Intravenous administration of high-dose pentobarbital has been proposed as a treatment for elevated intracranial pressure refractory to other measures in brain-injured patients. The purpose of this clinical study was to examine the pharmacokinetics of high-dose continuous intravenous infusion of pentobarbital in this critical care setting. Six patients received a 25–34 mg/kg intravenous loading dose followed by a 1–3 mg/kg/h continuous infusion for 61–190 hours. Dosing rates were adjusted based on the patient's clinical status. The mean clearance was 0.72 ml/min/kg, with a volume of distribution (Vd) of 1.03 L/kg and a terminal half-life of 19.1 h. Considerable variation in individual patient parameters was observed. In addition, a change in clearance was suggested in patients requiring a longer infusion duration.
MarshallLF, SmithRW, ShapiroHM. The outcome with aggressive treatment in severe head injuries. Part 1: The significance of intracranial pressure monitoring. Part 2: Acute and chronic barbiturate administration in the management of head injury.J Neurosurg1979; 50: 20–30.
2.
BruceDA, GennarelliTA, LangfittTW. Resuscitation from coma due to head injury.Crit Care Med1978; 6: 254–69.
3.
MillerJD, BeckerDP, WardJD, SullivanHG, AdamsWE, RosnerMJ. Significance of intracranial hypertension in severe head injury.J Neurosurg1977; 47: 503–16.
4.
BruceDA. The pathophysiology of increased intracranial pressure.Kalamazoo, MI: The Upjohn Company,1978: 28–33.
5.
QuandtCM, De Los ReyesRA. Pharmacologic management of acute intracranial hypertension.Drug Intell Clin Pharm1984; 18: 105–12.
BayliffCD, SchwartzML, HardyBG. Pharmacokinetics of high-dose pentobarbital in severe head trauma.Clin Pharmacol Ther1985; 38: 457–61.
11.
HeinemeyerG, RootsI, DennhardtR. Monitoring of pentobarbital levels in critical care patients suffering from increased intracranial pressure.Ther Drug Monit1986; 8: 145–50.
12.
MarshallLF, ShapiroHM, RauscherA, KaufmanNM. Pentobarbital therapy for intracranial hypertension in metabolic coma: Reye's syndrome.Crit Care Med1978; 6: 1–5.
13.
VenesJL, ShaywitzBA, SpencerDD. Management of severe cerebral edema in the metabolic encephalopathy of Reye-Johnson syndrome.J Neurosurg1978; 48: 903–15.
14.
ReaGL, RockswaldGL. Barbiturate therapy in uncontrolled intracranial hypertension.Neurosurgery1983; 12: 401–4.
15.
BelopavlonicM. Barbiturate therapy in cerebral ischemia.Anaesthesia1980; 35: 235–45.
16.
SafarP, BleyaertA, NemotoEM, MoossyJ, SnyderJV. Resuscitation after global brain ischemia-anoxia.Crit Care Med1978; 6: 215–26.
17.
HudsonJB, DennisAJ, HobbsDR, SussmanHC. Extended hemodialysis in short acting barbiturates poisoning: case report.South Med J1969; 62: 457–60.
18.
IversonBM, WillassenY, BakkeoM, WallemG. Assessment of barbiturate removal by charcoal hemoperfusion in overdose cases.Clin Toxicol1979; 15: 139–47.
19.
LaffertyJJ, KeykhahMM, ShapiroHM, Van HornK, BeharMG. Cerebral hypometabolism obtained with deep pentobarbital anesthesia and hypothermia.Anesthesiology1978; 49: 159–64.
20.
AlbrechtRF, MiletichDJ, RosenbeergR, BehroozZ. Cerebral blood flow and metabolic changes from induction to onset of anesthesia with halothane or pentobarbital.Anesthesiology1977; 47: 252–6.
21.
ShapiroHM, GalindoA, WyteSR, HarrisAB. Rapid intraoperative reduction of intracranial pressure with thiopentone.Br J Anaesth1973; 45: 1057–62.
22.
EhrneboM. Pharmacokinetics and distribution properties of pentobarbital in humans following oral and IV administration.J Pharm Sci1974; 63: 1114–8.
23.
DempseyDT, GuenterP, MullenJL. Energy expenditure in acute trauma to the head with and without barbiturate therapy.Surg Gynecol Obstet1985; 160: 128–34.
24.
MarkLC. Metabolism of barbiturates in man.Clin Pharmacol Ther1963; 4: 4–12.
25.
MaynertEW. The alcoholic metabolites of pentobarbital and amobarbital in man.J Pharmacol Exp Ther1965; 150: 118–21.
26.
TangBK. N-hydroxylation of pentobarbital in man.Drug Metab Dispos1977; 5: 71–4.
27.
KlotzU, ReimannI. Delayed clearance of diazepam due to cimetidine.N Engl J Med1980; 302: 1012–4.
28.
CohenIA, JohnsonCE, BerardiRR, HyneckML, AchemSR. Cimetidine-theophylline interaction: effects of age and cimetidine dose.Ther Drug Monit1985; 7: 426–34.
29.
SomogyiA, GuglerR. Drug interactions with cimetidine.Clin Pharmacokinet1982; 7: 23–41.
30.
StjernholmMR, Katzfh. Effects of diphenylhydantoin, phenobarbital, and diazepam on the metabolism of methylprednisolone and its sodium succinate.J Clin Endocrinol Metab1975; 41: 887–93.
ChristiansenJ, DamM. Influence of phenobarbital and diphenylhydantoin on plasma carbamazepine levels in patients with epilepsy.Acta Neurol Scand1973; 49: 543–6.
