Organophosphate poisoning presenting as out-of-hospital cardiac arrest: A clinical challenge

Abstract

Out-of-hospital cardiac arrest (OHCA) remains a challenge for physicians since effective management and definitive salvage depend upon correct determination of the etiology and the extent of injury. Definitive diagnosis of organophosphate poisoning (OP) requires physicians’ clinical awareness of a typical toxidrome, that is, characteristic signs and symptoms of poisoning, and laboratory confirmation. Here we report a case of an OHCA patient with OP, which was initially misdiagnosed as an acute ST segment elevation myocardial infarction based on the patient’s medical history and clinical manifestations.

<Learning objective: Organophospate poisoning is associated with an increasing mortality with widely used pesticides in the developing world. Differential diagnosis of out-of-hospital cardiac arrest should include such etiology that can be reversed by early intervention.>

Introduction

Studies show that the incidence and survival rate of out-of-hospital cardiac arrest (OHCA) vary both regionally and globally [1]. Effective OHCA management with appropriate intervention depends upon determining the etiology and extent of injury. Among patients with OHCA, cardiovascular events account for the majority of deaths, while coronary artery disease (CAD) is often present even in the absence of an acute ST segment elevation myocardial infarction (STEMI). The presence of ventricular fibrillation or pulseless ventricular tachycardia is also highly associated with CAD. Several studies have also investigated the prevalence of non-cardiac etiology of OHCA and reported trends that have occurred in various populations [2]. Park et al.[3] described the epidemiologic features and outcomes found in the Korean emergent medical system and reported that poison-induced OHCA was responsible for 4.4% of non-cardiac etiology OHCAs. However, heterogeneity of poison-induced OHCA makes it especially difficult to differentiate the underlying mechanisms responsible for each type of poisonous substance. Here we report a 60-year-old OHCA male patient with a history of undergoing coronary intervention for triple-vessel disease, whose cardiac status on admission gave the initial impression of new-onset STEMI. However, an emergency coronary angiogram showed negative results and laboratory examination indicated organophosphate poisoning (OP). We suggest, therefore, that poisoning, especially OP, should be considered in the differential diagnosis of OHCA.

Case report

A 60-year-old man with a history of triple coronary disease and stent implantation was found unconscious and unresponsive in the park for an unknown amount of time and was brought to our hospital at midnight by emergency medical technicians. There were no witnesses to his collapse and no suspicious bottles, containers, knives, or liquid spills were found near him. Initial arterial blood gas studies revealed severe acidemia, metabolic and respiratory acidosis (pH 6.9, PaCO₂ 103.5 mmHg, HCO₃• 19.9 and base excess −15.5), and severe hypoxemia (PaO₂ 28.8 mmHg). Cardiopulmonary resuscitation and cardiac defibrillation were implemented and the patient regained pulses after 13 min of these attempts to resuscitate. The initial 12-lead electrocardiogram (ECG) showed wide QRS rhythm and infero-lateral ST segment elevation (Fig. 1A), raising high suspicion of OHCA due to STEMI. However, emergent coronary angiogram showed no obvious stenotic artery or thrombosis (Fig. 2). Clinical laboratory tests on the patient’s blood sample drawn when he arrived at the hospital revealed no significantly elevated cardiac enzymes [hs-TnT: 0.015 ng/ml (<0.1)] suggestive of myocardial infarct. Routine urinalysis was performed as well as urine screening for illicit drugs, and all results were negative.

Fig 1.

(A) The initial 12-lead electrocardiogram (ECG) at emergency room arrival disclosed wide QRS rhythm and infero-lateral wall ST elevation. (B) After admission to cardiac care unit, accelerated idioventricular rhythm was noticed after administering atropine and pralidoxime (Day 1). (C) After receiving 3 ampules of atropine infusion, the 12-lead ECG then showed sinus tachycardia (Day 2). (D) On the second night of hospitalization, the 12-lead ECG showed infero-lateral wall ST segment elevation.

Fig. 2.

Emergency coronary angiogram identified no obvious infarct-related artery. (A) Right anterior oblique view. (B) Spider view. (C) Right anterior oblique cranial view. (D) Subcostal view.

