Achiel L. Bleyaert

Thiopental Amelioration of Brain Damage after Global Ischemia in Monkeys

The authors studied the effect of thiopental in ameliorating permanent brain damage in monkeys after 16 min of global ischemia of the brain produced by a high-pressure neck tourniquet and systemic arterial hypotension. Intensive care and life support, including monitoring of physiologic variables, w

Success rates of blind orotracheal intubation using a transillumination technique with a lighted stylet

The technique of guided orotracheal intubation using a lighted stylet depends on the transillumination of the soft tissues of the neck to direct the tube through the glottis and into the trachea. We conducted an operating room study of this technique, recording success rates and intubation times of 50 patients undergoing elective surgery. All patients were intubated successfully, 35 of 50 (70%) on the first attempt, 12 of 15 (80%) on the second attempt, and three of three (100%) on the third attempt. The average time for intubation was 37 seconds. A new design of the lighted stylet method resulted from the experience gained. Intubator training and experience influenced initial success rates, and the cadaver laboratory was of particular value in teaching the technique.

Augmentation of postischemic brain damage by severe intermittent hypertension.

The neurological recovery and histological changes were studied in monkeys after intermittent postischemic arterial hypertension after 16 min of global brain ischemia. Ischemia was produced with a high pressure (1500 mm Hg) neck tourniquet and systemic arterial hypotension. Intensive care and life support, including monitoring of physiological variables, were provided for 7 days. Postischemia all monkeys were immobilized; ventilation was controlled and mean arterial pressure was maintained between 85–115 mm Hg for the first 48 hours. Immediately postischemia in four monkeys, intermittent arterial hypertension (i.e., 150–190 mm Hg) was induced by norepinephrine infusion for 3–5 min. Hypertensive episodes were repeated at 15, 30, 60, and 120 min postischemia, once every hour for the first 24 hours and once every 2 hours between 24 and 48 hours. Thereafter, the monkeys were allowed to breathe spontaneously. Four control monkeys were similarly treated except that arterial hypertension was not induced. Neurological recovery was evaluated by EEG, intracranial pressure, neurological deficit scoring, and histological examination of the brain after killing on day 7 postischemia. The neurological deficit score (100% = brain death; 50% = vegetative state; 0% = normal) in control monkeys on day 7 was 17.8 ± 1.8 (SEM) % compared to 46.3 ± 6.5% (p < 0.05) in the hypertension group. EEG recovery was delayed and the postischemic increase in intracranial pressure was prolonged in the hypertension group. Histological damage scores in the brain correlated with neurological deficit scores. Severe intermittent hypertension has a deleterious effect on neurological recovery after global brain ischemia.

Free fatty acid accumulation in the pathogenesis and therapy of ischemic-anoxic brain injury

Energy depletion and lactate are at plateau levels within five minutes of complete ischemic-anoxia in the brain; however, irreversible brain injury has not occurred in this time. Brain free fatty acids (FFA) rise sharply during the first five minutes of ischemic-anoxia, but then continue to rise during the following hour without plateauing. Barbiturate anesthesia preischemia attenuates the FFA rise. Other agents which also attenuate the FFA increase include, among others, phenytoin and Innovar. The Ca2+ antagonists flunarizine and gallopamil also attenuated FFA rise, but were not as effective as pentobarbital during ischemia. Protective effects of Ca2+ antagonists may be more important during recirculation than during ischemia.

Attenuation of brain free fatty acid liberation during global ischemia: a model for screening potential therapies for efficacy?

