The Effect of Hyperglycemia on Cocaine Neurotoxicity and Death in Mice

Abstract

Abstract. Objective: Cocaine toxicity frequently manifests as seizures and status epilepticus. Frequently, dextrose is administered to patients with cocaine-induced seizures. The objective of this study was to examine the effect of pre-existing hyperglycemia on cocaine neurotoxicity and death in mice. Methods: Swiss albino mice received intraperitoneal dextrose at a dose of 1 g/kg (12.5%) (hyperglycemic group, n = 98). The euglycemic group (n = 98) received an equal volume of 0.9% saline. After 60 minutes, all the animals received intraperitoneal cocaine at a dose of 90 mg/kg. The times to onset of ataxia, seizure, and death were recorded in seconds. Times to events were compared using a Kaplan-Meier method and results were compared using the logrank test. The overall percentage outcomes were compared using chi-square. Results: The ataxia rates (hyperglycemic 97%, euglycemic 97%, 2 = 0, p = 1), seizure rates (hyperglycemic 85%, euglycemic 82%, 2 = 0.292, p = 0.589), and survival rates (hyperglycemic 62%, euglycemic 51%, 2 = 0.2514, p = 0.113) were similar between the groups. The survival following a seizure was significantly higher in the hyperglycemic group (hyperglycemic 57%, euglycemic 41%, 2 = 4.439, p = 0.035). The median ataxia time was earlier in the hyperglycemic group (190 sec) than in the euglycemic group (166 sec) (p = 0.031). Seizures occurred no earlier in the hyperglycemic group (331 sec) than in the euglycemic group (342 sec) (p = 0.207). Survival times were not different for the hyperglycemic group (9,133 sec) and the euglycemic group (7,593 sec) (p = 0.394). Survival times following seizures were not different for the hyperglycemic group (8,095 sec) and the euglycemic group (5,816 sec) (p = 0.0752). Conclusions: In mice with pre-existing hyperglycemia, ataxia occurred earlier and survival following cocaine-induced seizures was longer than for euglycemic mice. No significant difference in the overall percentage of seizures and death was detected. Pre-existing hyperglycemia had minimal effect on worsening cocaine toxicity in mice. Key words: cocaine; neurotoxicity; hyperglycemia. ACADEMIC EMERGENCY MEDICINE 2000; 7:974-979 C OCAINE is a frequent cause of seizures and status epilepticus treated by emergency physicians and out-of-hospital care providers. The initial management of all seizures includes stabilization of the airway and cervical spine, ensuring adequate oxygenation, and evaluation and treatment of hypoglycemia. Glucose determination is important because hypoglycemia is a common cause of seizures and status epilepticus, and can easily be corrected by the administration of dextrose. 1Many out-of-hospital care protocols administer dextrose without an evaluation of the glucose level. In addition, some physicians recommend the administration of dextrose if the bedside determination is less than 120 mg/dL because these tests may not detect hypoglycemia if a lower level is used. 2Hyperglycemia worsens neurologic outcome and increases mortality in experimental models of cerebral ischemia.3-5 Co...