Strychnine poisoning is an uncommon but potentially fatal poisoning and most patients die before reaching hospital. In the case presented here, the patient presented early after ingestion. He was initially asymptomatic but rapidly developed severe muscle spasms leading to respiratory arrest. With meticulous supportive care in the ICU he made a complete recovery.
The mechanism of action causing strychnine toxicity is well understood. This poison is a competitive antagonist of the inhibitory neurotransmitter glycine at receptors in the spinal cord, brain stem and higher centres [5]. It results in increased neuronal activity and excitability, leading to increased muscular activity. The classical features of strychnine poisoning occur from 15 to 30 minutes after ingestion and include heightened awareness, muscular spasms and twitches and hypersensitivity to stimuli. In large ingestions, these can progress to painful generalised convulsions, during and after which the patient retains consciousness. The cause of death is usually respiratory arrest secondary to respiratory muscle spasms [6], although prolonged muscular spasm can lead to hyperthermia, rhabdomyolysis and associated renal failure due to myoglobinuria [7,8]. Severe metabolic acidosis can occur due to increased lactate levels following repeated muscular activity, although the lactate is rapidly removed once the muscular spasms have been controlled [7].
Prompt recognition of poisoning and initiation of treatment are required to prevent deterioration and death. Control of convulsions and muscular spasms requires either high doses of benzodiazepines, such as 1 mg/kg diazepam [9,10], or, in resistant cases, paralysis with neuromuscular blockers such as pancuronium [11]. In addition, meticulous supportive care is required, and careful monitoring and observation for complications such as acute renal failure.
Clinical effects of strychnine ingestion have been seen at doses as small as 2 mg in a child and 20 mg in an adult [12,13]. Survival after ingestion of large amounts has been reported: 480 mg (24 mg/kg) in a child and 3750 mg in an adult [14,15]. Death from strychnine ingestion has been reported in adults after doses as low as 5 to 10 mg [16]. Since severe, life-threatening features have been reported after the ingestion of small amounts and patients can deteriorate rapidly, strychnine ingestion should be regarded as potentially fatal and the patient should be admitted to an ICU for close observation and appropriate treatment. In this case, as with many other reported cases, both the concentration of strychnine in the preparation ingested and the amount taken were unknown.
The serum strychnine concentration of 4.73 mg/l at 1.5 hours postingestion is the highest reported concentration that a patient has survived. In previous reports, concentrations of 2.1 mg/l at 3 hours [17] and 3.8 mg/l at 0.5 hours [8] caused death. The potential fatal serum concentration of strychnine is not known and clinical features rather than the serum concentration should guide management. At a postmortem, less than 4 hours after an intentional ingestion of strychnine, a serum concentration of just 0.33 mg/l was found [4]. A postmortem study showed that a strychnine concentration of 3.32 mg/l in the blood of the inferior vena cava was associated with concentrations of 11.4 mg/l, 2.42 mg/kg, 2.32 mg/kg and 98.6 mg/kg in bile, brain, skeletal muscle and liver, respectively [18]. Of the 50 reported cases of strychnine poisoning in the past 36 years, only two nonfatal cases have included data on serum strychnine concentrations [19,20]. Both of these patients had much lower concentrations (1.6 mg/l at 4 hours after ingestion and 2.17 mg/l at 6 hours after ingestion, respectively) than that found in our patient.
The elimination and metabolism of strychnine are poorly understood. Strychnine is rapidly absorbed from the gastrointestinal tract, with symptoms occurring within 10 to 20 minutes of ingestion [6,21]. It is also absorbed through other mucous membranes, as in poisonings when strychnine has been mistaken for cocaine [3]. Strychnine has been shown in animal studies to be metabolised in the liver by cytochrome P-450 microsomal enzymes [22], but 1–30% is excreted unchanged in the urine [17,23]. The proportion of strychnine excreted unchanged appears to be smaller when larger amounts are ingested [21,24].
In our patient, elimination of strychnine obeyed first-order kinetics with a half-life of 12 hours. Only three other papers have reported on the elimination kinetics of strychnine, and these provide conflicting views of its toxicokinetics. Edmunds and colleagues were the first authors to describe the elimination of strychnine and theirs is the only other report on the kinetics of strychnine in a patient who survived [19]. They reported a 42-year-old man who ingested an unknown quantity of strychnine and developed severe muscle cramps and convulsions and had a respiratory arrest 35 minutes after ingestion. In that case, the elimination of strychnine obeyed first-order kinetics with a half-life of 10 hours, based on 19 blood samples collected over a 53-hour period, the first of which was taken at 4 hours after ingestion. Palatnick et al. also reported first-order kinetics with a half-life of 16 hours, based on 18 serum concentrations over a 51-hour period in a 34-year-old man after ingestion of 125 ml of a 2% strychnine solution [17]. Heiser et al. reported zero-order kinetics in a fatal case in a 51-year-old man who presented after ingesting 4.8 g of strychnine [8]. His serum concentrations were measured in only five samples, ranging from 3.5 mg/l at 0.5 hours after ingestion to <0.1 mg/l at 43 hours after ingestion.
The differences in the kinetics of strychnine found in our patient from the kinetics in the above three cases almost certainly reflect the influence of clinical parameters such as different periods of hypotension, metabolic acidosis and renal impairment, all of which would influence hepatic metabolism and renal elimination of strychnine. However, the calculated half-life of 12 hours in our patient is comparable to the half-lives previously reported (10 hours and 16 hours), suggesting that the true elimination half-life of strychnine lies between 10 and 16 hours.
