Uncontrolled seizures and unusual rise in leucocyte counts: transfluthrin, liquid mosquito repellent suicidal poisoning.

Transfluthrin is being used as fast acting insecticide and liquid mosquito repellent. This is a case report of poisoning with transfluthrin (90 ml liquid containing 792 mg of transfluthrin) by a 25-year-old female. Tonic-clonic convulsions were not controlled with conventional drugs. In intensive care unit, patient was managed with muscle paralysis by neuromuscular blocking drug vecuronium and elective mechanical ventilation for more than 48 h under care of the anaesthesiologist with uneventful recovery.

INTRODUCTION

Transfluthrin is a synthetic pyrethroid insecticide,[1] available in the market as 0.88% w/w liquid vaporiser. It is a repellent insecticide, generally used for the control of mosquitoes in the household. It is also the primary insecticide in certain products for killing wasps and hornets, including their nests.[12] Pyrethroids are 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size, and lower body temperature.[3] In humans, their ingestion give rise to burning facial sensation, itchy face sensation, tingling face sensation, paresthesia, skin irritation, mucosal irritation, respiratory tract irritation, headache, dizziness, nausea, epigastric pain, vomiting, anorexia, fatigue, muscle twitching, salivation, running nose, and convulsions.[4]

CASE REPORT

A 25-year-old female was brought to the emergency department with a history of nausea, vomiting, dizziness, abdominal pain, and altered sensorium. She was weighing around 55 kgs. She had given history of ingestion of two bottles (refills) of mosquito repellent available in the house, 2 h before she was brought to the hospital. (Each refill containing 45 ml (396 mg) transfluthrin). On examination, patient was conscious, pupils bilaterally semi constricted and sluggishly reactive to light. On auscultation of lungs crepitations were present bilaterally. Respiratory rate was 28/min. Blood pressure was 110/70 mmHg. In emergency ward, gastric lavage was performed and then continuous gastric aspiration was started through Ryles tube. Oral syrup charcoal 10 ml was given, and Ryles tube was closed at proximal end for some time. Then again aspiration through Ryles tube was continued. Atropine 0.6 mg, pantoprazole 40 mg and ondansetron 4 mg were given intravenously. Tonic-clonic convulsions were observed after 1 h of admission in the emergency ward. Injection phenytoin 700 mg bolus, injection diazepam 10 mg, injection hydrocortisone 100 mg, injection frusemide 20 mg, were administered intravenously. Oxygen enrichment was continued. However, patient had continuous uncontrolled convulsions. Then patient was shifted to intensive care unit and midazolam 5 mg and propofol 100 mg (80 mg + 20 mg) were administered intravenously. Endotracheal intubation was successfully performed with 7.5 mm ID endotracheal tube, and cuff was inflated and oxygen enrichment at 4–6 L/min via T-piece was initiated. Midazolam 4 mg/h and propofol 200 mg/h IV infusions were started. SpO2 was maintained at 100%. Blood pressure was 94/62 mmHg. Pulse rate was 74/min. Arterial blood gas (ABG) reports were normal. Neurophysician advised IV mannitol (20%)100 ml twice a day and IV phenobarbitone (SOS) for seizures.

Patient was seizure free for few hours but again seizures started, and not controlled even with repeat doses of phenytoin, midazolam, propofol, and phenobarbitone. At that time blood pressure was 80/40 mm of Hg, respiratory rate was 35/min, pulse rate was 190/min, and SpO2 was 95%. Serum potassium, calcium, and sodium were 2.98 mmol/L, 2.5 mmol/L and 129 mmol/L, respectively. Injection dopamine was started at 10 μgm/kg/min. Potassium chloride 1.5 g and hypertonic saline were administered. Despite repeated doses of phenytoin, midazolam, propofol and phenobarbitone, seizures were not controlled. Elective ventilation was planned after muscle paralysis to control seizures. Patient was paralyzed by injection vecuronium 4 mg bolus and 4 mg/h IV infusion , and put on controlled mechanical ventilation (CMV) mode for elective ventilation. Vecuronium was continued at 4 mg/h. Blood pressure further decreased gradually and dopamine dose was increased and propofol infusion was stopped. ABG reports did not show any changes. Computed tomography scan of brain and chest X-ray were normal. Input/output charting for fluids was maintained. Central venous pressure remained at 5-8 cm H2O. Patient was kept on a ventilator for 48 h electively and then gradually weaning started. Vecuronium and midazolam infusion were stopped, and mode of ventilation was changed to synchronized intermittent mandatory ventilation (SIMV). Airway pressure support was set to 15 cm H2O with positive end expiratory pressure of 4 cm H2O. Patient's pulse rate was 102 beats/min, blood pressure 132/82 mmHg and SpO2 remained above 96%.

