Richard A. Theye

Pathophysiology of hyperkalemia induced by succinylcholine.

: SCh is unequivocally contraindicated in the management of patients who have sustainded thermal trauma or direct muscle trauma and those who have neurologic disorders involving motor deficits, including tetanus. The mechanism is clear in some, but not all, of these conditions, and is related to increased chemosensitivity of the muscle membrane due to the development of receptor sites in extrajunctional areas. Though SCh induces a small release of K+ in normal muscle, it produces a potentially lethal efflux in the presence of increased sensitivity. This K+-releasing action of SCh begins about 5 to 15 days after injury and persists for 2 to 3 months in patients who have sustained burns or trauma, and perhaps 3 to 6 months in patients with upper motor neuron lesions.

The Effects of Anesthesia and Hypothermia on Canine Cerebral ATP and Lactate during Anoxia Produced by Decapitation

ATP and lactate in the canine brain were determined before and during cerebral anoxia induced by decapitation, both at 30 C during halothane anesthesia (0.8 per cent) and at 37 C during four anesthetic circumstances (nitrous oxide, 70 per cent; halothane, 0.8 per cent; halothane, <0.1 per cent; and halothane, 0.8 per cent, with thiopental, 46 mg/kg). The anesthetic circumstances chosen for study at 37 C provided a wide range of mean values for cerebral oxygen consumption rate (CMRo2) (5.9 to 2.9 ml/100 gm/min). At 37 C the CMRo2. associated with the combination of thiopental and halothane (2.9 ml/100 gm/min) approached that at 30 C (2.8 ml/100 gm/min). At 37 C, postdecapitation rates of ATP depletion and lactate accumulation were not influenced by the anesthetic At 30 C, these rates were approximately 40 per cent less. These findings suggest that anesthesia and hypothermia, although they have potentially similar effects on CMRo2, alter cerebral metabolic rate by dissimilar mechanisms, and cannot be expected to provide similar degrees of cerebral protection in the event of anoxia.

Cerebral protection by thiopental during hypoxia.

The effects of thiopental on rates of cerebral ATP depletion and lactate accumulation in dogs anesthetized with N2O during two different circumstances of impaired oxygen delivery were examined. In ten dogs, five with and five without prior thiopental (13 mg/kg), acute hemorrhagic shock (mean arterial pressure 25–30 mm Hg) was produced and maintained for 9 minutes. The EEG remained active in all these dogs. In the dogs given thiopental, cerebral ATP was sustained at a significantly higher level and cerebral lactate accumulation was significantly less in the initial 5–7 minutes of hypotension. In another ten dogs, five with and five without prior thiopental (15 mg/kg), Fio2 was decreased abruptly to zero and hypoxia, progressing rapidly to anoxia (Pao2 < 5 mm Hg), was maintained for 9 minutes. After 3 minutes, the EEG was flat in all dogs, but activity persisted for a significantly longer period (35 see) in dogs given thiopental. The rates of ATP depletion and lactate accumulation were greater than with hypotension and were not significantly altered by thiopental. It is concluded that in the circumstance of hypoxia with continued cerebral function (active EEG), thiopental does afford some cerebral protection; in the absence of function (flat EEG), no protection is apparent. The authors suggest that anesthetics such as thiopental diminish energy requirements of the brain only by reducing its function and hence can provide cerebral protection only when the extent of hypoxia is insufficient to abolish function.

Effects of ketamine on canine cerebral blood flow and metabolism: modification by prior administration of thiopental.

NPLEASANT dreams or hallucinations U are reported by up to 30 percent of adult patients following the anesthetic state produced by ketamine hydrocholoride. 112 Such an effect is not common to other anesthetics when administered in effective concentrations. This study was designed to test the hypothesis that this unusual cerebral functional r&ponse to ketamine may be accompanied by an unusual effect on cerebral metabolism as well. Such a relationship between functional and metabolic effects has been established for sodium thi0pental.3

Simultaneous cerebral blood flow measured by direct and indirect methods

Abstract By diversion of the sagittal sinus blood flow of the dog, obliteration of the extracerebral veins communicating with the sinus, and determination of the amount of brain drained by the sagittal sinus, direct cerebral flow was measured and compared to indirect measurements determined by the modified Kety-Schmidt method using krypton-85 (85Kr) as the tracer gas. Twenty-two comparisons were made in 7 dogs at flows ranging from 25 to 98 ml. per 100 gm. per minute. In individual dogs small systematic differences in the values for cerebral blood flow generally were observed; the discrepancies could not be accounted for entirely by the method of converting direct flow (milliliters per minute) to flow per unit weight (ml./100 gm./min.). For the group no systematic difference was apparent and the results are considered confirmative evidence of the validity of the modified Kety-Schmidt method. When the calculations of indirect flows were made from a 10-minute saturation period with 85Kr and without extrapolation of the arteriovenous difference of 85Kr to infinity, a systematic error was introduced, resulting in a 5 to 10% overestimation at normal and low flow levels. The method for direct measurement of sagittal sinus flow offers promise for further laboratory studies of cerebral blood flow and metabolism.

