Br. 7. Anaesth. (1974), 46, 263 ACID-BASE CHANGES IN ARTERIAL BLOOD AND CEREBROSPINAL FLUID DURING CRANIOTOMY AND HYPERVENTILATION T. V. CAMPKIN, R. G. BARKER, M. PABARI AND L. H. GROVE SUMMARY Several studies in healthy man and animals have shown biochemical evidence of a change in cerebral glucose utilization to anaerobic metabolism during hyperventilation and hypocarbia. The increase in lactate in the cerebrospinal fluid was moderate at a Pa,,, of 20 mm Hg but became more marked at lower values of Pa,,,. In this investigation patients were studied, during craniotomy, both at normal body temperature and under hypothermia. Arterial blood was sampled at hourly intervals and one sample of ventricular c.s.f. was obtained during the period of hyperventilation. With the exception of one patient in the hypothermia group no evidence of an excessive increase in c.s.f. lactate (indicative of deficient cerebral oxygenation) was seen at Pa,,, values of approximately 20 rnrn Hg. The use of controlled passive hyperventilation during neurosurgical procedures avoids both deep anaesthesia and the well known deleterious effects of hypercarbia on cerebral blood flow and intracranial pressure. Hyperventilation with its attendant fall in Pa,,, produces cerebral vasoconstriction, reduced cerebral blood flow and a reduction in brain size in the majority of patients with normal or raised intracranial pressure. For this reason it has become routine in the techniques of anaesthesia in most neurosurgical units. However, much discussion has centred around the optimum level of hyperventilation and Pa,,, since excessive cerebral vasoconstriction might induce cerebral ischaemia. If this were the case, an alteration in the metabolic pathway of glucose from aerobic to anaerobic metabolism would occur and lactate should accumulate in the brain and c.s.f. Studies in the dog by Plum and Posner (1967), under carefully controlled conditions, showed a marked increase in c.s.f. lactate during severe hyperventilation to a Pa,,? of approximately 10 mm Hg over a period of several hours, while a smaller increase in lactate was seen at an arterial Pco, of 2C mm Hg. The authors concluded that cerebral ischaemia was the cause of the c.s.f. changes at Par,, levels of 20 mm Hg and less. Wollman and associates (1965) reported a reduction in cerebral blood T. V. CAMPKIN, M.B., F.F.A.R.c.s., D.A.: R. G. BAKER, B.SC.; M. PABARI, M.B., F.F.A.R.c.s.; L. H. GROVE, M.B., F.F.A.R.C.S.; Midland centre for Neurosurgew and Neurology, and The Queen Elizabeth Hospital, Birmingham. flow of 50% in healthy male volunteers hyperventilated with nitrous oxide and oxygen to a mean arterial Pco, of 18 mm Hg. Mean jugular venous Po, fell to 19.8 mm Hg, a level which is suggestive of inadequate cerebral oxygenation. In a further study (Alexander et al., 1965) the same hyperventilation technique was used, to a Pa,, level below 20 mm Hg and was associated with evidence of increased cerebral anaerobic metabolism of glucose and electroencephalographic changes compatible with mild but reversible cerebral ischaernia. These investigations indicate that at Pa,,, levels below 20 mm Hg cerebral ischaemia and anaerobic metabolism may occur. At these levels cerebral blood flow is reduced and further reduction of the arterial Pco, does not produce a further decrease in blood flow (Harper and Glass, 1965; Reivich, 1964). It is assumed that hypoxic vasodilatation of cerebral vessels occurs and this prevents any further vaso- constriction as the Pa,,, falls. It is usually suggested that hyperventilation during craniotomy should maintain an arterial Pco, in the range of 20-30 mm Hg in order to avoid possible cerebral hypoxia and in patients with increased metabolism (e.g. fever or thyroid disease) or in those with cerebral arterial disease, who may have im- paired autoregulation, higher Pa,,, values should perhaps be maintained. In this unit controlled hyverventilation has been used routinely for neurosurgical overations for more than a decade asd during the last 3 years we have frequently cannulated the radial artery for continu-
