Acid-base balance during and after cardiopulmonary bypass procedures

Acid-Base

Balance

Cardiopulmonary

During

and After

Bypass Procedures* A. CLOWES, JR., M.D

Charleston,

Carolina

T

and a heat exchanger all connected with tubing are necessities to accomplish the procedure. Usually, a sucker is also required. Any or all of these components are capable of variousl\, irrjuring blood in its passage through them.?,:’

HE SAFE conduct of a patient through a cardiac operation dependent upon the extracorporeal maintenance of circulation and respiration requires an exact understanding of the metabolic consequences of the procedure in its entirety and to assess and correct such abnormalities as may occur. The postoperative metabolic state is the cummulative result not only of the perfusion itself but of the patient’s preoperative condition, the adequacy of the cardiac repair and the ability of the circulation and lungs to respond to the postoperative demands.’ In contrast to the biochemical homeostasis of the adequate perfusion are the disorders arising from one which is inadequate. These include (a) a state of metabolic “hypoxic caused acidosis,” (b) the effects of hypocapnia by excess removal of carbon dioxide from the blood by the oxygenator and (c) the abnormal postoperative response of the brain, the lungs and the cardiovascular system. Simply stated, the metabolic derangements and injuries initself are almost flicted by “total perfusion” entirely related to inadequate supply of oxygen to tissues and damage to blood elements. The latter includes destruction of cells, protein denaturation, reduction of clotting factors 1,). intravascular clotting, and embolization. Space does not permit discussion of the variety. of apparatus developed to perfuse artificiallythe entire body of man. The advantages and shortcomings of the devices will become apparent as the problems of perfusion are reviewed. Suffice it to state that, dependent upon the use of heparin for the prevention of clotting, venous blood is drawn from the right heart or venae aerated to exchange carbon dioxide cavae, and oxygen, heated or cooled, and returned under pressure to the systemic arterial tree. Cannulas, an oxygenator, one or more pumps

OXYGEN

SUPPLY AND ACIDOSIS

“Hypoxic acidosis,” engendered as it is byan insufficient delivery of oxygen to the tissues secondary to poor oxygenation of blood or to an insufficient perfusion rate, is manifested by the release of the acids of anaerobic metabolism. The intracellular and extracellular buffer systems become saturated. Although the hydrogen ion concentration may remain relatively normal during an inadequate perfusion by a severe reduction of the blood carbon dioxide content, a serious state of uncompensated metabolic acidosis may take place when the arterial pCO2 returns to normal upon restoration of normal respiratory control. For this reason, measurements of the reduction of buffer base or the increase of lactic acid concentration are better indexes of acidosis than mere recording of the arterial blood PH.~ Metabolic Acidosis: The degree of metabolic acidosis, or the increase of so-called “fixed acids” in the blood relative to the cation concentration, is inversely related to the factors affecting availability of oxygen to the tissues. During normothermic or hypothermic perfusions at various tlow rates in man, oxygen consumption and the ultimate deficit of buffer base bear an inverse proportion to each other.” This confirms experimental data obtained by Paneth” in dogs. Thus, “hypoxic acidosis” is contributed to by an extracellular increase of lactate, pyruvate and inorganic phosphate. Root’s careful work on hypovolemic shock in dogs disclosed a similar pattern following periods of low cardiac output.’

* From the Department of Surgery, Medical College of South Carolina, Charleston, S. C. NOVEMBER1963

671

672

Clowes

Experimental data” indicate that the oxygen consumption by the whole bodb- is about onehalf the basal normothermic value when the perfusion rate is 30 cc.,/kg. body \vt. min. and rises to 80 per cent when the rate is 100 cc. ,‘kg. body wt., min. At temperatures of 30” c. and 20” c:. there is a proportional decrease in oxygen used ; but to attain maximal oxygen uptake even at these temperatures. high flow rates are required. Only when the body temperature is reduced to 10” C. can a maximal consumption he attained at a flow rate of Although the 60 ct./kg. body wt.,/min. oxygen requirement at 10” c. is but 10 per cent of the basal normothermic value. a moderately high perfusion rate (60 cc., ‘kg. body wt., min.) is still required to satisfy the needs of the entire organism. Schwartz et a1.g have demonstrated a decrease in oxygen tension at 37’ c. in the skeletal muscles and viscera of dogs kvhen the perfusion rate is below SO cc. kg. body wt. 1 min. Failure to supply tissues throughout the body with the full measure of oxygen required to maintain aerobic carbohydrate metabolism leads to anaerobic glycolysis for the necessar) production of energy. This is manifested b) the release of lactate and pyru\;ic acid from the cells. Huckabee’” expresses the osidative potential of the cell by the formula :

