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·NEW WAYS
OF TREATING URAEMIA
THB ARTIFICIAL KIDNEY, PERITONEAL LAVAGE
INTESTINAL LAVAGE
BY
W. J. KOLFF M.D
umcipal Ilaspilul ,,Engelenbergsluhning" Kampen (Holland,
With the cooperation of
J. VAN NOORDWIJK, P. S. M. KOP,
N. X. M. DE LEEUW and A. M. JOEKES
LONDON
J. & A. CHURCHILL LID
104 GLOUCESTER PLACE
MORTMAN SQUARE
1947

·Printed in Holland ·CONTbus help from Prof R. number of inhabitants PART 1 ARTIFICIA special reference to CHAPTER ers of the staff of Nurse M TER BRIEF SURVEY OF ATTEMPS AT BLOOL (IW ESKES CATION IN RENAL VRAEMIA Excretion ng the gastro intestin b Excretion through the skin с Excretion through serous membranes d Kidneytransplantation and crossed bloodu e Bloodcleansing by venasection or plasmap f Vividialysis a CHAPTFR IT THE ARTIFICIAL KIDNEY 1S IT IS USED NOW IN THE CLINIC Principle Methods of dialysis Details of construction The Blood flow through the kidney Cleaning and sterilising Keeping of the mounted kidney Rinsing fluid Splashboards Results of an experimental dialysis Measurements of pressure during dialysis Advantages of this apparatus Comparison of the artificial kidney with the human glomerular apparatus 18 22 22 23 23 24 25 25 CHAPTER II TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY GAINED IN CLINICAL USE AND HINTS FOR THE USE OF THE KIDNEY IN FUTURE Fractionated dialysis Continuous dialysts About heparin and haemorrhages About the composition of the bath water 27 27 27 31 32

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·In this work I had the most generous help from Prof R BEINKMAN, Groningen and from a great number of inhabitants of the town of Kampen, but I wish to make special reference to Mr H TH J BERK and to the following members of the staff of the municipal Hospital Engelenbergstichting, Nurse M TER WELLE +. Miss AJ W VAN DER LEY en Miss W ESKES

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·1 PART I. ARTIFICIAL KIDNEY. CHAPTER I BRIEF SURVEY OF ATTEMPS AT BLOOD- (AND TISSUE-) PURIFICATION IN RENAL URAEMIA. 1 1 The clinical notion of uraemia embraces much, and is not at all sharply defined By uraemia an intoxication is understood, caused by an unphysiological rise of the concentrations in the body fluids of a number of products of metabolism, mostly of protein origin by retention or (and) increased formation According to the origin three forms of uraemia are distinguished Uraemia through renal insufficiency, 2 Uraemia through extrarenal causes, 3 Uraemie d'origine mixte, where both extrarenal and renal factors play a part The uraemia of extrarenal origin is not discussed in this treatise It may improve with the correction of the extrarenal factors, and should not be treated with the artificial kidney With uraemie d'origine mixte first of all the extrarenal factors must be treated Any uraemia of purely renal origin will eventually be aggravated by the addition of extrarenal factors, which should again be dealt with The way in which this takes place, is incidentally mentioned in the description of the patients in our Dutch book, but it does not form the object of the discussion in this treatise There remain a considerable number of patients in whom kidney function does not improve with treatment It is with this group, where protein katabolic products must be removed by some channel other than the kidney, that we are concerned Excretion through the gastro-intestinal canal The old way of trying to remove retention products through the intestinal wall has not yet been done away with, it can, however, contribute but little to excretion, just like vomiting and loss of saliva Diarrhoea may have its meaning, it is, if possible, not suppressed in uraemia Intestinal washings are no longer ap- ·8 SURVEY OF BLOOD-PURIFICATION plied by clinical men with much experience, though a physiological basis is present for this therapy (PENDLETON) The use of an isolated intestinal loop, through which the fluid runs, as a vividialysator will be discussed in the last chapter of this book b Excretion through the skin By the usual sweating-cures not more than 24 grs of urea N can be excreted per 24 hours, clinicians with great experience such as Fishberg have ceased applying them for years pomp 1991 pomp NO 2 vena arterie vena arterie SOUND DOG KIDNEYLESS DOG Fig 2 The artery of one dog is connected with a vein of the other dog and conversely The protracted immersion of the patient in a hot bath may probably attain something more, an experiment done by WITTER MANS gave a cutaneous urea' loss of about 1 g per hour, with a blood urea of 40 mgrs per 100 cc It seems probable that in this way something more might be obtained. L MEYLER tried it in a uraemic patient but had to abandon this form of therapy because the patient got too exhausted I have had a similar experience C Efcretion through serous membranes Peritoneal lavage is discussed on p 91 d Kidneytransplantation and crossed bloodtransfusion The methods of crossed circulation between experimental ani ·SURVEY OF BLOOD-PURIFICATION 9 mals with and without kidneys and the efforts at kidneytransplantatrons, have had only experimental value hitherto Transplanted organs atrophy in a short time (ENDERLEN and BORST) In case of crossed bloodtransfusion (W NYIRI, W THALHINER) or 50-called exchange transfusion one proceeds as has been shown on fig 2 An artery of one dog is connected with the vein of the - kogellager ijzeren frame rol stelschroef regelklem metalen mantel rubber búis bak waomn reductie Transmissie 27 Fit 3 Through this httle pump as much blood goes from left to right per timeunt es conversely Lancet 1938 other dog and conversely Through a special pump as much blood goes from the kidneyless dog to the healthy dog per time unit as conversely (fig 3) (W THALIIIMER, SOLANDT and BEST) The Tesult is that the total quantity of urea is soon equally divided over both dogs One sees this depicted in the curve in fig 4 I would not connect a healthy donor with a patient suffering from acute glomerulonephritis One does not know beforehand, how the kidneys of the healthy donor would react to this in some other conditions, especially when the patient is a child, one might try the crossed transfusion in man The simplest technics are then those of the ordinary direct transfusion, in which the pump turns alternately to the nght and to the left ·10 SURVEY OF BLOOD PURIFICATION e Bloodcleansing by venesection or plasmaphaerests The withdrawal of half to three quarters of a liter of blood which may be so beneficial in conditions like eclampsia and acute left ventricular failure has no direct significance for the removal of uraemic poisons, the rest 220 2500 N is usually up after loss of blood. Intensive plasma 200 2300 phaeresis ie the with 180 2100 drawal of blood and the replacement of the red 1900 cells in saline gives better 140 1700 results 160 1 Mg Urea N 1 100 com bloed Mg Urea N in ur ne per uur 1500 60 40 20 SOOD 0 2 10 34 50 74 92 106 4 AL TL 1 AT 4. AL f Vrvidralysis 1300 In the end we come 1100 therefore to the method 900 called by ABEL et al ,Vivi diffusion" It was origin 700 ally intended to demon strate the circulation of glucose and amino acids 6 8 in vivo, but is in addition uren probably the most effect ive means of removing non colloidal particles from the circulating plasma bu diffusion, ABEL ROWN TREE and TURNER used in equally uvideu uver Down duudis this connection the expres sion , artificial kidney! An ideal vividialysis must fulfil the following demands 1 the blood must be kept in a closed system outside the body, 2 It must be possible to sterilise this system, 3 the dialysing area must be as large as and the volume of the system as small as possible, 4 the blood must be kept liquid in a harmless way For keeping the blood liquid ABEL et al used hirudine for which purpose they extracted thousands of leech heads in the case of animals this hirudine did not seem to have any injunous results but experience teaches us, that it cannot be used for human beings The weak point remained the dialysing capacity of their apparatus They employed celloidine tubes with a bore of 6-8 mm and a length of 20-50 cms connected partly in series and partly parallel ·SURVEY OF BLOOD PURIFICATION 11 hth The blood was pressed through these tubes by the arterial tension, and flowed back into a vein In fig 5 is seen, how the blood flows through the celloidine tubes, while the rinsing fluid flows round at in a glass mantle As rinsing-fluid they used a NaCl solution of 0,55 or 066, as oedemas of the ex perimental animal appeared Fug 5 when using 09", NaC? Dialysator according to ABEL, ROWNTREE and TURNER Canule A is attached in an An apparatus with 32 artery of an animal Hirudine flows in tubes had an area of 3200 sq cms, and a volume of 500-800 cc An apparatus only carried out on paper as far as I know, with 192 tubes would have an area of 8179 sq cm, but a volume of 2123 Ls As ABEL et al could not dialyse more than Ys of the total amount of the animals blood at a time without causing a fall of the bloodpressure, which was already critical this apparatus was only serviceable for a calf or another animal of the same size The cleaning of the apparatus is a problem in itself After cleaning the apparatus was fil led with saturated thymol solution, by which it was kept ste rile for the next use An example of application is the following A dog of 22 Kgs got an injec- Fig 5a The arterial canule used by ABEL tion of I gr of salicylas natricus ROWNTREE and TURNER With an apparatus of 32 tubes A comes into the artery Through C the hirudine is added tapers in 7 hours 19,1 % of the injected to a point which ends close be salicylas natricus could be recoand the point of A The blood is vered. With another dog 24 3% led through D to the dialysator J Pham and Exp ther 1913 '14 A control dog excreted in about the same time 175 % with the urine It was remarkable that during the dialysis the urineproduction of the kidneys almost stopped (reduced bloodpressure?) After ·14 SURVEY OF BLOOD PURIFICATION to 40 cms The tubes were tied up at one end, and at the other end provided with a doubly-pierced plug, through which a long and a short glass tube projected The long tube was connected with the artery, the short one with a vein The whole was im mersed into a tank with a physiologic saline solution In 3–5 hours 200-700 mgrs of urea nitrogen could be removed by dialysis. THALHIMER hoped to make further experiments in cooperation with Best, but hitherto nothing is known to me of these Reviewing the literature we see that the clinical application of the artificial kidney has run aground on the following difficulties 1 The want of a harmless and sufficiently reliable agent for the prevention of clotting, 2 the unreliability of the earlier dialysing membranes for which collodion, celloidine or peritoneum were used, 3 the insufficient capacity of the dialysers As we have at present at our disposal a serviceable means of preventing clotting, 1 e heparın, and excellent dialysing mem branes i e cellophane, the only thing remaining is the building of a dialyser with sufficient capacity * ·CHAPTER 11 THE ARTIFICIAL KIDNEY AS IT IS USED NOW IN THE CLINIC. We pass by the various apparatuses built in the last few years to describe only the artificial kidney that was used therapeutically In cooperation with Mr H TH J BERL the apparatus depicted in fug 12, 13, and 14 has been built in the Kampen Enamelworks It was our first artificial kidney, suitable for clinical use It had been made for the greater part of aluminium. Become Wiser by experience we built second and a third kidney, after that finally a series of 4 at a time (see frontispiece) partly of wood, they are based on the same principle VOORAANZICHT ZJAANZICHT BOVENAANZICHT Buret Patient Fig 10 A cellophanetube 19 wound like a spiral round a big cylinder The blood in the cellophanetube always sinks to the lowest point if the drum turns round, the blood moves from left to night Principle. A big cylinder turns with its undermost segment through a tank with rinsing-liquid Round this cylinder a long cellophanetube has been spirally wound The tube contains only a small quantity of blood This blood sinks by gravity always to the lowest point of the spiral line When the cylinder rotates in the direction of the arrow in fig 10, the blood runs through the spiral line from left to right, always sinking to the lowest point It enters and ·16 THE ARTIFICIAL KIDNEY USED IN THE CLINIC leaves the cylınder through the hollow axles, in each of whic is fixed a rotating coupling By connecting the take up and exhaust tubes with each othe a closed circuit is formed in which the blood circulates rapidl; air bubbles are dragged along Methods of dialysis. 1 Fractionated dialysis This has only historical significancı we used this method to see how our first patient would react t the dialysing of a small quantity of blood Pament ܒ݁ܡܰܕ݂ܒ݁ܬ݂ܳܐ See Fig 11 Scheme of fractionated dialysis I Connection with dialyser shut the patient into the burette - II uremie blood flows out of the bu patient shut off, burette low cle burette. - IV Connection with flows out of the burette into the patient. A side tube is attached to the circuit branching into two oni branch to the patient and the other one to a burette By raisingol lowering the burette, blood may be let into or out of the patient and into or out of the dialyser (see fig 11) Using this method only one single venipuncture is necessary In the tube passing to the patient there is a cellophane window, through which may be seen directly, whether there exists a positive or a negative pressure, and by which one may check if blood is flowing (see fig 20) 2 Continuous dialysis A much greater effect is obtained, if the blood is drawn from one bloodvessel, and, after having traversed the kidney only once, led back into another one We did this first

·Fig 12
Front view of the frst artificial kidney
L +12 th a thin film of blood are seen tound
rovided with ridges To this
ough a single venipuncture,
pat ent sein
Fug 13
f
w
the alumi
on the
ith the

·WON
Fig 14
The first artificial kidney half lateral view The cellophane tube is seen to
pass into the rubber tube afterwards going to the centre of the cylınder
and coming out through the hollow axle

·Fig 15 The latest model of an artificial kidney The cylinder 13 made of varnished athwork and rotates with its lower segment through a tank with rinsing 1 quid The splashboards are seen on either side of the cylinder

·Fig 14
The first artificial kidney half lateral view The cellophane tube is sex
pass into the rubber tube afterwards going to the centre of the cyli
and coming out through the hollow axle

·THE ARTIFICIAL KIDNEY USED IN THE CLINIC 17 by taking up into the circuit at each end of the kidney a sidetube with a burette, which could be raised and lowered At present we let the blood flow of its own accord from the arteria radialis, and the blood is led back into a vein by means of a rubber tube pump BURET DIALYSATOR UCHTVANGER ARTERIA RADIALIS 971 П a i CELLOPHAAN VENSTER POMP AFGESLOTEN CIRCUIT Fig 18 Chain Mhe blood from e side into the ped back by a In the artery and in the vein a glass canula is tied In order to prevent airembolism, a bubblecatcher has been taken up into the circuit to the patient, in which also clots are sifted A burette serves for measuring the velocity of the current and can be used to give intravenous infusions to the patient Details of construction, (Plans with all measurements are found in the appendix) The cylinder The cylinder is made of varnished lathing The laths have been screwed on two wooden wheels and project 5 cms over the wheel at the end of the cylinder The cylinder turns with its lower segment through a tank with rinsing-liquid and has two short hollow axles, through which the blood is brought in and led out (fig 15) The iron frame The hollow axles of the cylinder turn in two plain open bearings (plan III), which are fitted on a rectangular angle-rron frame This frame is provided with legs and can be lifted with the cylinder from the underframe (fig 16) Resting on ratchets, the frame can rotate round a long side, so that the whole upper part of the kidney may be turned up with the cylinder (see fig 19) Kot

·ny
Fig 16
The angle iron frame is provided with legs and can be I fted wth the
cylinder from the frame
Fig 17
The frame with the enamel bath and the outlet The heating element has
been brought in the switch has been put on the bath at the back

·Fig 21 Frontview of the artificial kidney with tubepump and airbubblecatcher The course of the tubes can be seen from the air catcher the blood goes to the patients vein through the tube which goes almost straight down on this photo ·18 THE ARTIFICIAL KIDNEY USED IN THE CLINIC The bottom of the cylinder can be well seen then, and the bath can be easily refreshed or cleaned The under-frame is a tube-iron construc tion on wheels, it bears the enamel rinsing tank In the rinsing-tank is a heating element Formerly we used the bottom of electrical kettles, for thus purpose now a more elegant apparatus Fig 19 Rather than a very vulnerable automatic It may be fixed in the heatregulation with a contactthermometer ulted position with 3 little plank, which is very we use baththermometers, and a simple convenient when refresh heating-element, provided with a switch ing the rinsing liquid and checking the cellophane with two positions, resp 1000 and 2000 Watt tube in case of leaks (see fig 17 and 22) The Bloodflow through the kidney The canula and the cellophane-window A glass canula is introduced into the arteria radialıs, and the rubber tube, connected with this, is provided with a cellophane window, by means of which one immediately sees if the tube is under positive or negative pressure, and by means of which one can estimate the flow by pinching the tube below the window, the arterial pressure then pumps up the window immediately Canula and pressure-window are found depicted in fig 20 THE PRESSURE WINDOW OF THE OUTFLOW TUBE FROM THE PATIENT 5 mm canule canula cellophaandarm ligatuur cellophane gut ligature Fig 20 One can immediately see by means of the pressure-window whether the tube 18 under positive or negative pressure, and if the pressure, is negative the rapidity of the bloodcurrent may be estimated by squeezing the tube for & moment the window is then directly filled with blood It did not prove to be an advantage to put in a pump in this part of the circuit, when using an artery it is not necessary, when using a vein one runs the risk that the wall of the vein is sucked into the canula

