Failure of thiopental to modify global anoxic injury.

Abstract

SUMMARY To corroborate thiopental protection from cerebral anoxia after cardiopulmonary arrest, 23 sedated, curarized, adult dogs were asphyxiated by plugging the endotracheal tube. Cardiopulmonary resuscitation (CPR) was started 7 minutes after electrocortical silence. Twelve animals received no other treatment (controls), 10 regained consciousness and spontaneous respirations, but remained decerebrate, blind, unable to drink or feed. Two dogs returned to a normal neurologic state. Ten dogs were treated with thiopental after CPR, 7 received 15 mg/kg the first minute, followed by 23 mg/kg over 1 hour; 3 received 60 mg/kg in the first 3 minutes, followed by 30 mg/kg over 1 hour. Except for 1 dog in the low-dose group that recovered neurologically, thiopental-treated dogs showed no neurological or survival improvement over the controls.Stroke, Vo! 10, No 2, 1979LABORATORY DEMONSTRATION of central nervous system recovery after prolonged ischemic anoxic injury 1 has resulted in renewed interest in the treatment of post-anoxic states.Several studies have demonstrated the effectiveness of barbiturate anesthetics in ameliorating the effects of focal ischemic injury.2 Clinically, patients may do surprisingly well after deep barbiturate coma and anoxia.3 Several laboratories have reported beneficial effects of barbiturates in models of global anoxic injury. 49 We attempted to demonstrate a similar benefit in a model closely paralleling the clinical situation of hypoxic cardiac arrest. MethodsTwenty-two, 8 to 16 kg adult mongrel dogs were fasted for 12 hours prior to the experiment. They were anesthetized with a combination of fentanyl and droperidol (Innovar-Vet), 0.1 cc/kg body weight and paralyzed with pancuronium bromide, 0.1 mg/kg. They were then intubated and placed on a piston ventilator with an in-line CO 2 meter (Godart Capnograph). Tidal volume and respiratory rate were adjusted to achieve an expired CO 2 content of 3.5 to 4.5% throughout the experiment. Biparietal scalp EEG leads, ECG electrodes, and a rectal temperature probe were attached. Intravenous dextrose 5% in water, 60 cc per hour, was given throughout the experiment (approximately 5 hours). Normal saline with 1000 U heparin/1 was used as a flushing solution. Through an inguinal incision, a Swan-Ganz catheter was passed via the femoral vein and placed in the right atrium as confirmed by pressure tracings. A femoral arterial line was inserted into the aorta and attached to a Statham strain gauge. Arterial blood pressure (AP), heart rate, and EEG were monitored throughout the experiment.The animals were allowed to emerge from anesthesia to the point of regaining a pedal withdrawal reflex and minimal respiratory efforts. At this time, pancuronium was re-administered and the endotracheal tube plugged after emptying the chest by compression. The EEG was observed until it became isoelectric. This state was maintained for 7 minutes. At that time, standard cardiopulmonary resuscitation was begun with Ambu bag ventilation with 100% oxygen and closed chest card...

Brain tissue pH after global brain ischemia and barbiturate loading in rats.

“…The degree of neurologic damage observed by Steen and Michenfelder was less than observed by Goldstein et al resulting in a reduction in the severity of neurologic damage between control and pentobarbital dogs. Snyder et al 20 reported that postinsult thiopental administration after asphyxial arrest in dogs failed to improve neurologic recovery. However, thiopental treated dogs suffered episodes of severe arterial hypotension with MAPs as slow as 20 torr during thiopental infusion.…”

Brain Free Fatty Acids, Edema, and Mortality in Gerbils Subjected to Transient, Bilateral Ischemia, and Effect of Barbiturate Anesthesia

“…Several reports have documented a protective effect of various barbiturates in regional cerebral ischemia when they are administered before or shortly after the onset of ischemia or even after the end of ischemic insult (Smith et al, 1974; Hoff et al, 1975; Levy and Brierley, 1979). The effectiveness of barbiturates in ameliorating diffuse cerebral ischemia, however, is controversial, particularly when the ischemia is complete (Snyder et al, 1979; Steen et al, 1979). Complete cessation of cerebral blood flow (CBF) results in flattening of the EEG 15–20 s after the onset, in depletion of brain energy reserves, and in the attainment of plateau levels of lactate within 5–10 min (Lowry et al, 1964; Ljunggren et al, 1974), indicating that both energy‐producing and ‐utilizing reactions are arrested.…”

Anesthetic-mediated protection/preconditioning during cerebral ischemia

“…In contrast, the protective efficacy of barbiturates following global cerebral ischemia is still somewhat controversial (Goldstein et al, 1966;Yatsu et al, 1972;Bleyaert et al, 1978;Steen et al, 1979;Snyder et al, 1979;Todd et al, 1982;Gisvold et al, 1984). In the initial studies of global ischemia, barbiturates administered prior to, during and post-cardiac arrest improved neurological outcome; however, later studies failed to show this same neuroprotective efficacy of barbiturates following global cerebral ischemia.…”