Studies on the cardiovascular and respiratory effects of rapidly acting barbiturates in the dog.

Abstract

The potency of three barbiturates (thiopentene, thiamylal and methohexitone) used in intravenous anaesthesia in dogs was compared. Thiamylal compared with thiopentone (l) was found to have a potency of 1.06 (laryngoscope reflex) and:l.22 (pedal reflex). The ED50 for thiamylal was shown to be l8.4_mg_kg"1 at which dose 38% of dogs developed apnoea. Thiamylal did not cause full depression of reflexes until at least two and a half minutes after administration. Methohexitone compared with thiopentone (l) was found to have a potency of 2.0 (larnygoscope reflex) and 2.64 (pedal reflex). The E050 for methohexitone was shown to be 9.7mgkg'1 at which dose 52% of dogs developed apnoea. Thiopentone was found to have an E050 of l9.4mgkg'] at which dose l7% of dogs developed apnoea. At the accepted clinical dose rates recovery with methohexitone was approximately half the duration of thiopentone and thiamylal.

The administration of thiopentone produced tachycardia, mild nwocardial depression, systemic vasodilation and pulmonary vasoconstriction. Immediate reversal of the systemic vascular effects (except heart rate and stroke volume) occurred as a result of sympathetic nervous system stimulation. These effects were consistent with stimulation of both a and B-adrenergic receptors and appeared to be a direct effect of the drug rather than a reflex response. Thiopentone caused moderate hypoxaemia and mild transient respiratory depression.

The administration of thiamylal produced tachycardia, mild myocardial depression, systemic vasodilation and severe pulmonary vasoconstriction. Immediate reversal of the effects on the heart and systemic circulation (except heart rate and stroke volume) occurred as a result of sympathetic nervous stimulation. The effects were consistent with stimulation of both a and B-adrenergic receptors and appeared to be a direct effect of the drug rather than a reflex response. Thiamylal caused moderate hypoxaemia and mild respiratory depression.

The administration of methohexitone produced tachycardia, moderate myocardial depression, severe hypotension, systemic vasodilation and pulmonary vasoconstriction. The initial effects on the heart and systemic circulation (except heart rate and stroke volume) were partially reversed by sympathetic nervous system stimulation. The systemic effects were consistent with B-adrenergic stimulation only. Methohexitone produced moderate hypoxaemia and very transient respiratory depression.

When equipotent doses were administered methohexitone produced a more profound fall in aortic pressure, which returned to control more slowly than the thiobarbiturates. Methohexitone produced a greater rise in aortic flow and contractility after the initial depression than the thiobarbiturates. Thiamylal produced the most severe pulmonary vascular changes and the most severe and longest lasting respiratory depression.

When thiopentone was administered to dogs in B-adrenergic blockade there was less increase in heart rate and a slower return to control of the arterial pressure fall than in autonomically intact dogs. There was a greater rise in left atrial pressure, systemic vascular resistance and pulmonary vascular resistance. Contractility was depressed. These findings indicated that B-adrenergic stimulation markedly modifies the cardiovascular responses of dogs to thiopentone anaesthesia.

When thiopentone was administered to dogs in a-adrenergic blockade ‘ there was a greater rise in heart rate, contractility and aortic flow and less rise in pulmonary vascular resistance than in autonomically intact dogs. These findings indicate modification of the cardiovascular responses of thiopentone anaesthesia by a-adrenergic stimulation, particularly during the first minute after 'administration.