·Fug 24
The supply end of the dalyser half lateral
The blood coming on through the rubber tube to the left flows into th
rotation coupl ng mounted in the hollow axle and from there into a secon
rubbertube which passes nto the cellophanetute on the outside of the drum
(This is not a photo of the latest type of k dney but of the second kidne
which was constructed)
mistes

·* *
www
Tag 22
The scaledivision in the bath and the
heating element seen from above.
Fig 23
Such a sieve cannot be used for the
artificial kidney, on the inner side,
down current a thick velvety clot.
stratum is formed

·appréf
AD
..
Fig 24
The supply end of the dialyser half lateral
The blood coming on through the rubber tube to the left flows into the
rotation coupling mounted in the hollow axle and from there into a second
rubbertube which passes into the cellophanetule on the outerde of the drum
(This is not a photo of the latest type of kidney, but of the second hidney
which was constructed )
micut
Fig 25
A rotationcoupling, half drawn out of the hollow axle The winged nut 13
seen with which the coupling is fixed in the axle A counternut has been
screwed against the screw cap

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·THE ARTIFICIAL KIDNEY USED IN THE CLINIC 19 An accurate plan of the tubes is found later on in the mountingscheme A (p 78) The blood reaches the hollow axle of the cylinder, and the rubber tube passes here into the ratation-coupling (see ug 24) The rotation-coupling was one of the most difficult parts of the arubicial kodney It is depicted in lig 25, fug 27 (and plan II) The inner tube stands still the outer tube rotates with the hollow axle of the cylinder Shutting off as brought about by a cotton packing, soaked in vaseline pressed on to the inner tube by means of a strew socket Fr 27 Rotationcouplings. The shutung off is brought about by clinching a cotton packing round the inner tabe by mans of a Berew-cap Nowadays a counter mut 19 moreover put against the scretcap The outer tube is fixed inside the hollow axle by means of a Winged screw If this fixation does not take place exactly in the centre, the free end of the nonrotating tube whips, so it must be fixed loosely In fig 24 this supple fixation is brought about by a spiral iron wire, on fig 21 in the latest kidneys by a resilient metal plate with a groove in it The blood flows on leaves the rotation-coupling, and enters the cylinder through a rubber tube This rubber tube is seen on fig 25 It gets out through the spokes of the wheel passes between 2 laths reaches the outside of the cylinder in this way Here it passes into the cellophane tube This is wound in a spiral round the cylinder The blood sinks to the lowest point in the slack moist cellophane tube and when the cylinder turns it runs through the spiral, till at the end of the cylinder it cannot go anywhere else but again into a rubber tube A narrow cellophanetube gives a regular flow, it is advisable to have especially the last piece of the cellophane tube narrow If the cellophanetube springs a leak, it is cut and if necessary one winding is taken out and the ends are joined ·20 THE ARTIFICIAL KIDNEY USED IN THE CLINIC together, ie both ends are tied with a double ligature round a piece of rubber tube of about 5 cms length, into which a glass tube has been pushed for rigidity ?) The blood leaves the cylinder through the other hollow axle, and through the second rotation-coupling It flows some way through the side tube TH28 side tube runs over the long side of the iron frame from one hollow axle to the other and is switched off during dialysis it serves for the rinsing of the kid ney and for removing the air bubbles (see Sketch Ep 83) Moreover a direct infusion may be made into the patient from the bu rette through the sidetube to the patient During the dialysis the blood im mediately leaves the first part of the sidetube, and it is pressed back by the tubepump into the patient. So the tubepump does not serve for moving the blood in the cellophane tube, that happens through the influence of gravity The tubepump must work ou for hours without disturbances It appeared to us that the modern French (Jouvelet) and Swiss (Transfusor) transfusionpumps were not fit for our purpose, be- Fig 28 The air and clotcatcher The blood enters through the night tube, airbubbles gather in the burette on top Clots remain be hind before the glass sieve The left tube leads the blood to the patient s vein 1) First one or must check (20) to took place From rhart 3 1 ·THE ARTIFICIAL KIDNEY USED IN THE CLINIC 21 cause the tubes had been mostly mangled to pieces within half an hour The original apparatus of BECK has larger cylinders, and a wider tubecase, and can be used with some alterations Fig 26 (plan IV) shows the tube pump It is mounted on a footplate (plan II), on which it may be shifted after the loosening of a few winged nuts The pump is driven by means of a bicyle-chain On fig 27, one sees at the back of the chainwheel the button with which the freewheel is switched on and off Fig 29 Before the blood goes back to the pa- The rubber stopper is kept in its place by means tient's vein, at passes an airbubble- and of two screws, otherwise clotcatcher, depicted on fig 28 and 29 the chance exists, that it will fly off, if the pres The blood flows in through the right sure in the burette be tube, and leaves the bubblecatcher through comes high the glass sieve next to it Airbubbles which come along with the blood go up in the burette, and remain there If too much air gets into the bubblecatcher, it may be let out at the top of the burette If the rubber tube is not tied round the burette, it serves as a safety-valve It is always better that this tube flies off than that the burette bursts Fig 21 shows the front view of the kidney with pump aircatcher and tubes Instead of the primitive glass sieve in the aircatcher, as is to be seen on fig 28 we also used much finer rustproof metal szeves, eg the sieve of a Baxter-transfusionapparatus, depicted on fig 23 On the inner side of this sieve, down current, a thick velvety clotstratum is formed, probably because heparın is neutralised locally So these metal cannot be used for the kidney The blood is finally led back into a superficial vein for which again a glass canula is used The motor The power necessary to rotate the cylinder when the cellophane tube and the bath are filled, is greater than one TITL Is 23 the Ar NEM II Cort Ge ·22 THE ARTIFICIAL KIDNEY USED IN THE CLINIC would think A motor of V4 HP will do As the number of revo lutions of our motors amounts to from 1500 to 3000, this must be converted to 35--50 revolutions per minute with a reduction transmission (as is to be seen on fig 15 and 16) One should not forget to provide the apparatus, especially t? bath with an efficient ground-wire Cleaning and sterlising. L.L. nutfen lana not into contact with bloo and bubblecatcher as cle. togenic substances, ar sterilised with the same care as with which an apparatus for bloodtransfusion is treated Whether rigors occur or not is for ti greater part dependent on this The tubes and the glass may be sterilised an autoclave or boiled before dialysis, for whu we had a big pan made, the dimensions a found on p 81 New cellophane is pyrogenfre and need only be rinsed and boiled, for whic purpose it is wound on a wooden reel (fig 30 We take a new cellophanetube for each dialys The other parts of the kidney which do ni Fig 30 come into direct contact with blood, must 1 Wooden reel, on clean, but need not be sterile Cellophane is ir which the cella phane tube 29 permeable for bacteria and viruses So the steri wound before cellophane tube can be seized with the han The water of the bath is not sterile either, ar need not be so, if it is made up freshly") Expulsion of air from cellophane tube and tubesystem is simpl If the kidney is filled with 14 L of saline, made to turn, and 11 saline is streamed through regularly, all airbubbles are take along by the current See further mountingscheme being boiled Keeping of the mounted kidney, If possible the dialysis should directly follow mounting If th is impossible, the mounted kidney may be kept ready for u (without bathwater'), when it is filled with a desinfecting solutio At first we used a superolsolution (1/1000 sulphate) The greatest dış, vantage is th layer of g ittle Its 3 1 deprived as it is of the turer gave it, and oxychinol e gets dr e manufa mes tai 1) In the beginning som the artificial ladney, they in the blood of the patient of the bl unless !

·THE ARTIFICIAL KIDNEY USED IN THE CLINIC 23 round the cylinder, and cracks Afterwards we rinsed the kidney with absolute alcohol, and smeared the cellophane tube with glycerine Indeed the tube dned up less, but one sliould be very sparing with glycerine, and this must be very carefully washed away with big quantities of water later on, as otherwise haemo- Jysis of the blood occurs VAN NOORDWIJK has been able to demonstrate the strong haemolysing action of vestiges of glycerine in vitro and in experiments with the kidney fuid, Rinsing fluid. (Bathwater as it is used now) In the beginning we used 70, afterwards 100 Ls of rinsing kept at a temperature of 37-39° C by a heating element. For the rnsing-fluid clean tapwater is used, clean though not sterile, as cellophane is impermeable to bacteria and viruses The composition has changed in course of time Now we use the following composition Naci 0,6 % KCI 004 NaHCO3 0,2 % Glucose 1,5—2 To avoid haemolysis the addition of glucose was necessary If the patient has marked oedemata we add more glucose (up to 3%) to draw the oedema fluid into the bathwater A weighed-out quantity of salts is put on the bottom of the bath and after that the bath is filled with tepid water as far as the fulling-mark for 100 Ls One should take care that the blood-filled cellophane tube does not get into contact with ordinary water, as haemolysis appears very soon in that case It is useless to add Cacl, to a bath of this composition as the Ca is precipitated by NaHCO3 (One should give Calcium gluconate intravenously) In the following chapter the composition of the bathwater is discussed Splashboards. In order to check the splashing of the bathwater we make use of two splashboards on either side of the kidney They are of alıminium which has been covered with a layer of boatlacquer, and can be easily removed (fig 31) A cellophanescreen along one long side of the kidney between the two splashboards described Fig 32 Fig 31 above is useful.

