Metabolic acidosis during profound hypothermia*

Transcription

1 VOL 19 NO ANESTHESIA JULY 1964 Metabolic acidosis during profound hypothermia* G.W. BURTON, BSc, MB, ChB, FFARCS Lecturer in Anssthetics University of Bristol During the past three years we have used profound hypothermia in cardiac surgery on ninety-four occasions, employing the technique described by Drew 1. After re-warming, our first sixteen cases showed an extreme degree of peripheral vasoconstriction. There was a delay in the recovery of consciousness; one patient was unconscious for a period of five days and another for two days. In five cases this condition was associated with epileptiform convulsions and in two cases with renal suppression. Six cases had a fatal outcome and in only five out of the sixteen was there a reasonably uneventful recovery. It is likely that this condition is related to that which has been described by Brooks21, in which a state of metabolic acidosis was found to develop during cardiac bypass and persist into the postoperative period. This condition has been treated and sometimes prevented by the administration of appropriate amounts of sodium bicarbonate. During one of our early cases, we attempted to measure the percentage of carbon dioxide in some end-expiratory gas samples, using a bicarbonate-indicator solution (prepared by the British Oxygen Company, Medical Division). The concentration was so low that, using this crude method, we could not detect the presence of any carbon dioxide. We therefore investigated the effect of an increase in the Pco 2 upon the clinical condition of these patients. This paper outlines some of our findings, later supplemented by other aspects of the changes in metabolic state associated with profound hypothermia. In common with other observers, we have found that at normal body temperatures, even the most enthusiastic hyperventilation is seldom able to reduce the arterial Pcoz below 15-20mm/Hg. 4,56 Where the production of carbon dioxide is normal, it is unlikely that serious harm may arise solely due to a low Pco 2. Although there will be a reduction in the cerebral blood flow, this may be adequately com- *Paper read at Annual Meeting of the Association of Aniesthetists at Harrogate

2 66 ANESTHESIA pensated by an increase in the proportion of oxygen removed from the perfusing blood7. During profound hypothermia, the metabolic rate and therefore the production of carbon dioxide, is reduced to only a small fraction of normal81 9. Under these conditions, if ventilation is maintained at a level which would be regarded as normal, at normal body temperatures, the tension of carbon dioxide will fall to only a few mm/hg. The combined effects of low temperature and low PCO~ reduces the availability of oxygen to the tissues In spite of the reduced oxygen requirements at low temperatures, this may prevent adequate compensation for the reduction in cerebral blood flow produced by a low Pco~. Similarly in other tissues one may expect an increase in the production of lactic and other organic acids, formed as a result of these extremely low tensions of carbon dioxides~6~ We therefore believe that it is dangerous to allow a profound fall both in the Pco2 and the temperature in any patient. We thought that the reduction in the PCO 2 might have contributed to the abnormal character of the electroencephalographic and clinical condition seen in our first sixteen cases. Therefore in the following nine cases, during the period of bypass, small but increasing amounts of carbon dioxide were added to the anzesthetic circuit. This produced an improvement both in the character of the electroencephalogram and the clinical condition of the patient. Although this suggested that the addition of carbon dioxide was beneficial, it did not give any indication of the optimum level at low temperatures. In vitro, provided that the Pco 2 is maintained constant, alterations in the temperature of a sample of blood are found to produce only slight changes in the ph The effects of the changes in the protein and inorganic buffering systems are found to cancel out those caused by a change in the solubility of carbon dioxide. With Sir Joseph Barcroft 17, we believe that it is unusual for a physiological phenomenon (or homeostatic mechanism) not to have significance in the body. We have, therefore, taken this lack of change in ph with temperature to indicate that the optimum conditions for the body, at all temperatures, may be a ph in the region of 7.4 and a Pco2 in the region of 40mm/Hg. In the remaining sixty-nine cases in our series, we have attempted to maintain the arterial Pcoz in the region of 40mm/Hg at all temperatures of the patient. We have used a high minute volume both to minimise the effects of the increase in physiological dead space produced by hypothermia 1 8, 1 9$20 and to allow easy control and measurement of the alveolar Pco 2. In most cases the lungs were inflated to a pressure of approximately 20cm/H 2O at a rate of 8-10 per minute. In the average adult this gave a minute volume of about ten litres. The carbon dioxide tension of the