BRITISH JOURNAL OF ANAESTHESIA ous arterial pressure measurement, a technique which has afforded the opportunity for serial arterial blood-gas analysis during craniotomy. Arterial Pco, levels below 20 mm Hg were recorded not infrequently and the present investigation was undertaken to determine whether or not there was evidence of suboptimal cerebral oxygenation. Bloodgas, lactate and pyruvate estimations were made on arterial blood and ventricular c.s.f. in twelve patients undergoing craniotomy at normal body temperature, and in a further eleven patients who were moderately hypothermic. PATIENTS AND METHOD Control group. Three unsedated, awake patients with a normal conscious level and no gross neurological deficit were studied during ventriculography under local analgesia. Blood was obtained from the radial artery and the ph, Pco,, Po,, standard bicarbonate, and the concentrations of lactate and pyruvate were measured or derived. The same estimations were ' performed on ventricular c.s.f. obtained during the procedure. Arterial samples were drawn into a heparinized glass syringe which was immediately capped. ph, blood-gas and bicarbonate measurements employing the Astrup method were made within a few minutes and never more than 1 hour after sampling. Cerebrospinal fluid samples were collected in an unheparinized glass syringe. For lactate and pyruvate analysis both arterial blood and c.s.f. were immediately precipitated with cold 8% perchloric acid and the estimation performed later the same day using an enzyme method (Sigma procedure no. 826 U.V. for lactate and no. 726 U.V. for pyruvate). Normothermia group. Twelve patients were studied during craniotomy at normal body temperature. Four of these had intracranial aneurysms, while the remainder had space-occupying lesions. No patient, however, was comatose or drowsy. In eight patients a blood sample was obtained by radial or femoral artery puncture immediately before induction of anaesthesia. In all patients a 16gauge Venflon cannula was introduced into the radial or ulnar artery at the wrist after induction and arterial samples taken at hourly intervals during the operation. The same biochemical estimations were made as in the control group of patients. Premedication was with atropine 0.6 mg only or diazepam 10 mg and atropine 0.6 mg. General anaesthesia was commenced with thiopentone and a non-depolarizing muscle relaxant (curare or pancuronium). After endotracheal intubation, ventilation was controlled using an East-Radcliffe ventilator set to deliver a minute volume of 8-10 1. of 50% nitrous oxide and 50% oxygen. A small concentration (0.5-1.0%) of halothane was added if there was no clinical evidence of raised intracranial pressure. Moderate arterial hypotension to 80-90 mm Hg systolic using trimetaphan (0.1% solution), or sodium nitroprusside (0.01%) was induced after elevation of the flap, and maintained for the duration of the intraaanial part of the operation. A single sample of ventricular c.s.f. was obtained by the surgeon as soon as the dura was open and the brain exposed. In this group the c.s.f. was obtained after approximately 1 hour of hyperventilation. Hypothermia group. Eleven patients were studied during craniotomy combined with moderate hypothermia to 3&31 C using surface cooling. All these operations were for clipping of an intracranial aneurysm but no patient had a deterioration of conscious level. In five patients a preoperative arterial sample was obtained and in all cases hourly samples were taken during the operative procedure. Premedication and the induction of anaesthesia was similar to group I1 patients but in all cases halothane was employed to produce cutaneous vasodilatation and facilitate cooling. Ventilation was adjusted during the procedure, a level of 8-10 1. being used at 37 C but this was progressively reduced as the body temperature fell and at 30-31 C a minute volume of 3-4 1. was employed. Moderate arterial hypotension to 80-90 mm Hg systolic was induced in this group after dual opening. The blood pressure was further lowered to 60-65 mm Hg systolic for a short period (usually 10-15 min) during exposure and clipping of the intracranial aneurysm. The single sample of c.s.f. was obtained after approximately 2 hours of hyperventilation as the operation was not started until the oesophageal temperature had fallen to 33-34 C. ph and Po, estimations on blood and c.s.f. were made at the appropriate body temperature by adjustment of the bath temperature of the electrodes. In all cases ph and gas estimations were performed within a few minutes of sampling.