·26 THE ARTIFICIAL KIDNEY USED IN THE CLINIC Artificial krdney Human krdne 24000 sq cm 20000 sq cm 2500000 one 3L 10 cc 30-45 m 775 km Dialysing, resp filtrating area Number of glomerulı Total contents of the cellophanetube resp of the glomeruli Length of the cellophane tube resp total length of the glomerular loops Minutevolume 1 e quantity of blood flowing through the kidney per minute Clearance per minute, 1 e quantity of blood which is perfectly purified of urea Dialysationmembrane resp glomerulusmembrane permeable for molecules of the following magnitude 100 200 cc 1200 2000 80 150 cc 54 75 cc no haemoglobin haemoglobin mol weight 671 170 L Quantity of ultra filtrate per 24 hours Circulationtime of the blood through the cellophanetube resp through the loops of one glomerulus 1,5-4 minutes Part of circulationtım which is 12 18 ·CHAPTER II TECHNICAL EXPERIENCES WITH THE ANTIFICIAL KIDNEY GAINED IN CLINICAL USE, AND HINTS FOR THE USE OF THE KIDNEY IN FUTURE. Fractionated dialysis In the case of our first patient we applied a fractionated disysis in the beginning By way of a single venipuncture 50 cc I blood were drawn oft dialysed and infused again In all only 1 of blood flowed through the kidney at the first dialysis Ve did not dare to do more At each of the following dialyses of the same patient more blood was dialysed To reduce the bloodtrea to a normal level by a fractionated dialysis was a very lengthy srocedure, therefore we changed to a continuous dialysis in which he blood 25 drawn from one blood vessel and returned into another Continuous dalysis. Venipunctures In the beginning we made it our aim to draw the blood from 1 vein, and did this by preference with an ordinary ventpuno ture needle In the case of the second patient 151 of blood flowed through the kidney in this way in 7 hours time, and in the case of the third 281 in 8 hours The fifth patient furnishes a good example of a succesful dialysis with only two venipunctures, 36 l of blood flowed through the kidney in 8 hours time The eight patient was also treated with two senipunctures Nevertheless we aban ned this method. Puncture of the arteria femoralis was abandoned as well, per haps without due reason Glass canulas There are facts which suggest that heparin is rendered inactive in places where it comes into contact with metal The metal rotating couplings of the artiiicial kidney got coated inside with a layer of clots (therefore the bore must be a wide one) This was the reason why we ceased using needles, and at present we use exclusively glass canulas of the type shown in figure 20 They ·28 TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY taper conically the narrow point being as short as possible Pyrex glass is said to give less rise to clotting than ordinary glass. Before dissection of the ven and the artery, we connected a ten cm rubber tube closed with a glass stopper to the glass canulae (fig 32a) This rubbertube was filled with heparine (20 mgr ) and saline We found such small tubes easy to manipulate and when both the artery and the vein are prepared and the canulae are tied in the vessels, the glass stopper is removed and the tubes of the artificial kidney are connected Fig 32a This rubber tube is filled with heparn and saline The dissection of a vern Before the dialysis starts the vein is dissected. We prefer not to take a cubital vein as we like to reserve these for venipunctures on the following days We take either a large vein on the back of the foot or the vena saphena, which is to be found just above the malleolus medialıs or a vein on the forearm Local anaesthesia is administered through one injection opening and we make this exactly above the vein The hole serves us as a landmark when we have to find the vein in the edematous swelling caused by the anaesthetic No adrenalin is to be added to the novocain as this increases the chance of haemorrhages after some hours Bear in mind that each incision may start bleeding because of the strong heparinisation of the patient, and therefore make the wound as small as possible Our first patient and patient no 11 had such profuse haemor chages from superficial incisions that transfusions were necessary If one does not know very exactly where the vein goes, the incision is to be made at right angles to the vein's course The incision should not be longer than 2 cms If the vein is dissected by a surgeon, he must be asked to make small incisions The dissection of the artera radialis We have experienced very troublesome haemorrhages from the wound necessary for the dissection of the arteria radialis A surgical assistant without any experience in this respect dissects an artery practically just as he is used to do that with a vein He pushes a closed pincette under the artery and slides it to and fro with some force But an artery gives off a number of small side branches (see figure 33), which a vein does not, These side branches are pulled off by the treatment mentioned ·TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY 29 above, and this gives rise to very pertinacious haemorrhages in the case of an heparınısed patient Before starting a haemodynamo meter sleeve may be laid round the upper arm The incision must not be longer than 14 to 2 cms As high as the ligamentum carp! volare the arteria radialis gives off quite a large branch, the ramus volaris superficialis Therefore the incision must not be made through this ligament, but rather somewhat higher up Again and again one feels with the fingertip in the wound to find out where exactly the artery is pulsating In this way unnecessary burrowing and therefore unnecessary chances of haemorrhages may be avoided The fascia covering the artery is divided A radialis A ulnaris Kleine zutókjes vd A radials os pisiforme Volaris superficialis lig.carpe transversum naar arcus Volaris superficials Fig 33 The arteria radialis gives off a number of small side branches (after TALDER LOPSCH) ܥܝ The arteria radialis lies in a sort of sheath of connective tissue accompanied by veins and sometimes by a smaller artery as well One need not isolate the artery from this sheath, provided these separate vessels are ligated as well The artery must be lifted from its bed as little as possible, and it is never feasible to lay it free over a longer distance than is necessary for pushing the ligatures underneath At least four bgatures are laid, one around the distal end is tied at once, tuo are knotted round the canula and the fourth remains open for the time being, to close the artery later on when the canula is taken out When progress is thus far the haemodynamometer-sleete round the upper arm is inflated to a point far above the systolic blood ·30 TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY pressure, or the proximal thread under the artery is pulled taut. Now the artery is shipped with a pair of scissors and the canula brought into place Take care to get right into the lumen, and see to it that the arterial wall does not split See to it that the canula and the tube are fixed on to the arm immediately, as otherwise they are liable to revolve round their axis and in doing so strangle the artery Only when the arterial canula lies perfectly is the patient hepa rinised One minute later the tubes of the artificial kidney can be con nected, and the dialysis started Both wounds, that of the vein and that of the artery, are closed with clips and provided with a compressive bandage, from which the tubes project In the case of the patients no 7, 9, 10, and 12 to 25 a vein and the arteria radialis were dissected according to the rules mentioned above without any haemorrhage worth mentioning The removal of the canulas After the end of the dialysis both tubes are cut off and closed blind, which is done most conveniently with a glass stopper The canula in the vein may be used if necessary for giving bloodtransfusions, infusions of saline etc, if the patient's condition should make this necessary in the first twenty-four hours follow ing the dialyses This happened eg in the case of patients no 12 and 13 From the arterial canula samples of the patient's blood may be taken or blood may be withdrawn should pulmonary oedema become imminent The blood in these stretches of tube may be prevented from clotting by injecting 50 mg of heparın into the tube from time to time, using a fine needle Only when the patient's clottingtime and bleedingtime have become normal again, so that there is no longer any chance of troublesome haemorrhages, in any case pot before the next day, the canulas may be removed from the blood vessels First the arterial canula is removed, if this is pulled outward somewhat it is generally possible to tie the ligature round the artery proximally of the canula Not a single drop of blood need to be spilt! Objections to the tyrng of the arteria radtalts If the arteria radialis is tied the pulse may often still be felt distal to the ligature Functional consequences of the tying of ·TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY 31 the arteria radialis never seem to occur For each subsequent dialysis the arteria radialis may be taken a few cms higher up! About heparin and haemorrhages. Haemorrhages from dissection wounds may in all probability be prevented by good technique The bleeding from the nose and the gums during the dialysis of the first patient was not serious We repeatedly saw small haemorrhages in the case of the other patients as well, eg from fissures at the corner of the mouth or small spots of blood in the patient's vomit The intestinal bleeding in the case of the 15th patient caused by her colitis mercurialis was very serious The patient developed shock, the haemoglobin contents sank to 35", so that 1200 ccm of blood were required to raise it again to 63% Patient no 9 passed very bloody urine (haemoglobin 30%), but he had done this previously as well Patient no 13 developed a haematothorax in addition to a pneu mothorax after an unsuccesful paracentesis caused by the puncture-opening of the needle which had penetrated into the lung and did not close in future we had better abstain from such punctures one day after the dialysis One must therefore be warned in case of patients with a colitis mercurialis to keep an amaple supply of blood ready, in addition cutting operations are to be avoided shortly after the dialysis but for the rest I believe that we need no longer fear serious bleedings in future, now that we have learned to dissect the blood vessels in the way described above and now that moreover we require less heparin than formerly Heparin We must aim at giving as little heparin as possible in the high doses such as we employ (1–3 & each time) heparin not only prolongs the clottingtime, but also the bleedingtime, and it causes a haemorrhagic diathesis which it is hoped will remain latent At first the quantity of heparin increased with each patient up to 3350 mgr! This was done chiefly because thrombosis occurred in the metal needles When we changed over to the use of glass canulas we were not afraid to use less heparin, and we could suffice with 1200 mgr per dialysis A single clot in the airbubble-catcher must not seduce us to give more and more heparine! Fleparın sometimes causes undesirable reactions urticaria, pain ·34 TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY In the second dialysis the KCl was omitted, because with uremic patients the potassium level is increased rather than lowered. In the third dialysis CO, was bubbled through the bath water to lower the pH, this was however not done intensely enough In the fifth dialysis a bath water was used in which NaH.PO was present, in the hope of obtaining a inore favourable pH, the composition was as follows 0,57 % NaCl, 0,34 % NaHCO3 004% KCI, 001% NaH.PO, In the sixth dialysis the phosphate was left out again, because the phosphate is generally raised in patients suffering from uraemia It struck us then that the blood coming out of the kidney after dialysis became haemolytic if kept until the next day We attri buted this chiefly to mechanical injury of the erythrocytes, we thought we observed this especially when the cellophane tube was swept clean with the hand at the end of the dialysis, during which the hand repeatedly struck the ridges on the cylinder Whether Superol was run through the kidney or not appeared to make no clear difference The mechanical injury may be compared with the haemolysis which is seen when blood is ejected from a syringe with too much force against the wall of a glass tube We then remembered that bloodbanks add glucose to blood for conserving it in order to strengthen the erythrocytes And now, since we add glucose to the bath water, we have not been troubled any more by haemolysis (provided the cellophane tube did not contain glycerine) In the seventh dialysis the bathwater consisted of tapwater with 07% NaCl and 1,5 % glucose for simplicity's sake There was not a trace of haemolysis This pleased us so well that we maintained the same composition of the bath water for the fol lowing dialyses In the case of patients suffering from oedema (patient no 7 10, 12, etc) we added more glucose namely 2 to 3% instead of 1,5 % As it takes some time before all the glucose has dialysed in an event which does not take place anyway if the blood flows through the kidney only once, an osmotic water movement towards the bath water takes place Indeed we saw the patient's oedema shrink rapidly so that in some cases wrinkles appeared on the skin It remains an open question however, whether we must go on with this high concentration of glucose in the bath water Perhaps we shall prefer acacia or Oncocapain a substance therefore which has an osmotic effect but cannot pass through the cellophane itself The quantities required would, however, be very large and perhaps the foaming will become a drawback ·TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY 35 The NaHCO, we left out for the time being after the seventh dialysis as we did not trust it altogether with regard to haernolysis Only in the case of the 5th patient we became so scared of increasing a probably existing acidosis that 0,2% NaHCO3 was added to the bath water In the case of patients treated in Kampen we have kept to this later on We did not consider it necessary to add KCl to the bath water as the potassium content of patients suffering from a serious vraemia is generally raised Only much later when in one dialysis 120 litres of blood ran through the kidney it became clear to us that too extensive changes in the mineral spectrum of the blood may occur which in such a large dialysis apparently cannot be compensated by the organism From then we added 004 % KCl to the bath water Regarding the calcium content of the bath water With the 6th patient we were surprised to see that the calcium content of the blood from the kidney (8 mgr per 100 ccm) had sunk so little Only about 40% 4 mgr per 100 ccm therefore of the calcium present in the blood is present in a rapidly dialysable state The tapwater proved to contain 4 mgr of calcium per 100 ccm therefore an equilibrium existed on both sides of the membrane It CaCl is added to a bath containing NaHCO3 as well the calcium is precip tated in the form of CaCO3 Consequently in the case of the 15th patient (first dialysis) we saw little result from such an attempt (the addition of 0027 Caci, to the bath water) The calcium contents of the bath water fell to 1,3 (duplicate 19) mgr per 100 ccm and the calcium content of the patients blood serum fell from 10 to 63 mgr per 100 ccm The solution might be found in having the cylinder rotate in a closed space eg under a cover inside which a mixture of air or gas with 5 % CO, is maintained which might bubble through the bath water as well -- a pH desirable in all respects might then be obtained and in this case the CaCl would remain dis solved We have shrunk from the technical execution and for the time being we give 1 or 2 grams of gluconas calcicus intravenously le in the tube during the dialysis In practice it is easy to choose the composition of the bath water in such a way that it may be used for various patients The mineral spectrum of the patient follows the bath water and if the composition of the bath water is adapted to a normal mineral spectrum as much as possible the patients plasma will be nor malised in this sense as well The composition of the bath water which we recommend at present is NaCl 06 NaHCO3 0,2 KCI 004 glucose ·36 TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY 1,5-2%, do not forget 2 X 1 gram of gluconas calcicus intra venously If one compares the concentrations of the various ions in the bath water with those in the blood plasma, the following calcu lation is obtained for the bath water Bath water everything expressed in mgr per 100 ccm 600 Naci 364 Cl for 236 Na 40 KCI 19 C1 200 NaHCO3 53 vol % CO 55 Na =53 vol % CO. + 21 K + 383 CI - 291 Na 21 K + + The normal values for the bloodplasma are 50-70 vol % CO 16--20 K 340-389 C1 and 310-330 Na These numbers are expressed per 100 ccm of plasma, to obtain a correct comparison for the dialysis the startingpoint must be the plasma water Assuming that the bloodplasma contains 8 % albumen, which however, is much too high an estimate for many of our patients the above numbers must be multiplied by 100/9, = + 1,1 Thus we obtain 1 the normal values in the plasmawater expressed in mgt p 100 cem 55-77 vol % CO, 18-22 K 370-420 CI 340-360 Na We are still on the low side with our bath water, and especially the sodium content is too low for the following reasons The bath water is alkaline, and we dare not let too much NaHCO3 dialyse in at a time 2 The electrolyte level of most patients is generally lowered. By introducing large quantities of NaCl one risks pulmonary oedema We see that our last bath has nearly the same composition as DARROW's , interstitial salt solution", which we used in our very first dialysis! On revient toujours Foaming If foaming of the bath water 15 excessive during the proceedings, blood (albumen') has entered it, most often there is a leak then. The foaming may be very troublesome, an argument in any case for changing the bath somewhat earlier and looking for the leak") 1) If there was no leak in the cellophane tube we could not detect any albumen in the bath water with the usual methods ·TECHNICAL EXPERIENCES WITH THE ARTIFICIAL KIDNEY 37 Evaporation The evaporation of the bath water during the dialysis is marked sometimes 10 % The addition to the bath of some tapwater from time to time is advisable as otherwise the concentration becomes too high The losses by splashing must not be replaced in this way Haemolysis Haemolysis of the blood in the artificial kidney is accelerated by 1 Incorrect composition of the bath water Hypotonicity incom pletely dissolved salts in the beginning 2 Too little glucose 3 Mechanical injury to the erythrocytes (see page 34) We therefore reduced the speed of the cylinder to 25 revolutions per minute 4 A long stay of the blood in the hidney erythrocytes running through quckly soon recover again when they are back in the patient 5 Use of banked blood more than one day old for transfusion during dialysis 6 Presence of glycerine J VAN NOORDWIJK could demonstrate with experiments in vitro and in an experiment with cow s blood in the kidney that small quantities of glycerine increase the chance of haemolysis ·CHAPTER IV CLINICAL PICTURES, IN WHICH TREATMENT WITH THE ARTIFICIAL KIDNEY IS TO BE CONSIDERED SURVEY OF THE FIRST 23 PATIENTS TREATED WITH THE ARTIFICIAL KIDNEY. Uraemic conditions suitable for treatment with the artificial kidney but of which we lack experience up till now -- such as anura following a crush syndrome, anura following eclampsia gravid arum, anura in cases of symmetrical necrosis of the renal cortex, - are not discussed neither is the possible treatment of intoxication by hypnotics ) I Chronic and subchronic uraemias. (Patient no 1, fig 40) A woman of 29 years with a malignant hypertension and contracted kidneys was sent in for treatment under the motto that nothing was to be lost and perhaps a temporary improve ment to be gained On arrival she had a haemoglobin of 35 %, and severe cardiac failure with orthopnoea Within a few days the following compli cations developed a pericarditis, parotitis, pleuritis and an otitis media The hope that the renal function would recover to some extent has not been fulfilled the patient could finally be kept alive for 26 days with her blood urea remaining at a constant level, although she excreted only very little urine (Patient no 2) Man of 60 years with bilateral renal tuberculosis, cachexia and uraemia One dialysis was applied in which the dehydration and the shock were combatted as well The next day the man was in a much better condition the diures19 increased the pains in the bladder were of such a nature that we believed we had no right to prolong this man's life any further (Patient no 18) A married woman of 54 years Four months before admission she had an acute glomerulo nephritis and was afterwards seen as out patient by Dr SCHALS Many red cells were always present in the urine and the blood pressure rose to 240/125 A sudden anuria developed, with no abnormal findings on cystoscopy and pyelography The blood pressure fell to 140/70, presumably left ventricular failure had set in ..) Note at the correct on Dr EG L Bywaters Br tish Postgraduate Medical School Hmm. emil ·MIT 20 21 22 23 24 25 26 27 28 29 3 > 0 1902 31 SITO 19 20 2 22 23 24 25 26 27 28 29 0 1 2 > 6 Albordpress. 07 Bodo vimo . Fone al blood het wus reyes U poned by a abyss 1-11 19 uy W Unde por un 160 por hou . 06 . Ball nimi mudhalimlin.limuna. 000001 ി ക Fig 34 Graph of patient do 1, a woman of 29 years suffermg from .. malignant hypertension with contracted kidneys She was the first patient to be treated with the artificial kidney In the top of the figure the systolic and diastolic bloodpressures have been Indicated, the difference between them being shaded the percentage of urea of the blood has been indicated by a drawn line It is shown to sink each time after a large dialysis, eg from 339 to 278 mgr per 100 cc The dialyses are reproduced by columns. The white column indicates the quantity of blood dialysed, the shaded one the quantity of wrea removed by dialysis Right at the bottom the quantities of urine passed per 24 hours are found represented by white blocks, the quantities of urea excreted with this urine are indicated by shaded blocks ·TREATMENT WITH THE ARTIFICIAL KIDNEY Eight days after the onset of anuria she was dialysed The blood urea fell from 304 to 46 mg %; the chloride content of the blood (expressed as NaCl) rose from 530 to 550 mg %, the alkalıresene rose from 26 to 42 vols % Every effort was made to increase her blood pressure, and the day after dialysis it had risen to 160 90, and she passed 30 cc of urine. The same evening venesection was performed on account of pulmonary oedema, and the following evening she died from heart failure Post morten Subchronic glomerulo nephritis (Patient no 23) An unmarried woman of twenty History of in definite illness for only a few weeks She became progressively uraemie with muscle twitchings and convulsions Her blood pressure was 150/120 She was taken into the hospital at Kampen and immediately connected to the artificial kidney The blood urea fell from 382 to 170 mg % per 100 cc, the dialysis removing 69 gr of urea Plasma chlorides (as NaCl) fell from 685 to 662 mg per 100 cc, and the alkalıreserve rose from 19 to 53 vols During and after dialysis the patient had convulsions suggestive of tetany The calcium plasma level was 55 mg before, and 5,3 mg per 100 ce after dialysis, although 0,5 gr calcium gluconate had been given intravenously Despite a further 2 gr of calcium gluconate the calcium level remained 5,2 mg per 100 cc The general condition of the patient deteriorated rapidly, perhaps aggravated by an unfavourable reaction to morphine, and she died 28 hours after dialysis Post mortem Contracted kidneys were found, weighing 54 and 48 xrams It is clear that the first two patients could not be saved by the artificial kidney Patient no 18 was treated only because there was no other hope for her The phenomenon of anuria after a sudden fall of blood pressure in a hypertensive may be encountered both in chronic and acute uraemia Patient no 23 was treated as it was not certain that a chronic nephritis formed the background of her uraemia, the intractable hypocalcaemia precipitated death Generally speaking, the chronic uraemias are no indication for treatment with the artificial kidney. There are chronic uraemias which are aggravated temporarily by an intercurrent infection, a dysenterylike diarrhoea, an operation, and so on If this infection or the operation is over and the patient does not succeed in overcoming the aggravation of his uraemia by himself, one might try to restore by a dialysis the patient to the level on which he formerly kept his equilibrium The uraemia caused by hypertrophy of the prostate, temporarily aggravated by an operation, can be a favourable example and is discussed later Apart from that, one has to consider in every case of uraemia with contracted kidneys whether the patient suffers chiefly from his uraemia or from the consequences of the hypertension The latter are not done away with by the dialysis' The cerebral pheno mena, the retinitis, the angina like complaints and failure of the left ventricle are all mainly caused by the hypertension 1

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·42 TREATMENT WITH THE ARTIFICIAL KID VEY urine when the artificial kidney had to be placed next to their beds through lack of space, but I do not want any one to beliere that the druresis was started by placing the artifical krdney next to the bed in my opinion one had better abandon all methods 17- tended to start the diuresis in patients with glomerulo-nephritus (Patrent no 3) Man of 43 years, acute glomerulo nephritis For 14 days he passed less and less urine, until he produced only 50 cc of urine a day His doctors being at their wits' end, both kidneys wer decapsulated and both kidney stalks denervated After that the patiec passed even less urine but clinically he still made a good impressio and he was 1 per 100 cc pfore th dialysis the with th artificial kic le end o the dialysis 460 mg Von 2 3 5 6 7 8 9 11 Pat 6 1944 600 0630 500 400 300 + + 250 200 203 157 100 Ureumgehalte wie bloed in mg per 100CC 162 9 ureum verwydera 0 601 bloed gewasse? 400 CC urine per 24 uur voor het laatst geur neend per 200 catheter Fig 36 Graph of patient no 6, a woman of 34 years with an acute glomerulonephritis Before the dialysis she produced only very little urine. (Patient no 6) A woman of 33 years enormously fat, developer an acute glomerulo nephritis at the beginning of scarlet fever Duria the last five days before the dialysis she passed less and less urine her

·Fig 37
Kidney of patient no
9 The right kidney with extensive carcinoma
The left with acute glomerulo nephritis

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·TREATMENT WITH THE ARTIFICIAL KIDNEY 43 bloodpressure before the dialysis was 130/80 The blood urea was 630 mgr per 100 cc The patient slept almost continually and when she awoke for a few moments she was desorientated During the dialysis she awake and became fully conscious The urea fell to 167 mgr per 100 cc The bloodpressure rose to 170/80 The diuresis started! Two days later she died unexpectedly of broncho pneumonia with pul monary oedema (Patient no 9) A man of 51 years suffering from an acute glome rulo-nephritis which had started with ileus like symptoms, had anuria for 6 days fſe was treated with the artificial kidney, 96 gr of urea Vora vamine on hy anto. And #ha hrad ette. Aon. inn 7 8 9 10 11 12 13 14 19 Pat 11 1944 9425 320 345 mg ureum per too cr bloer f + 140 BDO 1967 unum verwiderd Cc urine Der 14 UUT 600 wol bloed' gohossen 400 200 0 Fig 38 Graph of patient no 11, a man of 19 years, with a glomerulonephritis of 20 days duration (Patient no 11, fig 38) A man of 19 years had a glomerulo- Dephritis for 20 days The quantity of urine sank to 150 ccm a day The bloodpressure was 185/110 and the patient was ominously pale The blood urea was 425 mgr per 100 ce before the dialys18 146 grame of Wres were removed by the dialysis and the blood urea fell from 425 to 140 gr per 100 cc .

