Experimental study of the detrimental effect of dopamine/glucagon combination in d,l-propranolol intoxication.
1. Respiratory and cardiovascular failure are the principle toxic effects of beta-blocker overdose. Respiratory arrest is the primary cause of death in beta-blocker intoxicated rats. 2. The effect of glucagon, dopamine and the combination of glucagon/dopamine on respiratory and cardiovascular function and survival time in beta-blocker overdose was investigated in a model of acute d,l-propranolol (resp. 30 and 15 mg kg-1 h-1 in rat and rabbit) intoxication in spontaneously breathing rats and artificially ventilated rats and rabbits. 3. Glucagon (initial dose of 100 micrograms kg-1 (bolus), followed by 1 microgram kg-1 min-1), dopamine (25 micrograms kg-1 min-1) or the combination of glucagon/dopamine did not improve survival time (ST) in d,l-propranolol intoxicated spontaneously breathing rats and artificially ventilated rats and rabbits, although some haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP), left ventricular pressure (LVPmax) and the differentiated left ventricular pressure (LVdp/dtmax) temporarily improved. 4. Survival time was considerably reduced in d,l-propranolol intoxicated spontaneously breathing and artificially ventilated rats treated with a combination of glucagon/dopamine, which induced a decrease in PaO2 and pH and an increase in PaCO2 partly due to ventilation/perfusion mismatch. 5. The combination of glucagon/dopamine should be used carefully in the treatment of beta-blocker overdose in man.
Toet
A E
AE
National Poison Control Centre, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Wemer
J
J
Vleeming
W
W
te Biesebeek
J D
JD
Meulenbelt
J
J
de Wildt
D J
DJ
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D004347:Drug Interactions; D062787:Drug Overdose / Q000188:drug therapy; D005934:Glucagon / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000097:blood; D008297:Male; D010313:Partial Pressure; D011433:Propranolol / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000188:drug therapy / Q000401:mortality; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D013237:Stereoisomerism; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D007773:Lactates; D005934:Glucagon; D011433:Propranolol; D002118:Calcium; D004298:Dopamine