The Effects of Isoflurane on Canine Cerebral Metabolism and Blood Flow

The cerebral metabolic and vascular effects of isoflurane (Forane) were investigated in six unmedicated ventilated dogs. At the MAC of this anesthetic (1.4 per cent, end-expired) there was a 23 per cent decrease in the rate of cerebral oxygen consumption (CMRO2) (compared with values at end-expired concentrations of <0.1 per cent). At a higher concentration of isoflurane (2.4 per cent, end-expired), a 30 per cent reduction in CMRO2, was observed. Cerebral blood flow (CBF) increased by 33 and 63 per cent at the 1.4 and 2.4 per cent concentrations, respectively. The increase in CBF was due entirely to a decrease in cerebral vascular resistance (CVR) and occurred despite an accompanying significant decrease in arterial blood pressure. The response of CBF to change in PaCO2 was appropriate during isoflurane anesthesia and was not different from that previously observed during halothane and metboxyflurane anesthesia.

Canine systemic and cerebral effects of hypotension induced by hemorrhage, trimethaphan, halothane, or nitroprusside.

In 62 dogs, hypotension to a mean arterial pressure of either 40 or 50 torr (equivalent to a cerebral perfusion pressure of 30 or 40 torr, respectively) for one hour was induced by hemorrhage (oligemia), trimethaphan, halothane, or sodium nitroprusside. Before and during the period of hypotension, the following were measured: mean arterial blood pressure, cardiac output, whole-body O2 consumption, cerebral blood flow, cerebral O2 consumption, arterial blood gases, blood O2 content, and lactate, pyruvate, glucose, epinephrine, and norepinephrine concentrations. At the end of the period of hypotension, brain biopsies were taken for determination of adenosine triphosphate, phosphocreatine, lactate, and pyruvate concentrations. In an additional eight dogs following one hour of hypotension (at 40 torr) induced by one of the four techniques, the brains were perfused with carbon black, removed, and examined. In another ten dogs following hypotension (at 40 torr) induced with either halothane or trimethaphan, the animals were observed for three days and then killed for examination of the brain. Dogs maintained at a mean arterial pressure of 40 torr, despite differences in cerebral blood flow, demonstrated metabolic disturbances compatible with systemic and cerebral hypoxia. These were greatest in those dogs given nitroprusside in excess of 1.0 mg/kg, presumably due to cyanide toxicity. In dogs maintained at 50 torr, metabolic disturbances were minimal or absent in the halothane- and nitroprusside-treated dogs but were still apparent in the oligemic and trimethaphan-treated dogs. Carbon black infusions revealed no evidence of non-homogeneous flow. Three of the ten dogs observed for three days had persistent post-hypotension neurologic dysfunction. Two of these were given trimethaphan. The results suggest that the systemic and cerebral effects of halothane and nitroprusside (at doses less than 1.0 mg/kg) are similar and at a mean arterial pressure of 50 torr are of little consequence. By contrast, hypotension induced by trimethaphan or oligemia results in detectable metabolic alterations even at a pressure of 50 torr.

The Effect of Nitrous Oxide on Canine Cerebral Metabolism

Cerebral blood flow and arterial–sagittal differences for oxygen have been measured in unpremedicated dogs maintained at, 37.0 C. All were paralyzed, had received a spinal anesthetic, and were artificially ventilated. In each of a first group, measurements with and without halothane were carried out with 70 per cent N2O in O2 and with 70 per cent N2 in O2. In a second group, either N2O or N2 was used throughout and measurements were made in the absence of halothane and at 0.1, 0.4, and 0.7 per cent halothane (alveolar). In the absence of halothane and at 0.1 per cent halothane, the average rate of consumption of O2 by the brain (CMRo2) was 11 per cent greater with N2O than with N2. At 0.4 and 0.7 per cent halothane, CMRo2 was greater with N2O but the differences were not significant. It is concluded that N2O per se is not a cerebral metabolic depressant and that the anesthetic action of N2O is not based on generalized cerebral metabolic depression.

The Effects of Morphine and N-Allylnormorphine on Canine Cerebral Metabolism and Circulation

The effects of morphine and nalorphine on cerebral metabolism and circulation were examined in 18 dogs. Incremental doses of morphine caused progressive decreases in CMRo2 and CBF to 85 per cent and 45 per cent of control, respectively, until a dose of 1.2 mg/kg had been given in a one-hour period. Subsequent doses had no further significant effect. The decrease in CBF resulted from both a direct action of morphine (approximately 30 per cent) and the effect of time on experimental canine CBF. A single large dose of morphine (2 mg/kg) had similar effects on CMRo2 and CBF. These effects were reversed by nalorphine (0.3 mg/kg), which initially produced overshoots in both CMRo2 and CBF. Subsequent doses of nalorphine had no further effect. EEG changes correlated with CMRo2 changes caused by morphine and nalorphine. Nalorphine given alone (0.3 mg/kg) produced small decreases in both CMRo2 and CBF, an effect not magnified by subsequent larger doses.

Halothane-induced Porcine Malignant Hyperthermia: Metabolic and Hemodynamic Changes

Metabolic, hemodynamic and neuroendocrine responses to halothane were measured in five normal and five malignant hyperthermia-susceptible (MHS) swine. Constant-volume ventilation was used. There was no therapeutic intervention. In MHS animals, blood lactate concentrations increased first, and the initial increases appeared to be non-hypoxic in origin. Lactate concentrations increased progressively to more than 20 µm/ml. Whole-body oxygen consumption increased almost twofold, and hind limb muscle oxygen consumption increased almost threefold. Extrapolated increases in muscle oxygen consumption accounted for about 55 per cent of the increase in whole-body oxygen consumption. Respiratory and metabolic acidosis, marked hyperkalemia, and increases in catecholamines and temperature occurred secondarily and were accompanied by progressive circulatory failure.