Organophosphate Poisoning Presenting As Acute

246 Abdel Ghany and Abdel Satar

ORGANOPHOSPHATE POISONING PRESENTING AS ACUTE RESPIRATORY DISTRESS IN A NEONATE:

CASE STUDY

Eman A. Abdel Ghany*, Mokhtar F. Abdel Satar**

Pediatrics Department *, Forensic Medicine and Clinical Toxicology Department **, Faculty of Medicine, Cairo University, Egypt

ABSTRACT

Organophosphate poisoning [OP] is a potentially fatal but completely treatable condition that is still very prevalent in our country. Early recognition is paramount in preventing fatality. Although rarely reported, it does occur in infants, where history may not be forthcoming and initial presentation often misleading. We report the case of neonate admitted to neonatal intensive care unit (NICU) of Abu El- Reish Hospital; Faculty of Medicine; Cairo University with respiratory distress, pinpoint pupils and hypotonia. The symptoms appear after spraying the home by insecticides. Plasma pseudocholinesterase level appeared to be low, consistent with acute intoxication with organophosphate insecticide.

Management of organophosphate poisoning consists of airway management, administration of oxygen and fluid, as well as atropine in increasing doses and obidoxime (Acetylcholine esterase reactivator). Plasma pseudocholinesterase analysis is a cheap and an easy indicator for organophosphate insecticides intoxications and could be used for diagnosis and treatment monitoring.

Keywords:

Organophosphorus compound; pseudocholinesterase; intoxication; neonate

Egypt. j. forensic Sci. appl. Toxicol Volume 11 (2) December 2011

246 Abdel Ghany and Abdel Satar

INTRODUCTION

Organophosphate intoxication (OI) induces irreversible inhibition of acetylcholinesterase. Organophosphates phosphorylate the serine hydroxyl group of acetylcholine, leading to accumulation of acetylcholine at the cholinergic synapses (Aygun, 2002).

This accumulation leads to weakness and fasciculation of the muscle. In the central nervous system, neural transmission is disrupted. If this blockade is not reversed within 24 h, large amounts of acetylcholinesterase are permanently destroyed (Leibson & Lifshitz, 2008).

Organophosphorus compounds are commonly used in agricultural products, including insecticides and defoliants. They are rapidly absorbed by all routes of exposure, including dermal, respiratory and gastrointestinal, and irreversibly inhibit the enzyme acetylcholinesterase at cholinergic synapses, resulting in excess cholinergic stimulation at the neuromuscular junction, the sympathetic and parasympathetic nervous systems, and the CNS (Leibson & Lifshitz, 2008).

Acetylcholinesterase is found in red blood cells as well as in nicotinic and muscarinic receptors. To determine the severity and/or the elimination time of OI, one should measure cholinesterase in blood, either by measuring plasma pseudocholinesterase (PCE) or by measuring the cholinesterase in erythrocytes (which is thought to reflect the cholinesterase in neurons and neuromuscular junctions). The first method is widely available and therefore commonly used (Aygun, 2002).

Management of organophosphate poisoning consists of airway management, administration of oxygen and fluid, as well as atropine in increasing doses and pralidoxime. Treatment is aimed at decontamination, reversal of muscarinic signs with atropine and enzyme reactivation by oximes (Hoffman RS, Nelson 2007).

CASE REPORT

We report a case of pneumonia whose evolving symptomatology made us diagnose OP poisoning. A previously healthy full term male (2940 grams) baby, born by uncomplicated vaginal delivery , he is the third infant of non consanguineous parents with a rural background and presented at day 11 with vomiting whilst breast feeding followed by respiratory distress and hypotonia. No prior history of fever, respiratory illness, seizures or drug intake. On examination, he was a well thriving infant, who was afebrile with severe respiratory distress. He was hypotonic with small sluggishly reacting pupils, heart rate was150 beats/min (normal heart rate for age of this patient is 110-160) (Advanced Life Support Group, 2005), heart sounds were normal with no audible murmur; the respiration was shallow, respiratory rate was 60 /min (normal respiratory rate for age of this patient is 30-40) (Advanced Life Support Group, 2005) with subcostal and intercostals retractions with bilateral wheezing and bronchial secretions. Oxygen saturation was 81% in air. His blood pressure was 80/60 mmHg with adequate perfusion. Abdominal examination revealed no abnormality. He was stabilized with oxygen administration through nasal prongs and intravenous fluids. Empirical antibiotics in the form of ampicillin and gentamycin were started for possible aspiration pneumonia/sepsis and other supportive treatment was started. Blood counts, culture, chest radiograph and metabolic profile were normal.

In the next few hours his pupils became pin pointed and unreactive to light. Copious oropharyngeal secretions and diarrhea were also noted. This constellation of symptoms made us suspect cholinergic hyperactivity. To confirm cholinesterase [ChE] level (El-Naggar et al, 2009) was done and was found to be 2030U/L (laboratory reference level more than 3000U/L) Atropine infusion was immediately instituted at 0.02 mg/kg/hour (Hoffman & Nelson 2007), titrated to drying of secretions. As the nature of OP compound unknown empirical dose of obidoxime, 5 mg/kg was given to reactivate ChE enzyme (Hoffman Nelson 2007). In next 24 h baby showed good improvement in motor tone and power with drying of secretions. Retrospectively parents revealed that insecticide was sprayed around the house on that day and child most likely got exposed by inhalation. Atropine was continued for 2 days and then weaned over 24 hrs.

