Organophosphate poisoning in two pediatric patients

Case

In a district hospital in South Africa, two previously healthy siblings of three (male) and five (female) years old were brought into the Emergency Department with confusion, increased breathing, rhinorrhoea, drooling and muscle tremors. According to their mother, they were both in good health and playing in the garden before they were found there approximately one hour prior to presentation. Mother suspects the children might have ingested pesticides which were stored in soda bottles.

The physical examination showed hypersalivation, rhinorrhoea, confusion, crying, pinpoint pupils, decreased reflexes and decreased breath sounds on auscultation. The clinical condition of the three-year-old boy was worse compared to his older sister as he also had a reduced Glasgow Coma Scale (CGS) of 10. His vital signs upon arrival were a heart rate of 170-180 beats/minute and a respiratory rate of 36 breaths/minute with an oxygen saturation of 93-96%; his random blood sugar was 8.3 mmol/L. He weighed 15.9 kilograms.

The provisional diagnosis was organophosphate poisoning based on clinical presentation and the relatively high incidence in this rural area.

Setting

This case is from a rural district hospital in South Africa. The hospital has approximately 400 hundred beds with capacity to conduct laboratory tests, X-rays, and (mostly obstetric) ultrasounds. Specialist advice is possible through telephone consultations with a specialist in one of the other hospitals in the area.

Emergency management

The siblings were immediately started on intravenous (IV) fluids with normal saline, oxygen support, and IV atropine. They received 0.5 mg, 1 mg, 2 mg, and 4 mg of IV atropine at 5 to 10-minute intervals. The older sister responded well on four repeated bolus of atropine. However, the boy needed a last bolus of 8 mg atropine IV and had three seizures during the resuscitation, lasting less than thirty seconds. The seizures were stopped with two doses of 3 mg IV diazepam. His oxygen saturation remained above 93%, and he maintained his own airway. The symptoms waned after the fifth dose. His secretions decreased, pupils were normalized and reactive, and his chest had good air entry bilaterally. The drowsiness and confusion persisted during observation in the Emergency Department, but his tachycardia improved and remained between 110-130 beats/minute.

Blood gas facilities were unavailable, and therefore emergency blood samples were sent off to the laboratory. The brother’s and sister’s initial investigations, including complete haemogram, renal function, coagulation and liver function tests were normal, except for their bicarbonate of 18 and 20 mmol/L and anion gap of 20 and 21 mmol/L, respectively, thus indicating a mild metabolic acidosis with an increased anion gap.

Follow-up

The patients were treated with continuous atropine infusion for 24 hours. The boy received a loading dose of phenytoin 18 mg/kg. Once they were clinically stable, they were admitted to the ward for further management: vitals monitoring, pupil size checks, mental status observation, and supportive management in case of seizures, bronchospasms or hypotension. Within 24 hours, the children improved considerably and the atropine administration was discontinued. The next day, they were discharged home. Further outpatient evaluation of the siblings two weeks later showed normal clinical findings and no residual symptoms.

Background

Incidence – Organophosphates are commonly used in agricultural products such as pesticides and herbicides, and also as therapeutic agents, including ecothiopate used in the treatment of glaucoma. However, many products containing organophosphates are sold illegally for domestic use, such as the ‘street pesticide’ terbufos.

Organophosphate poisoning results in significant morbidity and mortality in low- and middle-income countries and is therefore an important public health problem. The incidence of organophosphate poisoning is estimated to cause 250,000 to 350,000 fatalities per year worldwide.[1,2]

Pesticide poisoning is a major component of poisoning accounts in children, particularly in low- and middle-income countries with large agricultural communities. Pest proliferation is partly caused by poor social circumstances such as overcrowding, unhygienic living conditions, and lack of housing, causing individuals to look for cheap and sometimes illegal solutions. This increases the risk of accidental exposure in children.[3]

Pathophysiology

Organophosphates are rapidly absorbed through multiple routes of exposure, such as skin, mucosa and the respiratory and gastrointestinal tracts. They irreversibly inhibit acetylcholinesterase and plasma cholinesterase enzymes. Acetylcholinesterase is responsible for hydrolysis of acetylcholine to choline and acetic acid. Inhibition of these enzymes causes overabundance of acetylcholine at cholinergic synapses. This results in an acute clinical syndrome of cholinergic overstimulation at the neuromuscular junction of the sympathetic and parasympathetic nervous systems and the central nervous system. The clinical significance of inhibition of plasma cholinesterase enzyme remains unclear.

