This is the first case of cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, in which percutaneous cardiopulmonary bypass was required for the patient to survive.

With regard to cardiotoxicity, Leonard et al. [14] investigated the association between exposure to antidepressants and emergency department or in-patient admission for sudden cardiac death and ventricular arrhythmia (SD/VA). Among 1.3 million person-years of antidepressant exposure, they identified 4222 SD/VA outcomes, which amounted to a rate of 3.3/1000 person-years (95% CI, 3.2–3.4). In comparison to paroxetine (a referent with a reportedly favorable cardiovascular risk profile), the adjusted hazard ratio (HR) for mirtazapine was 1.26 (1.11–1.42). They concluded that of the antidepressants that were studied, only mirtazapine had a statistically significantly greater SD/VA risk than paroxetine. A massive ingestion of boric acid generally induces metabolic acidosis, renal failure, and skin disturbance. However, boric acid can also induce lethal arrhythmia and cardiac failure [3, 4]. Accordingly, both boric acid and mirtazapine could have caused fatal cardiac arrest due to direct cardiac intoxication in this case. Regarding the toxic effects of sennosides in laboratory animals, the lethal dose 50 value was approximately 5000 mg/kg, and the cause of death was extensive water and electrolyte loss following massive diarrhea [15]. However, the patient in the present case did not ingest a fatal dose and dehydration was not observed; thus, the possibility that sennosides were involved in the patient’s cardiac arrest could be denied.

Percutaneous cardiopulmonary bypass may be helpful in cases of exposure to multiple serious toxicological agents that results in temporary cardiorespiratory failure or metabolic dysfunction. Percutaneous cardiopulmonary bypass alone does not remove or neutralize any toxins but does provide hemodynamic support and oxygenation until the toxins can be eliminated or end-organ recovery is achieved. A case series of 62 patients in France showed similar survival rates of 76% in patients receiving percutaneous cardiopulmonary bypass due to severe acute drug intoxication, with a lower overall mortality rate than in patients who received supportive care alone [16, 17]. The cardiotoxic effects of antidepressants are reported to be temporary, and there have been some cases in which patients who have exhibited unstable circulation due to overdose have also achieved social rehabilitation after percutaneous cardiopulmonary bypass treatment [18, 19]. The present case also demonstrated that the cardiotoxicity induced by the massive ingestion of mirtazapine and boric acid was a temporary effect.

However, whether or not percutaneous cardiopulmonary bypass can improve the survival in patients with cardiac arrest due to toxicological agent exposure remains unclear. Attempting to initiate percutaneous cardiopulmonary bypass during cardiac arrest is difficult, as it may require pausing cardiopulmonary resuscitation in order to cannulate and initiate the procedure, which may result in an unfavorable outcome. In addition, thoracic cage injury induced by chest compression may result in fatal complications due to coagulopathy after the initiation of percutaneous cardiopulmonary bypass, requiring heparinization [20]. Furthermore, our attempt to use percutaneous cardiopulmonary bypass to obtain social rehabilitation failed due to hypoperfusional cerebral ischemia induced by prolonged cardiac arrest, which has also been reported in patients who underwent percutaneous cardiopulmonary bypass after experiencing cardiac arrest triggered by other causes [21].

The indication of percutaneous cardiopulmonary bypass for poisoned patients remains a major problem. First, substantial resources and costs as well as a multidisciplinary team including toxicologists, intensivists, and surgeons, are required to perform and manage percutaneous cardiopulmonary bypass, so few facilities are equipped to activate it in a timely fashion [5]. Second, percutaneous cardiopulmonary bypass is associated with a number of potential complications, including limb ischemia, compartment syndrome, cerebral ischemia, acute kidney injury, bleeding, emboli, and infection [5]. Third, several factors must be considered on an individual basis, such as the patient’s age, comorbidities, risk for complications, survivability, specific drug or chemical involved in the exposure, and time of hypoperfusion or cardiac arrest [5]. Accordingly, further studies are needed in order to establish criteria for considering percutaneous cardiopulmonary bypass in poisoned patients.