FINAL DIAGNOSIS: STRYCHNINE TOXICITY
Figure 2 shows the total ion chromatogram with the peaks annotated:
Identification of some of the peaks was achieved by comparison of the electron impact spectra of compounds from the patient sample with a library of GC/MS spectra. The following drugs were definitively identified by GC/MS (Figure 2): nicotine, two nicotine metabolites, caffeine, atropine (provided at the hospital), cocaine metabolite (ecgonine methyl ester), and cocaine. The identification of parent cocaine suggests recent use of cocaine (i.e., likely within 6-12 hours of presentation). Additional peaks labeled in Figure 2 correspond to cholesterol, additional unidentified compounds (labeled as 'contaminants'), and the internal standard (IS) barbital. The largest peak is found at 30.23 minutes. The electron impact spectrum for this compound corresponds closely to a library spectrum for strychnine (Figure 3):
Strychnine is a bitter, colorless, odorless crystalline alkaloid, C21H22N2O2 (Figure 4)
The most common source is from the seeds of the Strychnos nux vomica tree (Figure 5), found in southern Asia and Australia. Strychnine is an extremely toxic compound and acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor (GlyR) (Figure 6), a ligand-gated chloride channel in the spinal cord and the brain. Inhibitory receptors are ligand-gated chloride channels which act to hyperpolarize neurons, making them less likely to fire action potentials.
Most general anesthetics in current clinical use effectively stimulate inhibitory receptors, slowing down central nervous system transmission and leading to unconsciousness, amnesia, and analgesia. Convulsants block inhibitory receptors, creating an inhibition of inhibition, and leading to overstimulation. The glycine receptor is the major inhibitory receptor in spinal cord, but is also found in brain. Antagonists at the glycine receptor cause characteristic convulsions (example: strychnine).
Strychnine can be introduced to the body by inhalation, swallowing, intravenously, or absorption through eyes or mouth. Strychnine toxicity produces some of the most dramatic and painful symptoms of any known toxic reaction, and can be fatal. For this reason, strychnine poisoning has been used often throughout literature and film. Several minutes after exposure muscles begin to contract and spasm, typically starting with the head and neck and spreading diffusely. The convulsions are nearly continuous, and can increase in intensity with the slightest stimulus. Death occurs from asphyxiation caused by paralysis of the neural pathways that control breathing, or from the sheer exhaustion due to the severity of the muscle convulsions. A patient will die within several hours of exposure.
"Strychnine can lead to an atrocious death¡ Doses of ten to twenty milligrams lead to dyspnoea and unbearable feelings of anxiety. Twitching and spasms gradually develop and lead to violent tetanic seizures in which the head is bent right back to the buttocks, so that the spine may be broken. Breathing may cease for intervals of one to two minutes at a time; in this event the seizures may also stop, only to recommence at the least excitation - a loud noise or a gentle touch - until death from exhaustion finally supervenes. No death could be worse than this and no man is likely to endure greater agonies." Gustav Schenk, "The Book of Poisons"
There is no specific antidote for strychnine and treatment of strychnine toxicity is purely symptomatic. An activated charcoal infusion may initially absorb any poison within the digestive tract that has not yet been absorbed into the blood. Anticonvulsants or general anesthetics including phenobarbital, diazepam, or propofol may be administered to combat convulsions. Neuromuscular agents such as vercuronium, and muscle relaxants such as dantrolene may also be used to combat muscle rigidity. If the patient survives past 24 hours, the prognosis is good and a full recovery is probable.
Low doses of strychnine have stimulant effects, and historically small doses of strychnine were used in stimulant medications, laxatives, and other stomach remedies (Figure 7). The dosage for medical use ranged from roughly 1 milligram to over 6 milligrams. People have died as a result of ingesting doses within that range, however, and the use of strychnine in medicine was abandoned once safer alternatives became available. Strychnine is still used in some rodent baits, although since 1990 most baits containing strychnine have been replaced with zinc phosphide.
There have been numerous noteworthy strychnine poisonings throughout literature and history. Strychnine was also introduced into popular culture when it was featured as the first of many poisons used by Agatha Christie in her debut novel The Mysterious Affair at Styles in 1921. Norman Bates used strychnine to kill his mother and her lover in the infamous Psycho thriller film. In the 1904 Olympics Thomas Hicks from the United States won the marathon event, but then collapsed, having reportedly taken a brandy tonic mixed with strychnine for the stimulant effects. A tonic laced with arsenic and strychnine was also part of the training regimen for legendary racehorse Phar Lap (Figure 8), and it has been suggested that this may have contributed to his premature death. Famous Delta Blues legend Robert Johnson drank from a whiskey bottle laced with strychnine and died.
In this case, our patient was discovered in time to receive appropriate medical care and experienced a full recovery. His CPK and troponin levels normalized. A dramatic feature of the case was the marked acidemia (pH 6.55 with reference range 7.35-7.45) in the initial arterial blood gas from the patient. His hospital stay was complicated by both alcohol and cocaine withdrawal symptoms, but no lasting effects from strychnine toxicity were observed. The patient is receiving psychiatric follow up care.
In conclusion, strychnine is a highly toxic substance which can still be found in rodent baits. If ingested, it can cause dangerously severe toxicity, exemplified by diffuse muscle contraction through inhibition of inhibitory nervous system receptors. Standard urine drug screens by immunoassay will not detect strychnine. However, this compound can be identified by GC/MS, as it was in this case. In this case, a rare toxic compound was identified by comparison to the known GC/MS spectrum for strychnine and the patient was treated accordingly.
Contributed by Amber Henry, MD and Matthew Krasowski, MD, PhD