Since the lactate and pyruvate arc freel>- diffusible, the concentrations of these substances in extracellular water quite accurately reThus, the flect the intracellular situation. expression “excess lactate” or that amount of lactate present above the normal ratio has been employed as a measure of the degree of anaerobic metabolism qoing on at a - wt./min., 60 per cent mortality; 60 ct./kg. body wt.,” min., 40 per cent mortality; 90 to 100 cc.,‘kg. Subbody wt./min., 20 per cent mortality. sequent data obtained both in animals and man suggest that it is not the alteration of hydrogen ion concentration which severely affects the circulation, but rather, the metabolic deficiencies manifested by the metabolic acidosis. Patients who have undergone a period of severe metabolic acidosis are prone to exhibit a

lo\\- cardiac output for periods of 24 hours or more thereafter. This is not due entirely to impaired cardiac function, for the venous pressure is apt to he low even when the blood \rolume is normai. Work b>, Ankeneylz suggests that in dogs a Treater volume of blood is required adequately, to fill the \renous system after perfusion, although Litwak et al.‘” report that in patients there is usually a deficit in the blood volume after perfusion. It appears that the \.ascular responsiveness to catecholamines is reduced as is their capacity to increase venous return b>. venous constriction. Or possiblythis is related to splanchnic trapping of blood by mechanisms such as the liver venous sphincters which are known to exist in dogs and certain other animals.‘-’ Since the extent of oxygen extraction from the blood is proportional to tissue oxygen tension, the excess lactate present during a perfusion, as might be expected, is proportional to the mixed venous oxygen content.‘” Although removal of lactate from the blood by the liver is possible up to a given rate, this is dependent upon its oxygen supply. _4ndersen, Norberr: impaired liver and Senning Ifi,I7 demonstrated function in various ways during perfusion in animals. No doubt a reduction of lactate metabolism in the liver also takes place. The inorganic phosphate concentration of the plasma is known to increase in states of hypoxia or hypercapnia amounting to between 3 and 10 mg.,‘lOO ml.‘” This is true also in perfusions at low flow rates. This is in conformity with the findings during low cardiac output in shock.lg Probably hyperphosphatemia reflects saturation of the intracellular phosphate buffers and the breakdown of high energy phosphate bonds during periods of inadequate production of energy in the absence of an adequate supply of oxygen. Moderate increases of the extracellular chloride may take place during perfusion, and this phenornenon is more pronounced at low flow rates. Litwin et al.‘” observed values of 114 to 120 mEq./‘L. after perfusion, a situation similar to that found in respiratory alkalosis. The intracellular space becomes proportionately more acid than the extracellular fluids. Compensation probably is accomplished by a shift of anions (chloride and phosphate) out of the cells and cations into them. Furthermore, he has demonstrated both experimentally and in man that pretreatment with amonium chloride, sometimes used in the therapy of heart failure, THE AMERICAN

JOURNA’.

