Eugene D. Robin, MD; Ronald J. Wong, BS; Kay A. Ptashne, PhD
Study Objective: To determine the effect of massive cocaine intoxication on lung water and ascites accumulation and the effect of beta- and alpha-adrenergic blockade on survival in massive cocaine intoxication in the mouse.
Design: The effect of massive cocaine intoxication on lung water, ascitic fluid accumulation, and survival following LD 100 doses of intravenous cocaine with and without alpha- and beta-adrenergic blockade was determined.
Interventions: Cocaine hydrochloride (0. 15 mg/g body weight) was administered intravenously with no other interventions; with propranolol hydrochloride intravenously (0.5 mg per mouse) before and after cocaine; and with phentolamine intravenously (10.5 µg per mouse) before cocaine.
Measurements and Main Results: Intravenous cocaine hydrochloride resulted in an increase in lung water (saline controls, 4. 17 it 1.3 [standard deviation] mg water per mouse; cocaine hydrochloride, 5.94 + 0.9 mg water per g mouse; P < 0.002). Cocaine hydrochloride always resulted in the accumulation of transudative ascitic fluid (saline controls, no measurable ascitic fluid; cocaine administration, 20.2 ± 12.9 µg per mouse; ascitic fluid protein concentration, 23.5 ± 8.5 g/L). Propranolol hydrochloride administered before or after intravenous cocaine hydrochloride resulted in a striking reduction in mortality (84 of 84 mice without propranolol died [mortality = 100%]; 7 of 39 mice with propranolol died [mortality = 18%]; P < 0.001).
Conclusions: Massive cocaine intoxication is associated with increased lung water and transudative ascites. Fluid accumulation is not prevented by either alpha- or beta-adrenergic blockers. Propranolol, administered either before or after cocaine, sharply reduces mortality. The results should be extrapolated to treatment in humans with caution.
Robin ED, Wong RJ, Ptashne KA. Increased Lung Water and Ascites after Massive Cocaine Overdosage in Mice and Improved Survival Related to Beta-Adrenergic Blockage. Ann Intern Med. 1989;110:202–207. doi: 10.7326/0003-4819-110-3-202
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Published: Ann Intern Med. 1989;110(3):202-207.
Pulmonary/Critical Care, Tobacco, Alcohol, and Other Substance Abuse.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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