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Experimental study of the detrimental effect of dopamine/glucagon combination in d,l- propranolol intoxication

National Poison Control Centre, National Institute of Public Health and Environmental Protection, PO Box 1, Department of Intensive Care and Clinical Toxicology, Utrecht University Hospital, PO Box 85.500, 3508 GA Utrecht, The Netherlands

J. Wemer

Laboratory of Toxicology, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands

W. Vleeming

Laboratory of Toxicology, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands

JD te Biesebeek

Laboratory of Toxicology, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands

J. Meulenbelt

National Poison Control Centre, National Institute of Public Health and Environmental Protection, PO Box 1, Department of Intensive Care and Clinical Toxicology, Utrecht University Hospital, PO Box 85.500, 3508 GA Utrecht, The Netherlands

DJ de Wildt

Laboratory of Toxicology, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands, Rudolf Magnus Institute for Neuroscience, Department of Medical Pharmacology, Utrecht University, PO Box 80.040, 3508 TA Utrecht, The Netherlands

1 Respiratory and cardiovascular failure are the princi ple toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats.

2 The effect of glucagon, dopamine and the combination of glucagon/dopamine on respiratory and cardiovas cular function and survival time in β-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 artifically ventilated rats and rabbits.

3 Glucagon (initial dose of 100 µg kg^-1 (bolus), followed by 1 µg kg ^-1 min^-1), dopamine (25 µg kg^-1 min^-1 ) or the combination of glucagon/dopamine did not im prove survival time (ST) in d,l-propranolol intoxicated spontaneously breathing rats and artificially venti lated rats and rabbits, although some haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP), left ventricular pressure (LVP_max) and the differentiated left ventricular pressure (LVdp/ dt_max) temporarily improved.

4 Survival time was considerably reduced in d,l- propranolol intoxicated spontaneously breathing and artifically 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 β-blocker overdose in man.

Key Words: dopamine • glucagon • propranolol intoxication • re spiratory function • cardiovascular function • survival

Human & Experimental Toxicology, Vol. 15, No. 5, 411-421 (1996)
DOI: 10.1177/096032719601500509


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