·44 TREATMENT WITH THE ARTIFICIAL KIDNEY Diuresis did not set in The bloodpressure remained high He died of cardiac failure four days after the dialysis Patient no 17 A woman of 67 years was admitted 3 9 45 to the surgical ward by my colleague Dr KEHRER in a serious condition She had a high fever a very painful and distended abdomen, an enlarged and palpable gall bladder with much infiltration 1 slightly yellow skin and almost com plete anuria The small amount of urine still produced was cloudy, a dark red brown and contained very much albumen erythrocytes leuco. cytes and casts The blood pressure was 150/60 Thus she was suffering from 1st cholecystitis with pericholecystitis and jaundice, 2nd an acute glomerulo nephritis with almost complete anuria, (1 hepato renal syndrome if you like) B. 8 9 10 11 2.1.14 5 16 17. 8 19 20 2.22 23 24 25 26 27 28 29 30 1 2 3 4 Patient 17 1945 34439G 152 200 mg ureum DOM Toocc bloed 710 121 100 eol bloed gewassen 60 gr ureum verwyderd cc grla uwe uncern 2800 201 2400 24 2000 80 600 16 200 12 800 6 L TA Fri 1 i 1 400 4 Fig 39 Graph of patient 17 woman 67 years old with glomerulo nephritis Dramatic improvement by dialyses recovery For 212 days the patient was given sulphathiazole (6 gm per day) after that no more as the sulphathiazole reaction in the blood against the anuria remained constant (on 11 9-40 the free sulphathiazole in the plasma was still 8 mgr per 100 cc The temperature of the patient dropped slowly, but the production of urine did not recommence and after 8 days on 11 9 45, the urea con tent of the blood rose to 396 mgm per 100 ce The potassium content of the blood had risen alarmingly to 55 mgr per 100 cc and the alkalı reserve was 40 vols The clinical condition of the patient had become much worse She slept and snored the whole day long after much shouting at her she stammered with difficulty one word with a very dry mouth and im mediately fell asleep again A few days before then she had been able to speak more her mind wandered She had oedema of the back and legs Her pulse was still good and her blood pressure 160/110 On 10 9 Dr KFHRER performed a cystoscopy the right ureter has ·TREATMENT WITH THE ARTIFICIAL KIDNEY 45 healthy, in the left ureter the catheter could not rerch further than 2 cm from the bladder A pyelogram showed a normal pelvis on the right side, the production of urine did not commence after the renal pelvis had been washed On 11 9 the patient was treated with the artificial kidney 80 liters of blood flowed through the kidney in 111 hours, 60 grams of urea were removed by the dialysis and showed in the bathwater The blood urea dropped from 396 to 121 mgr per 100 cc During the dialysis her condition was very alarming for some hours but at the end her general condition was good The blood pressure was 160/80, the potassium content (that could be determined in spite of the heparine) had dropped to 19 mgr per 100 ec! The clinical improvement was clearly to be seen after some hours of the dialysis and a day after that her mind was completely clear again She was not sleepy, talked much and easily and made sengible plans for the future She had a moist normal looking tongue her temperature was be tween 365–37 3° C and her pulse was between 78--110 Her haemo globin was 65 The oedema remained unchanged Although we liga tured the left arteria radialis 2 cm above the ligamentum carpi volare the pulse could be felt The production of urine during the first few days was still not sufficient The urea rose to 172 mgr a day while the concentration of the urine slowly improved After the dialysis the patient vomited . Pann. A fun 09:00Onaindfllanon Fig 40 Graph of patient no 24, a girl aged 13 with acute glomerulo-nephritis anuna for a week and pulmonary oedema with bronchopncumonia She recovered ·46 TREATMENT WITH THE ARTIFICIAL KIDNEY considerably for some days, while her abdomen was still painful and distended, his however, recovered soon Two months after the dialysis 11-9-45, the patient was very well The urine still contained some albumen and sometimes some erythrocytes The blood-pressure was 175/90 7 months after dialysis I saw her again in excellent condition. pe Blender ve Pater , 151 e pa soce 1 MO relinnal n... 11. el 200 we DO Fig 41 Graph of patient no 25 Man of 54 years old with acute glomerulo-nephrit? pulmonary congestion, etc. Recovery Time will prove whether a chronic nephritis will develop from th acute glomerulonephritis which she survived in September. But even if i does, the threatened danger to life, based on the acute uraemia, has bee dispelled with success. (Patient no 24) Girl of thirteen Got soaked through in a walkın contest, and one week before coming into hospital developed acut maulanauh. * L. f. 1. 3 -31 1.1 svul and a lialt juulo oi uidiysis 4U Xidm ures were rellius and the blood urea fell from 364 to 140 mg per 100 cc Not only wer no transfusions given but blood was drawn off to combat the pulmonar, oedema Penicillin was administered for the tung infection. Diuresis started during dialysis gradually increasing afterwards an the patient made an uneventful recovery. (Patient no 25) Man of 54 with acute glomerulo-nephritig, Nin days before admission complained of general malaise; the next day h ·TREATMENT YITH THE ARTIFICIAL KIDNEY 47 twice fell down due to giddiness and then remained in bed with pain in the abdomen and back and facial oedema developed On admission (9 8 46) he had passed very little urine during the last five days and complained of lack of sleep headache nausea and biccoughing On examination he showed uraemic exanthema mild oedema was dyspnoeic and a chest x ray showed left sided cardiac enlargement and pulmonary congestion Bloodpressure 170 90 Y jectively improved when a further 250 cc of blood was removed This 1000 ce of blood was not returned to the patient at the end of dialysis The condition of the patient was very good after treatment and diuresis slowly increased Four weeks after dalys 3 he was very well and was discharged with slight albuminuria and 1 few red cells in the urine Reviewing the short case histories of the above mentioned seven patients with an acute glomerulo-nephritis it is clear that patient 10 9 in whom an extensive carcinoma existed may be left out of further discussion Patient no 3 was connected with the artificial kidney too late Iere we see for the first time that a patient clinically apparently well suddenly gets worse Patient no 6 died unexpectedly of bronchopneumonia with pul nonary oedema Apparently she had not sustained the previous ntoxication with impunity A great pity for the diuresis setting in made us hope for the best Patient no 11 died of failure due to hypertension It is probable however that his whole organism and his heart too had already suffered greatly by the previously existing serious uraemia When patients such as the above arc treated with the artificial kidney one must count upon only a few being so fortunate as to be saved. Forms of glomerulo nephritis with gradually decreasing diuresis show less tendency to recover than cases beginning with acute anuria Patient no 17 seemed clinically so desperately ill that the author considers she would have died without the aid of the artificial kidney Patient no 24 a thirteen year old girl proves that a manifest pulmonary oedema need not be a contra indication to Ircating a patient with the artificial kidney if a severe anuria makes it desirable The blood coming from the radial artery was dark and oxygen was given for several days Penicillin was ad manastered for the bronchopneumonia Apart from a slight albumu nura the girl is in perfect condition now three months after treatment ·50 TREATMENT WITH THE ARTIFICIAL KIDNEY 2 22 23 24 25 26 27 28 29 pat. 13 1944 704 263g ureum verwyderd Img ureum per 100 cc bloed. + 386 303 192 g6g ureum verwyderd 120/ bloed gewassen 72/ bloed gewassen grammen ureum 600 6 400 - 4 incontinent + 2 + ? 2002 5 Fig 43 Graph of patient no 13, a man of 38. for 3 weeks suffering from a glomerulo-nephritis. Although he produced about 1 litre of urine a day at home, the blood urea rose to 700 mgr per 100 ccon (Patient no 16) A man of 67 a history of four weeks malaise, and one week symptoms of acute glomerulonephritis, vomiting, oedema and headache On admission he was drowsy and disorientated Urinary out put was 200 cc per 24 hours Bloodpressure 230/110 Pulse 116 Gallop rythm of the heart Two days later he was connected to the artificial kidney 123 grams of urea were removed, and the blood urea fell from 472 to 172 mg per 100 cc The day after dialysis the patient's general condition was very good, and his mental state normal Despite all efforts diuresis did not set in, and six days after dialysis his blood urea had again risen to 423 mg per 100 cc Two drys later he died, just before he was going to be connected to the kidney for the second time (Patient no 19) A married woman of 48 An attack of acute glomerulonephritis, and one week later pulmonary congestion, which she sur vived Her daily urinary output went up to 2 litres and her blood pres sure rose to 170/100 in the course of a few days a complete anuris developed and her blood pressure fell to 110/80 It would seem that the ·TREATMENT WITH THE ARTIFICIAL KIDNEY 51 beart could no longer maintain the pressure demanded by the kidneys She was admitted to hospital three weeks after the start of her illness when marked oedema was present Haemoglobin 36%, blood urea 380 ng per 100 cc, alkalı reserve 38 vols and xanthoproteins 93% In the hope of improving the blood pressure and the haemoglobin evel carefully controlled blood transfusions were given, but a tempoary auricular fibrillation set in Dialys13 was started next day, 80 yrams of urea were removed, and the blood urea fell to 162 mg per 100 cc, and the xanthoprotein to 60, the alkalı reserve rose to 47 rols Sc, and the haemoglobin to 57% After the dialysis the patient's condition was good The same day, n company with the nurse who was attending her, she developed rhinitis ind a sore throat and the general picture of influenza with a high emperature In the afternoon she started fibrillating again, and died hat might 1n cardiac failure 3 5 6 7 8 10 Patient 16 1945 472 423 . 405 346 mg ureum per 100 (C bloed 122 + 143 urine Hoed 50 storwassen 123 gr UPPUTZ verwijderd 400 4! 300 31 grureum 200 2 100 TH M Fig41 Graph of patient 16, a man of GT years Glomerulo-nephritis for 5 (?) weeks Diure513 did not improve Patient no 8 came under treatment so late because it was wrongly thought that a chronic nephritis was present The production of 1 to 2 litres of almost clear urine a day with & SG of 4 1,011 does not yet prove the existence of a chronic nephntis, nerther does it exclude an acute one!

·52 TREATMENT WITH THE ARTIFICIAL KIDNEY Patient no 13 has reached a blood urea of a height rarely reached by any one This man too we should have preferred to treat earlier The life of patient 16 was probably lengthened for a week by dialysis Patient 19 died from heart failure as was expected. It seems to us that the prognosis of this group of patients us extremely bad although dialysis may prolong life for a few days B ACUTE URAEMIA AFTER OPERATIONS 1 Forms of acute post-operational uraemia progressing with oliguria or anuria 4 Ť 0162 (Patrent no 4) In a man of 68 years both the ureters had beer transplanted into the sigmoid because of carcinoma vesicae No urine entered the rectum The man's circulation was bad and the patient wa! in shock before the dialygis started During the dialysis the diuresis set in but the urine did not 27 28 29 m 2 reach the sigmoid a 5 was planned it entered the peritoneal cavity Pat 7 1944 from which at emerged 400 373 through the wound and mg vreum per 100 cc bloed the dressings Q324 300 287 When we observed 233 248 this the dialy 913 was 250 200 stopped 0142 (Patient no 7, 118 100 15) In a man of 3 989 ureum years in whose case the 0 verwyderd diagnosis "carbuncle of the kidney had bet! carefully made 769 umur verw galerd right kidney was taker away After the opera tion a complete anurus arose The patient as twice treated with the artificial kidney and died of the consequence 40/ bloed 68/ bloed of his staphylococcal gewassen gewassen sepsis of which th: carbuncle of the kidnes had only been ? part At necropsy an aplas tic left kidney was Fig 45 found in which even Graph of patient no 7, a man of 30 years whose right kidney containing a carbuncle was removed microscopically no renal tissue could be discov After the operation andra ered (fig 43) th

·ERCEFIEREHEHE
Fug 46
Bladder of patient no 7 Right ureter ligated
(in the top of this photograph) after nephrectomy
Left ureter gradually narrowing till completely
obliterated Right at its top the atrophic left kidney

·No text on this page.

·Pum per ca TRE ITMENT WITHI THE ARTIFICLAL KIDNEY 53 (Patient no 14) A man of 48 years had acute dilatation of the stomach, and after an exploratory taporatomy in the lower abdomen a resection of the stomach was performed After the operation a pneu- MAN.dantes -L th sulphathiazole Eight days after was combatted with intravenous 14 ulea content of Lne ploud rose to 648 mgr per 100 ccm The potassium content of the blood gerum rose to 25 mgr per 100 cc, and the nikal reserve was 36 vol a The patient was dying on arrival in Kampen, nevertheless he was treated with the artificial kidney, but The survived the dialysis only by a few hours No one will blame the dialysis for not having been able to help these three patients. Concerning the cause of patient no 14 's ollgurta we are still in the dark 18 19 20 21 22 23 24 25 26 27 pat. 5 1944 600 bloed 531 500 450 400 320 300 258 200 110 g ureum berwyderd 361 bled somassen 3000 CC Urine per 24 uur 2000 incontent 1000 Fs 47 Graph of patient no 5, suffering from a traema originating efter an operation and an infection The digresis was ample, but the concentration of the urine 83 poor ·54 TREATMENT WITH THE ARTIFICIAL KID VEY 2 Forms of post operational utaemia where the patient does pass urine, but where the concentration of the urine is so bad that nevertheless uraemia arises or persists (Patient no 5 fig 47) A min of 58 years in excellent health came into hospital for an inguinal hernia Following the operation he devel oped a high temperature an exanthema and a pulmonary infiltration, which was treated with sulphathizzole After 5 days he was drowsy and and urhemic After 14 days the diuresis rose to 2 litres per 24 hours, but the mans general condition deteriorated rapidly On arrival in Kampen he was in a bid condition Before the dialysig he was precomatose but during the dialysis he awoke and spoke with his family Sudden death through apnoea In the case of this patient we are all at sea as to the cause of the uraemia just as in the case of patient no 14 The former s uraemia persisted in spite of a druresis of at least 2 litres per 24 hours Microscopically no pathologic signs of any importance were to be found in either of these two patients' kidneys 1 e not a trace of a nephritis We have not been fortunate with these two patients as they came in for treatment too late yet I believe that the post operational uraemia and anuria must belong to the most promising indications for treatment with the artificial kidney, complete recovery must be possible In addition one is less encumbered by a hypertension with all its unpleasant consequences, as is the case with a glome rulo nephritis с ACUTE URAEMIA CAUSED BY OR ACCOMPANIED BY INTOXICATIONS 1 Mercury bichloride intoxication Mercury bichloride itself is scarcely removed by the dialysis as the Hg ion forms non dialysable compounds with the plasma albumen (Patient no 12) A woman of 24 years irrigated herself by mistak with a solution of 1 gram of mercury bichloride in 250 ccm of water The consequences were necrosis of the vaginal walls violent pain and necrotic ulcers in the mouth diarrhoea and vomiting besides almos instantaneous anuria Her general condition deteriorated rapidly although by a dialysis five days after the intoxication the urea conten' of the blood was reduced from 265 to 89 mgr per 100 cc Two day later she died of broncho pneumonia (with pulmonary oedema) probably due to aspiration of the gangrenous discharge from the terrible ulcer ating mouth and throat (Patient no 15 fig 48) A woman of 47 years took a table spoonfu of a draught, by mistake made with chloretum hydrargyricum 10/30 instead of hydras chlorali The main ensuing developments were serious gastro enteritic troubles with diarrhoea and very soon a complete anuria After eight days the urea content had risen to 289 mgr per 100 cc and it fell to 159 mgr per 100 cc after the first dialysis The abdo ·TREATMENT WITH THE ARTIFICIAL KIDNEY 55 and the antant in minal symptoms caused the greateet worry the second dialysis. She was al second dialysis started She h which the heparinisation will could be controlled by blood transfusions 22 25 24 25 29 30 31 mm 26 27 28 0390 315 Pat.15.1944 256 O 179 228 mg ureum per 1000€ bloed 159 $59 ureum verwyderat ma 701 bloed gewassen CC urine en grammen urpum per 24 uur gram w 300 +3 2002 1001 0 719 Urpum verwyderd 65/ bloed gewassen incontinent Fig 48 Graph of patient no 15, a woman of 47 years with anuria from mercunal nephrosis These two patients did not die of the consequences of their anuria The first died of aspiration pneumonia from the gangrenous stomatitis The second died of the intestinal complications, especially of her colitis Taught by experience we hope in future to prevent the former by sucking away the saliva, and the latter by cutting out the colon absolutely in such cases of serious colitus with a double-mouthed ileostomy, to prevent the thin corrosive faeces from running down the ulcerating colon. Nevertheless the traemia due to mercurial nephrosis must be a good indication for treatment with the artificial kidney. ") Especially as the mercurial nephrosis regenerates to a miraculous extent of the patient remains alive, but this takes time In the case of our second patient, the diuresis was already starting again, and in the ·mg ureum per roocc bloed 56 TREATMENT WITH THE ARTIFICIAL KIDNEY 200 104 100 postmortem examination of the kidneys regeneration was clearly visible The chances of recovery rise with every day gained for the patient in this period 2 Uraemia after use of chemotherapeutics Several chemotherapeutics, eg sulphathiazole and sulphapyti dine may give rise to blocking of the urinary passages by crystals Apart from this mechanical obstruction another form of anuria is supposed to occur not accompanied by the formation of crystals (Patient no 10 fig 49) A man of 50 years developed an extensive pulmonary embolism three years ago and after that he was under medical treatment for fibrillation with a dila 15/16 17 18 19 20 21 22 ted heart Three weeks before Pat 10 1944 coming in for treatment 300 he developed a pneumonia which was treated with sulphamethylthia zole, and a week before coming in he got a re currence of his pneumo nia which this time was ---- 0 41 treated with sulphapy ridine Anuria followed 52g ureum verwyderd After four days the blood urea had risen to 51/ bloed gewassen 222 mgr per 100 cc the patient had apart from cccc urine en grammen ureum/) per his fibrillation and his 4000 24 uur u tgescheiden dilated heart a conti nuous hiccough 3000 -30g was connected with the artificial kidney with 2000 - 209 out delay 52 grams of urea were removed blood urea sank to 104 1000 109 mg per 100 cc After one day's rest a cystoscopy was perfor med and the pelves were Fig 49 washed out Immedia Graph of patient no 10 a man of 50 years with tely after this the dra an anuria after using sulfapyridine resis started The pa tient recovered As a rule the first thing to be done is to have a cystoscopy per formed when dealing with an anuria after the use of chemothera peutics In the case of patient no 14, where the chemotherapy might have been the cause of the anuria Iconsequently had that done first Not always, however is the cystoscopy followed by the desired result, i e by diuresis while after a cystoscopy one must wait till n He IMA O

