Chloroform is a recognised cause of acute liver injury, although now rarely encountered in clinical practice. We present a case of inhalational chloroform self-poisoning in a 47-year-old man that presented to hospital initially with reduced conscious level and later developed acute liver injury that was treated with intravenous acetylcysteine. This paper reviews the existing literature and presents a summary of the mechanisms of chloroform hepatotoxicity. Published cases show that there is a characteristic delay of 24 to 48 hours between chloroform exposure and elevation of liver transaminase activity. Therefore, clinicians need to provide an appropriate duration of monitoring in order to detect the occurrence of this important toxic effect.

[download-attachments container="div" style="list" display_icon="1" display_count="1" display__size="0"]

References

1. Singer PP, Jones GR. An unusual autoerotic fatality associated with chloroform inhalation. J Anal Toxicol 2006; 30: 216-218.
2. Gaillard Y, Masson-Seyer MF, Giroud M et al. A case of drugfacilitated sexual assault leading to death by chloroform poisoning. Int J Legal Med 2006; 120: 241-245.
3. Harada K, Ichiyama T, Ikeda H et al. An autopsy case of acute chloroform intoxication after intermittent inhalation for years. Nihon Hoigaku Zasshi 1997; 51: 319-323.
4. Greenblatt EP, Meng X. Divergence of volatile anesthetic effects in inhibitory neurotransmitter receptors. Anesthesiology 2001; 94: 1026-1033.
5. Flanagan RJ, Ruprah M, Meredith TJ et al. An introduction to the clinical toxicology of volatile substances. Drug Saf 1990; 5: 359-383.
6. Schroeder HG. Acute and delayed chloroform poisoning. A case report. Br J Anaesth 1965; 37: 971-975.
7. Kang YJ, Ahn J, Hwang YI. Acute liver injury in two workers exposed to chloroform in cleanrooms: a case report. Ann Occup Environ Med 2014; 26: 49.
8. Vlad IA, Armstrong J, Gault A. A painless burn: systemic toxicity after dermal exposure to chloroform. Emerg Med Australas 2014; 26: 648-649.
9. Environment Protection Agency (EPA). Chloroform. https://www.epa.gov/sites/production/f iles/2016-09/documents/chloroform.pdf
10. Gemma S, Ade P, Sbraccia M, Testai E et al. In vitro quantitative determination of phospholipid adducts of chloroform intermediates in hepatic and renal microsomes from different rodent strains. Environ Toxicol Pharmacol 1996; 2: 233-242.
11. Kalsi SS, Wood DM, Waring WS et al. Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose? Open Access Emerg Med 2011; 3: 69-76.
12. Lionte C. Lethal complications after poisoning with chloroform: case report and literature review. Hum Exp Toxicol 2010; 29: 615- 622.
13. Kim H. A case of acute toxic hepatitis after suicidal chloroform and dichloromethane ingestion. Am J Emerg Med 2008; 26: 1073.e3-e6.
14. Jayaweera D, Islam S, Gunja N et al. Chloroform ingestion causing severe gastrointestinal injury, hepatotoxicity and dermatitis confirmed with plasma chloroform concentrations. Clin Toxicol 2017; 55: 147-150.
15. Sridhar N, Krishnakishore C, Sandeep Y et al. Chloroform poisoning: a case report. Ren Fail 2011; 33: 1037-1039.
16. Dell’Aglio DM, Sutter ME, Schwartz MD et al. Acute chloroform ingestion successfully treated with intravenously administered N-acetylcysteine. J Med Toxicol 2010; 6: 143-146.
17. Eyer F, Felgenhauer N, Murgan I et al. Delayed acute liver and renal failure after deliberate chloroform inhalation. Clin Toxicol 2011; 49: 208.
18. Oder M, Põld K. Oral chloroform poisoning. Clin Toxicol 2013; 51: 320-321.
19. Olives TD, Regelman H, Lange R et al. Don’t DIY: youtube, chemistry, texts, and down home chloroform synthesis. Clin Toxicol 2016; 54: 740.
20. Waring WS. Onset and recovery of hepatic and renal injury after deliberate acute paracetamol overdose. BMJ Case Rep 2009; 2009pii: bcr08.2008.0806.
21. Ramachandran A, Visschers RGJ, Duan L et al. Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives. J Clin Transl Res 2018; 4: 75-100.
22. Reiter R, Burk RF. Formation of glutathione adducts of carbon tetrachloride metabolites in a rat liver microsomal incubation system. Biochem Pharmacol 1988; 37: 327-331.
23. Laurenzi RG, Locatelli C, Brucato A. N-Acetylcysteine: A proposal for therapy in acute poisoning due to highly hepatotoxic organic solvents. Vet Human Toxicol 1987; 29(Suppl 2): 95.
24. Waring WS. Novel acetylcysteine regimens for treatment of paracetamol overdose. Ther Adv Drug Saf 2012; 3: 305-315.
25. Kalsi SS, Dargan PI, Waring WS et al. A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose. Open Access Emerg Med 2011; 3: 87-96.
26. Rutter KJ, Ubhi T, Smith D et al. Reported dose as a measure of drug exposure after paracetamol overdose in children. Curr Clin Pharmacol 2013; 8: 164-168.