3 ANESTHESIA 67 gas in the endotracheal tube was continuously monitored using an infra-red gas analyser (Ird-o--Meter, manufactured by Infra-Red Development Co). Using these high tidal volumes, we have found that the end-expiratory Pc02 has agreed fairly closely with the arterial level as determined by the Astrup interpolation technique, where the ph and Pcoz are measured at the oesophageal temperature of the patient The Pco2 was maintained in the region of 40mm/Hg by a variation in the proportion of the expired gas passed through the absorber, and when necessary, by the addition of carbon dioxide to the fresh gas supply to the system. During the period of cooling, we have found that an increasing amount of carbon dioxide must be added, up to a maximum of five per cent. During rewarming, only a small addition is required2. In these sixty-nine cases, we have not found the profound peripheral vasoconstriction which had previously been seen after rewarming. Instead the patients were usually warm, dry and pink. After operation these patients have rapidly regained consciousness and had a short duration of amnesia. Only one has shown postoperative convulsions ; this patient was thought to have had a cerebral embolus. There have been two cases with renal suppression; one of these had a high degree 20 C During Cooling 0v Curing Rewarming - Day. after Operatm f--% pc% Allowed to Fall During Cooling Figure 1 EEGs taken from similar patients, both having a repair of ASD. On the right, tracings show the typical spikiaess and slow wave activity seen in those cases in which the Pc02 was allowed to fall. On the left, tracings taken at similar points show the absence of this type of activity and rapid return to a normal EEG in those cases in which the Pcoz was maintained in the region of 40mmlHg.

4 68 ANESTHESIA of haemolysis (for an unknown reason) and the other was our only case which required two separate periods of hypothermia. Figure 1 shows a comparison of typical electroencephalograms taken on similar patients, both having a repair of ASD at a nasopharyngeal temperature of 15 C. In those cases in which the Pco2 was allowed to fall, it was usual to see this spikiness and the high voltage slow waves. This has not been seen in those cases in which the Pcoz has been maintained in the region of 40mm/Hg. Unfortunately we have no data on the acid-base state in the first twenty-five cases, in which the Pco2 was allowed to fall. In forty of the sixty-nine cases in whom the Pco2 has been maintained in the region of 40mm/Hg we have measured changes in acid-base state. In none of these, which it must be stressed, included even the worst operative risks, have we found any significant degree of metabolic acidosis to persist after the return to normal temperature. In the remaining twenty-nine cases in which the acid-base state was not moni- tored (apart from the end-expired Pco~), there has been no suggestion of any postoperative metabolic upset. id-/.4 P&C cxces, meqll meqll MI lmin 15- Base Excess 0 I I I / TIME Mins Figure 2 The changes in the metabolic state produced by the infusion of acidcitrate dextrose (ACD), either alonc or contained in preserved blood, at normal body temperatiires

5 ANESTHESIA 69 We have found a metabolic acidosis during the period of hypothermia, probably due to two factors: (a) the inability to metabolise the acid-citrate-dextrose in preserved blood. (b) the presence of lactic and other organic acids formed during periods of anoxia and abnormal tissue metabolism. Taking first the effects of the sodium acid citrate anticoagulant. At normal temperatures (figure 2), we have found that rapid administration of acid citrate alone, or that contained in preserved blood, produces a metabolic acidosis, or fall in base excess24, as measured by the change in position of the ph: log. Pc02 buffer line However, citrate is rapidly metabolised and removed from the circulation, freeing sodium ions; this produces a metabolic alkalosis. Profound hypothermia prevents the metabolism of citrate25.26, so that the metabolic acidosis produced by the acid citrate in the blood used to prime the pumps cannot be completely reversed until after the patient s temperature has risen again, as shown in figure. Figure 4 shows the changes in Pco~, carbon dioxide content (Tco~) and base excess in one of our cases. Apart from an initial in TIME Mins Figure Changes in the metabolic state produced by the infusion of preserved blood, followed immediately by the rapid cooling of the patient. The metabolism of ACD is delayed until the temperature has risen again.

6 70 ANESTHESIA 5- C / TIME Hours Figure 4 Changes with temperature in the levels of Pcoz, carbon dioxide content (Tco~) and base excess, found in a typical case of profound hypothermia. significant lapse in the maintenance of the Pco~, both the tension and plasma content of carbon dioxide have remained remarkably constant. There was a fall in base excess which was reversed as the temperature returned to normal. The concentration of pyruvate in the blood is related to the metabolic rate27. It may be seen from figure 5 that there was a fall in concentration of pyruvate coinciding with the period of hypothermia and reduced metabolism, but upon return to normal temperatures there was a marked rise associated with an increase in the metabolic rate. Excess lactate indicates an upset in the lactate : pyruvate ratio. At normal temperatures this indicates the presence of anoxic metabolism27. However, it is possible that at low temperatures other disturbances of cell metabolism may also affect the lactate : pyruvate ratio. We have found that the total concentration of lactate has risen progressively during bypass. During the period of hypothermia and arrest, a large part of this was excess lactate caused by abnormal metabolism or anoxia. However, on return to normal temperatures, the high lactate appears to be related to the high rate of metabolism, indicated by the high pyruvate concentration.

