DEVELOPMENT OF THE TOXICOLOGY SECTION OF THE AMERICAN HEART ASSOCIATION'S (AHA) GUIDELINES 2000 FOR CARDIOPULMONARY RESUSCITATION AND EMERGENCY CARDIOVASCULAR CARE (ECC)

Background: The evidence- and consensus-based development of these published guidelines for poisoned patients will be reviewed.[1] The scarcity of RCT on these topics made an exclusively evidence-based evaluation impossible. This work highlights the need for properly designed clinical studies in developing medical toxicology treatment guidelines. The following topics, evidence overview and recommendations will be discussed. Use of alpha- and beta-adrenergic receptor antagonists in the management of cocaine-associated, acute coronary syndrome (Coc-ACS): The reviewed evidence consisted of 2 randomized clinical trials (RCT) of very good quality, 1 prospective study and 4 cath lab studies of very good to excellent quality, three case series of poor to fair quality and 4 animal studies of good to excellent quality. Recommendations: First line therapies of Coc-ACS include nitrates and benzodiazepines. The use of an alpha-adrenergic receptor antagonist (i.e. phentolamine) should be considered in Coc-ACS patients refractory to vigorous nitrate and benzodiazepine therapy. The use of non-selective beta-adrenergic receptor blockers (i.e. propranolol) is contraindicated in Coc-ACS. Non-selective beta-adrenergic receptor blockers may worsen cocaine induced hypertension and/or coronary vasoconstriction. The use of selective beta-adrenergic receptor blockers (i.e. esmolol and metoprolol) and mixed alpha/beta-adrenergic receptor blockers (i.e. labetalol) are not recommended in Coc-ACS. Use of bicarbonate, lidocaine, propranolol and epinephrine in cocaine-associated, ventricular tachycardia or fibrillation (Coc-VT/VF): For bicarbonate in Coc-VT, two very small case series of good quality and 7 animal studies of fair to good quality were reviewed with most addressing the electrophysiological effects and only one specifically addressing Coc-VT. For lidocaine in Coc-VT, one retrospective clinical study of good quality and 5 animal studies of fair to good quality were reviewed with most addressing the electrophysiological effects and only one specifically addressing Coc-VT. On the safety of lidocaine when given in cocaine toxicity, three animal studies were reviewed. For propranolol in Coc-VT/ VF, 2 animal studies of good quality were reviewed with both addressing ventricular arrhythmias. There were no studies of the efficacy of epinephrine in Coc-VF. Recommendations: First-line drug therapies for hemodynamically stable Coc-VT or refractory Coc-VF are sodium bicarbonate and lidocaine. The use of non-selective beta-adrenergic receptor blockers (i.e. propranolol) is contraindicated in Coc-VT. Use of calcium in calcium channel blocker (CCB) and beta-blocker (BB) poisoning: Evidence evaluated included 2 case series of fair to very good quality, 10 animal studies of good to excellent quality and numerous case reports concerning the use of calcium in CCB poisoning. There are more than 130 published case reports on the use of calcium in calcium channel blocker poisoning. Because multiple treatments were usually attempted and severity of poisoning quite varied, it was impossible to reach definitive conclusions from them. Recommendations: First-line drug therapy for calcium channel blocker CCB drug-induced shock (DI shock) remains catecholamine type vasopressors. Calcium chloride infusions (1-3 gm slow IV push) are recommended in CCB-induced shock refractory to conventional catecholamine vasopressor therapy. Additional calcium infusions via bolus or constant infusion would be warranted in patients demonstrating a beneficial hemodynamic response to the initial calcium infusions. Calcium infusions may be beneficial in other types of drug induced (DI) shock but cannot be recommended because of limited supportive data. Use of insulin euglycemia in CCB and BB poisoning: Evidence reviewed included 1 small case series of fair quality and 8 animal studies that were of very good to excellent quality. Recommendation: Insulin-euglycemia '-pump or -clamp' therapy may be beneficial in CCB-DI shock and BB-DI shock but cannot be recommended because of limited supportive data. Timing of assisted ventilation and dose of naloxone in opiate-induced respiratory failure: There were no articles, which compared the safety and efficacy of naloxone