ABSTRACT
BACKGROUND: High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. METHODS: This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. RESULTS: 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. CONCLUSION: HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.
Subject(s)
Disease Models, Animal , Heart/drug effects , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Poisons/toxicity , Shock, Cardiogenic/drug therapy , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/poisoning , Animals , Animals, Inbred Strains , Arterial Pressure/drug effects , Blood Glucose/analysis , Cardiac Output/drug effects , Dose-Response Relationship, Drug , Glucose/administration & dosage , Glucose/metabolism , Heart/physiopathology , Heart Rate/drug effects , Hypoglycemic Agents/therapeutic use , Infusions, Intravenous , Insulin/therapeutic use , Placebos/administration & dosage , Propranolol/administration & dosage , Propranolol/antagonists & inhibitors , Propranolol/poisoning , Prospective Studies , Shock, Cardiogenic/chemically induced , Shock, Cardiogenic/metabolism , Shock, Cardiogenic/physiopathology , Sus scrofa , Vascular Resistance/drug effectsABSTRACT
We performed a retrospective review of data based on poison center exposure inquiries related to chlorpyrifos (CP) and the corresponding poison center-determined medical outcomes reported to the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers. Ten y (1985-1994) of TESS data were obtained. Medical outcomes representing all inquiries, accidental/unintentional inquiries, and intentional/suicidal inquiries were tabulated. Published TESS data was also tabulated to allow comparison of CP exposure inquiries to all non-pharmaceutical and insecticides/pesticides exposure inquiries for like time periods. Frequency of antidote use, product sales data, CP-related fatality reports, and pertinent issues related to telephone derived surveillance data were also reviewed; 36, 183 CP exposure inquiries were identified. Of all CP exposure inquiries, 27, 473 (75.9%) were assessed as having no significant health consequences; 4,511 (12.5%) outcomes were judged unrelated and 2,980 (8.2%) were unable to be followed. Reported significant medical outcomes for the remaining exposure inquiries were moderate 1,092 (3.0%), major 119 (0.3%) and death 8 (0.02%). Considering only calls with outcomes judged causally related to CP, where a given level of effect could reasonably be determined, 95.8% (27,473/28,692) of these calls resulted in no significant health effects. Use of antidotes specific to organophosphates were infrequent [atropine, 1.0% (385) and 2-PAM, 0.5% (177) of all cases respectively]. Despite the number of reported CP exposure inquiries, relatively few resulted in outcomes of consequence. TESS data suggested that the majority of patients undergoing medical evaluation and/or treatment after a suspected CP exposure do not require specific antidotes. TESS data serves as a useful first step in evaluating product safety. Assessment of product toxicity requires additional investigation of reported adverse effects and circumstances related to the incident.
