suction to legs 68 Pneumonectomy 95 Polycythema 89 vera 91 Porta caval shunt 96 Portal vein 70 Position of patient 6 104 abdominal surgery 28 abdomino perineal resection 28 cardiac output 61 craniotomies 27 during and after complete sym pathetic blockade 29 effect on arterial pressure 26 head down 29 tilt 28 head up 29 tilt 27 intra thoracic operations 27 ischemia of brain 69 to vital organs 27 jack knife 27 kidney operations 28 lateral jack rufe 28 29 lithotomy 28 29 lower extremities operations on 28 methonium compounds 54 neurosurgical procedures 27 post operative 105 posterior fossa explorations 27 prone jack knife 29 radical mastectomy 27 radical pelvic surgery 28 repair of pelvic floor 28 semi Fowlers 27 side tilt 27 sitting 27 supine jack knufe 28 30 degree Trendelenburg 28 upper abdominal surgery 27 28 Posterior fossa explorations 27 Post operaure care 105 Postural ischemia 25 29 Preganglionic sympathetic fibers blocking of 22 procaine 43 Pregnancy hypertensive complications of 56 toxemic states of 50 ·SUBJECT INDEX 159 Tonsillectomy 91 Total spinal analgesia 43 44 Total spinal block basic leatures of 43 44 in controlled Prypotension advantages 45-46 disadvantages 46 Tourniquets 11 Toxemia 6 Toxiary high degree of 5 Tracheotomy 85 Transfusion avoidance of 98 reactions 98 Trendelenburg posicion 45 68 Teverse 27 45 68 30 degree 28 Trichlorethylene 52 Tubular reabsorption 72 'Tumors Vascular 6 brain 96 reynoval of 31 94 Vascular sclerosis 51 Vascular tension 98 Vagal tone increase in 69 Vaginal plastic operation 96 Vasoconstriction 9 62 8G agents 45 54 artcriotomy 55 fibers 40 impulses 20 22 interruption of 21 48 peripheral 13 31 Vasopressor agents 54 of Shorr 71 reactionary hemorrhage 76 use of 73 74 Vasodilatation 7 50 88 92 and carbon dioxide absorption 10 during deep general anesthesia 8 effect of muscle relaxants 9 spinal analgesia 42 Vasomotor center depression 20 in medulla oblongata 20 reflex inhibition of 20 Veins small contraction of 20 Venodilatation 25 29 Venous congestion 5 9 Venous drainage 25 104 gravitational 67 12 Venous ooze 10 12 Venous pressure 9 63 increased 5 Venous return 17 63 and continued arculation 29 spinal analgesta 14-45 Ventilation 72 Ventricular failure acute 50 Veratrum alkaloids 22 Vesico-vaginal fistuia 96 Vision blurred 77 Vital organs ischemia to 27 28 U Ulcer duodenal 50 gastric 50 Ulcerative colitis sympathetic over activity 56 Urea 71 Urine formation 72 suppression of 71 Urological surgery 96 Vascular bed capacity of following sympathet 10 blockade 26 dilated 101 Vascular deficiency 5 Vascular disease 102 Vascular lesions rernoval of $1 Vascular ooze $ 7 9 11 46 58 abnormal 5 control of 14 Y Yawning 68 ·158 CONTROLLED HYPOTENSION oxygen saturation 63 peripheral blood low 66 low 66 penipheral respiratory paralysis position of patient 12 14 and bleeding 67 Uncomplicated and elective 89 92 99 vascular core 3 vasoconstrictor substances at op cratne sitt li Sueating 92 Sympathetic blockade 22 97 64 73 and capauty of vascular bed 26 severe hypotension 29 Sympathetic chain block 40 Sympathetic ganglia 48 blockade 22 Sympathetic paralysus 22 70 total 22 43 44 vasodilatation 42 Spinal anesthesia 12 14 high 81 86 87 Spinal block 90 coronary flow 65 differential 42 68 total 14 41-46 sn controlled hypotension 24 Spinal fusion 96 Splanchaic blood flow 65 Splanchnic vasodilatation 62 Subarachnoid block 42 Succinylcholine and muscular re laxation 9 Superior maxilla CXOsIon of spinal analgesia 41 Surgery bleeding during 3 5 10 and posiuon of patient 63 anesthetic factors 7 10 control of 11 15 factors influenang 6 bloodless operative site 3-4 coagulation effect of chloroform 7 effect of cyclopropane 7 effect of ether 7 effect of ethylene ? effect of intravenous bətbifu rates 7 effect of nitrous oxide 7 cergeno 98 head and neck 95 hemorrhage during 3 involving glandular tissue 6 involving mudes 6 Lemper fenestration 3 muscular relaxation 9 of the extremiges 11 Tachycardia 59 63 64 Tachyphylaxis 59 Tetraethylammonium bromide 22 Thiophansum compound 55 Thorax pump action of negatisc pres sute 25 wall bit of 9 Thorac lumbar splanchnicectomy position of patient 27 Thoraco-lumbar sympathectomy 96 position of patent 27 Thoracoplasty 95 Thyroidectomy 6 95 spinal analgesia 41 subtatal for toxic goster 84 Thromboplastın defiaency 5 Thrombosis 67 Thrombotic phenomen3 78 83 Thrombus fotination 29 88 89 Tissue anoxia 40 glandular surgery sovo]ying 6 oxygenation 104 level of pressure 40 vascularity of a

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