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Makhlof, Kandeel, Ahmed, and Hammoda: Delayed recovery from unusual and late-onset complications of organophosphate poisoning


Ingestion of organophosphorus pesticides causes inhibition of esterase enzymes in synapses and on red blood cell membranes. This inhibition of acetylcholinesterase results in an increase in acetylcholine in the synapses of the autonomic nervous system and the central nervous system (CNS) and overstimulation of its receptors at neuromuscular junctions.1 The excess stimulation muscarinic and nicotinic receptors by acetylcholine in the CNS results in one of three clinical presentations: (1) acute cholinergic crisis; (2) intermediate syndrome; or (3) delayed polyneuropathy.2

Clinical suspicion is raised by the characteristic clinical signs (e.g. salivation, lacrimation, urination, diarrhoea), the smell of pesticides and reduced butyrylcholinesterase or acetylcholinesterase activity in the blood, which point to the diagnosis. Patients with severe organophosphate (OP) poisoning typically present with pinpoint pupils, excessive sweating, reduced consciousness and poor respiration.1

Reported cardiac complications and electrocardiographic abnormalities associated with OP poisoning are hypertension, hypotension, non-cardiogenic pulmonary oedema, sinus tachycardia, sinus bradycardia, a prolonged QTc interval, prolonged PR interval, ST-T wave changes and conduction defects. The major predisposing factors are hypoxaemia, electrolyte derangements and acidosis.3

Ludomirsky et al.4 described three phases of cardiac toxicity after OP poisoning: phase 1 is a brief period of increased sympathetic tone; phase 2 is a prolonged period of parasympathetic activity; and in phase 3 QT interval prolongation is followed by torsade de pointes ventricular tachycardia, and then ventricular fibrillation.

Case presentation

A 75-year-old man presented to our hospital with cardiac arrest 1 hour after attempting suicide by ingesting an OP compound. He had a history of type 2 diabetes mellitus, chronic essential hypertension and depression.

On examination he was unresponsive, apnoeic and pulseless with a Glasgow Coma Scale (GCS) score of 3. His pupils were pinpoint and there were copious oral secretions. His relatives reported that he had ingested an unknown amount of pesticide about 1 hour prior to presentation.

As cardiac monitoring revealed asystole, advanced cardiac life support was instituted immediately. After 3 minutes of resuscitation, spontaneous circulation was restored and the patient exhibited a palpable pulse and recordable blood pressure. Cardiopulmonary resuscitation was discontinued; however, the patient failed to regain consciousness and was commenced on continuous mechanical ventilation. Administration of vasopressors was necessary to achieve an adequate mean arterial pressure. An initial dose of 173 mg intravenous (i.v.) atropine was followed by a continuous atropine i.v. infusion at a dose ranging from 4 to 7 mg per hour for 11 days to maintain full atropinization. Infusion of 30 mg/kg pralidoxime i.v. was followed at a rate of 8 mg/kg/h, administration of 70 g of activated charcoal by nasogastric tube over 4 hours and lung-protective ventilation for acute respiratory distress syndrome. An on-demand temporary transvenous pacer was inserted for recurrent episodes of complete heart block not responsive to atropine (Figure 1).


The patient’s electrocardiogram showing complete heart block.


On day 5 following admission, following cessation of sedation, the patient exhibited quadriplegia, external ophthalmoplegia, neck muscle paralysis and areflexia and had a GCS score of 3/15. Six days after admission, the patient’s heart rhythm had stabilized and the pacemaker was removed. Pralidoxime infusion continued for a total of 11 days for intermediate syndrome and was stopped once improvement in red blood cell acetylcholinesterase was observed. Sensorimotor nerve conduction studies of the upper and lower limbs showed diffuse axonal polyneuropathy, predominantly of motor nerves. Electroencephalography showed a mild diffuse slow-wave background with no focal or paroxysmal epileptiform discharges or any lateralization. Non-enhanced multislice computerized tomography of the brain revealed no evidence of extra- or intra-axial areas of fresh blood density or collections, and no focal or diffuse areas of abnormal attenuation. Consciousness improved gradually, GCS score reaching 15/15 after about 2 months, and the patient was weaned successfully from ventilatory continuous positive airway pressure support after being tracheostomized. He started to communicate with his eyes, then motor power in his upper limbs gradually returned to normal, followed, with the aid of physiotherapy and neurotonics, by return of power to the lower limbs. This left residual bilateral foot drop after 4 months with no recurrences of any cardiac arrhythmias during follow-up.