·F: 50
Roentgenogram of the chest of patient no 10
Ileart enlarged specially to the nght Pneumonia on
the right side not yet cleared up

·58 TREATMENT VITH THE ARTIFICIAL KIDNEY 51 grams of urea were removed, and the blood urea fell from 278 to 162 mg per 100 cc Dialysis was discontinued owing to the extremely bad condition of the patient, and she died soon afterwards (Patrent no 21) Man of 74 Under the care of Dr GEELEN in Dr ENNEKING's ward at Nimegen Prostatectomy ten years ago Dys uria and incontinence during the last four years Four months ago multiple vesical calculi removed by operation Three weeks ago symptoms of pyelo cystitis began, fever, almost continual hiccough and pain in the back Admitted 7 6-46 The prostate gland was found to have en larged again and on x ray the shadow of a stone was seen at the right pelvo ureteric junction Blood pressure 115/75 Blood urea 320 mg, plasma NaCl 660 mg % Patient seemed moderately dehydrated Dia lysis was started next day, but owing to the arterial cannula having too small an aperture the flow through the artificial kidney was slow and only 33 grams urea were removed in 7 hours The blood urea fell to 203 mg per 100 cc After dialysis the patient was very tired and slightly icteric but his general condition was not bad and diuresis set in Sıx weeks later he went home relatively well (fig 51) (Patient no 22) Man of 68 He had an indwelling catheter on ac count of prostatic hypertrophy for 4 to 5 months Subsequent prostat ectomy with a progressive post-operative rise in bloodurea and deterioration of his general condition Admitted to Kampen sixteen days after operation with pronounced CHEYNE STOKES breathing, blood urea of 309 mg % and alkalıreserve 28 vols % Dialysis removed 66 grams of urea the blood urea fell to 82, and the alkalıreserve rose to 44 The cardiac condition however remained very bad, and two days later he died of cardiac failure and pulmonary congestion Post mortem, congenitally atrophic left, kidney, marked hydro nephrosis with infection and scarring of the right kidney In patient 20 a blood urea of 278 mg per 100 cc suggested that uraemia was not the cause of her uncosciousness. Dialysis was nevertheless performed at the request of the neurologist and for the training of the "artificial kidney staff”, as it seemed that nothing would be lost Had patient 22 come in ten days earlier, it might have been possible to return his blood chemistry to the same position as it was at the end of five months of indwelling catheter The recovery of patient 21, a man of 74, shows that age in itself need not be a contraindication to using the artificial kidney This man's improvement after treatment by dialysis will Have been only partly due to the removal of retention products, and probably more to correction of extrarenal factors present at the time It is quite possible that a similar improvement could have been obtained by intravenous infusions alone In face of the result, however, no regret need be entertained that he was treated with the artificial kidney Our impression is that the kidney function of patients wih prostatic hypertrophy, calculi or other forms of renal obstruction, is regained once the obstruction is removed The artificial kidney may help to tide over a difficult period ·CHAPTER V THE CLINICAL SYMPTOMS OF URAEMIA DURING AND AFTER THE DIALYSIS As some "pressor" substances, which seem to play a part in many forms of raised blood-pressure are dialysable one might expect a lowering of the blood-pressure by dialysis in case of hypertension caused by renal ischaemia However it seems unlikely to me that any influence can be exercised on the angiopasms of acute glomerulo nephritis by dialysis (literature no 7, 15) Our first patient, the only one of our series of patients, who may have had this pressorsubstance in a considerable degree in her blood, showed å fall in bloodpressure after each dialysis, clearly to be seen in curve 34 on p 39 It is highly probable that these falls must be conceived as a more or less prolongated shock, but the clinical aspect was difficult to ascertain The fall in bloodpressure which appeared in other patients during dialysis, must certainly be conceived as a symptom of shock This will be discussed in the chapter about reaction of the patient during dialysis The ocular symptoms The ocular symptoms in chronic nephritis depend more on hypertension than on uraemia In the first patient with contracted kid neys (patient no 1) we treated, a striking improvement of the fundi and the vision appeared Both are either accidental or due to the decline in hypertension during this period It would be interesting to know if the white foci in the fundus oculi improve after dialysis This was temporarily the case with patient no 1 The mental condition Several patients were comatose and dying when they were connected with the kidney They did not regain consciousness during treatment Some of the patients who were praecomatose became Patient no 5 awoke during the dialysis, and spoke more clearly with his relations than he had done for days. Patient no 6 regained consciousness in the night while she was on the kidney, and she began to talk about her relations, so that fully concious ·60 THE CLINICAL SYMPTOMS OF URAEMIA DURING THE DIALYSIS I had morphine administered to her to make her sleep again Patient no 11 who was very sleepy, improved much after the dialysis in that respect Patient no I never made that stuporose and indolent impression which we mostly see in uraemic patients Patient no 14, no 15 and 18 remained fully conscious till shortly before their death It cannot be assumed that this would have been possible without dialysis Patient no 17 in a stuporose condition had her mind completely cleared after dialysis Vomiting Some patients vomited, but in the first 15 patients we had no case where vomiting was so desperate after a dialysis as we formerly often saw in uraemia) TABLE 1 in which is tabulated the improvement or deterioration of the diuresis after dialysis home Patient died too early to form an opin on Diuresis after treatment Set Im Remai Declined going proved ned equal Remarks + 1 Ureter got loose from sigmoid Urine in the peritoneum 700 cc of urine in the bladder 5 + + covo + 8 9 10 + + No kidney left Much blood in urine After cystoscopy 11 12 + Mfuch blood in urine Hb 30% Qurotities hard to es timate 13 14 15 1) The 18th patient has vomited much during and after dialysis We hare investigated if the high bloodsugar played a part but no evidence was found.

·THE CLINICAL SYMPTOMS OF URAEVIA DURING THE DIALYSIS 61 The diurests From the curve on p 39 one gets the impression that the urine production of our first patient became less after the greater dia lyses We have ascribed this to the temporarily reduced blood pressure (or to shock if one likes), and to the steady aggravation of the contraction of the kidney At any rate we thought it desirable to investigate in the following 15 patients if the dialysis could have an unfavourable influence on the diuresis The above table shows that in 6 patients the diuresis has been improved or set going while it has only decreased in the case of 2 patients (our first patient included), presumably because the high blood pressure was no longer maintaineri Uraemic eranthema Patient no 13 and patient no 25 showed a very clearly papill: form and blotched exanthema After dialysis it disappeared within a few days ·CHAPTER VI REACTIONS OF THE PATIENT DURING DIALYSIS AND THEIR THERAPY. Rigors. We are doing our utmost to prevent rigors, yet on 29 consecutive dialyses 8 occurred We tried to prevent rigors by cleaning the tubes and all the material coming into contact with blood carefully as the tubes used for a blood-transfusion Some rigors have been caused by heparin Others have arisen from the use of liquids given intravenously during dialysis which were not so pyrogen free as the manufacturer hoped Shock. When too much blood is allowed to run from the patient into the kidney, the patient will develop a clinical condition generally described as shock He will recover when the blood is led back at once, or when a bloodtransfusion is given If shock is repeated several times the patient does not recover completely, it may take hours, sometimes days before the blood pressure reaches its former level again There are, however, conditions very similar to the clinical picture of shock that are not due to or not entirely due to loss of blood Peripheral venous construction may occur It may herald the unset of a rigor, it may be due to heartfailure, in which case therapy must be different The patients often showed the clinical picture of shock before dialysis started, especially when they were dehydrated If the venous pressure was not raised and the heart was not thought to be the primary reason of the condition, the shock could sometimes be improved by giving bloodtransfusions during dialysis A very good example of this we saw in patient no 6 The blood pressure at the beginning of the dialysis was 130/85 at the end 170/80 This seems too high at first glance, but in a woman ·of morphine are given. Theophylline may be tried REACTIONS OF THE PATIENT DURING DIALYSIS 63 of 100 kilos and with an acute glomerulo nephritis one may etpect a Bular blood pressure and then the blood pressure 130 85 must be taken 28 too low Therapy Shock should be treated at once and effectuarly Salinesolutions given into the bloodstream tend to leave it immediately again The longer a shock exists the more it is necessary to fight it with colloidal solutions blood bloodplasma capain In a patient who has a disposition to shock the 12 to 34 L of blood necessary to fill the kidney must be replaced at once in these mostly seriously ill patients one must always hover between shock and overloading of the circulation with as its most serious consequence pulmonary dedema Occasionally we gave medicaments to fight shock but I never got the impression that they were of any use in serious cases No more have I seen any evidence of the value of remedies for the heart digitalis preparations ouabaine etc for the treatment of the acute failure in these patients Pulmonary oedem Patients with uraemia run a greater risk of pulmonary edema than others they often have oedema and often hypertension so a disposition towards left failure pulmonary congestion pulmon ary oedema. Strong anaemia and aspiration pneumonias which may occur as the patients are often semicomatose and may vomit further increase the chance of pulmonary oedema The same holds good if a deficit of salt is calculated in a patient and the calculated quantaty 15 administered too quickly This should be done carefully in the course of a few days When one fights a shock one is compelled to supply big quan ities of fluid intravenously in a short time If too much saline solution or 5% of glucose is used or if it is given too quickly then one runs great risk of failure the shock contmues and pulmonary edema appears One should use for this purpose blood bloodplasma of an equivalent substitute in these patients Therapy When pulmonary oedema appears or one is afraid of pulmonary bedema owing to much bronchial and pulmonary congestion then of blood if it happens during dialysis one may add extra glucose 20 the bathwater by which fluid is drawn from the blood (and out of the tissues) into the bathwater Moreover 10 or 20 mgrs ·64 REACTIONS OF THE PATIENT DURING DIALYSIS Restlessness of the patient and its treatment with narcotics. Uraemic patients may be desorientated and restless Since we fix glass canulae into the bloodvessels of the patient, and after that bandage the whole arm, we need no longer be so afraid of any restlessness of the patient, as when we were working with venepunctures My impression is that patients with uraemia sometimes reacted badly to the high dose of morphine which we injected formerly We shall have to be as economical as possible with narcotics in future Factors which promoted or caused death When we know with what symptoms "the patients to whom an artificial kidney is applied" die, and what factors contributed towards death, then we may perhaps postpone or prevent the end by minimising these factors For this purpose the gloomy Table 2 is given on p 64 We see pulmonary oedema 8 times and bronchopneumonia 4 times In some of the subsequent patients it has been possible to reduce pulmonary oedema with which they were admitted , It should be realised that uraemic patients usually die from pulmonary oedema and that the artificial kidney cannot be held responsible for these deaths Not only can we reduce the pulmonary oedema by dialysis but we can now also fight bronchopneumonia with penıcıllıne TABLE 2 Patient No Factors which promoted or caused death 1 2 3 4 6 7 8 9 10 11 12 13 14 15 Uraemia Dehydration, acidosis Coma after collapse caused by acute insufficientia cordis Shock, Urine in the abdominal cavity, Ca with meta stases Bronchopneumonia and pulmonary edema Delirium Sepsis (of which the kidneycarbuncle was only a part) Coma and pulmonary edema ? (no pulmonary edema) Ca with metastases Cured Pulmonary edema after distinct left insufficiency Pulmonary edema and bronchopneumonia Pulmonary edema, haematothorax and pneumothorax Dehydration Pneumonia. Haemorrhage Shock, Coma Pulmonary edema ·CHAPTEN VII INVESTIGATION ON SUBSTANCES WHICH WERE REMOVED (OR SUPPLIED) BY THE DIALYSIS WITH THE ARTIFICIAL KIDNEY. Non-protein nitrogen Whether a substance is dialysable or not depends inter alea on the size of its molecule and whether it is bound to the plasma proteins TABLE 3 The rest nitrogen of the blood, expressed in mors per 100 cc before and after dialysis Patient and dalysis Rest N of blood of patient before Id after dialy513 the dialysis Rest N of blood from kidney 49 1x) 8 188 840 after 13280 10 142 91 54 it is clear that the restnitrogen of the blood falls by dalysts. We have further given up determinations of restnitrogen, and ther determined its separate components "ed. Normal quantity in the blood 15-50 mgrs per 100 cc nathally intens the urine per 24 hours " Patient no 1, dialysis no r of this patient 5 ·66 INVESTIGATION ON SUBSTANCES WHICH WERE REMOVED TABLE 5 The urea of the blood, expressed in mgrs per 100 cc, before and after having flowed once through the kidney Patient and dialysis Urea of the blood before going into the kidney Urea of the blood after it has flowed once through the ladney 51 71 7 11 238 142 89 + 600 30 47 71 131 134 The height of the urea in the blood issuing from the kidney especially depends on the concentration of the urea in the bath water, and consequently on the question whether the bathwater has just been refreshed or not. Thus the concentrations of the bath water before it was refreshed, amounted to TABLE 6 Urea amount of bathwater expressed in mgrs per 100 cc before it was refreshed (this is mostly after 2 or 3 hours of dialysis) Patient and dialysis 1st bath 2nd bath 3rd bath 50 13 1 13 11 141 151 106 35 25 49 81 50 51 22 35 The success of the artificial kidney would be higher, if we had a reservoir with rinsingwater, flowing in the opposite direction of the bloodcurrent at our disposal instead of one bath of 100 Ls TABLE 7 The total quantities of urea which could be shown per dialysis in the bathwater 10 11 12 131 13 11 151 Patient and dialysis Quantity of urea in grams removed per dialysis 52 146 65 263 95 102 71 The blood which has been purified to a large extent of urea and other retention-products in the kidney, comes back into the cut ·INVESTIGATION ON SUPSTANCES WINCH WERE REMOVED culation of the patient, and is again directly provided with reten- Lion-products from all tissuefluids Indeed it takes some time before one begins to perceive some sign of a fall of the retention-products in the blood of the patient. In the table below the urea amount of the patient's blood be fore and after dialysis is compared for 10 patients The samples have been taken from the tube, as close as possible to the arteria radialis TABLE 8 Urea of the blood of the patient before and after dialysis Patient and dialysis 12 131 1311 14 16 1011 De3 704 356 648 359 373 Blood of patient before d:alysis Blood of patient after dialy$18 63 192 197 263 151 The greatest fall of the urea of the blood was 512 mgrs per 100 cc But not only urea, also other retention products are removed rom the blood by the artificial kidney Teatinin Normal concentration in the bloodplasma 0,7 to 9 mg per 100 cc Normal excretion with the urine per 21 hours 1,1-1,5 6 TABLE 9 The excretion of ereatinin by the artificial kidney, expressed in mgrs per 100 cc Patient and dialysis Blood of patient Blood of patient before the dialysis after the dialysis Blood from the kidney 5 4,7 1,7 2,5 7 11 9 12 131 14 5A 1,8 46 3,4 7 6,1 7 42 2,3 1.2 1,G 1,0 1.2 2.9 2.1 2,2 2,9 2,9 3,1 It appears from table 9 that the creatinin of the bloodplasma of a patient with uraemia may be exceedingly reduced by an er tensire dialysis, it continued for a considerable time, it may be brought back within normal bounds.