Serial monitoring of ChE levels showed a rise in titers to normal (3100U/L). The baby was discharged after 10 days and parents were counseled on the hazards of environmental exposure to OP compounds.

DISCUSSION

Our case had some elements of CNS depression; respiratory difficulty; hypersecretion and miotic pupils. This constellation of findings is highly suggestive of a cholinergic toxidrome, and additional inquiry revealed exposure to OP compounds.

In our patients the absorption was probably via different routes, the skin, and the mouth, and/or via the respiratory tract while they were spraying the solution at home.

Most instances of non-accidental and accidental poisoning in children are through ingestion, either of unwashed contaminated food or use of poorly marked containers, or an infant’s remarkable capacity to put everything in the mouth if unsupervised. There have been reports of transplacental passage of OPs causing toxicity in the newborn (Jajoo et al. 2010).

Statistics for pediatric cases are scarce but it is considered to be a significant problem. WHO quote figures from a study in Nicaragua which suggests that 19% of instances of occupational exposure there are in children less than 16 years of age (McConnell & Hruska 2008).

OP compounds inhibit ChE activity and affect central and peripheral muscarinic and nicotinic receptors (El-Naggar et al. 2009). Unlike adults infants mainly present with acute CNS depression and are characterized by the absence of typical muscarinic effects including fasciculation and bradycardia. The pupil examination is the key (Hon et al. 2008) and pin point pupils with diarrhea at presentation, is described as triage tool for early recognition in children (Bond et al. 2008). As with our infant, periodic pupil examination helped clinch the diagnosis.

The initial management should be directed toward securing and maintaining a stable patent airway and assuring adequate gas exchange and end-organ perfusion. Once these elements are stable and secure, efforts can be directed toward establishing a definitive diagnosis and treatment.

Tachycardia, rather than bradycardia, has been noted upon presentation in 49% of children presenting with OI (Zwiener & Ginsburg 1988).

The acute respiratory distress in our cases was likely multifactorial in origin, resulting from secretions and bronchospasm from muscarinic stimulation. In addition, stimulation of nicotinic receptors causes weakness and paresis of the respiratory muscles (Nel et al 2002).

The differential diagnoses in this case included infection (meningitis, intracranial abscess/empyema, severe pneumonia, and neonatal sepsis), hemorrhagic ischemic encephalopathy, head injury or other cause of intracranial hemorrhage, inborn errors of metabolism and poisoning, either accidental or deliberate. Exposure to poisons other than OPs is possible—various herbal remedies, alcohol, barbiturates, opiates, chloral hydrate and ketamine can all cause meiosis and reduced consciousness, but do not in themselves causing secretions and pulmonary oedema, and the latter four agents are difficult to obtain in rural settings. Severe pneumonia can cause respiratory symptoms and signs and reduced consciousness but is unlikely to cause meiosis. Meningitis may cause pupillary abnormalities if there is abscess formation but this is usually unilateral. Head injury may cause many of the presenting signs of OPP. However, the anterior fontanel was normal and there were no other injuries. Inborn errors of metabolism are possible causes but the normal blood glucose and the lack of any hepatomegaly made this unlikely (O’reilly & Heikens, 2011).

Acute OI is a clinical diagnosis. Red blood cell cholinesterase levels are usually markedly diminished, but this laboratory test is seldom readily available. Although plasma PCE levels may be diminished as well, still there is little correlation with acetylcholinesterase activity in either the brain or at the neuromuscular junction (Bardin et al. 1994). However, the decrease in PCE levels may serve as a marker of exposure to OP compounds and supports the diagnosis. The diagnosis is therefore based on a history of exposure, recognition of the cholinergic toxidrome, and improvement or resolution of symptoms after appropriate treatment (O'Malley, 1997).

Treatment is aimed at decontamination, reversal of muscarinic signs with atropine and enzyme reactivation by oximes. Frequent atropine doses or as continuous infusion titrated to achieve drying of secretions is used. Single dose of obidoxime or in severe poisoning a continuous infusion is used. Oximes are continued for 24 h after symptoms resolve or restoration of normal serum ChE levels (Hoffman & Nelson 2007)

Unfortunately, atropinization does not reverse either the central or nicotinic cholinergic signs or symptoms, particularly the muscle weakness and/or paralysis. A different dose of obidixime or a continuous infusion is used in severe poisoning up to the resolution of the symptoms or restoration of normal plasma PCE levels (Clark, 2002).

This antidote is best used as early as is reasonable before irreversible inhibition of acetylcholinesterase occurs. A loading dose of 4 to 8 mg/kg followed by a repetitive administration or a continuous infusion of 1 mg/kg per hour is administered until muscle weakness and fasciculation resolve (Schexnayder 1998).

OPP is a potential cause of respiratory distress and reduced consciousness in children and must be considered even in the absence of a corroborative history of exposure, especially in countries where use of these products is common in rural areas. A history of possible topical exposure, particularly in a neonate with a relatively large surface area, should be considered. To our knowledge this is the youngest infant reported to have been poisoned with Ops in Egypt.

CONCLUSIONS

Misuse of organophosphate insecticides, even in case of domestic application, can be life threatening

PCE analysis is an easy indicator of OP poisoning and can be used for treatment monitoring.

Atropine should be used as soon as possible to counteract the muscarinic effects. Appropriate management and early recognition of the complications may decrease the mortality rate.

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Egypt. j. forensic Sci. appl. Toxicol Volume 11 (2) December 2011

246 Abdel Ghany and Abdel Satar

Egypt. j. forensic Sci. appl. Toxicol Volume 11 (2) December 2011