Patient had total leucocyte count on day 1 of 7200/mm3 and it increased to 22,000/mm3 on the day 2, 32,000/mm3 on the day 3 and 13,000/mm3 on the day 4, all with neutrophilia without other signs of septicaemia, although antibiotics were continued. The counts decreased to 4000/mm3 on day 6. After 48 h on ventilator, dopamine infusion was tapered down in next 6 h and then stopped. About 6 h on SIMV mode, spontaneous respiration was noticed at 16 breaths/min. Muscle relaxation was reversed with inj. neostigmine 2.5 mg and inj.glycopyrrolate 0.4 mg. Patient started breathing spontaneously with adequate tidal excursion and followed verbal commands and then extubated. Oxygen through mask was given at flow of 4–5 L/min. Respiratory rate was 25 breaths/min, blood pressure was 108/72 mmHg and pulse rate, 119/min. Pupils were normally reacting to light. Patient was nebulised with mistabron 3 mg, repeated 8 hourly. Patient was referred to psychiatrist for counselling. On the day 4, patient was shifted to ward and discharged uneventful from hospital on 7th day.

DISCUSSION

The pyrethrins are a pair of natural organic compounds normally derived from Chrysanthemum cinerariifolium that have potent insecticidal activity. Pyrethrins are neurotoxins that attack the nervous systems of all insects.[5]

In the 1800s, it was known as ‘Persian Insect Powder’, ‘Persian Pellitory’, and ‘Zacherlin’. They affect the flow of sodium out of the nerve cells in insects, resulting in repeated and extended firings of the nerves, causing the insects to die.[6] Transfluthrin is a pyrethroid available at home as liquid mosquito repellent. In humans after oral ingestion highest levels of the transfluthrin in tissues are found in liver and kidney, lowest levels are found in the brain. Excretion is rapid, 74-90% in urine within 48 h. There are no indications of its accumulation in the body. The liver is the main organ responsible for metabolism.[7]

Increased neutrophilic counts were a matter of worry because it was thought to be due to some fulminating infections, but there were no other signs of sepsis. Literature search revealed that the poison causes severe neutrophilocytosis, and this decreases over 3–4 days.[8910] The same happened in the present case.

Seizure in pyrethroid neurotoxicity is believed to be due to its ability to modify sodium, chloride and calcium channels of the neurons. Their main effects are on sodium and chloride channels. Pyrethroids modify the gating characters of voltage-sensitive sodium channels to delay their closure. If the delay is sufficiently long it lowers the action potential threshold and causes repetitive firing, which may be the mechanism of paraesthesia. Relatively high concentration of pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures.[3] Convulsions generally occur after consumption of doses above 500 mg and their frequency can be 10–30 times a day. Severe cases may be associated with pulmonary oedema.[11] Tachycardia in this case raises the possibility that the cardiac arrhythmia due to pyrethroid poisoning can occur due to its effect on sodium channels in the heart. This patient had seizures not controlled by conventional drugs like phenytoin, midazolam, propofol and phenobarbitone. The patient had to be paralysed and ventilated with management of haemodynamics, leading to successful recovery.

CONCLUSION

Tranfluthrin poisoning may lead to unusual increases in leucocyte counts which is self limiting. The seizures can however be resistant to standard anti convulsants and may need neuromuscular paralysis and controlled mechanical ventilation.