title: Hemodynamic actions of acute ethanol after resuscitation from traumatic brain injury.
abstract: BACKGROUND
  The purposes of this study were to determine how clinically relevant levels of acute ethanol (EtOH) influence cerebral perfusion pressure (CPP), cerebral venous O saturation (Scvo ), and systemic hemodynamics after fluid resuscitation from traumatic brain injury (TBI); and to test the hypothesis that the actions of EtOH on these variables are mediated by adenosine.
  
  
  METHODS
  Anesthetized swine were ventilated (Fio = 0.4) and instrumented. In protocol 1, EtOH (3.5 g/kg, n = 11) or its vehicle (n = 17) was administered orally before TBI + 40% hemorrhage. At 90 minutes post-TBI, resuscitation consisted of shed blood + saline. In protocol 2, either saline (n = 15) or an adenosine-regulating agent (5-amino-4-imidazolecarboxamide riboside) in saline (1 mg/kg bolus + 12 mg/kg/h intravenously [i.v.]) (n = 5), was administered i.v. before TBI + 45% hemorrhage. At 90 minutes post-TBI, resuscitation consisted of saline only (three times shed blood volume). In protocol 3, EtOH was administered i.v. (1 g/kg; 20% vol/vol in saline) followed by either an adenosine receptor antagonist (theophylline, 10 mg/kg) or an adenosine uptake inhibitor (dipyridamole, 0.25 mg/kg).
  
  
  RESULTS
  In protocol 1, with no EtOH, 11 of 17 (65%) survived post-TBI hypotension. Mean arterial blood pressure, cardiac index, and mixed venous oxygen saturation were stable for 1 hour at 40% to 60% below their respective baselines, whereas lactate increased three- to fourfold (all p < 0.05). After fluid resuscitation, most variables rapidly corrected, but intracranial pressure was increased 10 to 15 mm Hg (p < 0.05). With EtOH, 9 of 11 (82%) survived post-TBI hypotension (p = 0.42 vs. no EtOH). After resuscitation from TBI, there were significant effects of EtOH on systemic hemodynamics (mean arterial pressure, cardiac index, mixed venous oxygen saturation), on CPP, on lactate, and on Scvo at normo- and hypercapnia (all p < 0.05). The data from protocol 2 showed that essentially none of these changes were duplicated with an adenosine-regulating agent. In protocol 3, i.v EtOH produced small but significant changes in Scvo, intracranial pressure, and lactate, at normo-, hyper-, and hypocapnia. Dipyridamole and theophylline tended to have opposite, albeit small and not statistically significant, effects on these variables relative to EtOH alone.(2) (2)
  
  
  CONCLUSIONS
  Acute EtOH (200-300 mg/dL) did not increase mortality after TBI + secondary hypotension, as long as cardiopulmonary support was provided. With EtOH, CPP was maintained and cerebral blood flow appeared to be adequate, if not excessive, with respect to cerebral metabolic demand, as judged by changes in Scvo at normo-, hyper-, and hypocapnia. These changes were probably not mediated, but might have been modulated, by increases in endogenous adenosine.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fabian
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Proctor
mesh_terms: D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology* / Q000628:therapy; D002245:Carbon Dioxide / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D005440:Fluid Therapy; D006439:Hemodynamics / Q000502:physiology*; D007427:Intracranial Pressure / Q000502:physiology*; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism*; D012151:Resuscitation / Q000379:methods; D012265:Ribonucleotides / Q000494:pharmacology; D013552:Swine; D013806:Theophylline / Q000494:pharmacology
chemical_list: D012265:Ribonucleotides; D002245:Carbon Dioxide; D000620:Aminoimidazole Carboxamide; D000431:Ethanol; D004176:Dipyridamole; D013806:Theophylline; C031143:AICA ribonucleotide; D010100:Oxygen