Brian J. Zink

Life sometimes creates interesting confluences, and these should not be ignored. I was the Chair who sat on the other side of the desk during the job interview of the author of this remarkable essay. I hired her, and her husband. I was pleased to bring them both on board as promising new faculty members.

Ethanol predisposes to traumatic injury and causes respiratory depression and cardiovascular compromise in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). Endogenous opioids may play a role in ethanol intoxication and TBI. We studied the effects of ethanol and the opiate antagonist agent naltrexone (NTX) in a TBI/HS model. Fifty-six pigs (20 kg) were anesthetized with isoflurane, intubated, instrumented, and subjected to fluid percussion TBI with concurrent 30 ml/kg hemorrhage over 30 min. Seven groups were studied: Control, EtOH, NTX, INJ, INJ/EtOH, INJ/NTX, and INJ/EtOH/NTX. Ethanol (2 g/kg IV) was given preinjury, followed by infusion of 0.4 g/kg/hr. NTX 0.3 mg/kg intravenous was given 5 min postinjury. Parameters monitored for 120 min postinjury included minute ventilation (VE), blood pressure (MAP), cerebral perfusion pressure (CPP), cerebral venous lactate (Lac), arterial and cerebral venous blood gases, and brain tissue PtiO2. Ethanol levels at injury were 220 mg/dL. Ethanol-treated animals had depression of hypercapnic ventilatory response, which was reversed by administration of naltrexone. MAP and CPP were significantly lower in injured animals, but were not significantly improved by NTX. Cerebral venous pH was lower and lactate was higher in ethanol-treated animals. In this TBI/HS model, NTX reverses ethanol-induced depression of hypercapnic ventilatory response but does not improve MAP, CPP, or metabolic acidosis. This suggests that the respiratory effects of ethanol in TBI, but not the hemodynamic effects, may be mediated by opiate receptor activation.

Object. Traumatic brain injury (TBI) is exacerbated by hypotension and hypoventilation. Because previous studies have shown a potentiating effect of ethanol (EtOH) on TBI and hemorrhagic shock (HS), the authors investigated the effects of EtOH on the early physiological response to TBI with and without HS. Methods. Anesthetized swine, weighing approximately 20 kg each, underwent fluid-percussion TBI of 3 atm with or without 30 ml/kg hemorrhage for a period of 30 minutes. The mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure (CPP), cardiac output, cerebral venous oxygen saturation, and metabolic parameters were monitored for 3 hours postinjury. Ventilation and the response to hypercapnia were also measured. Regional cerebral blood flow and renal blood flow were measured using dye-labeled microspheres. Five groups were studied: control, TBI, TBI/EtOH, TBI/HS, and TBI/HS/EtOH. The EtOH (3.5 g) was given intragastrically 100 minutes preinjury. The TBI/HS/EtOH group demonstrated a 3-hour mortality rate of 56% and postinjury apnea requiring ventilation in 44% of animals compared with 0% in all other groups. Minute ventilation and the hypercapnic ventilatory response were significantly reduced in the postinjury period in the TBI/HS/EtOH group. The animals in this group had significantly lower CPP and cardiac output in the first 60 minutes postinjury, as well as lower renal and cerebral blood flow. Postinjury cerebral venous lactate levels were higher, and cerebral venous pH was lower in the TBI/HS/EtOH group. Conclusions. In this model of TBI, acute EtOH intoxication in the presence of HS potentiates the physiological and metabolic alterations that may contribute to secondary brain injury.

Objectives: Given that clinical and laboratory studies suggest that ethanol and hemorrhagic shock (HS) potentiate traumatic brain injury (TBI), the authors studied the effects of ethanol in a model of combined TBI and HS. Methods: A controlled porcine model of combined TBI and HS was evaluated for the effect of ethanol on survival time, hemodynamic function, and cerebral tissue perfusion. Anesthetized swine (17–24 kg) were instrumented, splenectomized, and subjected to fluid percussion TBI with concurrent 25‐mL/kg graded hemorrhage over 30 minutes. Two groups were studied: control (n= 11) and ethanol (n= 11). Ethanol, 3.5 g/kg intragastric, was given 100 minutes prior to TBI/HS. Systemic and cerebral physiologic and metabolic parameters were monitored for 2 hours without resuscitation. Regional cerebral blood flow (rCBF) and renal blood flow were measured with dye‐labeled microspheres. Data were analyzed with 2‐sample t‐test and repeated‐measures ANOVA. Results: Ethanol levels at the time of injury were 162 ± 68 mg/dL. Average TBI was 2.65 ± 0.35 atm. Survival time was significantly shorter in the ethanol group (60 ± 27 min vs 94 ± 28 min, p = 0.011). The ethanol group had significantly lower mean arterial pressure, cerebral perfusion pressure, and cerebral venousO₂ saturation in the postinjury period. Cerebral O₂ extraction ratios and cerebral venous lactate levels were significantly higher in the ethanol group. A trend toward lower postinjury rCBF in all brain regions was observed in the ethanol group. Conclusion: In this TBI/HS model, ethanol administration decreased survival time, impaired the hemodynamic response, and worsened measures of cerebral tissue perfusion.

Motor vehicle crash (MVC) studies have found that alcohol (ALC) is associated with increased mortality and decreased time to death (TTD). Clinical and experimental data suggest that ALC potentiates central nervous system injury (CNSI). We hypothesize that ALC-intoxicated, MVC fatalities with CNSI are more likely to die in the immediate postinjury period than are sober victims with CNSI. Methods; A retrospective cohort of 401 MVC fatalities from four Michigan counties for the time period 1985 to 1991 was studied. Medical examiner records were reviewed to determine age, blood alcohol concentration (BAC), and TTD. Injury severity was calculated with the Abbreviated injury Scale (1985 version). Anatomical profile scores and G scores were also calculated and used to identify CNSI subjects. chi 2 and Student's t test were used, and odds ratios with 0.95 confidence intervals (CIs) were calculated. ALC(+) cases (BAC > or = 100 mg/dl) (n = 99) were significantly younger and more frequently had TTD < 1 hr than ALC(-) cases (n = 233): odds ratio 1.62[0.95 CI (1.02 to 2.58)]. Overall, CNSI cases (n = 297) were significantly younger and had fewer thoracic injuries, but did not have significantly shorter TTD, compared with non-CNSI cases. However, ALC(+) CNSI cases (n = 77) were over twice as likely to have TTD < 1 hr ¿odds ratio 2.04 [0.95 CI (1.13 to 3.70)]¿. For ALC(+) isolated CNSI cases, the odds ratio for TTD < 1 hr, compared with nonisolated CNSI cases was 8.25 (0.95; CI 0.66 to 102.5). Injury Severity Score, anatomical profile, and G scores were not significantly different for ALC(+) CNSI cases, compared with ALC(-) CNSI cases, whether isolated or nonisolated. These data suggest that alcohol intoxication is associated with increased frequency of early death in MVC victims with CNSI, despite there being no detectable difference in anatomical injury scoring.