Catecholamines should be tested as the next step for refractory CCB overdose. The predominant mechanism by which all catecholamines increase cardiac function and systemic vascular resistance is through binding to two membrane receptors. Activation of the b1 adrenoreceptor increases cardiac cAMP in a postreceptor manner identical to glucagon and causes increased heart rate and force of cardiac contration. Activation of the a 1 receptor causes an increase in vascular smooth muscle tone and increases cardiac inotropy via a mechanism separate from the cAMP-protein kinase pathway. Dopamine is the most commonly used agent and can be given in doses standard for cardiogenic shock (1-20 pg/kg/h).16 Other catecholamines such as dobutamine, norepinephrine, and isoproterenol have been used in patients and animal studies with variable success. Epinephrine also has shown benefit in CCB-intoxicated humans and animals. —I8 and !9 However, in one clinically relevant dog model of verapamil toxicity, epinephrine tended to worsen heart function and did not improve survival compared with saline treatment. 20 If epinephrine is used, a trial of 0.1 pg/kg/min can be titrated to a maximum of 1.0 pg/kg/min. If there is no satisfactory improvement within 5 min of the maximum infusion rate, then epinephrine should be discontinued in favor of an alternative agent.
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