A Fatal Chronic Ketamine Poisoning
L. Y. Tao,1 M.D.; X. P. Chen,1 M.D.; and Z. H. Qin,2 Ph.D.
J Forensic Sci, Jan. 2005, Vol. 50, No. 1
Paper ID JFS2004258
Available online at:
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ABSTRACT:
A few papers in the literature reported incident deaths by acute ketamine poisoning. In this paper, we report an unusual homicide caused by chronic ketamine poisoning. The victim was a 34-year old married woman with no previous medical history (except as reported herein) who died in her own home. The court investigation revealed that she was chronically poisoned by her husband over a period of about one year in an act of homicide. Determination of ketamine concentrations in autopsy specimens was carried out with gas-chromatography/mass spectrometry (GC-MS). The results showed that ketamine concentration was 21μg/mL in gastric contents, 3.8μg/mL in blood and 1.2μg/mL in urine.
The most striking forensic findings were cardiac muscle fibrosis and hyaline degeneration of small arteries in victim’s heart, the pathological features of ketamine poisoning previous reported only in animal studies.
....Determination of ketamine concentrations in autopsy specimens was carried out with gas-chromatography/mass spectrometry (GC-MS). The results showed that ketamine concentration was 21 μg/mL in gastric contents, 3.8 μg/mL in blood and 1.2 μg/mL in urine. Reported LD50 is 224±4mg/kg in mice and 229±5mg in rats. The administered doses of ketamine in this case were 100–300 mg, well below LD50, thus ruling out the possibility of acute poisoning.....
.....After receipt of the initial autopsy report, the police decided to detain the husband and investigate him as a suspect. Finally, the husband confessed that he had been using ketamine to poison his wife since September 2002, because the lover wanted to marry him, but he did not want to lose assets in a divorce settlement. At first, he added one vial (100 mg) of ketamine to his wife’s coffee cup. After four or five such additions, he found no noticeable symptoms of toxicity. He then added two vials (200 mg) to her drink. The victim began to show some symptoms of ketamine toxicity. Each time such intoxication occurred, the husband informed the victim’s family and sent her to hospital for clinical examination.....
Discussion
The autopsy revealed cerebral oedema, over-inflation of lungs, pulmonary oedema accompanied by hyperaemia, inter-alveolar and interstitial haemorrhages. All these signs pointed to an asphyxial death as defined by Walsh et al. (5). But there was no evidence of mechanical asphyxia, or autoerotic asphyxia in this case. We found widespread fibrosis of cardiac muscle fiber around the small arteries and heart-failure cells in the lungs.
What caused these changes? The victim had no history of bouts of myocarditis, hypertension or cocaine abuse. Autopsy examinations also did not support any of the abovementioned possibilities. The presence of ketamine and cardiac fibrosis were the only positive results in our forensic examinations. Ketamine is an anaesthetic with a stimulatory effect on the cardiovascular system, producing tachycardia, increasing blood pressure and myocardial oxygen consumption, and causing mild respiratory depression. Respiratory depression is enhanced by overdosing, or by rapid intravenous injection (6,7). Ketamine induces characteristic changes in breathing patterns, causing phases of deep, less frequent breaths with brief apneustic episodes, as well as phases of sighing inspirations with high tidal volumes and an end-inspiratory plateau. The apneustic episodes are probably caused by hyperventilation (8). Perhaps all these respiratory effects may have caused the asphyxia phenomenon in this case. Both anoxemia and/or the misuse of ketamine could have caused the cerebral oedema.
Ketamine is seldom used on psychiatric patients because of its tendency to cause hallucinations and bizarre nightmares (8). Because of its hallucinogenic effects, ketamine became a drug of abuse at the end of the 1970s (9). In recreational settings, it is typically used in low anaesthetic dosages (50–120 mg, i.m.), which produces marked synesthesia and euphoria (10,11). The combined effects of ketamine in some aspects may be similar to the experience of sexual orgasm (12).
In the case being reported, police and Court investigations excluded non-medical abuse and sexual use of ketamine. Toxicological analysis of blood taken from the heart revealed a ketamine concentration of 3.8 μg/mL. At investigation, the husband confessed that 100–200 mg of ketamine was added to her drink on each occasion. The last time he added 300 mg of ketamine to the coffee, all well within the therapeutic range (1.0–6.0 μg/mL).
We suggest that the actual concentration in the blood at the time of death in this case is because ketamine is metabolised with a short half-life through the hepatic cytochrome P450-dependent enzyme system, and is further conjugated to glucuronide derivatives, which subsequently undergo renal elimination (7). Ketamine’s effect of increasing intracranial pressure makes this anaesthetic unsuitable for use in patients with neurosurgical intervention (5,6). Marini et al. have described myocardial fibrosis in rabbits after chronic exposure under anaesthesia dosage to ketamine (4).
In this report, we suggest that the widespread myocardial fibrosis and hyaline degeneration of the small arteries was caused by large doses of ketamine; i.e., chronic ketamine poisoning. The husband’s confession of systematically administering non-lethal doses to the victim is consistent with our observations at post-mortem examination.
If our pathological examinations had revealed dosages of ketamine in excess of LD50, we would have concluded that this was a case of acute ketamine poisoning. However, toxicological examination showed much less than LD50, which leads us to conclude that this is a case of chronic poisoning using ketamine in non-lethal dosages (100 mg–300 mg per dose), administered over a period of time by which caused the observed myocardial fibrosis and hyaline degeneration of the small arteries. The large area of myocardial fibrosis resulted in heart failure and death, and some asphyxial phenomena were caused by the side effects of the last dose of ketamine.
These findings are also consistent with the pathological features of chronic ketamine poisoning previously reported in animal studies by Marini et al. (4).
Finally, we conclude that the chronic ingestion of ketamine leads to myocardial fibrosis in humans and eventually causes cardiac failure. In the reported case, drug-induced cardiac damage and respiratory depression caused the victim to become inadequately oxygenated, resulting in hypoxia that led to brain death.