Whole brain free fatty acids (FFA) continue to rise appreciably even 1 h after decapitation, which may reflect the evolution of ischemic brain injury at least during global ischemia. If so, the attenuation of FFA liberation by various drugs may reflect their efficacy in ischemic brain injury. Rats were pretreated with either 0.9% NaCI (controls), ketamine, halothane, lofentanil, etomidate, Y-9179, R41-468, Innovar-Vet®, pentobarbital, thiopental, or phenytoin and decapitated 15 to 30 min thereafter. The brains were kept normothermic for 10 min until they were frozen in liquid nitrogen. Whole brain FFAs were quantitated by gas–liquid chromatography. After 10 min of ischemia in controls, total FFAs and arachidonic, stearic, oleic, and palmitic acids increased by 8- to 10-fold. The drugs, in order of decreasing effectiveness in attenuating FFA liberation, fell into the following three groups: (1) phenytoin, thiopental, pentobarbital, and Innovar-Vet; (2) R41-468, Y-9179, and etomidate; and (3) lofentanil, halothane and ketamine. The three groups reduced total FFAs by about 23%, 13%, and 8%, respectively. The effectiveness of the drugs in attenuating FFA liberation appears to correlate with their efficacy in ischemic brain injury. However, a cause and effect relationship between FFA liberation and the evolution of ischemic brain injury must be established before accurate predictions of efficacy can be made by this method. The limitations of the proposed method of evaluation are discussed.

Effect of postcirculatory-arrest life-support on neurological recovery in monkeys.

The existence of treatable postischemic (PI) changes which influence neurological outcome has been documented by this group before. A global brain ischemia model without cardiac arrest was developed in monkeys. It includes high-pressure neck tourniquet inflation plus hypotension for a reproducible ischemic insult; survival with reproducible neurological deficit (ND) under continuous PI life-support for 7 days with control of extracranial variables; and new ND and histopathological damage scoring systems.Hypoxemia, hypercarbia, hypotension, uremia, sepsis, and other extracranial complications PI in 50 unsatisfactory experiments led to immediate worsening in ND and brain death (ND = 100%) in most of these monkeys. In contrast, all monkeys with the same initial insult, with life-support according to protocol, survived with a 7 day ND of 60% or less.In 46 experiments of seven treatment groups, after 16 or 18 min ischemia, life support was according to protocol for 7 days. The control 1 protocol (spontaneous breathing when feasible) resulted in a mean 7-day ND score of 53% (including quadriplegia). Immobilization with pancuronium and controlled ventilation ameliorated deficit to an ND score of 19% (P < 0.05) (including quadriparesis); this became control 2 protocol. Immobilization resulted in less neuronal damage in the neocortex. Severe repetitive hypertension worsened ND to 46%, versus 19% in controls (P < 0.05). In separate series, neither heparinization over 72 hours PI, nor hemodilution to hematocrit 25% with dextran 40, changed final ND significantly from that of their control groups. Histopathological damage scores correlated with ND scores.

Amiodarone-induced sinus arrest successfully treated with ephedrine and isoproterenol.

Amiodarone is an antiarrhythmic agent that is effective against a wide spectrum of tachyarrhythmias. Properties of this drug that may create problems for the anesthesiologist include myocardial depression (1,2), peripheral vasodilation and hypotension (3-5), prolonged duration of action (3), and atropine-resistant bradycardia (6). Sinus arrest secondary to amiodarone administration has been reported in four patients, all of whom required ventricular pacing for treatment (7-9). None of these four patients were anesthetized, but we recently encountered sinus arrest during anesthesia in a patient who was taking amiodarone for refractory atrial fillibration. The arrest was treated successfully with ephedrine and isoproterenol.

Comparison of the effects of succinylcholine and atracurium on intracranial pressure in monkeys with intracranial hypertension.