ACID-BASE CHANGES DURING HYPERVENTILATION 265 RESULTS Control group. Values for this group are depicted in table I and with the exception of arterial Po, all estimations were within the normal range. Mean value for arterial PO, was 74.5 mm Hg. Normothermia group. Mean values and standard deviation for this group are shown in table 11. Following the induction of anaesthesia and hyperventilation the fall in Paco2 to a mean value of 24 mm Hg was reflected by a corresponding rise in ph to 7.57 at the end of 1 hour and 7.55 after 2 hours. Mean arterial Po2 rose to 159 mm Hg at the end of 1 hour and 194 mm Hg after 2 hours reflecting the high oxygen concentration (50%) in the inspired gas mixture. Although arterial blood lactate rose to 15 mg/ 100 ml, a value within the normal range, blood pyruvate also rose and the lactate-pyruvate ratio remained unchanged. In the c.s.f. a mean ph of 7.39 and Pa, of 36.5 mm Hg reflected the changes in arterial blood. The mean Po, of 57 mm Hg was well above normal values for c.s.f. PoZ. Hypothermia group. The values for ten of the patients in this group are shown in table 111. One further patient who had biochemical evidence of cerebral ischaemia is considered separately. Because of the longer duration of these operations under hypothermia it was possible to obtain arterial samples for three consecutive hours. Mean Pa,,, fell to 24 mm Hg at the end of the first hour and TABLE I. Mean arterial blood and c.s.f. values in 3 conscious patients during ventriculography. Po Pco, Hco,' Lactate Pymvate ph (mm HR; (mm HR) (m.equivll.) (mgllo@ ml) (md100 ml) LIP ratio - -...... -... -. Arterial blood 7.47 74.5 37.1 26.1 14.6 0.88 16.5 +0.02 f 15.5 f 6.5 51.1 f1.3 f 0.2 f 2.3 (4.7-15.1) (0.41-1.10) Cerebrospinal fluid 7.31 46.2 51.7 24.5 13.4 1.O 13.3 f0.03 f20.1 f8.0 f 1.2 rtl.0 +0.2 ~k2.7 (11.6-27.0) (0.55-1.26) - All figures in this and succeeding tables are expressed as mean f standard deviation. Figures in parentheses are normal values taken from Documents Geigy. TABLE 11. Mean arterial blood and c.s.f. values in I2 patients during craniotomy, notmothetmia. Po2 Pco, Hco,' Lactate Py mvate ph (mm Hg) (mm Hg) (m.equiv/l.) (mg1100 ml) (mg/100 ml) LIP ratio Preoperative arterial 7.43 82.1 42.3 26.9 9.6 0.5 17.2 1-hour arterial zko.04 7.57 f13.0 159.0 i4.4 24.1 f0.05 f68.9 f 2.9 2-hours arterial 7.55 194.5 24.7 f0.05 f 52.8 f3.3 f2.6 f 3.9 f0.5 f6.7 Cerebrospinal fluid 7.39 57.0 36.5 22.1 19.3 1.3 13.2 1 hour f0.03 f21.0 k5.8 f1.9 f3.23 &0.17 f3.4 TABLE 111. Mean arterial blood and C.S. f. values in 10 patients durinf craniotomy wirh hypothermia. Po 2 Pco, Hco,' Lactate Pymvate PH (mrn Hg) (mm Hg) (m.equiv/l.) (mg1100 ml) (mg/100 ml) LIP ratio Preoperative arterial 7.44 88.8 39.4 26.7 12.0 0.7 18.1 10.02 rt14.9 f2.5 f 1.02 f0.2 f0.2 f6.0 1-hour arterial 7.54 142.7 24.0 24.6 14.3 0.7 23.4 f 0.03 156.3 f4.1 f 2.0 f3.9 f0.4 f 12.2 2-hours arterial 7.56 150.1 22.7 23.9 16.1 0.8 20.6 f0.08 f 77.3 f 3.4 f 1.8 *3.7 f 0.3 f 8.6 3-hours arterial 7.54 149.6 23.2 23.9 16.2 0.9 17.7 f0.08 f64.2 16.0 f2.2 f7.0 k0.5 f6.6 Cerebrospinal fluid 7.42 39.3 31.2 20.1 19.0 1.5 13.2 2 hours f 0.06 &7.7 f 10.9 f2.4 r3.1 f 6.4 f 3.4
BRITISH JOURNAL OF ANAESTHESIA remained above 20 mm Hg throughout the operation. Some individual values, however, fell below 20 mm Hg and the lowest recorded Pa,,,, after 3 hours hyperventilation, was 14.5 mm Hg. Although blood lactate increased slightly during the period of hyperventilation this was associated, as in the preceeding group, with a corresponding rise in pyruvate levels, lactate-pyruvate ratio remaining within normal limits. In the c.s.f., mean Po, was 39 mm Hg, a somewhat lower value than in the normothermia group. Cerebrospinal fluid lactate of 19.0 mg/loo ml was within normal limits while mean pyruvate of 1.5 mg/100 ml was slightly higher than normal. One patient in this group showed biochemical