Most of the cardiotoxic drugs are membrane stabilizing agents (MSA). Already in the 1980s, Henry and Cassidy [1] showed that, for any pharmacological class of drugs, the mortality rate from poisoning is significantly increased if the involved drugs possess a MS effect in addition to their main pharmacological activity.

Membrane-stabilizing effect consists in the inhibition or total abolishing of action potentials from being propagated across the cell membranes. Substances with such effect interact with phospholipids in the cellular membranes, closing the sodium channels and therefore preventing the cell depolarization (action potential phase 0). For all the excitable cells (smooth or striated muscle cells, neurons, heart conduction system cells), this translates into (a) increased excitability threshold and (b) reduced conduction and automaticity. Cardiovascular, respiratory, and nervous system are mostly affected. Drugs with MS effect are Vaughan Williams class I antiarrhythmics, beta-blockers, antimalarial drugs, tricyclic antidepressants, phenothiazine, and cocaine. Other cardiotoxic drugs (without MS effect) are digoxin and calcium channel blockers (particularly verapamil). MSAs, digoxin, and calcium channel blockers are commonly prescribed drugs (apart from cocaine, which – though illegal – is a popular recreational drug), and this explains the prevalence of their abuse, which is almost always intentional (aiming to suicide or toxicomania related). Notably, when used for suicidal purposes, poisoning relies on the intake of multiple MSA.

Besides symptoms and signs that are typical for each class of substances, all the cardiotoxic drugs (MSA especially) lead to a common clinical scenario ruled by respiratory depression, metabolic disturbances, and – obviously – cardiovascular effects. The most typical presentation of severe cardiotoxicity consists in hypotension and/or severe cardiogenic shock. The electrophysiological alterations induced by the MSA lead to alterations on the electrocardiogram, typically enlarged QRS complexes and prolonged QT interval. In the most severe forms, disturbances of the atrioventricular conduction and ventricular arrhythmias (from tachycardia to fibrillation) can appear.

The delay in onset of life-threatening events depends on the toxicant and its galenic formulation, the ingested dose, the duration of QRS length on echocardiogram for the MSA, and the occurrence of mixed cardiotropic poisonings [4]. The delay is up to two hours after ingestion for class I antiarrhythmics [5] and of about 6 h for polycyclic antidepressants [6], chloroquine [7], and beta-blockers [8]. As reported by Baud et al. in an interesting review [4], in a non-negligible portion of cases, drug-induced cardiovascular shock does not result from a decreased cardiac contractility, but rather from a combination between relative hypovolemia and arterial vasodilation. This is well recognized for calcium channel blockers [2], less known for polycyclic antidepressants and chloroquine, and can be underestimated for labetalol poisoning. Therefore, in drug-induced cardiovascular shock with apparent refractoriness to conventional treatment, it is mandatory to perform a hemodynamic examination (using either right heart catheterization or echocardiography) to assess the mechanisms of shock before considering indication to mechanical support. In the same article by Baud, it was reported that, in 137 consecutive cases of severe MSA poisoning, survival rate for medically treated patients (catecholamines support in addition to specific treatments) was 72 %. Once again, this confirms that conventional therapy and pharmacological inotropic support are effective in most cases, while mechanical support must be restricted to the most severe forms only.

When treatment fails, death is usually related to ventricular arrhythmias, electromechanical dissociation, asystolia (usually preceded by other disturbances of the cardiac rhythm not responding to medical therapy), refractory cardiogenic shock, or cerebral death (the latter being common in patients who were found by rescuers in cardiocirculatory arrest).

Already in 2001, long before the resurrected interest in extracorporeal membrane oxygenation (ECMO) in many intensive care units around the world (fueled by the surprisingly good outcomes for its support in the 2009 A/H1N1 pandemic influenza), the toxicologic-oriented advanced cardiac life support (TOX-ACLS) guidelines stated that evidence supported the use of circulatory assist devices such as intra-aortic balloon pumps (IABPs) and emergency cardiopulmonary bypass (CPB) in the management of drug-induced cardiovascular shock refractory to maximal therapy [9].

Evidence comes from experimental studies and small clinical series. Five experimental studies with control group have been published [10–14]. In all of these studies, cardiogenic shock from MSA intoxication was induced. Drugs involved were lidocaine in 6 dogs [10], amitriptyline in 6 dogs [11] and 9 swines [12], desipramine in 6 dogs [13], and propranolol plus procainamide in 17 dogs [14]. The animals were assigned either to maximal supportive measures (i.e., correction of acid-base disturbances, fluid resuscitation, antiarrhythmics, inotropic support, or cardiopulmonary resuscitation, but no specific therapy for the intoxicant) or to mechanical support to circulation, by means of extracorporeal life support (ECLS) [10–13] or IABP [14]. In all of the studies, mechanically supported animals were all successfully weaned, while weaning rate in control groups ranged from 10 to 25 % only.

Clinical reports of mechanical support for cardiogenic shock in drug intoxication will be examined later in this chapter.

Mechanical circulatory support in cardiogenic shock due to drug intoxication may rely on the use of IABP, CPB, or ECMO.