7 ANESTHESIA 71 meq IL PLASMA meqll BLOOO LOCLOtC' 0 T Pre Op Post-op Py""ote, >;=-% TIME Hours Figure 5 Changes with temperature in the levels of lactate, pyruvate and 'excess lactate' found in the same case as shown in figure 4. Tn finiirp C; thm rnntiniiniic line rpnracpnta tha magciirml XICAIIIPP nf 1.1 "6"" ", CllW V"IICI.IU"UU Ull" IwyLwUwIIC" CllW lll"ciulu"u.uiu"o "I base excess and the interrupted line, values corrected for the differences between the levels of total and 'excess lactate'. This indicates that during the phase of rapid metabolism associated with the return to normal temperature, it is likely that there is also a rapid correction of the metabolic acidosis which was caused by the period of arrest or abnormal tissue metabolism associated with hypothermia. It is interesting to note that in our series the thigh muscle temperature also rapidly returned to normal during this phase of increased metabolic rate (figure 7). In the curves published by other workers who allowed the Pcoz to fall excessively, there is a considerable delay in the return to normal of the thigh muscle temperaturez. It is possible that an extremely low tension of carbon dioxide may prevent the phase of increased metabolism and blood flow, which we have also found, so accounting for the persistence of the metabolic acidosis seen in some of their cases.

8 72 ANESTHESIA - -- I I 1 Prc-Op Post-op TIME Hours Figure 6 Continuous line represents the measured values of base excess. Interrupted Line represents the values corrected for the difference between the levels of total and excess lactate ; in the same case as shown in figure 4. This demonstrates the rapid correction of the metabolic acidosis which was caused by abnormal metabolism. The overall figures for the mortality in our first ninety-four patients are shown in Table 1. Out of the sixteen deaths, eight occurred in the first twenty-five cases. In the sixty-nine cases in which the Pco2 has been maintained in the region of 40mm/Hg there have been only eight deaths, giving an 11.5 per cent mortality rate. SUMMARY Acid-base balance has the two components of the respiratory and metabolic states. Optimum conditions of either component are not known at low body temperatures. However, the simple technique of the maintenance of the Pco2 in the region of 40mm/Hg at all temperatures, enables the body to spontaneously correct any metabolic imbalance caused either by the addition of acid to the circulation or by the procedure of cooling. We have found that the adoption of this technique has been accompanied by an improvement in the clinical condition of the patients and the avoidance of brain damage which had been seen in those cases in which the Pco 2 was allowed to fall.

9 ANESTHESIA 7 c*g Arrest, Rewarming u W (L k- Q [r w a I w I Left Atrial Drainage 10- -, Thigh Muscle ATRIAL SEPTAL DEFECTS Primum defect Secundum defect Other complications TABLE 1 VENTRICULAR SEPTAL DEFECTS Uncomplicated Tetrallogy of Fallot Infundibular or Pulmonary Stenosis Other complications VALVULAR LESIONS Aortic Mitral Pulmonary (and Infundibular) MISCELLANEOUS TOTAL CASES DEATHS I 0 I6 References ~DREW, c.e., KEEN, G. and BENAZON, D.G. (1959). Profound Hypothermia, Lancet, 1,145 =BROOKS, D.K. (1962). Modern Trendsin Anaesthesia, Part2,Aspectsofhydrogen ion regulation and biochemistry in anaesthesia, p102, ed. by EVANS, F. T. and ORAY, T. c., Butterworths, London KENYON, J.R., LUDBROOK, J., DOWNS, A.R., TAIT, I.B., BROOKS, D.K. and PRYCZKOWSKI, J. (1959). Experimental deep hypothermia. Lancet, 2,41?ROBINSON, J.S. (1961). Some biochemical effects of passive hyperventilation. Brit. J. Anaesth.,,62