·68 INVESTIGATION OV SUBSTANCES WHICH WERE REMOVED Unic acid Normal content of unic acid of the bloodplasma 2-4,5 mg, per 100 cc Normal excretion with the urine per 24 hours 0,4–1g TABLE 10 The excretion of uric acid by the artificial kidney Uric acid expressed in ingrs per 100 cc Patient and dialysis Blood of patient Blood from Bathwater Ibid after dialysis the kidney lv 3 5 19 23 57 36 53 97 149 7,1 102 8 94 88 11 7,4 20 47 86 52 58 53 8 52 5 7 8 11 132 11 14 063 3 24,7) 98 Just as with the urea, it is clearly shown that the dialysis is most effective of the concentration of the unc acid in the blood is high Indoxyl Normally the blood contains only 0026 to 0,85 mgrs per 100 cc plasma. In uraemia one would find up to 7 mgts of indoxyl per 100 of bloodplasma TABLE 11 Indoxyl of the bloodplasma expressed in mgrs per 100 cc Patient Blood of patient before dialysis Ibid after dialysis Blood from the kidney Bathwate 3 + + 0,4 trace 09 6 trace HAAS showed that indoxyl can be removed from dogs by dialysi We had no further reason to doubt this, and therefore did nu perform further determinations Substances, causing the Fanthoprotein-reaction The normal xanthoprotein reaction is 15-30of the standard B net 1) Agonal increase of unc acid ·69 INVESTIGATION ON SUBSTANCES WHICH WERE PESO ED the bloodserum of patients with uraemia can give These substances are probably bound to the plaema albumen but it is questionable how firm this connection is For a great part of the above-mentioned substances it has been roved by ABEL, ROWNTREE and TURNEP that they can be removed rom the blood by dialysis with celloidinmembranes One would xpect that the xanthoprotein-reaction would become lower after a successful dialysis However it does not always prove possible to read accurately the colour-reaction in plasma of heparinised blood On the whole our impression was that the vanthoprotein decreased by the dialysis Minerals Something has already been stated in this respect in Chapter III when discussing the bath water in the very large dialyses the moncentration of several minerals in the blond plasma (to be exact the plasma-water) followed the corcentration of the same sub ances in the bath water more and more Finally these two con entrations would become equal to each uther (at least in so far is the minerals concerned are dissociatt i n the bloodplasma calcium for example is only dissociated for 50 Minerals may be extracted from the patient by leaving them out of the bath water Minerals may be supplied ! the p tien by adding them to the bathwater In so far as they might be of importance the bfferent minerals are discussed below Sodium. The normal sodium percentage of the lo xl rum 3.0 Jul mgr per .00 ccm While the chloride content at the bloodplasma tends to be owered in vraemia, this is usually not the ca with the solum content TABIT 12 Sodium of the patient s bloodplasmi ni 100 ern Temarks After the Bio dialysis ant and Brora tbA dialysis dialysis FIE 5 3 131 11 $10 311 320 Iemained normal 35 129 (371) lowered but not enough (73) 321 134 Bacoma too bigh 376 Varmal part 874 Somall 331 (3121 (939 9.7 wat normal Bath 102 300 gr na per 100cc The values between were determined some days preciou lv 151 ·70 INVESTIGATION ON SUBSTANCES WHICH WERE REMOVED In none of our patients the sodium percentage had been lowered greatly. If sodium is retained fluid is held in the body outside the cells as well, and this means edema Therefore we are afraid of supplying sodium Certainly if the patient already has edema and the more so as in all these patients an overloading of the left side of the heart with pulmonary edema is imminent Potassium The normal potassium level of the bloodserum is 16–20. mgr per ann Ivepealeuy & SLong lise ve lhe pocassiulll luncent of the wioduselul is noticed in patients with uraemia shortly before death It mostly impossible to determine the potassium percentage of the heparinised bloodplasma We cannot therefore determine the potassium content of the bloodserum during and after the dialysis, as long as the patient is still under the influence of the heparinisation Therefore we must be content with the potassium level some days after the dialysis in the table below, and try to draw our conclusions from these TABLE 13 Potassium content of the patient's bloodserum, expressed in mgr per 100 cc Patront Pota8910 m of blood serum before the dialysis ibid some days after the dialysis idem later Potassium demonstrated in the bath water (later on it has been added to it) 2 3 19,4 18 88 34 mgr per 100 ccm (8 brs post mortem) 222 37 175 7,9 mgr per 100 ccm 83 273 273 27 235 21,5 14,8 25 6 14,8, 17,6, 207 19 17 55 19 Noting the potassium of patients nos 7 and 13 after dialysis it becomes very likely that patassium is removed by the dialysis, in patient no 13 to such a degree, that it appeared desirable to add potassium to the bath water henceforth, to prevent a too strong decline 7 9 10 13 15 ·71 RIGATION ON SUESTANCES WHICH WERF RESOSED um The normal calcium of the blood serum is 9-11 mgr per 100 ccm Data concerning phosphate are to be found on page 73 The calcium in the blood plasma is 1/3 to 1/3 free ie in diffusable state if the per centage of free calcium falls through dialysis the calcium albumen dissociates again to a larger extent so that it would be possible to remove finally all the calcium by dialysis We have determined the total content of calcium, but especially the calcrum in of importance for the appearance or absence of tetany TABLE 14 Calcium and phosphate of the blood plasma expressed in mgr per 100 cc Klood for the kidney Allar d alyss Pbospbate expressed 29 Inicium Phospbate evreused as P Calcium Before dialysis Tatient Add Phosphate dialysis Calcium expressed as 4 94 15 5 B 10,4 96 6,8 09 10 123 76 11 8 B 10 62 69 75 yu 61 later latar 60 5 88 12 10 78 1) 11 1 9 112 131 11 16 1187 9. 6 The table shows that the calcium usually was about normal in the patients where it was determined occasionally it was lowered some times raised! The calcium of the patients blood has mostly been lowered by the dialysis sometimes to 5 mgr per 100 cc Tetany we never noticed ') Neither did the uraemic luitchings become more serious during dialysis Sometimes they improved perhaps ollowing the administration of calcium gluconate intravenously In the chapter concerning the bath water it has already been stated that no CaCl, is to be added to the bath already containing NaHCO, Therefore we inject calcium gluconate intravenously (1 e into the tube') Magnesium This is normally present in the blood plam: to an amount of 2,3 to 4 Mgr per 100 ccm, and GO.-90 % of this is d ffusible It was thought that the magnesium would not be raised in traemos RROOKFIELD (lit no 22), howeser is of opinion that in uraemis the magnesium content may certainly has been raised especially 16 sulphate of magnesium has been a iministered to the pauent as a laxa- Note at the correction le saw tuo cases non with low bloodcalcium belote dialysis showing convulsions with some tetanic caracterieties Giving alkali to such patients may reduce the jonized calciam and cater telania ·72 INVESTIGATION ON SUBSTANCES WHICH WERE REMOVED tire. In exceptional cases the magnesium content should even be able Ahom the natent effort may become apparent Even if Chloride The chlonde percentage 13 nearly alsays given as NaCl percentage n the atung, sweating and diarrhoea, partly also by the fact that detective kidneys when they are still producing urine, can only do so by excreting chloride as well, however acute the shortage in the body may be Moreover these patients as a rule take up very little or no chloride with their food If one corrects a chloride shortage of the blood plasma, one supplies chloride mainly in the shape of NaCl Not always, however, does a patient react favourably on a too rapid correction of his NaCl! The possibility of pulmonary edema should always be kept in mind TABLE 16 CI of the patient's bloodplasma, expressed as Naci an mgr per 100 ccm Patient and dialysis NaCl NaCl before arter dialysis dialysis NaCl percentage of the bath Remarks 581 819 750 842 653 5 2 700 700 050 700 700 600 6 515 604 683 536 become too high dulý fallen? patient was exsiccated bucoma too high En Korde what, but not yet normal normalised 71 605 II 9 10 11 12 131 508 515 626 1 626 595 And 650 600 650 700) 14 151 I! . This table very clearly shows that the NaCl of the blood plasma parallels the bathwater. So it is of great importance to choose the Cl-ion concentration in the bathwater well; both a shortage and 1) See FISTIBFRG (litt no 5) ·IVYESTIGATION ON SUBSTANCES WHICH WERE REVOSED 73 a surplus are corrected. When comparing the amount of neg lons (C, HCO,) in plasma and bathwater the DonA1-equilsbrium should be considered because within the membranes indiffusible neg 100s (albumen) are found By this the CI and HCO3- amount of the bathwater is 1020 higher than that of the plasma when in equilbrium Bioreover the NaCl amounts of the blood. plasma have been expressed per 100 cc of plasma while actua}ls the percentage of the plasma water is concerned which les about 10% higher RCUT Phosphate In the norganic form phosphoru n the bord + 11 PO. and 33 PO. The phosphate is expressed as phosph ru Vorral phosphate of the bloodplasma 2-4 mets per 100 ce for larci o mor per 100 cc In patients with uraemia nearly always an increase of the phos phate is found in table 14 the phosphate at the beginning of the dalysis varies between 7,8 and 15 mgr per 100 cc Phosphate us quickly removed by the dialysis Aikali tesETS 3 The normal alkalı reserve amounts to CO2 The CO2 *Alch > made free at the determination of the ahal resere comes for the greater part from the NaHCO (s wiumb carbonates of the blood plasma 1 vol % CO, corresponds aith mgr 8IICO TABLE 17 Alkal teserye in % volume of the blood of the patient Patient Before dalyala After dalysts Bloou fut the kidnev IBAT Buh Ya BCO, 73 37 } 2001 Diger 44 3% rol CO2 309 (41) 10 20 wrki (rol.) 10 13 151 16 17 18 19 47 3 t! 35 42 23 3 43 * Petermination of the alkal nu serve of the bathwater fer th dialysis ·74 INVESTIGATION ON SUBSTANCES WHICH WERE REMOVED From the above table it is seen that the patients mostly have a moderately reduced alkalı reserve in the beginning which is improved after dialysis In dialysis 711 and in dialysis 13 the patient's alkali-reserve is higher (better) after the dialysis than before No extra NaHCO3 was given intravenously Presumably retained acids have been removed by the dialysis The blood from the kidney had a lower alkalı-reserve (24 resp 27 vol %) than the patient's blood One may take into account that the CO2 dissolved in the blood, which is included in the determination of the alkalı-reserve, will have escaped through the cellophane during the dialysis, this however only makes a difference of about 3 vol % Only twice a determin ation has been performed of the alkalı reserve of the bathwater after dialysis With the 15th patient the alkalı reserve of the bath water after the first dialysis was only 31 vol % (in the beginning 53 vol % is to be expected) This would indicate that large quan tities of acid left the patients blood for the bathwater, and that there they expelled the CO, from the NaHCO3 It is necessary that more determinations are performed and if this single observation should be confirmed we need not be surprised at the low values of the alkalı reserve of the blood from the kidney Extra NaHCO3 might be added to the bathwater during dialysis but then a rather high sodium concentration is obtained We have been afraid that a high percentage of NaHCO3 and a strongly alkaline bathwater would influence the pH of the blood with possibly unfavourable results If oxygen with 5% CO, were bubbled up through the bathwater continually, the desired pH would be obtained To perform this one would have to make a cellophane hood over the kidney to provide the air inside this hood with 5% CO. The 5% CO2 would be mixed very intensely with the bathwater by the rotating cylinder An additional advantage of a bathwater with a correct pH would be that one could add calciumchloride to the bath water without the calcium being precipitated as calciumcarbonate As long as we do not possess a cellophane hood over the artificial kidney, and do not have CO2 bubbling through the bathwater, we repeatedly give small quantities of NaHCO3, 5%, diluted with saline intravenously to patients who are connected with the artı ficial kidney in a state of strong acidosis The alkalı reserve must be checked to see whether enough has been given ') 1) Calciumgluconate should be given at the same time otherwise tetania may be provoked ·75 INVESTIGATION ON SUESTA CES WHICH WERE REVOVFD Glucose Normal percentage of glucose of the blood for the blood plasma) 70-130 mgr per 100 ccm After a meal up to 100 TABLE 18 Glucose in mgr per 100 com in the blood and n the bath water in the case of pat ent no 1 V IV Salysis AO Blood of patient before dialysis V11 114 101 11+ 106 5.0 40+ 3 + 1 + 1500 01 189 01 200 Blood from kidney after dialys s Bath water Blood from patient after dialys 3 Bath wate Bath water tout UCOPA with glucose As is to be seen from the table above in uur f rst patient the glucose of the blood from the kidney proved to fall very strongly il no glucose was added to the bathwater Ifter that we added 1% glucose to the bathwater to prevent the haemolysis of the blood in the kidney TABLE 19 Glucose of the blood n mgr per 100 cem Bath Blood from the doey Blood after the d alyse Blood before tho dalysis Pati at sod dialysis 1000 160 1500 147) 189 01 391 434 63 309 31 10.00 100 144 84 4G 9 131 Later we added still more glucose (39) to the bathwater in order to draw oedema fluid ton ards the bathwater by osmotic force We received the impression that with a bath glucose content of locven in the larger dialysis the patients bloodsugar did not become very much higher than 535 mgr per 100 ccm We do not believe this carries with it any disadvantage for the patient The glucose will probably be consumed gratefully ·INSTRUCTIONS FOR FITTING UP AND CLEANING THE ARTIFICIAL KIDNEY. For each dialysis the following are required: I A packet of tubing, previously sterilized in autoclave, and packed in a sterile condition (tubes, glass vessels and couplings may also be boiled before dialysis) Contents of the parcel of tubing The wide tubes have a diameter of 6 mms inner section and 11 mms outer section The narrow ones have a diameter of 4 mms inner, and 7,5 mms outer section The numbers in front of the tubes refer to the fitting up diagram A luchtvanger inzetbuisje las 11 inzetbu sje koppel ng D] 12 MAIN hoppelny parent ON slangenpo no 3 Tstuk met Emade durm Soral dorm و انار პ wbeen 0 10 9 T stuk mer nowbeen buret TU von painot glas Fitting up Dagam A inzetbuisje insertion tube las joint koppeling = coupling luchtvanger air catcher T-stuk met nauwbeen = zeefje = sieve T piece with one narrow end slangenpomp = tube-pump breede darm = zijbuis = side tube wide cellophane tube smalle darm van patient = from patient narrow cellophane tube ·INSTRUCTIONS FOR FITTING UP AND CLEANING 79 THE PRESSURE TVIVDOIV OF THE OUTFLOW-TUBE FROΣ THE PATIENT cellophaandarm cellophane gut igatuu" ligature Sketch B canule canula 1 a wide tube, about 125 cms long for the burette 2. a narrow tube, 170 cms long, with pressure-window (see Sketch B) 3 wide tube, 50 cms long (T-piece to coupling) 4 a wide tube, 60 cms long, with a glass insertion piece (coupling to gut) 5 a narrow tube, 150 cms long, finishing in a small glass tube close to the end the return-tube to the patient (This latter prece of tubing is used when tapping samples of blood, the tube is pricked with a needle and the blood sucked up by means of a syringe ) 6 a wide tube, 60 cms long, with a glass insertion prece (gut to coupling) 7 a wide tube, 50 cms long (coupling to T pjece) & a narrow tube, 45 cms long (running through the tube-pump to the air-catcher) 9 and 10 five wide tubes of about 10 cms in length, connectingpieces between the glass T-pieces and the glass parts of the side-tube 11 a couple of joints (glass tubing covered with rubber) 12 the rubber stop of the air-catcher, with intet tube and filter 13 two glass T-pieces, with one arm tapering and a normal T-prece 14 the couplings 15 the wooden reel upon which are wound either 10 ms of narrow and 30 m of wider, or 45 m of narrow cellophane gut 16 two packings (cotton threads of 12 cms) 17 one or two artery forceps (to be placed on top so as to be immediately accessible) 11 A parcel of larger glass vessels, either dry sterilized or boiled. Contents of the parcel of larger glass Lessels a burette with a pierced cork 2. an ar-catcher, with a small rubber tube of about 3 cms on its spout ·80 INSTRUCTIONS FOR FITTING UP AND CLEANING 3 the side-tube, in 3 parts of 30 cms in length each, outer section 9 mms III Sterile canulae A collection of glass canulae for the veins and arteries should be present, each of them packed sterile in a test-tube closed with cottonwool, to two canulae a 10 cm piece of rubber tubing with a glass stopper is connected fig 320 IV 15 litres of sterile, apyrogenic salıne, at least 11 litres of blood compatible to the patient, or (blood) plasma, while between 2 and 3 litres of blood should be available at short notice Preparation of apyrogenic salt solution The saline solution is prepared in special enamel vessels with a capacity of about 8 litres The vessels are brushed out with a hot soda solution, and repeatedly rinsed with hot water They are finally rinsed three times either with fresh tapwater or with fresh apyrogenic water After this the vessels are filled with fresh apyrogenic distilled water or fresh tapwater, to which 9 g of NaCl per litre is then added A piece of gauze is stretched across the opening of the vessel, and over this a piece of taffeta Of thıs, a slip should be left free at the spout to allow steam to escape during boiling, each vessel being allowed to boil for at least a quarter of an hour The taffeta is then tied so as to close the vessel the latter being cooled in a bath of cold water V Medicaments, instruments and spare accessories See that the following are available 1 Heparin (maximum of 1000 to 2000 mg for each time) 2 Ready-weighed quantities of salt for renewing the bath water, for a bath of 100 L 600 grs of NaCl, 200 grs of NaHCO3, 40 grs of KCl, and 1500 or 2000 grs of glucose 3 Cottonwool, ether and alcohol, plaster, scissors, sterile syringes, and a collection of long and short needles, 4 Spare glass 'T-pieces, links, joints, glass stops to shut off tubes, all kept sterile in alcohol 5 Thread to fasten ligatures, piece of elastic, talcum, grease oil, screw-driver and pliers 6 A rack provided with both sterile and non-sterile test-tubes and one provided with tubes containing sodium oxalate and paraffin, for samples for determining the alkalı reserve Labels should not be forgottent ·LNSTRUCTIONS FOR FITTING UP AND CLEANING 81 7. A number of bottles of 100 and 300 cm with glass funnels for samples of the bath water 8 Lists to enter observations and samples 9 A spare driving belt for the motor 10 Earth wires both of the heating element and the motor should be checked Fitting up and mıking ready for the The tubes glass work ete may be sterilized in the autoclave and kept in a dry sterile condition in this case the extremities of the tubes must be moistened with alcohol in order to ensure their being easily fixed to the glass parts and couplings The tubes and the glass work may also be boiled in a large pan (see Sketch C) immediately be fore dialysis The cellophane gut is wound on a wooden rrel (fig 30) and boiled for a quarter of an hour in the pan with plenty of water in order to remove as far as possible the glycerine in which it was soaked or cms Fitting the couplings Take the inner tube ir the hand holding it by the protruding cross piece and push the screu -cap on at Sketch c Measures A (inside) against the cross piece Length, 53 cm Width 30 5 cm The counternut should be turned He ght 125 cm on to the wider tube first Height B Underneath B 4 szal! legs Soak a sterile cotton thread 12 cms 08 cm in he ght long in a pot of sterile vaseline and wind this thread with the aid of a sterile forceps around the inner tubo Then push the scren cap as far as possible over the packing and push the inner tube into the wider one The screw cap may now be turned on without any risk of the fibres of the cotton thread blocking op the screw thread Push the tube with the glass inset piece on to the wider tube No. 4) and introduce this tube through the hollow axis of the kidney The coupling is then fixed by mcans of a screw Fix thu Ince extrematy of the coupling with a wire or a brace In the same way the second coupling is fixed in the hollow axis at the other end of the cvlinder Do not forget the driving belt' 6 ·82 INSTRUCTIONS FOR FITTING UP AND CLEANING The cellophane gut The rubber tube (No 4) with the little glass tube inserted in the end of it is now led outside through the spokes of the wheel and passed between the laths to the outside of the cylinder The end of the tube is wiped off with alcohol, the beginning of the cellophane gut is pushed on to it and fixed with two ligatures over the rubber tube with the glass insertion-piece After this the gut is wound tightly around the cylinder Be careful not to let the windings overlap, they should lie closely side by side When the first length of gut has been wound upon the cylinder, 'a second length is attached to the first by means of a joint (No 11) Both guts have to be fixed round the rubber piece with a double ligature The second length of gut is then also wound on the cylinder, and its extremity connected with the tube (No 6), which at that point, protrudes through the other hollow axis of the cylın der This tube may have to be lengthened by nearly half the circumference of the cylinder so that the cellophane gut may be tightened when after some hours of dialysis it has stretched (see Sketch D) THE SHIFTING OF THE TUBE 6 DURING DIALYSIS slangb *-darm elastiekje k tube 6 at beginning of dialysis after a few hours Shetch D The figure on the left is not quite correct, inasmuch as the tube 6 will always have to run a little way over the outside of the roll before it is fixed to the cellophane gut Elastiekje elastic band The way the remaining part of the circut is mounted follows from the Sketch A The tube which is led through the tube pump must be rubbed with plenty of talcum beforehand in order to obviate any damage by the rolling of the pump Rinsing When the tubes are fixed, about 10 litres of sterile, apyrogenic salt solution, in portions of 400 cm", are let in via the burette and allowed to pass through the tubes and the gut, the circuit should ·INSTRL CTIONS FOR FITTING UP AND CLEANING be temporarily interrupted in the side tube (see Sketch E) Sce to it that the ar-catcher and both in and outflow tubes are rinsed then close these tubes with a Ciamp and protect the open ortremt es either in sterile tubes or with sterile gauze THE CIRCUIT INTERRUPTED DURII son بطار zjbus sd 2 Sketch After making sure that there are no le n the gut about hall latre of salt solution with 400 mgs of heparine is poured into e burette This is allowed to c rculate Ster le glass canulac ore en fixed on both outflow and return tubs after which these :ssages are also rinsed with the salt solut n and heparine care ng taken that as little as possible of in prece neprine is alt ckages When the kidney has been sufficiently rinsed the cellophane it is carefully tested for leakage If necessary the frame with emotating-cylinder of the kidney is raised in order to cramine nditions underneath the cylinder (see fig 19) Alcak may some mies be localized by binding off the gut at different points with tape The Irquid then accumulates in the windings in front of € stricture When a leak is found the cellophane gut is cut rough at the point where the opening is and a joint is made Deed be one may also remare å length of gut a little shorter in one winding and connect the remunng ends with a joint a bit of rubber tubing with a small glass tube inside for Double ligalures should be placed everyul cre round the cello mane gut when the cellophane gets act it very easily slips from der a thread and therefore the thread should be round round in rellophane gut as many as 10 of 12 times mness) ·SUMMARY OF PART I ARTIFICIAL KIDNEY. As early as 1913 ABEL ROWNTREE and TURNER were able to remove products of katabolism from the blood of experimental animals by means of dialysis The blood is prevented from clotting and flows outside the body through a system of dialysing tubes The substances with small molecules to which nearly all the products excreted with normal urine belong, can be removed by dialysis, whereas large molecules such as proteins cannot pass through the membrane In spite of some later efforts, vivi-dialysis has not found a lasting place in clinical use At present we have greater oppor tunities than earlier workers, because we have excellent dialysingmembranes (cellophane) and a reliable non toxic anticoagulant (heparine) at our disposal The first thing we had to do was to construct a dialysator effective for clinical use A good dialysator must spread a small quantity of blood over a very large surface, the blood must circulate in a closed system and the blood as well as the washing liquid must be kept in continuous movement We must be able to clean and sterilise all those parts that come into contact with the blood so that they do not cause any pyrogenic reactions After many earlier endeavours, briefly described elsewhere an artificial kidney was constructed in cooperation with Mr H TH J BERK, an artificial kidney which is suitable for clinical use A detailed description of this artificial kidney is given, and a full set of drawings is given for its construction, so that any good instrument maker should be able to construct an artificial kidney Moreover instructions are given for its cleaning and sterilisi This is important in avoiding undesirable reactions of the patie such as rigors etc Detailed reports of the first 15 patients wi were theated with the artificial kidney have been published the Dutch edition our experience with the artificial kidney h been analysed, the mistakes have been exposed in the hope making an uninterrupted vividialysis possible in this way lat treatments took place practically without technical interruptiar. Through the dialysing membrane molecules go both in and ou therefore much attention has been paid to the composition of t? rinsing-liquid, as, in no circumstances may the patients be d