evidence of cerebral ischaemia (table IV). This patient, aged 58, underwent operation for clipping of an anterior communicating aneurysm. Arterial Pco, remained above 20 mm Hg for most of the operation but had fallen to 18.3 mm Hg after 3 hours. Arterial Po, was 101 mm Hg at the end of the first hour, but fell to 48 mm Hg by the end of 2 hours. In the sample taken at 3 hours it had risen to 177 mm Hg. Cerebrospinal fluid samples after 2 hours hyperventilation showed a low value for PoZ of 27 mm Hg. The c.s.f. lactate-pyruvate ratio was 92.5 and this high value was obtained because c.s.f. lactate rose (although still within the normal range) while the level of pyruvate had fallen. DISCUSSION Studies in healthy man on the cerebral metabolic effects of hypocarbia have suggested that a reduction in Pa,,, below 20 mm Hg is accompanied by an increased anaerobic utilization of glucose and an increase in cerebral lactate production. These changes, although only moderate at an arterial PcoZ level of 20 mm Hg, become more marked at lower levels of hypocarbia (Alexander et al, 1965; Alexander et al., 1968). In this investigation we sought confirmation of the findings of other authors, since similar Pa,,, levels are not infrequently recorded during craniotomy and hyperventilation. It has been widely accepted that alterations in cerebral metabolism are reflected by changes in the c.s.f. (Posner, Swansson and Plum, 1965; Davson, 1967; Gordon, 1971). However, some doubt has been cast 03 the validity of accepting c.s.f. Po, as an index of the oxygen tension of the brain since animal experiments have suggested a direct transfer of oxygen from arterial blood to c.s.f. (Kazemi et al., 1968). In an investigation of neurosurgical patients Gordon (1970) concluded that c.s.f. Po, was a reliable index of the state of cerebral tissue oxygenation. In our patients ventricular samples of c.s.f. were obtained and we expected to find metabolic evidence of suboptimal cerebral oxygenation if the level of hypocarbia during the operation was producing excessive cerebral vasoconstriction. Such evidence was not seen in the normothermia group of patients in whom c.s.f. Po, was well above normal values and both c.s.f. pyruvate and lactate within the normal range. Similarly, in the operations under hypothermia there was no evidence of ischaemia with the exception of the one patient in this group whose values are shown in table IV. It should be emphasized, however, that all the patients in this investigation received an inspired gas mixture of 50% oxygen and it is possible that with lower oxygen concentrations impaired cerebral oxygenation might occur at Pa,,, levels of 20 mm Hg and below. It is necessarv to reduce the minute volume of inspired gas as kody temperature falls. Total body production of carbon dioxide falls as metabolism decreases during hypothermia and the maintenance of a normal or high minute volume at low body temperature will produce an excessively low level of hypocarbia. The majority of patients in this study received halothane (0.5-1.0%) and the possible effect of this agent on cerebral blood flow and oxygenation should TARLE IV. Arterial blood and c.s.f. values in I patient (no. I1 hypothennia group) showing biochememrcal evidence of cerebral ischaemia. Po, PC% Hco,' Lactate Pyruvate ph (mm Hg) (mm Hg) (m.equiv/l.) (mg/100 ml) (mg/100 ml) L!P ratio Preoperative arterial 7.43 77 34.0 24.0 10.3 0.53 19 1-bour arterial 7.52 101 22.5 21.1 9.9 0.35 27 2-hours arterial 7.52 48 21.1 21.5 11.4 0.42 26 3-hours arterial 7.53 177 18.3 20.6 12.2 0.54 22 Cerebrospinal fluid 2 hours 7.39 27 28.2 17.9 22.5 0.24 92.5
