title: Barbiturate infusion for intractable intracranial hypertension and its effect on brain oxygenation.
abstract: OBJECTIVE
  Barbiturate-induced coma can be used in patients to treat intractable intracranial hypertension when other therapies, such as osmotic therapy and sedation, have failed. Despite control of intracranial pressure, cerebral infarction may still occur in some patients, and the effect of barbiturates on outcome remains uncertain. In this study, we examined the relationship between barbiturate infusion and brain tissue oxygen (PbtO2).
  
  
  METHODS
  Ten volume-resuscitated brain-injured patients who were treated with pentobarbital infusion for intracranial hypertension and underwent PbtO2 monitoring were studied in a neurosurgical intensive care unit at a university-based Level I trauma center. PbtO2, intracranial pressure (ICP), mean arterial pressure, cerebral perfusion pressure (CPP), and brain temperature were continuously monitored and compared in settings in which barbiturates were or were not administered.
  
  
  RESULTS
  Data were available from 1595 hours of PbtO2 monitoring. When pentobarbital administration began, the mean ICP, CPP, and PbtO2 were 18 +/- 10, 72 +/- 18, and 28 +/- 12 mm Hg, respectively. During the 3 hours before barbiturate infusion, the maximum ICP was 24 +/- 13 mm Hg and the minimum CPP was 65 +/- 20 mm Hg. In the majority of patients (70%), we observed an increase in PbtO2 associated with pentobarbital infusion. Within this group, logistic regression analysis demonstrated that a higher likelihood of compromised brain oxygen (PbtO2 < 20 mm Hg) was associated with a decrease in pentobarbital dose after controlling for ICP and other physiological parameters (P < 0.001). In the remaining 3 patients, pentobarbital was associated with lower PbtO2 levels. These patients had higher ICP, lower CPP, and later initiation of barbiturates compared with patients whose PbtO2 increased.
  
  
  CONCLUSIONS
  Our preliminary findings suggest that pentobarbital administered for intractable intracranial hypertension is associated with a significant and independent increase in PbtO2 in the majority of patients. However, in some patients with more compromised brain physiology, pentobarbital may have a negative effect on PbtO2, particularly if administered late. Larger studies are needed to examine the relationship between barbiturates and cerebral oxygenation in brain-injured patients with refractory intracranial hypertension and to determine whether PbtO2 responses can help guide therapy.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsyvania 19104, USA.
authors.forename: H Isaac
authors.initials: HI
authors.lastname: Chen
authors.forename: Neil R
authors.initials: NR
authors.lastname: Malhotra
authors.forename: Mauro
authors.initials: M
authors.lastname: Oddo
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Heuer
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Levine
authors.forename: Peter D
authors.initials: PD
authors.lastname: LeRoux
mesh_terms: D000328:Adult; D000368:Aged; D001463:Barbiturates / Q000008:administration & dosage*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D003422:Critical Care / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D019586:Intracranial Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010100:Oxygen / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001463:Barbiturates; D010100:Oxygen