reversal of opioid overdose before or after the initiation of artificial ventilation. The impact of naloxone therapy on blood catecholamine levels was evaluated in two prospective human trials of good quality and four animal studies of good to very good quality. Four cases series of good to very good quality were reviewed for data on efficacy and safety of opioid reversal in ECC. Recommendation: Assisted ventilation and reversal with an opioid antagonist, such as naloxone, should be attempted as soon as possible and prior to intubation in patients with a palpable pulse. Naloxone therapy need not be withheld until assisted ventilations have begun. In opioid dependent patients, a lower initial dose of naloxone (i.e. 0.1-0.2 mg IV, repeated until 0.4 mg) is preferable to a larger initial dose (i.e. 2.0 mg IV). When an opioid overdose is suspected, one should not conclude that the patient was unresponsive until a total naloxone dose of 4-6 mg has been given. Systemic alkalosis in tricyclic antidepressant (TCA) poisoning: The evidence supporting the proposal consisted of four case series (n = 3, 4, 5 and 91) that were of good quality and 24 animal or in vitro studies that were of good to excellent quality. There was one small case report (n = 2) of fair quality with questionable opposing evidence. The numerous published individual cases reporting beneficial effects of systemic alkalosis in TCA poisoning were not included in this review. Recommendation: Sodium bicarbonate is the drug of choice for ventricular dysrhythmias and/or shock due to tricyclic antidepressant (TCA) poisoning. The beneficial effects of sodium bicarbonate result from systemic alkalosis and hypertonic sodium effects. More rapid systemic alkalosis may be achieved via hyperventilation but further benefit often results from the hypertonic sodium. In cases of serious TCA-induced CV toxicity, the goal is a systemic pH of 7.50-7.55. Intermittent bolus sodium bicarbonate administration is preferable to a constant infusion until the desired pH is attained. Procainamide for TCA-induced ventricular dysrhythmias: The panel members could find very little evidence on the use of procainamide in TCA-induced VT/VF. Reports of use in one dog and two rabbits and two case reports were reviewed. Recommendation: When TCA-VT/VF is resistant to sodium bicarbonate, lidocaine is the antiarrhythmic of choice. The use of procainamide for TCA-VT/VF is contraindicated. Because both procainamide and TCA have class Ia antiarrhythmic properties, procainamide would be expected to worsen TCA CV toxicity. Use of high dose vasopressors in DI shock in cases refractory to conventional therapy: Evidence supporting high dose vasopressors consisted 9 case reports of very good quality. Two animal that were either neutral or opposing were of good quality. Recommendation: In DI-shock refractory to conventional therapy, high dose vasopressors may be life saving. While most patients with refractory DI shock have a very low systemic vascular resistance (SVR), some patients have a very high SVR. Therefore, central hemodynamic monitoring should be implemented in patients with DI shock refractory to high dose vasopressors. In most cases vasopressors may be rapidly titrated until shock is adequately treated or recurrent ventricular dysrhythmias, signs of severe peripheral vasoconstriction or an excessively high SVR is observed. Use of circulatory assist devices (IABP or emergency bypass) in DI-shock refractory to maximal medical therapy: Evidence supporting the use of cardiopulmonary bypass consisted of 6 animal studies of very good quality and more than 30 case reports. Evidence supporting the use of the intra-aortic balloon pump consisted of 1 animal study of fair quality and more than 10 case reports. Recommendation: Circulatory assist devices may be live saving in DI-shock refractory to maximal medical therapy. If these heroic measures are to be effective, they must be implemented before the stage of irreversible shock has been reached. Early implementation usually requires advanced planning and approval from multiple disciplines including cardiology, cardiothoracic surgery and cardiopulmonary perfusion. Reference: [1] Circ 2000;102(suppl I):223-228.
Martin TG, Latorre F de, Ross MP, Albertson TE, Dawson A, Hoffman RS, Hollander JE, Jaeger A, Kerns W. UW Medical Toxicology Program, University of Washington Medical Center, Seattle, Washington, [...]