The effects of succinylcholine (1.5mg·kg-1 IV) administered five minutes after a defasciculating dose of curare (0.05 mg·kg-1 IV), were compared with the effects ofatracurium (0.5 mg·kg-1 IV) on intracranial pressure (ICP) in 13 cynomologus monkeys with intracranial hypertension (ICP· 25 mmHg). Neither succinylcholine nor atracurium increased ICP during general anaesthesia with 60 per cent N2O/O2, 0.5-1 per cent halothane. During a rapid sequence induction and intubation with thiopentone 5 mg·kg-1 IV, ICP increased equally with intubation following both atracurium (25 ± 1 to 32 ± 2 mmHg) and succinylcholine (25 ± 1 to 31 ± 2 mmHg) (p < 0.05). Intubation was also associated with significant increases in PaCO2, CVP and MAP. We conclude that in this primate model of intracranial hypertension, neither atracurium nor succinylcholine (when given following a defasciculating dose of curare) elevates ICP. In terms of the elevation of ICP associated with intubation, atracurium was found to offer no advantage over succinylcholine.RésuméLes effets de I’administration de succinylcholine (1.5 mg· kg-1) cinq minutes après une dose qui empêche la fasciculation de curare (0.05 mg·kg-1 IV) ont été comparés avec les effets de l’atracurium (0.5 mg·kg-1 IV) sur la pression intracrdnienne (ICP) chez 13 singes cynomologus avec hypertension intracrdnienne (ICP · 25 mmHg). Ni la succinylcholine ni l’atracurium ont augmenté la pression intracrânienne lors de l’anesthesie générate avec 60 pour cent de protoxyde d’azote/ oxygène, et 0.5-1 pour cent d’halothane. Lors de l’induction à séquence rapide et l’intubation avec le thiopentone 5 mg·kg-1 IV, la pression intracrânienne a augmenté également avec l’intubation suite à l’atra-curium (25 ± 1 à 32 ± 2 mmHg) et le succinylcholine (25 ± l à 31 ± 2 mmtig) (p < 0.05). L’intubation a aussi été associée avec une augmentation significative de la PaC02, la pression veineuse centrale et la pression artérielle moyenne. On conclut que pour un seul modèle de primate en hypertension intracrânienne, ni l’atra-curium ni la succinylcholine (lorsque donné après une dose de curare empêchant lafasciculation) n’augmentent la pression intracrânienne. Quant à l’augmentation de la pression intracrânienne lors de l’intubation, I’atracur-ium n’a pas qffert davantage sur la succinylcholine.

Cerebral Cortical Oxygenation and Perfusion during Hetastarch Hemodilution

Clinically, hemodilution may be induced under various circumstances such as intraoperatively during cariopulmonary bypass (1) or therapeutically (2,3). However, aside from its clear-cut efficacy in polycythemic patients (3) and in other pathologic circumstances (2), there is some doubt as to whether tissue oxygenation is improved by hemodilution to subnormal hematocrits (4). With regard to oxygen delivery to the myocardium, Lundsgaard-Hansen (4) concluded that hemodilution should not exceed the lower normal range of hemoglobin or hematocrit (Hct), namely, 12.0 to 12.5% and 35 to 36%, respectively. Our aim in this study was to determine the effects of progressive, normovolemic hemodilution with hydroxy ethyl starch over Hct ranging from 40 to 5% on cerebral cortical oxygenation and perfusion.

Amelioration of Postischemic-Anoxic Brain Damage by Thiopental

Therapies for postischemic-anoxic encephalopathy are based on the tacit assumption that not all of the ultimate degree of neurologic deficit sustained following cerebral ischemia-anoxia is a result of the initial insult, but that postischemic (PI) pathologic processes add further damage. This assumption appears well founded on the basis of clinical observations, where patients are frequently observed to improve after brain ischemia-anoxia such as cardiac arrest or asphyxia, only to subsequently deteriorate and terminate in brain death. Clinical and animal studies have now confirmed that PI hypoperfusion, or the so-called “no-reflow phenomenon” (1), does indeed occur (2, 3). We have shown that cerebral blood flow (CBF) is reduced to approximately 50% of normal within 60 minutes PI after 15 minutes of global brain ischemia in dogs (Fig. 28–1) (3). We also concluded that the reduction in CBF is not a matching of CBF to decreased brain metabolic rate (since low cerebral venous oxygen contents were measured) but, that PI, the brain is truly hypoperfused and continues to be ischemic, which probably contributes to further brain damage.