The patient was admitted to the cardiac care unit with vital signs as follows: body temperature 31.2 °C, pulse 58/min, respiratory rate 16/min under intubation and mechanical ventilation, and blood pressure 86/43 mmHg. The fluid challenge technique was employed, and he was given dopamine infusion (13.6 mcg/kg/min) and warm coverings but shock status and hypothermia were still evident. We noticed that he had a large amount of sweat that drenched his whole body. He also had massive tears, saliva, and naso-gastric tube aspiration with the smell of organic-solvent. Pin-point pupils (bilateral 1 mm) with poor light reflexes were also found. Because of these abnormal physical findings as well as high anion gap metabolic acidosis, we strongly suspected cholinergic toxidrome, which we considered to possibly be associated with organophosphates or carbamyl agent intoxication. Additional blood tests revealed low cholinesterase activity, which corresponded clinically with organophosphate and carbamate intoxication (Table 1). We then administered continuous infusion of atropine 1 mg/h and pralidoxime 500 mg/h. The subsequent 12-lead ECG showed accelerated idioventricular rhythm (Fig. 1B). After receiving 3 ampules of atropine infusion, the 12-lead ECG then showed sinus tachycardia (Fig. 1C), and the patient’s pupil size returned to 3 mm bilaterally with positive light reflexes. His overall physical status seemed to be stabilizing gradually, despite that he was still unconscious.

Table 1.

Detailed laboratory data during hospitalization. Reference range of CHE: >5000 U, AchE activity >20 μmol/s/L. CHE: cholinesterase; AchE: acetylcholinesterase; CK: creatine kinase; QTc: corrected QT interval.

		Day 1	Day 1	Day 2	Day 2	Day 3	Day 3	Day 4	Day 4
		09:00	21:00	09:00	21:00	09:00	21:00	09:00	21:00
CK (U/L)		1571	1493	1189	793	1123	1016
CK-MB (ng/ml)		237	268	177	47.6	120	104
RBC AchE activity (μmol/s/L)		2.1	10.8	17.5	15.1	12.1	14.1	13.8	19.3
Pseudo CHE activity (μmol/s/L)		0.02	0.3	0.02	0.01	1.8	0.6	0.1	2.0
CHE (U/L)		<200.0
Infusion rate	Atropine (mg/h)	1		0.5		1		1
	Pralidoxime (mg/h)	500		500		500		500
QTc		587 (D1-11:55)	539 (D1-23:08)	478 (D2-09:45)

Circulatory shock due to both hypovolemic and distributive etiology was impressed. Hypovolemic status was recognized by fluid loss via massive cutaneous secretions, sweating, and tearing, which was salvaged by large volume of fluid challenge. We tailored the central venous pressure at the level of 11.0–13.0 cmH₂O, respectively. Distributive shock, driven by marked peripheral vasodilatation and corrected with administration of vasopressors, was associated with the direct effect of OP intoxication. Inotropic agents were administered as an adjuvant therapy to augment circulatory effort since profound shock was noticed with worsening tissue dysoxia and hypoperfusion, as measured by an elevated level of serum lactate.

On the second night of hospitalization, the 12-lead ECG again showed infero-lateral wall ST segment elevation (Fig. 1D) without significant changes in his cardiac enzymes (Table 1). Echocardiography revealed mild anterior wall hypokinesis but preserved systolic function of the left ventricle. No additional coronary angiograms were done because of the patient’s poor clinical status and his family’s request. Ventricular tachycardia and pulseless electrical activity occurred frequently and response to cardiopulmonary resuscitation and amiodarone was poor. He remained unconscious during the whole course of hospitalization. He then expired in the early morning of the 5th day.

Discussion

Based on the patient’s initial ECG findings and previous medical history of coronary triple disease and stent implantation, our initial tentative diagnosis was acute coronary syndrome. We performed emergent coronary angiography, but no acute thrombus or significant in-stent restenosis were found, which directed us toward other possible causes of OHCA. Because he had also found high anion gap metabolic acidosis and impressive physical findings such as massive mucosal secretion and symmetric meiosis, we considered the possibility of poison ingestion.

OP accounts for increasing numbers of incidental or suicidal deaths due to the current widespread use of pesticides in the developing world [4]. Diagnosis of OP is based on clinical suspicion, the unique impressive clinical presentation, hints of pesticide-like smells from body fluids, and reduced serum cholinesterase activity [5]. Several studies have reported that the mortality rate for OP depends upon the severity of poisoning as determined by a universal scoring system such as APACHE-II, the Glasgow Coma Scale, or the International Program on Chemical Safety Poison Severity Score (IPCS PSS) [6]. However, diagnosis can still be difficult with a more emergent condition, a lack of medical history due to unconsciousness, or no definite evidence of toxic exposure. Although non-cardiac causes of cardiac arrest should be considered in OHCA patients, poison ingestion, especially OP, are rarely mentioned in the literature or discussed as differential diagnosis.