ACID-BASE CHANGES DURING HYPERVENTILATION 267 be considered. Although halothane causes cerebral vasodilatation the reactivity of cerebral blood vessels is preserved during hypocarbia and cerebral blood flow tends to approach the same low level (Alexander et al., 1964). The hypothermia patient with low values of arterial and c.s.f. Po, is of interest. These levels were obtained after 2 hours of hyperventilation when the blood pressure had been reduced to 65 mm Hg systolic using sodium nitroprusside (0.01 %) for exposure and clipping of the aneurysm. It is probable that in addition to reduced cerebral perfusion a marked maldistribution of pulmonary blood flow occurred during the hypotensive period leading to inequality of ventilation and perfusion and arterial hypoxaemia. The very high value of lactatepyruvate ratio in this patient was derived from the rise in c.s.f. lactate (which remained within the normal range) and a fall in c.s.f. pyruvate. The significance of this increase in lactate-pyruvate ratio is uncertain and doubt has been cast on the concept of excess lactate and increases in lactate-pyruvate ratio as an index of oxygen deprivation (Tobin, 1964). This patient, although confused for 2 days after operation, made a complete recovery despite the biochemical evidence suggestive of a period of cerebral hypoxia. Finally, this study exemplifies the difficulties encountered in an investigation of this type carried out under clinical conditions during neurosurgery. Only one sample of c.s.f. was obtained during each operation when it would have been desirable to have had repeated samples throughout the period of hyperventilation. Further, it was not possible to provide controlled conditions and factors such as the neurological lesion, the level of blood pressure and the use of halothane varied from patient to patient. However, with the exception of one patient we found no metabolic evidence of anaerobic metabolism in the c.s.f. at arterial Pco, levels in the region of 20 mm Hg but this does not imply that localized cerebral ischaernia might not occur. ACKNOWLEDGEMENT The authors thank MI J. M. Stpall? F.R.c.s., for his help and cooperation in this invesugauon, and the Depanment of Mathematics and Computing, Wolverhampton Polytechnic, for assistance with the statistical analysis of data. REFERENCES Alexander, S. C., Cohen, P. J., Wollman, H., Smith, T. C., Reivich, M., and Van der Molen, R. (1965). Cerebral carbohydrate metabolism during hypocarbia in man. Anesthesiology, 26, 624. - Smith, T. C., Strobell, G. E., Stephen, G., and Wollman, H. (1968). Cerebral carbohydrate metabolism of man during respiratory and metabolic alkalosis. 3. Appl. Physiol., 24, 66. - Wollman, H., Cohen, P. J., Chase, P. E., and Behar, M. G. (1964). Cerebrovascular response to Paeo, during halothane anesthesia in man. 3. Appl. Physiol., 19, 561. Davson, H. (1967). Physiology of the Cerebrospinal fluid. London : Churchill. Gordon, E. (1970). The oxygen tension of the cerebrospinal fluid in patients with brain lesions. Acta Anaesth. Scand., 14, 173. - (1971). The acid-base balance and oxygen tension of the cerebrospinal fluid. Acta Anaesth. Scand., Suppl. 39, 22. Harper, A. M., and Glass, H. I. (1965). The effect of alteration in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. 3. Neurol. Neurosurg. Psychiatry, 28, 449. Kazemi, H., Klein, R. C., Turner, F. N., and Streider, D. J. (1968). Dynamics of oxygen transfer in the cerebrospinal fluid. Respir. Physiol., 4, 24. Plum, F. J., and Posner, J. B. (1967). Blood and cerebrospinal fluid lactate during hyperventilation. Am. 3. Physiol., 212, 864. Posner, J. B., Swansson, G., and Plum, F. (1965). Acidbase balance in cerebrospinal fluid. Arch. Neurol., 12, 479. Reivich, A. M. (1964). Arterial Pco, and cerebral hemodynamics. Am. 3. Physiol., 205, 25. Tobin, R. B. (1964). In vivo influences of hydrogen ions on lactate and pyruvate of blood. Am. 3. Physiol., 207, 601. Wollman, H., Alexander, S. C., Cohen, P. J., Smith, T. C., Chase, P. E., and Van der Molen, R. (1965). Cerebral circulation during general anesthesia and hyperventilation in man. Anesthesiology, 26, 329.