DORMEX-hydrogen cyanamide poisoning.

Case reports of acute and chronic exposure to hydrogen cyanamide (DORMEX(®)) have been reported but mainly as a result of occupational or accidental exposure and without any mortality. We report a case of acute hydrogen cyanamide poisoning in a young male due to suicidal intent. The patient was managed under intensive care with all the standard protocols for detoxification. However, in spite of aggressive management, patient could not be rescued. An extensive literature search did not yield any similar case reports. Hence, we report this case to the medical community to be aware of the entity.

INTRODUCTION

Self-poisoning with pesticide accounts for nearly one-third of the world's suicides.[1] Over the last few decades, agricultural pesticides have become major cause of self-poisoning in rural areas of the developing world due to their easy availability.[2] While organophosphorus compounds cause most self-poisoning deaths in southern and central India, aluminium phosphide causes most deaths in northern India.[34] Although accidental poisoning with hydrogen cyanamide is known, reports of self-poisoning with the same are limited.[56] We present a case of 22-year-old male who succumbed to hydrogen cyanamide following self-poisoning. Awareness of the incident is necessary to provide an early and aggressive management as there is no specific antidote for the same.

CASE REPORT

A 22-year-old male was brought in with alleged history of consuming approximately 150 ml of hydrogen cyanamide (DORMEX®-active ingredient: 520 g/L of cyanamide) about 2 hours prior to hospitalization. Patient was stuporous and responding to painful stimuli. Initial assessment revealed Glasgow Coma Scale (GCS) score of 7/15 (E2, M4, V1), pulse of 110 beats/min, blood pressure of 90/60 mmHg, respiratory rate of 30/min, and oxygen concentration of 88% (98% with 6L oxygen inhalation by mask) in supine position. He had occasional spontaneous jerky movements and weak cough reflex. Pupils were 5 mm and bilaterally reactive. The remaining physical examination did not reveal any significant findings. His central venous pressure (CVP) was 7 cm H2O.

His laboratory parameters [Table 1] were essentially within normal limits. Blood gas analysis revealed metabolic acidosis [Table 2]. Chest X-ray showed minimal pleural effusion, otherwise normal, and the electrocardiograph showed sinus tachycardia [Figure 1]. Computerised tomography (CT) brain and echocardiography were done as a part of initial assessment and were normal. Ultrasonography of abdomen revealed bilateral grade I nephropathy, mild ascitis, and minimal right pleural effusion. Comprehensive toxicology profile including serum pseudocholinesterase was normal and benzodiazepines and barbiturates were not detected on urine examination.

Table 1

Baseline and follow-up investigation reports of the patient

Table 2

Arterial blood gas analysis and the correction given for the metabolic acidosis at different timeline during patient's hospitalization

Figure 1

Electrocardiograph of the patient showing sinus tachycardia

Patient was given gastric lavage and fluid management was done according to CVP. As the patient was drowsy and responding only to painful stimulus, he was electively intubated and mechanically ventilated (SIMV Mode; FiO2-60%; PEEP-5 cm H2O). Sodium bicarbonate (25 mEq/h intravenously) was given to correct the metabolic acidosis and the dosage was adjusted by repeated blood gas analysis [Table 2].

Twenty-two hours after admission, the patient deteriorated into cardiogenic shock. CVP dropped to 2 cm of H2O. Dopamine was started at 5 μg/kg/min, followed by noradrenaline 5 μg/kg/min and dobutamine at 2μg/kg/min, which were gradually stepped up to their maximum dose (Dopamine 15 μg/kg/min, noradrenaline 20 μg/kg/min, dobutamine 10 μg/kg/min). Patient had persistent metabolic acidosis with lactic acidosis despite corrective measures. After 25 hours of admission, patient went into asystolic cardiac arrest. Cardio pulmonary resuscitation was started and atropine (1.2 mg IV) and adrenaline (1 mg IV) were given. This was followed by intravenous sodium bicarbonate (50 mEq). Atropine (0.6 mg IV) and adrenaline (1 mg IV) were repeated every 5 minutes over next one hour. In spite of all these measures, the patient could not be revived and was declared dead.

DISCUSSION

Although insecticide poisoning has been reported worldwide time and again, there are limited reports of poisoning with a plant growth regulator-hydrogen cyanamide.[56] Hydrogen cyanamide is an active ingredient of Dormex® (Degussa AG, Trostberg, Germany), which is used as a plant growth regulator designed to stimulate more uniform bud-break following dormancy, resulting in more uniform flowering and maturity at harvest.[6] Reports of the toxic effects of hydrogen cyanamide is limited.

The department of pesticide regulation of the california environmental protection agency have studied the toxic effects of hydrogen cyanamide and concluded that hydrogen cyanamide causes adverse effects in the liver, thyroid, kidney, ovaries, and testes of laboratory animals. It further stated that in the absence of additional data to the contrary, hydrogen cyanamide has the potential to cause similar effects in humans. In their study, approximately 40% of oral dose was recovered in the urine in the first 24 hours. The remainder of oral doses was excreted in the feces or exhaled as carbon dioxide.[7] There was no indication of hydrogen cyanamide being converted to cyanide in vivo.[8] The principal metabolite excreted in the urine was N-acetylcyanamide.

The adverse health effects from contact of hydrogen cyanamide include severe irritation and ulceration of the eyes, skin, and respiratory tract. The exact mechanism of action of this compound has not been established. Animal studies have indicated that at cellular level, cyanamide is activated by catalase, which in turn causes catalase inhibition resulting in uncoupling of oxidation and phosphorylation and inhibition of adenosine nucleotide synthesis.[9] The substance also inhibits aldehyde dehydrogenase and can produce Disulfiram-like syndrome (e.g., vomiting, parasympathetic hyperactivity, dyspnoea, hypotension, and confusion) when exposure coincides with alcohol use.[1011]

Cederbaum and Dicker[12] showed that ethanol prevented inhibition of catalase if given before or at the same time as cyanamide, suggesting that ethanol may protect against the activation of cyanamide by catalase. Also, the catalase mediated activation of cyanamide is inhibited by 3-amino-1,2,4-triazole in vivo.[13] The application of these principles in treating acute cyanamide toxicity is an option although there are no supporting studies for the same.

There are reports of cutaneous reaction to exposure to hydrogen cyanamide in India and worldwide.[56] Ingestion of hydrogen cyanamide has been reported in a 44-year-old male from Ragusa, Italy when he unintentionally ingested the product that had been placed in a plastic water bottle in refrigerator. Following consumption, he became seriously ill with third degree shock, coma, miosis, and hepatic necrosis and required care in an intensive care unit.[6] In our patient, we found similar manifestation of toxicity due to hydrogen cyanamide. Also, persistent metabolic acidosis and hypotension with lactic acidosis was noted. Since there is no known antidote for this compound, patient was managed symptomatically. The cause of death was inhibition of respiration at cellular level.

CONCLUSION

Poisoning with plant growth regulator has been described from Italy, USA, and India. Majority of these reports were incidents of adverse effects following the occupational or accidental exposure to the chemical. The present case is probably the first reporting hydrogen cyanamide ingestion with a suicidal intent, leading on to persistent metabolic acidosis, encephalopathy, and refractory shock with a fatal outcome.