BACKGROUND: Cocaine intoxication is found in a significant subset of emergency department (ED) patients presenting with traumatic brain injury (TBI). OBJECTIVES: To investigate the effects of acute cocaine intoxication on physiologic and metabolic parameters in a model of experimental TBI. METHODS: Under inhalational anesthesia, swine were instrumented and subjected to fluid percussion TBI of 3 atm. Two groups were studied: TBI and cocaine (n = 7) and TBI only (n = 7). Two sequential doses of cocaine hydrochloride were administered intravenously to the animals receiving cocaine: 4 mg/kg 10 minutes prior to injury and 2 mg/kg 1 minute prior to injury. Control animals received normal saline. Cardiorespiratory and cerebral physiologic data were monitored for 180 minutes following injury. Cerebral blood flow (CBF) was measured using dye-labeled microspheres. Serum cocaine levels were measured by gas chromatography/mass spectrometry. RESULTS: Mean (+/- SD) cocaine levels at the time of injury were 1,771 (+/- 403) ng/mL. All animals survived the 180-minute observation period. There was a trend toward higher intracranial pressure (ICP) in the control (15.4 +/- 8.2) vs. cocaine-treated (11.1 +/- 5.8) animals, although this did not reach statistical significance (p = 0.18). Cerebral venous lactate (CVL) levels also trended higher in the control (1.14 +/- 0.22) vs. cocaine-treated (0.91 +/- 0.19) groups (p = 0.06). Cerebral perfusion pressures (CPPs), however, did not differ between groups. The CBF values decreased significantly from baseline in both groups but were not different between groups. CONCLUSIONS: Cocaine-intoxicated animals subjected to TBI showed no significant difference in primary outcome measures of CPP or CBF, although a nonsignificant trend toward lower ICP was noted. Overall, acute cocaine intoxication did not adversely affect the physiologic parameters examined in this TBI model.