The pathophysiology of OP is irreversible inhibition of acetylcholinesterase in blood plasma, red blood cells, and cholinergic synapses, while carbamate poisoning is associated with reversible effects [7]. The outstanding clinical features of OP include accumulation of acetylcholine and overstimulation of acetylcholine receptors in synapses of the autonomic nervous system, central nervous system, and neuromuscular junctions. The classic manifestations of OP symptoms, which occur acutely within minutes to hours of poisoning, are defecation, urination, miosis, bradycardia/bronchospasm, emesis, lacrimation, and salivation, together known as DUMBELS [4], [7]. Cardiac complications are observed in about two-thirds of OP cases [7], but they are seldom described as the initial features.

Some specific mechanisms have been reported to result in cardiac complications, including: (1) sympathetic over-activity at first, followed by prolonged extreme parasympathetic activity, which is responsible for Q-T prolongation followed by polymorphous ventricular tachycardia (Torsades de Pointes) and ventricular fibrillation; (2) metabolic imbalance predisposing the patient to hypoxemia, acidosis, and electrolyte imbalances and leading to arrhythmic consequences; and (3) direct toxic effects of the poisonous compounds on the myocardium [8]. The earliest sympathetic activation may be responsible in part for the release of vasoactive agents, causing erosion of atherosclerotic plaques and leading to acute thrombo-embolic events. It is also possible that parasympathetic over-activity may result in coronary artery spasm [9], another important factor associated with myocardial ischemic changes, and thus with hypoxemia. Different types of cardiac complications have been reported in cases of OP, including various arrhythmias, blood pressure fluctuations and irreversible myocardial damage [8], [10]. In our case, the initial presentation of ST segment elevation seen in the 12-lead ECG and the absence of definitive thrombus formation in the coronary angiogram may be explained as a result of prolonged coronary artery spasm, academia, or direct myocardial damage as toxic effect of OP, while the potentially fatal ventricular fibrillation gave rise to the patient’s collapse.

Cardiac complications of OP may also present with atypical manifestations, which may lead to misdiagnosis. Cha et al. [8] investigated the prevalence of myocardial injury through cardiac biochemical markers such as troponin I (TnI), creatine kinase MB, and B-type natriuretic peptide in severe OP. They found that OP can cause direct myocardial injury during the acute phase, and monitoring of TnI may be needed in severe cases based on the Namba classification. However, more than 80% of severe cases in that study presented normal sinus rhythm regardless of the TnI level, which weakened the customary use of ECG alone for diagnosing cardiac complications in OP. Results of that study emphasized the importance of monitoring myocardial injury with biochemical markers rather than by ECG changes. Lionte et al. [11] reported a case of a 57-year-old woman with coma and acute non-cardiogenic pulmonary edema as a result of organophosphate ingestion, and she developed acute antero-septal myocardial infarction and died despite serum cholinesterase normalization. In our case, whether the myocardial infarction occurred or not in the end was still unclear, but the similarity of the trend of serum cholinesterase normalization might be a hint of recovery from OP while permanent insults of myocardial injury remained. Paul and Bhattacharyya [12] stated that elevation of ST segment was seen in 25.2% of 107 patients with acute OP, although it might not be the most common ECG change, it could sometimes mimic the manifestation of true acute coronary syndrome. We suggest to combine ECG changes and biochemical markers, simultaneous cardiac enzymes and serum cholinesterase, as parameters of myocardial injury in OP.

Joshi et al. [13] reported a case of OP followed by acute myocardial infarction, which they attributed to cardiac complications of OP. In our case, although we could not exclude myocardial infarction as a diagnosis or OP resulting in mortality, the cause of OHCA was surely cardiac complications as a result of OP. Recognition of myocardial injury in patients and timely symptom control are essential regardless of the etiology, but awareness of the typical symptoms of OP is also essential so that the appropriate antidote can be given for definitive salvage. The severity of toxicity as well as the related cardiac complications may define the patient’s prognosis [10].

Although cardiac complications associated with OP have been debated and are not fully appreciated by some physicians, most of these complications occur during the first few hours or even as the initial presentation of OHCA [10], as in our case. Diagnosis of OP remains a challenge in the emergency room, especially among unconscious patients. Park et al. [3] reported that patients with insecticide poisoning-related OHCA may have a relatively higher rate of spontaneous resumption of circulation and better overall outcomes due to the presence and availability of the appropriate antidote. Differential diagnosis of myocardial injury other than an ischemic event such as OP should always be kept in mind to help ensure better management of OHCA patients.

Funding

This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

All authors have no conflicts of interest to declare.