OF CARDIOI.OGY

;&id-Base

Balance

During

anal- seriously reduce the extracellular bufferhase value by increasing the extracellular chloride Thus, the postoperative acidotic concentration. In untreated situation may be made worse. patients he found the bicarbonate reduced to 17 mEq./L. at a pH of 7.35, while those given NH,Cl preoperatively had, on the average, but 10 mEq./L. of bicarbonate at a pH of 7.28 in the arterial blood. Bizarre patterns of acidEJects of Hypothermia: base balance may occur when hypothermia is employed in conjunction with perfusion. The metabolic acidosis becomes apparent especially if circulatory during rewarming, arrest has been instituted during the period of As was pointed out earlier, hypothermia.20~21 oxygen consumption of the entire body is Yet to reduced as the temperature falls. attain maximal oxygen uptake by the organism, hlood flow rates often as high as those employed during normothermic perfusions are required to avoid an oxygen debt and lactacidemia.R Because the visceral organs with large blood flows are cooled first, muscles and other tissues may maintain metabolic rates nearer to normal,“” If the perfusion is reduced or temporarily discontinued for any reason, a serious state of acidosis ma). supervene. Whole blood becomes more viscous as it is cooled, 155 per cent of normal at 15” c.21 Greer, Carey and Zuhdi,23 following the original suggestion of Gollan, have found that during moderate degrees of hypothermia (25” to 30” C. body temperatures) adequate oxygen can be furnished to the tissues by perfusions in which 5% dextrosr in water was used to prime the oxygenator. In their experience a dilution of the blood by 25 per cent did not result in any metabolic acidosis even at low flow rates. This concept has been extended more recently to greater dilutions with higher flow rates. In the author’s experience the degree of acidosis at any flow rate at or near normothermia is greater than when whoIe blood is used for priming. It is possible that by the reduction of viscosity a more satisfactory perfusion actually can be obtained by this method during profound hypothermia. THE EFFECTS OF BLOOD DAMAGE Severely traumatized blood has a variety of vasomotor and vasodilator reactions which influence the behavior of the circulation. This is true during perfusion in that blood appears to be trapped in the venous system when there NOVEMBER 1963

Cardiopulmonary

Bypass

67.7

More importantly, celis marked hemolysis. lular aggregation similar to that described in shock by GelirP4 has been found during perfusion. This led Long et a1.25 to advocate the use of low molecular weight dextran to prevent and the metabolic effects of tissue damage capillary blockage and inadequate tissue ox!genation when a bubble oxygenator is emThis has not been found necessary b)ployed. the majority of surgeons in this country. RPdwtion of clotting elements and of the platelets appears to go on within the vascular system and the extracorporeal apparatus particularly when inadequate heparin has been administered.“” Not only does this result in postoperative bleeding problems, but actual thrombi found in the oxygenator may wash out to lodge in the patients blood. These tendencies have been reduced bp an understanding of the surface phenomena and the avoidance of eddies. Lee et al.” bl; careful analysis of the protein chaliges caused by extracorporeal cardiopulmonary bypass have come to the conclusion that blood damage is caused by electric orientation and breakdown of protein molecules at an interface. Lipids are released from the lipoproteins. Among the oxygenators commonly employed, the)- found that the bubbles with their shearing action and large blood gas interface are the most traumatic in this respect while the membrane type produces the least protein alterations. The importance of these phenomena is brought out by the lipid accumulations in the brain observed by Adams et a1.27 after perfusions, and by the vasculitis of the lung described by Kontaxis et a1.28 Bjorkzget al. have pointed up the dangers to the brain and subsequent cerebral function caused by vascular occlusion with aggregates of blood. POSTPERFUSION METABOLIC

ABNORMALITIES

Correction of the acidosis and the other metabolic defects caused by perfusion and a cardiac operation is dependent upon the function of the respiratory and circulatory systems, both of which are directly controlled by activity of the nervous system. Serious brain injury with reduction of respiratory responsiveness may follow prolonged elevation of the pressure in the superior vena cava to levels above 20 cm. HzO. Severe acidosis and carbon dioxide accumulation also reduce cerebral activity and can result in a vicious circle of progressive respiratory acidosis and hypoxia. The auto-

674 nomic ner\.es and the endocrine glands influence and support the circulation during periods of serious derangements of the milieu interne. Subsequently, the kidneys become important in the final adjustment of electrolytes and water balance. CARDIAC FUNCTION