10 14 ANESTHESIA SAXELROD, D.R. (1961). Organic acids andcalcium in hyperventilation. J. Appl. Physiol., 16,709 ~PAPADOPOULOS, C.N. and KEATS, M.D. (1959). The metabolic acidosis produced by controlled ventilation. Anesthesiology, 20, 156 'IKETY, s.s. and SCHMIDT, C.F. (1948). The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J. Clin. Invest., 27,484 ~BJORK, V.O. (1960). An effective blood heat exchanger for deep hypothermia in association with extracorporeal circulation but excluding the oxygenator. J. Thorac. Surg., 40,27 9GORDON, A.S., MEYER, B.W.andJONES, J.C. (1960).Open-he~tsurgery~~ing deep hypothermia without an oxygenator. J. Thorac. Surg., 40,787 ~ O C A L L A G H A N, P.B., LISTER, J., PATON, ~.c.andsw~~, ~.(1961). Effects of varying carbon dioxide tensions on the oxyhaemoglobin dissociation curves under hypothermic conditions. Ann. Surg., 154,90 ~IOSBORN, J.J., GERBODE, F., JOHNSTON, J.B., ROSS, J.K., OGATA, T. and KERTH, W.J. (1961). Blood chemical changes in perfusion hypothermia for cardiac surgery. J. Thorac. Surg., 42,462 l2 M A L LE TT E, W. G., FIT Z G E R A L D, J. R. and E I S E M A N, B. (1961). Hypercapnia - a means of increasing oxygen availability during hypothermic perfusion. 1MULHAUSEN, A.R.O., ANDERSON, W.E. and MACDONALD, F.M. (1962). Primary hypocapnia: a cause of metabolic acidosis. J. Appl. Physiol., 17,28 14BALKE, B., ELLIS, J.P. and WELLS, J.G. (1958). Adaptive responses to hyperventilation. J. Appl. Physiol., 12,269 ISAUSTIN, J.H. and CULLEN, G.E. (1925). Hydrogen-ion concentration of the blood in health and disease. Medicine, 4,275 BREWIN IN, E.G., GOULD, R.P., NASHAT, F.S. ~ ~ ~ N E E. I L (1955)., An Investigation of problems of acid-base equilibrium in hypothermia. Guy's Hosp. Rep., BARCROFT, J. (198). Features in the architecture of physiological function. Chap. 1.5,~. 4. Cambridge University Press, London ~~SEVERINGHAUS, J.W. and STUPFEL, M. (1955). Respiratory dead space increase following atropine in man and atropine, vagal or ganglionic blockade and hypothermia in dogs. J. Appl. Physiol., 8,81 ~~OTIS, A.B. and JUDE, J. (1957). Effect of body temperature on pulmonary gas exchange. Am. J. Physiol., 188,55 ~ODILL, D.B. and FORBES, W.H. (1941). Respiratory and metabolic effects of hypothermia. Am. J. Physiol., 12,685 ~~ASTRUP, P. (1956). A simple electrornetric technique for the determination of C02 tension in blood and plasma, total content of CO2 in plasma, and HC0 content in 'separated' plasma at a fixed C02 tension (40mm/Hg). Scand. J. Clin. andlab. Invest., 8, ~~SIGGAARD ANDERSEN, 0. and ENGEL, K. (1960). A new acid-base nomogram - an improved method for the calculation of the relevant blood acid-base data. Scand. J. Clin. andlab. Invest., 12, 177 2CARSON, S.A. and MORRIS, L.E. (1962). Controlled acid-base status with cardiopulmonary bypass and hypothermia. Anesthesiology, 2,618 24ASTRUP, P., JORGENSEN, K., SIGGAARD ANDERSEN, 0. and ENGEL, K. (1960). The acid-base metabolism -a new approach. Lancet, I, 105 ~SLUDBROOK, J. and WYNN, v. (1958). Citrate intoxication- a clinical and experimental study. Brit. Med. J., 2,521 ~~HENNEMAN, D.H., BUNKER, J.P. and BREWSTER, W.R. (1958). Immediate metabolic response to hypothermia in man. J. Appl. Physiol., 12,164

11 ANESTHESIA 75 ~~HUCKABEE, W.E. (1958). Relationships of pyruvate and lactate during anaerobic metabolism, I. Effects of infusion of pyruvate or glucose and of hyperventilation. J. Clin. Invest., 7,244 Acknowledgements I should like to thank Mr R. H. B. Belsey for his encouragement and co-operation in this investigation upon his patients; Dr J. Clutton-Brock for his constant help and advice in the preparation of this paper; Dr G. K. McGowan and Mr B. C. Gray, of the Department of Biochemistry, for their advice and assistance in the estimations of the values of plasma carbon dioxide content (Tco2) and potassium; Mr A. L. Winter, of the Burden Neurological Institute, for his assistance in the recording and interpretation of the EEGS; the Medical Research Committee of theunitedbristo1 Hospitals for their grant towards the cost of apparatus which made this investigation possible.