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·88 SUMMARY OF PART I ARTIFICIAL KIDNES continue to give a chance to every severely uraemic patient who comes into our hands alive we shall never flatter our statistical results Some patients became uraemic owing to anuria or oliguria Others became uraemic though their diuresis was about 1 or 2 L a day, but the concentration of the urine was poor This may be the case both in patients suffering from acute glomerulo-nephritis and in patients after operation In cases of acute uraemia one should not postpone the treat ment until the general condition of the patient suddenly declines We have come to the conclusion, that these patients nearly always die unexpectedly, whereas a short time before they still made clinically, a good impression We propose to treat the patient with the artificial kidney as soon as the urea content of the blood rises over 350 mgr per 100 cc (3,5 grams per liter) and before that, if, moreover, the potassium content of the blood is higher than normal, or the alkalı reserve is too low If this is done, the urea-content can easily be brought under 100 mgr per 100 cc in one dialysis but this is usually not even necessary In the case of the 18th patient, the urea content was reduced to 46 mgr per 100 cc It is now possible to deliver a seriously uraemic patient of his uraemia in one dialysis, which lasts from 5 to 14 hours, so that, after the dialysis, he will have a several days' respite before the intoxication endangers his life again In the meantime there is a chance that the patient's own kidneys start excretion again

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·90 LITERATURE - La KOLFF, W J The artificial Kidney a dialyser mth a great area -- Acta Biedica Scandinavica Vol CXVII Fagc II Page 121 1944 Le rern artificiel un dialyseur à grande surface Presse Médicale No 7 Page 103 1944 11 KUHN, W, und K RYFFEL Herstellung Konzentrierten Lösungen aus verdunten durch blosse Membranwirkung Ein Modell tersuch zur Funktion der Niere - Hoppe's Seyler's Zeitschrift fur Physiologische Chemie Band 276 Heft 4/6 Seite 145—178 1942 12 LIM and NECHELES, Demonstration of a gastric secretory excitent in the circulating blood by vvrdialysis Proc Soc for exp biol and med Vol XIV, page 197 1926–1927 13 NECHELES, H, Ueber dialysieren des stromenden Blutes am Leben den - Klin Wochenschr 2 II Seite 1257 und Seite 1888 1923 14 Nyini W. Ezperim Untersuchungen uber gekreuzte Bluttrans fusion bet Uranie - Archiv fur Pathol und Pharmakologie 1926 Band 116 Seite 117 15 PAGE, JH, and OMHELMER A crystalline pressor substance (angiotonine) resulting from the reaction between renin and reninactivator - J of Exp Medicine 71, page 29 1940 16 PENDLETON A and WEST, Am Journ Physiol 101, 391 1932 17 POULSSON Lehrbuch der Pharmakologie 1919, blz 369 18 RIOADS JE, Peritoneal lavage in the treatment of renal insuff ciency Am J of the Med Sciences Vol 196, 1938, page 612 19 STARKENSTEIN, Lehrbuch der Pharmakologie, Toxikologie und Arznerverordnung 1938 blz 330 20 TIIALHIMER, W, Experimental exchange transfusion for reducing azotemia Use of artificial kidney for this purpose Proc. Soc for exper biol and med Vol XXXVII, page 641, 1938 21 THALHIBER, W, D L SOLANDT and C H BEST, Experimental exchange transfusion using purifred Heparin Lancet 1938 II, page 554 ·PART II L'ERITONE IL LAVAGH This work has been performed with the assistance of PSM kop 11 D Principal The principal of peritoneal lavage is very simple A large quan tity of rinsing fluid is allowed to run through the peritoneal cavity the peritoneum serving as semi permeable membrane According to Wegner the surface area of the peritoneum is 17 000 squ cm If this figure is correct the area is almost equ valent to the esu mated 20 000 squ cm for the total glomerular surface in the human kidneys The peritoneal surface area however ma not by the same as that of the underlying capillaries Development The idea of peritoneal lavage is not new rlthough t has only recently been resuscitated It is remarkable how widely preid in the medical literature of the world articles on the subject have appeared and equally remarkable how little the various author have been aware of each others work with the result that they have repeated the same experiments and the same mistahes In 1923 GANTER Published an article entitled Removal of poison ous substances from the blood by dialysis He injected a rinsing fiud into the abdominal cavity of guinea pigs after previously tying the ureters On subsequent removal of the fluid it was found to contain the same concentration of urea as the blood The same year TRACY PUTNAM investigated in detail the fate of various isoand hypertonic solutions introduced into the peritoneal cavity She was able to show that in certain circumstances the introduced fluid tends to become isotonic with the blood plasma it appeared that some water was always absorbed from the peritoneal cavity ) Note at the correction See al o the work of LANTER 1 ani CronxXL ·92 PERITONEAL LAVAGE In 1926 ROSENAK and SIWON used a continuous perfusion of the peritoneum in dogs They obtained the best results with 5% glucose, although the removed mineral constituants had to be replaced by mouth HEUSSER and WERDER in 1927 did experiments on dogs VON JENY, and ROSENAK and BALASZ undertook some experiments about 1930, on peritoneal lavage in corrosive sublimate poisoning, the last mentioned authors treating two cases RHOADS published in 1938 two cases in which he had used peritoneal lavage, both patients subsequently died with chronic nephritis The rather poor removal rate of solids in these cases can be accounted for by the fact that fractionated lavage, 1 e a volume of fluid introduced, left in the abdomen, and then removed, was used, although on one occasion 20 g of urea was removed No effects were noticed on the pulse, temperature, respiration or blood pressure In one of a series of cases published by WEAR, SISK and TRINKLE, the lavage brought about improvement in the patient's condition, a stone was subsquently removed from his bladder and he survived ABBOTT and SHEA in 1946 published some careful work on the composition of the blood using a fluid very similar to our own Their conclusion that better removal of solids is obtained with an intermittent than with a continuous lavage does not seem likely to us FORMIJNE is, to our knowledge, the first to have used perfusion of the peritoneum in the Netherlands FRANK, SELIGMAN and FINE (JAMA 19 March, 1946) published a successful case, in which anuria, following the use of sulphathiazole, was treated with lavage for five days, with only one period of intermission owing to some peritonitis That the authors should have had this therapeutic success was well deserved in view of their extensive work on dogs carried out beforehand Technique. A study of the literature has shown us no reason for changing the method we have developed, which, in principle, is no different from any other Up to the present we have performed 15 peritoneal lavages, and have so far no untoward experiences, except in the last case where a man with severe chronic uremia had a meteorastic abdomen A distended ileum-loop was perforated by the trochar, with the catheter in situ laparotomy was done, the hole was easily found and closed The patient died from uremia 3 days afterwards, at post mortem-examination no signs of peritonitis were found ·PERITONEAL LAVAGE 93 Composition and preparation of the rinsing fluid TABLE 21 Composition of ninsing fluidused by differer uten tyrode RINGER grams per liter DARROW RHOADS HARTMANN ADLOTS holi? att kune MOLTE netto 1 1 Naci 800 -- 650 145 600 61 600 100 3 2,50 y 200 Malico, КСТ 0 20 018 040 040 03 0 CaCl2 0,20 020 03 02 020 300 dextrose 10 30 10-30 lactic acid 240 141 005 VOT MaH PO, Месі, 010 0 35 We should like to stress at this point that the electrolyte conte 11 of the rinsing fluid should be compared not inth that the plasma but of the plasma water (cf page 36) We are not yet convinced that the addition o Vsci and NaH PO, is necessary for the correction of the comm inly prosent acidosis 200 mg NaHCO3 is added which is cquivalent to a Co, content of 53 vols To obtain a constant p!I of 71 after sterillsing 5% CO may be bubbled through the fluid uthough We ourselves have no experience of this In sornc cases of ordem It was necessary to add up to 34 glucose in one case is formed the impression that this caused abdominal pain durinr the lasage To cach litre of fluid 10 mg heparin is added in order to prevent clotting in the tubes of the protein contuning Muid flowing out of the abdomen initially 40 mg of hepann is injecte 1 into the 15. flow tube at the beginning of the invale Penicillin may be added to the rinsing fluid v hen cooled down after sierlısıng but It should also be given directly to the patient In order to minimise the risk of infection we insit that the tirsing fluid is sterilised in a closed system wiich is not opened orce sterile The resen oirs must be sufficiently large to alone ·94 PERITONEAL LAVAGE frequent changes from one to another during lavage, again redu cing the chance of infection The enamel reservoirs were made for us to the pattern shown in fig 52 by the Berk enamel factory at Kampen. It would be simpler to use a single tank with a central partition but this is difficult to make in enamel The inner tank is filled with 5 litres of fluid composed as follows 130 grams Naci, 112 grams NaHCO3, 11 grams KCI The large outer tank is partially filled with 23 litres, as follows 280 grams dextrose, 8 grams Caci. O aq, 192 cc HCI 10% The small tank is placed inside the large one, and the lid with a rubber washer, is screwed on the whole is sterilised by boiling for twenty minutes on a gasring Steam escapes through the small pipes covered with sterile gauze After boiling the reservoir is cooled by placing in a bath of cold water Heparin is then added and a sterile bung placed in the outlet tube The reservoir is now tilted 90°, the contents of the inner tank flow out into the outer and thourough mixture is ensured by shaking Arrangement and sterilisation of the tubes The arrangement of the tubes is obvious from fig 54 It is essential that the in-flow and out flow can be interchanged at a moment's notice At any time a loop of gut or a piece of omentum may block the out flow Not for nothing have several workers resected the omentum in their experimental animals before em barking on peritoneal lavage The tubes should be cleaned as those in a transfusion set as is described on page 85 Rate of flow. 1 Liter per hour proved to be satisfactory The introduction of the catheters into the abdomen Several investigators have used glass or metal drains particularly for the out flow We have only had experience of thin catheters introduced through a trocar into the left side of the abdomen The catheters are pierced by a large number of small openings The lavage may flow uninterrupted for many hours or may require frequent reversal of direction After carefully cleaning the skin and covering the surrounding area with sterile towels a small incision is made through the skin,