Low Outbut Syndrome: Work by the author and his associates30,3’ has delineated the usual circulatory behavior following surgery. As the patient regains consciousness accompanied by pain, coughing and muscular movements the cardiac output usually rises to values over twice that observed preoperatively under basal conditions. Normally, the blood catecholamine concentration is at the highest at this time. Yet in patients who have been rendered hypothermic, the usual stimuli do not evoke this reaction, and the cardiac output may remain low unless a very small dose of adrenalin is administered. Subsequently, as the patient the cardiac output returns becomes quiet, nearer to the basal level, but remains somewhat above it for a period of 10 days or until healing is completed. In the presence of inflammatory reactions or respiratory inadequacy, a. much greater demand may be made upon the circulation. If the cardiac output fails to meet these ordinary requirements, a state of compensated metabolic acidosis develops, similar but of a lesser degree to that observed in shock. This has come to be known as the “low output Under these conditions Boyd et syndrome.” al.“* demonstrated in man a greater extraction of oxygen from the circulating blood and a decrease in the mixed venous oxygen content. If the respiratory function is inadequate to maintain the ratio of carbonic acid to bicarbonate at or near the normal value of 1 to 20, a fatal uncompensated acidosis rapidly superlzenes. has shown that a complete Experience functional repair of a valvular disorder, septal defect or other abnormality is essential to avoid the problems of the “low output syndrome.” Also, damage to the myocardium either prior to or during the operation may be responsible for serious derangements of cardiac function. In the majority of instances, the operative damage is related to interference with coronary flow either by gaseous or particulate emboli or by intentional cessation of coronary perfusion by occlusion of the aorta and Gott et a1.33 and others34 have “anoxic arrest.”

shown that the concentrations of glycogen and high-energy phosphates (actomyosin, adenosinc triosphosphate, etc.) are seriously reduced in the myocardium during short periods of This ischemia under normothermic conditions. is accompanied by a subsequent reduction of myocardial contractile force on restoration of coronary circulation and subsequent heart failure. Haldane stated that lack of oxygen not only interferes with the system, it wrecks it. Various degrees of hypothermia accompanying cardiac ischemia proportionately prolong the length of time it can be tolerated without serious About 40 metabolic or morphologic changes. minutes at 15 o c. seems to be the safe limit. Distention of a ventricle during fibrillation or arrest is known to cause a state resembling rigor mortis during hypothermia and if not carried to this extent may result in subsequent heart failure. The cause for this is not understood, but it may well be related to disruption of the myofibrils and the mitochondria which lie in close association with them and which may be responsible for supply of energy to them by the oxidative phosphorylation system.35 PULMONARY

FUNCTION

.4s previosly mentioned, the patient’s biochemical status in the postperfusion period, particularly in relation to oxygen supply and the bicarbonate buffer system, is greatly influenced by the respiratory system: pulmonary and central nervous activity. Schramel et al.“” have demonstrated a decrease in the oxygen and carbon monoxide diffusion capacity in the lungs of patients who have undergone perfusion; it is more than three times as great as that encountered following other types of is probably related to the surgery. This vasculitis previously mentioned.21 It is of interest in this connection that dogs perfused for several hours, even on a partial bypass, usually die of pulmonary insufficiency. With the membrane type of oxygenator which Lee et aL2 showed to produce the least denaturation of blood proteins and the least breakdown of lipoproteins, the longest successful dog perfusions could be carried auf with survival. Pulmonary wnous hypertension during perfusion has also been recognized as another cause of the so-called “postperfusion lung.” As shown by Kolff and his associates, a number of factors necessitate venting of the left atrium or the pulmonary artery at all times to avoid damage which may result in edem&ous lungs incapable -rm