Clinical features

Symptoms and signs of organophosphate poisoning through oral or respiratory exposure usually manifest in thirty minutes to three hours, while symptoms of toxicity from dermal exposure may take up to twelve hours. The onset and duration of symptoms and clinical features and their severity vary depending on the type of organophosphate agent, route of absorption, and dosage. Patients with severe poisoning will typically present with excessive salivation, pinpoint pupils, declined mental state, and respiratory depression. The clinical features can be explained by the cholinergic overstimulation and can be broadly classified as secondary to the (a) muscarinic effects (b) nicotinic effects and (c) central nervous system effects (see Table 1). Ultimately, the clinical features may be determined by a multi-system manifestation involving the gastrointestinal, respiratory, cardiovascular and nervous systems, as well as involvement of skeletal muscle and other organs and metabolic effects.

Table 1. Clinical effects of organophosphate poisoning

Diagnosis

Diagnosis is made on the basis of history of exposure, recognition of clinical signs of cholinergic overstimulation, the typical garlic or petroleum-like smell, or improvement of symptoms after initiating appropriate treatment. Diagnostic tests are direct measurements of red blood cell acetylcholinesterase activity and plasma cholinesterase activity in the blood. Unfortunately, these laboratory tests are rarely available in rural hospital settings.[4]

Treatment

Management should start by checking the airway, breathing and circulation, and decontamination of the patient. Supportive care of the respiratory, cardiovascular and neurological systems is required by providing oxygen or a secure airway and obtaining IV access to start fluid infusion. The main aim of treatment is reversal of muscarinic effects with atropine, enzyme reactivation by an oxime such as pralidoxime (which is an antidote that binds specifically to organophosphate-inactivated acetylcholinesterase), and stopping seizures via diazepam.

A bolus of IV atropine should be administered and subsequent doses should be doubled every 5 minutes if there is no response until respiratory and muscarinic signs and symptoms are relieved. To maintain the effects, continuous atropine infusion may be required for a couple of days.

Atropine does not bind to nicotinic receptors and therefore is ineffective in treating neuromuscular dysfunction. Oximes can be given as these are effective in treating both muscarinic and nicotinic effects, but this was not available in our hospital. An IV bolus must be administered slowly in 30 minutes, also followed by continuous infusion. Oximes should only be given with concurrent atropine.[4]

Unfortunately, accidental ingestions of poisonous agricultural agents are common in children in low- and middle-income countries. Successful recovery from organophosphate poisoning is based on time from ingestion to initial presentation, rapid resuscitation, stabilization, and treatment with atropine.

References

1. Peshin, SS, Srivastava, A, Halder, N, Gupta, YK. Pesticide poisoning trend analysis of 13 years: a retrospective study based on telephone calls at the National Poisons Information Centre, All India Institute of Medical Sciences, New Delhi. J Forensic Leg Med. 2014;22:57–61.
2. Kır, MZ, Öztürk, G, Gürler, M. Pesticide poisoning cases in Ankara and nearby cities in Turkey: an 11-year retrospective analysis. J Forensic Leg Med. 2013;20:274–277.
3. Rother, H-A. Falling through the regulatory cracks: street selling of pesticides and poisoning among urban youth in South Africa. Int J Occup Environ Health 2010; 16:202–213.
4. Bird, S. Organophosphate and Carbamate Poisoning. UpToDate. Updated May 20, 2022.