·ris v2
The smalt tank is placed insi le the targe car and the lid with a rubber
washer, is screwed on The whole s ateribed by boiling for twenty minutes
on a gasitz

·Fig 53 After cool ng the reservoir 18 tilted 90 the contents of the inner tank flow out into the outer and thorough mixture is ensured by shaking

·DIAGRAM OF PERITONEAL LAVAGE
INNER TARK
IN TREC
KAW
XV
THERMOSTAT Det
METERS OF THIN WALLED RUOCER HAR
LOTTONWOOL INSULAY VM
IRFLOW
OurrLOW
fis
{
u serbal that the in-flow and oli nion can be interchangea ata memeris
Mict At any times loupot cut or a piece of omentum misy Hlora the out flow

·96 PERITONEAL LAVAGE and the trocar introduced with rotatory movements After inserting the catheter the cannula of the trocar is removed by slip ping over it. The catheter is fixed to the abdominal wall by sticking plaster, and the wound powdered with sulphanılamide The chance of infection is considered very slight with the skin fitting tightly round the catheter, especially if the catheter is not left in longer than 36 hours Other workers introduce catheters or glass tubes by surgical means The intestines appear to slip out of the way of the trochar In the case of marked abdominal retraction we have first injected 2 litres of rinsing fluid into the abdominal cavity by a needle in order to facilitate entry of the trochar by the artificial ascites The puncture is made between the umbilicus and the anterior superior ilac spine on the left side, the needle being directed obliquely downwards Care should be taken not to remain in the preperitoneal space, where the fluid will run in without any resis tance, although( of course, the signs of ascites will not develop Both stomach and bladder must be empty before starting Trocars should not be used when the bowels are distended by meteorism Patient A A man of 58 with a long history of bilateral renal and ureteric calculi The right pelvis became infected and this kidney ceased functioning An attempt to remove the stones from the right ureter 5 months previously failed owing to widespread Calcium depo sits and scarring The left kidney continued to function well until the onset of renal colic on this side when complete anuria developed 189 16 L LAVAGE LAVAGE JHwy 940 DOS To Fig 55 ·TERITONEAL LAVAGE 97 On cystoscopy a ureteric catheter could only be passed up to the stone on the left and digregis did not start when the blood urea had risen to more than 900 mg, peritoneal lavage was performed The results may be seen in figure 55 The lavage listed 16 hours and cavepd very little discomfort an incipient rigor *13 Aborted with dolantin and marked abdominal distension was reduced by tem porarily stopping the in flox Another lasage was performed later Diureais Bet in and the urine Volume slowly increased lle believe that a more serious praemii was presented from developing in this man bs peritoneal livage Patient B 118 5! 4 tiny littl girl of 9 sud to have been ! for 3 weeks *18 admitted with very pronounced uraemia Bloo 1 uren 550 mg per 100 cc alkalı resine 2014 rols haemoglobin P blood pressure 105/70 She was dehydrated irritat le psychotic sleepy and very cyanosed lasages have been necessiry and the question now arice, how long It will be posait le to continue with them') Indictions for peritoneul lavage It is still very difficult to give the indications for treatment with peritoncıl lavage It should be considered in every case of acute uracmia that might otherwise end fatally in chronic nephritis at most an extension of the patients life can be at ained The rulare therapeutic values of peritoncal lavage and the ruficial kidney cannot yet be assessed FRANK SFLICHIV and FIVE state that the rate of urca clearance obtuned with peritoneal lavage is in the region of 15 cc per minute with the artificial kidney it is certainly more than 100 cc per minute Peritoneal lavage is a more length operation which in itself entails many disadvantages on the other hind the artificial kidnes requires a more complicited apparatus Note at the correction She de after a corolt on extremely contractel caleil ed kidneys were found at the post mortem \lu have done 20 pentoneal lavazcy in 13 ratierts now of bich trensere Kelty ·MBq gy.ight ponte edhe arif pendente LT IG linger JKIL 14 3654 € ne .. N DOO Sad TIN! + +++ y Toys .* Harenbe W= . Lun 11 11 26 27 y. setentas Ortoder FI 56 Pat B Girl ot 9, presumably with chronic nephritis Temporanly kept alıse by peritoneal lavage Maximum 24 hour urca excretion in the urine was 25 % It was not always possible to collect the blood specimens esther immediately before, or immediately after lavage so that the salues are not strictly comparable one to the other Moreover the girl's welght fluct. uated considerably, first dehydration then oedema ·PBRITONEAL LAYAGE 90 Peritoneal lavage Artificial kidney + Danger of haemorrhages Contraindications Recent abdominal operations Irfection of abdomlaa! wall or skin Serious colitis Severe abdominal symptomg eg meteorism not wacommon in uraemia Old adhesive peritonitis Haemorrhages Dangers. Infection + + + Gut perforation Gut Invagination Haemorrhage Shock Pulmonary oedema Peritonitis Never seen Dog and patient of Frank et al Possible and observed, More likely with trochar than with surgical introduction of catheters Described in dogs Possible due to heparin Blood transfusions effect ivc Possible and observed Likely Can be treated Can be treated Possible and observed Possible and observed Aggravated by raised Treatment very citecture diaphragm Indeed patients may have Sometimes due to absorp- previously existing pul tion from pe itoneum monary oedema removed with reduced oulflow by treatment by arti difficult to combat, try ficial kidney Increased glucose in finsing fluid Possible, not scrious May be very serious Occasionally severe Apart from possible abdominal pain with rigors, nonc colic May fect very distended with somiting Frequently na discomfort! Rigors Discomforts. * 3

·-
LITERATURE PERITONEAL LAVAGE.
WEGNER, Arch / hlin Chur, p 64, 1877
GANTER, Alunchen Alun Wschr, 70, II, p 1478 1923
PUTNAM, Am J of Phys, 63, p 548 1923
ROSENAK and SIWON, Mitt Ⓡd Grenzgeb d Med u Chir, 39, P 391,
1926
HEUSSER and WERDER Beitr z hlin Chir , 141, p 38, 1927
VON JENEY, 2 scht f klin Med, 122, p 294, 1932
ROSENAK and BALASZ, Wien klin w schr , 47 851, 1934
WEAR, SISK and TRINKLE J of Urol, 39, p 53, 1938
RHOADS, Am J of the Med Sc, 196, p 642, 1938
ABBOTT and SHEA, Am J of the Med Sc, p 312, 1916
FORMIJNE, Ned Tijdschr v Geneesk , 90, p 1184, 1946
FRANK, SELIGMAN and FINE J Am Med 488 , 130, P 703, 1946
LANDSBERGER and GROINSKI, Compt rend Soc de Biol 93, p 787, 1925
SELIGMAN, A M, HA FRANK en J FINE, Treatment of experimental
rremia by means of peritoneal irrigation J of Clin Invest. 25,
p 211, 1946

·PART III. 1RE ATVENT OF SFRIOUS CHRONIC URAEVI I BY PFRFUSION OF AN ISOLATED INTESTINAL LOOP This work has been performed with the issistance of N KM de Leeuw It has already been indicated in chapter I that the treatment (uraemia by induced diarrhoea has rightly or wrongly been generally abandoned in 1941 Dr GROEN reintroduced this therapy in Amsterdam PENDLETON has done experimental work with dogs he tred the gut at different levels forming pouches into which he injected various solutions within a short time equilibrium was reached between the urea concentration of the blood and of the Ouid in the gut loops Lit scep 90 During the war I heard of work in Poland using isolated intes tinal loops in humans for dialysing I do not know the name of the responsible worker nor of any literature dealing with his attempts LANDSCERGER used the colon of animals making a appen dicostomy Lit see p 100 SELIGMAN FRANK and FINE have compared the results of dia lysing different sections of gut in dogs A constant length of 10 inches of jejunum and duodenum the alcum was slightly less and the colon much less satisfactory The clearance with a ten inch jejunal loop was about 10% of the normal kidney function A single attempt in a human subject using the terminal part of the Ilcum gave unsatisfactory results Lit see p 100 If the figurcs obtained with dogs are correct it would scem that it must be possible by using a longer loop of gut, to maintain dogs in urea balance by dialysis alone although the body level of urea will be higher than normal The unfavourable results of HESSEL, PEKELIS and MELTZER should therefore not cause us to abandon the possibility of this form of theraps Onn Frpenments ! Color lacage through an appendix fistula In two patients with severe hypertension, contracted kidneys uraemia and persistent somating an appendix fistula s as surgically Induced Apart from the immediate object this allowed an easy ·102 TREATMENT OF SENIOUS CHRONIC VRAEMIA replacement of the water and electrolytes lost by the vomiting with a resultant improvement in the general condition In the first patient the thin faeces caused by the perfusion leaked through the anus and further lavage seemed inadvisable The urca con centration in the escaping perfusate was 38 mg per 100 cc as com pared with a blood urea of 127 mg In the second patient the lavage was technically more satisfactory, as the sphincter anı had suf ficient tone to close the thick rubber tube placed in the rectum so preventing the escape of the perfusate Although the blood urea was 300 mg per 100 cc the concentration in the perfusate was only 10 mg % Colonic lavage seems of little practical importance as a method of dialysis II Lavage through an isolated loop of kleum Technique A length of small intestine is cut transversely at both ends leaving the blood supply intact and the ends are sutured into the abdominal wall The continuity of the remaining intestine is restored by end to end anastomosis We used one meter of the terminal aleum for the isolated loop but we shall in future take a greater length The ninsing fluid coming from the reservoir is led to the proximal end of the intestinal loop passing through a drip and a thermostatically controlled bath to bring it up to body temperature similar to the arrangement shown for peritoneal lavage The rubber tube between the warming bath and the gut opening must be insulated to prevent heat loss Regurgitation from the gut loop due to antı peristalsis may occur and therefore the inlet opening should also be included in the outflow cup Case HM 9831 (Fig 57) A man of 53 who had spent many years in the tropics had felt tired for two years six months before admis sion his symptoms became worse and albumen was found in his urine Despite a low protein and salt diet he steadily grew worse his vision became poor he suffered from insomnia and had vomited increasingly during the last four months Attacks of anginal pain sometimes very severe developed a few weeks before admission as well as nocturnal dyspnoea Muscular twitching and intense pruritus were also present #orn/105 and marked e liver was own to the hages were occasional cell the SG varied between 1005 and 1013 Exophthalmos and a basal metabolism of +20 to 50% suggested hyperthyroidism Thiouracil had no effect On x ray the heart was ·Opera 193 urs blood 121 27 METAL o Du wa w outflow V E diellit THI 77 . V. I 18 37 foutrendi ilcontory with the island terminal meter of the ele um was performed 11973 terhy ? Duit tos at ringle Ing through ite ileal loop was $ 370, und she let urca YPY 17. pin 19 heure It rasant poreil in to ve a gradual rise in the blonuna ·TREATMENT OF SERIOUS CHRONIC URAEMIA en to be enormously enlarged in both directions with bilateral pul onary congestion The changes in the blood ure can be seen in the accompanying "aph Chlorides and alkalıresere were within normal limits Hb 53 Diagnosis Malignant hypertension with contracted kidneys Uraemia d heart failure The functional capacity of the kidneys under optimal conditions was timated The body could be kept in ure, balance with a daily urinars itput of slightly less than 10 g of urea 1) The increased fluid intake quired for this however led to a deterioration of his general con tion Apart from the difficulty of administering sufficient fluid to vomiting patient the sudden onset of an acute psychosis decided us to tervene At our request an operation was performed on the patient by I LEHRER on 28/5/46 A double ended ileostomy with the isolated rminal meter of the sleum was performed the continuity of the rem ning gut being restored by end to end anastomosis Palpation of the dneys during the operation found them both very small and con acted Unfortunately a subcutaneous infection round the wound started st operatively and was only arrested by penicillin The concentric arring of the operation wound later resulted in contraction of the sto ata making perfusion of the loop exceedingly difficult This and some urther minor complications such as a boil over the sacrum prevented from doing lavage as regularly as we had hoped Frequently we had rest content with introducing 1 litre of fluid (with which it was sgible to replace the salt and water loss of the continuously vomiting trent) The largest quantity of fluid perfused at a single lavage through the I al loop was 8 litres and the best urea recovery was 5 g in 10 hours It was not possible to prevent a gradual rise in the blood ures His cardiac condition He was so eager to re e necessary apparatus ife who nursed him w Commentary 1 In graph 2 (fig 58) it can be seen that the urea concentration in the perfusate varies inversely with the speed of flow In a very slow running lavage that is when the return flow is very small the perfusion fluid may contain more than 200 mg urea 2 It will be seen from fig 59 that with a perfusion rate of 1 litre per hour the very good urea excretion rate of 0 48 g per hour is obtained. It presumably does not offer any advantage to perfuse faster The addition of MgSO4 to the perfusate may account for the excellent results of the dialysis on this occasion Had this patient been perfused during the whole twenty four hours he would have been maintained in urea balance The lavage 11 gram urea per diem Patients can remain h a daily output of between 1 and 3 grams tron At present we 1 ould have tred to reduce th s on P 108

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·106 TREATMENT OF SERIOUS CHRONIC URAEMLA 3 No diarrhoea or absorption abnormalities occurred that could be ascribed to the removal of a metre of ileum 4 Occasionally spasm and oedema of the stomata occurred, the outflow was checked, resulting in severe abdominal cramps It proved essential to start perfusion very slowly These cramps of the stoma could sometimes be reueved by inserting the little finger Urea removed in to hours tleum lavage gram urea s 4,8 4,0 4,0 3 2,9 2,6 2,7 ! O 124 flow %4 4 2 L/hour Fig 59 These figures are calculated for a dialysis of ten hours It was not always possible to carry out dialysis for the whole of this time 5 The perfusion fluid was the same as the bath-water in the artificial kidney, 1 e Naci 0,6 g %, NaHCO3 0,2 g %, KCI 0,04 g %. glucose 1,5 g % This, however, resulted in a calcium deficiency 12-6-46 Perfusion fluid before dialysis (1,3 11 mg % Calcium 3,2 mg % 05 23 after 13,3 Later 28 mg o CaCl, was added to the perfusion fluid 46 Perfusion fluid before dialysis (8,3 19,3 mg % Calcium after 8 88 mg % $ 33 ·TREATMENT OF SERIOUS CHRONIC URAESTA The perfusate flowing out of the gut did not have any irritating dfect on the surrounding skin The isolated gut loop lavage is still in the carliest experimental stages it is far too soon to predict that those hopeless cases of chronic nephritis may perhaps be brought to lead useful lives In the daytime they would work, and at night they would keep their leal lavage going ·PART IV. TREATMENT OF URAEMIA WITH HIGH CALORIC LOW PROTEIN DIETS I has been argued that at least 45 grams of protein is needed laintain protein equilibrium in man This figure however has other basis than the 7 gr of nitrogen excreted per day, by sle who are fasting and represents only the bodies effort to tits caloric requirements by breaking down its own protein I MPNER) J GG BORST in Amsterdam 1) and WALTER KEMP from Durham USA ) proved that if a patient is given high ric low protein diet that then after some time the body spares protein and the body protein consumption becomes so small ! the urea excretion in the urine falls to 1–3 gr per day! ISEMPNER gave a ricediet to a large number of patients suffering "1 hypertensive vascular disease and chronic nephritis He gve tal of 2000 calories This gives about 5 gr of fat and 20 gr of ein not more than 02 gr of chloride and 0 15 gr of sodium I' 'IPNER is afraid of fat as he thinks that injured kidney cells the ability to oxydıse keto acids KEMPNERS results are far 1 or than would have been possible with any other form of treat it > far our own experience although small seems to confirm this. BORST forces patients with severe uraemia to eat 200 gr of butter and 200 gr of sugar daily He is careful to see that if they vomit the lost quantity of butter and sugar is replaced The butter and sugar is served in the form of small balls from a refrigerator or is made into a kind of creamy soup by adding + 12 gram of flour and coffee Provided that the patients do not get diarrhoea and do not get too much meteorism the results are remarkable We have confirmed the fact that the urinary urea falls to 1 or 2 gr per day Thus it would be possible for a patient to have a complete anuria for 25 days or more, without contracting a serious uraemia 1 cture for the Algemene Ziektekundige vereniging Dec 1946 rth Carolina Medical Journal, February 1945, fol 6, no 2, and Bulle he New York Academy of Medicine July 1946 second series tol 22 358 370 ·DR. ROBERT HEILI