AMERICAN

~ouRNALOF O.~RDI~L~OY

Acid-Base

Balance

lhring

of adequate gas exchange following open cardiac procedures. When such a situation occurs, desaturated arterial blood is pumped through the arterial trees, and a much greater demand for circulation is established in all tissues to satisfy their oxygen needs and to avoid a metabolic acidosis. A cardiovascular system capahlc of meeting continuous demands for two or three times the normal basal output can compensate for such a situation; but ordinaril) if the condition is not corrected within a reasonable time, overwhelming acidosis and Infection and circulatory failure take place. pulmonary inflammation may add to this The means at hand for remedyvicious cycle. ing the situation are the use of adequate respirato:,s, respiratory gas mixtures containing high concentrations of oxygen, removal 01 bronchial secretions. and the use of corticoids 10 limit the inflammatory reaction. The respirator, usually employed with a cuffed tracheostomy tube? not only can more fully aerate the alveoli, but limits or removes the extra metabolic demands of respiratory work.Yi This in turn reduces the need for extra cardiac output and increases the arterial blood oxygen tension. The administration of corticoids is not to be undertaken lightly, because of the inherent dangers of adrenal suppression, but it ma)- be lifesaving. Inflammation is reduced with an improvement of gaseous exchange. In our experience, within two hours the oxygen tension of arterial blood has been found to At rise from 40 mm. Hg to over 80 mm. Hg. the same time, evidence suggests that an increased blood concentration of glucocorticoids ma); aid the cardiovascular system to mret unusual demands under adverse circumstances of acidosis and hypoxia .31 However, this therap)must never he employed routinely. WATER

BALANCE

AND

RENAL FLJNCTIOK

Renal plasma flow and glomerular filtration correlate well with perfusion rate and blood pressure during the extracorporeal maintenance of circulation. Clinical observations by Morris ct al.“x lead to the conclusion that perfusion flow rates of not less than 35 cc./kg./min. must t)e employed if renal function is to be present during the procedure. Studies of oxygen tension of renal parenchyma indicate that it remains surprisingly near normal even when the pumping rate is very low. This may- account for the surprisingly low incidence of renal shurclown (374) despite the presence of free

Cardiopulmonary

Bypass

075

hemoglobin values as high as 400 rng.7; in the circulating blood after certain prolong-ed perfusions in which the blood has been damaged.39 Ordinarily, with higher flow rates the urine production is sufficient to prevent the situation Clinical resembling lower nephron nephrosis. experience has shown that it is most likely to occur when inadequate cardiac output in tht postoperati\,e period results in the “low output accompanied I)) hypotension with syndrome” marked \.asoconstriction throughout the body. some degree of oliguria is not However, unusual in the early postoperative period; this is probably related to the continuing production of antidiuretic hormone. This has led Sturtz and his associates”” to limit the bvater intake to that of obligatory losses during the The author first few days to avoid overloading. has found that urine output is adequate without gain or loss of weight by limitin,? water intake per day to 1200 cc. ‘M?. surface area. provided blood loss I))- drainage tube is full! replaced.

SUM~IAR\The metabolic problems associated with perfusion of the body with an extracorporeal and oxygenator have been briefly pump reviewed. They are primarily related to the tissue injuries inflicted by inadequate deli\,er) of oxygen to the tissues and by trauma to various elements in the blood. Postoperaof normal conditions is tively-, maintenance adequate function of the dependent upon central nervous system, the lungs and the cardiovascular system. REFERENCES 1. C:LOWES.G. H. A.. JR.

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Extracorporeal maintrnance of circulation and respiration. Phvsiol. J&o., 40: 826 1960. 1.m. W. H et al. Comparison of the effwts of membrane and nonmembrane oxygenators on the biochemical and biophysical characteristics ofblood. S. /jorum, 12: 200, 1961. OSBORN, J. J. ct al. Hemolysis during: perfusion. Sources and means of reduction. .1. Thororic t?Y Cardiouas. Stq., 43: 459. 1962. DEWALL, R. A. et al. Total body perfusion fol open cardiotomy utilizing the bubble oxygrnator. .J. Thoracic Swg., 32: 591, 1956. CLOWES~ G. H. A., JR., NEVILLE, W. I<.. SABGA. G. and SHIBOTA, Y. The relationship of oxygen consumption, perfusion rate, and temperature associated with cardiopulmonary circulator> bypass. Sqery, 44: 220, 1958. P.ANETH, M. R. et al. Physiologic studies upon prolonged cardiopulmonary bypass with the pump oxygenator with particular reference to:

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low-flow pump oxygenator. Surg. Gynec. @ Obst., 107: 339, 1958. GREER, A. E., CAREY, .J. M. and ZUHDI, N. Hemodilution principle of hypothermic perfusion, a concept obviating blood priming. J. Thorn& & Cardiovas. Swg., 43 : 640, 1962. GELIN, L. E. Studies in anemia of injury. Actu chir. scandinav., suppl. 210, 1956. LONG, D. M., JR.: SANCHEZ, L, VARCO, R. L. and LILLEHEI, C. W. The use of low molecular weight dextran and serum albumin as plasma expanders in extracorporeal circulation. Sur.qery, 50: 12, 1961. WRIGHT, T. A., DARTE, J. M. and MUSTARD. W. T. Apparent increase in blood prothrombin during extracoporeal bypass and during slow coagulation in siliconed containers. Lam& I: 1157,195s. .ADAMS, J. E. et al. Experimental evaluation of pluronic F68 (a nondetergent) as a method of diminishing fat emboli resulting from prolonged cardiopulmonary bypass. S. Forum, 10: 585, 1960. KONTAXIS, A., TOMIN, R., WITTLES, B., NEVII.~.~, W. E. and CLOWES, G. H. A., JR. Pulmonary to prolonged perfusion. changes secondary S. Forum, 12: 52, 1961. B;ORK, V. 0. and HOLMADAHL, M. H. ‘l’he oxygen consumption in man under deep hypothermia and the safe period of circulatory arrest. J. Thoracic @ Cardiovas. Swg., 42: 392, 1961. CLOVES, G. H. A., JR., DEL GUERCIO, L. R. M. and BARWINSKY, J. The cardiac output in response to surgical trauma: a comparison between patients who survived and those who died. Arch. SWQ.. 81 : 212, 1960. CLOWES, G. H. A., .JR. et al. Results of open surgical correction of mitral valvular insufficiency and description of technique for approach from the left side. Surgery, 51: 138, 1962. R. E., SPENCER, F. C. BoYD, A. D., TREMBLAY, and BAHNSON, H. T. Estimation of cardiac output soon after intracardiac surgery with cardiopulmonary bypass. Ann. Surg., 150: 613, 1959. GOTT. V. L., BARTLETT, M., JOHNSON, J. t\., LONO, D. M. and LILLEHEI, C. W. High energy phosphate levels in the human heart during potassium citrate arrest and selective hypothermic arrest. S. f;orum, 10: 544, 1960. HIRSCH, H. and WERNITSCH, LV. Energy metabolism in circulatory arrest. In: L’Hypothermie Profondc en Chirurgie Cardiaque et Extra-Cardiaquc. L’Expansion Editor. p. 215. Paris, 1961. MILLER, D. R., RASMUSSEN, P., KLIONSKY, R.: COSSMAN, F. P. and ALBRITTEN, F. F., .JR. Elective cardiac arrest; its effect on myocardial Ann. Surg., 154: 751, structure and function. 1961. SCHRAMEL. R., CHAPMAN, W., WEIFFENBACII, I:. and CREGCH, O., JR. Treatment of respiratory insufficiency by prolonged extracorporeal cir./. Thoracic G? Cardiouas. Surg., 42: culation. 804, 1961. The cost of respiratory effort in '~HUNG, N. et al. postoperative cardiac patients. Presented to the Am. Heart A. Meet., Oct., 1962. MORRIS, G. C., JR., WITT, R. R., COOLEY, D. .A, ‘THE

AMERICANJOURNAL OF CARDIOLO~:Y

.kid-Base MOYER,

in

renal

J. H. and DERAKEY, M. hemodynamics during

tracorporeal circulation of aortic aneurysms. 1357. 39.

DOBERNECK,

CL, KEISC:K,

Acute renal failure utilizing extracorporeal

NOVEMBER

1963

Balance

Thorn&

Cardiopulmonary

Bypass

077

1;. Alterations controlled cs-

in the surgical .f.

Jhring

treatment

Sur,~,, 34: 590.

M. P. and LIL.LE~X. C. \I’. after open-heart surger! circulation and total hod!

40.

G. S.. KIRKLIN, .I. \V., BuRK~c, E. CL and POIVER, M. H. Water metabolism after cardiac operations involving a Gibbon-type pump oxyyenerator. I. Daily water metabolism, obligatory \vater losses and requirements. Circulation. 16. ‘)8X. 1957.

S.I.C.RTZ.