Relevant laboratory results for red blood cell acetylcholinesterase were 15.1 IU/g Hb (normal value 26.7–50.9 IU/g Hb) on admission and 19.5 IU/g Hb 1 week later. Echocardiography revealed good left ventricular systolic function, left ventricular hypertrophy and diastolic dysfunction.


Suicidal OP poisoning represents a serious emergency and a continuing tragedy in developing countries. This could be related to be the widespread use and the availability of OP pesticides.5 We report here the case of a patient who presented with the clinical manifestations of acute cholinergic crisis, showing the majority of the clinical symptoms described in the literature. Our patient developed intermediate syndrome on the fourth day after poisoning. This is a distinct clinical entity that occurs 1–5 days after the acute cholinergic crisis and precedes the onset of delayed neuropathy.68 The cardinal features of intermediate syndrome are proximal limb and neck flexor muscle weakness; multiple cranial nerve palsies are common.9 This syndrome carries the risk of death from associated respiratory tract infection, obstruction of the airways by secretion, pulmonary oedema and respiratory depression.10

The pathophysiology of intermediate syndrome due to OP toxicity includes alteration in post-junctional acetylcholine receptors.11 The most commonly reported casual agents are fenthion, dimethoate, monocrotophos, methamidophos and malathion.12 It is also suggested that delayed or inadequate oxime therapy may contribute to the development of intermediate syndrome. In our study the OP responsible was dimethoate and our patient received i.v. pralidoxime upon intensive care unit admission based on its ability to antagonize the toxicity of OP at nicotinic synapses, though it may also have other advantages by reducing CNS damage and central respiratory failure.13,14

A late clinical manifestation in our patient was the development of subacute quadriplegia, which was diagnosed as OP-induced delayed neuropathy (OPIDN), whose associated signs include foot drop and weakness of hip and knee flexors. The disease course of OPIDN is usually subacute and it typically presents within 2 weeks after the initial symptoms with sensory motor involvement of the peripheral nerves; however, pure or predominant motor axonal involvement similar to that seen in our patient has also been reported by Chuang et al.13 and Khosya et al.2

Rarely, some OPs result in delayed neurotoxicity, the onset of clinical symptoms occurring 1 or 2 weeks after exposure; OPIDN is thought to result from the phosphorylation and subsequent ageing of the neuropathy target esterase enzyme in axons.15

Cardiac complications are often associated with OP intoxication, and our patient presented with hypotension and resistant complete heart block requiring temporary pacing. A variety of electrogardiographic abnormalities have been reported in OP-intoxicated patients (e.g. sinus tachycardia or bradycardia, atrioventricular block, and ST segment and T-wave abnormalities) but extreme QT interval prolongation and ventricular tachydysrhythmia of the torsades de pointes type are not common.19 Recently, it has been reported that premature ventricular complexes trigger pleomorphic ventricular tachydysrhythmias after subclinical QT prolongation.17

Ludomirsky et al.4 described three phases of cardiac toxicity after organophosphate poisoning: phase 1 is a brief period of increased sympathetic tone; phase 2 is a prolonged period of parasympathetic activity; and in phase 3 Q-T prolongation is followed by torsade de pointes ventricular tachycardia and then ventricular fibrillation. Both sympathetic and parasympathetic overactivity have been shown to cause myocardial damage.

However, the extent, frequency and pathogenesis of cardiac toxicity associated with OP poisoning have not been clearly defined. Several mechanisms have been suggested, including sympathetic and parasympathetic overactivity, hypoxaemia, acidosis, electrolyte derangements and a direct toxic effect of the compounds on the myocardium and vascular system.18 Both sympathetic and parasympathetic overactivity have been shown to cause myocardial damage.19 Metabolic and electrolyte derangement, myocardial injury autonomic dysfunction and asynchronous depolarization may be involved in the genesis of the dysrhythmias in OP poisoning.19 Cardiac complications that arise on top of OP poisoning may be serious and are often fatal, but are potentially preventative if detected early and treated adequately.


Prolonged cholinergic manifestations of OP poisoning can be carefully managed by supportive care of the airway, oxygenation and administration of an adequate dose of atropine and rephosphorylation attempts by oximes. Moreover, careful follow-up is needed for rare complications such as intermediate syndrome and induced delayed neuropathy. This can be done through early detection and supportive care in patients with respiratory failure. In addition, physicians should be aware of these rare complications, and their clinical presentation and management.



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