ECMO: A ray of hope for young suicide victims with acute aluminum phosphide poisoning and shock.

Aluminum phosphide (ALP) is used commercially as an agricultural rodenticide/insecticide under various names in Indian subcontinent. Unfortunately, it has become a drug of choice among young adults for the purposes of suicide, especially in northern India, with very high mortality rates. When consumed orally it rapidly interacts with water and hydrochloric acid in the stomach to release phosphene gas, which is absorbed in the blood within 10–15 min. Therefore, if the victim her/himself does not vomit out the pills, the oral therapies administered in the emergency rooms to remove the toxic agent from the gastrointestinal tract are ineffective in majority of the cases. The dissolved phosphene gas in the circulation is distributed rapidly throughout the body and interacts at the cellular level with the mitochondria to inhibit oxidative phosphorylation in the multiple organs, especially the heart, lung, liver, and kidneys, within an hour. Therefore, by the time the victims arrive at the hospital (which in the present series was 7–8 h), the toxic effects on the organ systems are well established. Even if such patients are brought within an hour of ingestion of ALP pills, necessary antidote may not be available to neutralize the phosphene gas in the body, and all medical measures are aimed at supportive care in almost all cases, until the toxin is cleared via lungs and kidneys. If the patient survives, the cellular function returns to normal over the following five to seven days.

The major factor in mortality from acute ALP poisoning is the progressive development of severe left ventricular (LV) dysfunction, circulatory collapse, respiratory gas exchange impairment with development of systemic hypotension and metabolic acidosis. The reported variations in the mortality in various case reports may depend upon the level of cardiovascular and respiratory impairment in individual cases. In patients with milder degree of shock, supportive measures including fluids, ionotropic support, and intra-aortic balloon pump may help the patient survive until the phosphene toxin is cleared. However according to the available data, the mortality approaches 100% in patients with severe shock. As the LV dysfunction and respiratory impairment in patients with ALP poisoning are potentially reversible within 5–7 days, it may be useful to use extracorporeal life support system (ECLS) such as veno-arterial extracorporeal membrane oxygenation (VA ECMO) that can support both cardiovascular and lung functions temporarily in patients with severe shock, to potentially improve survival. How do we define “severe shock”. In the SHOCK trial, the cardiogenic shock was defined clinically as systolic blood pressure (SBP) of <90 mm of Hg for more than 30 min or use of inotropic support to maintain SBP >90 mm of Hg with evidence of systemic hypoperfusion (mental status change, decreased urine output, etc.). The authors defined “severe shock” based on the criteria of severe LV dysfunction (EF < 35%) associated with BP <80 mm of Hg in spite of ionotropic support, presence of severe metabolic acidosis (pH < 7.0), or both. The mortality rate of 87% with current conventional supportive care in their series does affirm the definition of “severe shock” and supports the indication for use of ECMO in this group of patients. Extracorporeal Life Support Organization (ELSO) guidelines suggest that ECLS should be considered, when the risk of mortality is 50% or greater, and is indicated, when the risk of mortality is 80% or greater. The survival rate of 67% in the patients with acute ALP poisoning (AALPP) treated with VA ECMO in the present series compares well with the data from ECLS registry report, in which the adults receiving ECMO for various respiratory, cardiac, and extracorporeal cardiopulmonary resuscitation indications had the survival rates to discharge or transfer of 58%, 40%, and 30% respectively.

The data for the use of ECMO in poisoning cases are limited. Recently Masson and colleagues published a retrospective cohort analysis of the role of ECMO in 14 out of 62 patients with cardiac arrest or severe shock due to poisoning from various cardio-toxic drugs at two French hospitals over a 10-year period.7, 8 The survival was significantly better in the patients receiving ECMO compared to conventional supportive therapy (86% vs 48%). ECLS support remained associated with lower mortality in multivariate analysis with an odds ratio of 0.18 (95% confidence interval 0.03–0.96, p = 0.04). Although this analysis does not include any patient with ALP poisoning, it nevertheless seems to support the use of ECMO in cases of severe shock unresponsive to conventional therapies in patients with cardiotoxic drug poisoning.

The pathophysiology of shock in patients with ALP poisoning may be multifactorial and different compared to other poisons, but the current observational cohort series do suggest that short-term mortality can be reduced significantly with ECMO in addition to conventional supportive measures. Even though mortality is improved with the use of ECMO in AALPP, it still remains high due to various factors such as the dose of the drug ingested, the time to presentation, time to initiation of care including ECMO, as well as the complications related to the device. The major complication related to ECMO is bleeding.6, 9 A recent meta-analysis by Cheng et al., analyzed the use of ECMO in a group of 1866 patients from 20 studies between 2000 and 2012, and discovered that ECMO utilized for cardiogenic shock or cardiac arrest was associated with major or significant bleeding rate of 41%. Acute renal insufficiency was present in 56% of patients with 46% requiring renal replacement therapy. It is difficult to know, whether progression of renal failure is part of the initial insult or worsening due to the device. The arterial ischemic complications’ rates due to the large size of the cannula are also high (lower extremity ischemia, 17%; fasciotomy or compartment syndrome, 10%; lower extremity amputation, 4.7%). However, the rates of these complications can be reduced with placement of distal perfusion sheath in the superficial femoral artery. Therefore, it is important that the use of ECMO for ALP poisoning with cardiogenic shock be restricted at centers with expertise in the use and management of extracorporeal life support systems. It is also important to consider the financial impact of ECMO on patients and their families, so its use can be avoided in patients already presenting late with severe multi-organ failure or after prolonged CPR with very low chance of survival. But it is also important to recognize that in India, the majority of these cases are young adults with no other significant comorbidities, who will have significant lifetime quality-adjusted life years gain.

In conclusion, the current cohort series published show that at tertiary care center in India, use of ECMO in patients with acute ALP poisoning with severe shock saves young lives, but the challenge is to first define the true incidence. The majority of the cases of AALPP are from rural areas and the incidence of poisoning and shock may be much larger than seen at tertiary care centers. Therefore, the question arises, whether it is feasible and practical to rapidly transfer all patients with suspected ALP poisoning and hypotension before the onset of shock and multi-organ failure to centers with availability of ECMO. Answer may be more affirmative. As the technology for percutaneous ECMO support like CardioHelp becomes more widely available, one can potentially also consider it prior to establishment of severe acidosis. However, the currently available data strongly suggest the use of VA ECMO in patients with AALPP with “severe shock”.

Conflicts of interest

The authors have none to declare.