Delayed onset of liver injury after intentional chloroform overdose: a case report and literature review.

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.

Of Penguins, Pinnipeds, and Poisons: Anesthesia on Elephant Island.

Although Ernest Shackleton's Endurance Antarctic expedition of 1914 to 1916 is a famous epic of survival, the medical achievements of the two expedition doctors have received little formal examination. Marooned on Elephant Island after the expedition ship sank, Drs. Macklin and McIlroy administered a chloroform anesthetic to crew member Perce Blackborow to amputate his frostbitten toes. As the saturated vapor pressure of chloroform at 0°C is 71.5 mmHg and the minimum alveolar concentration is 0.5% of sea-level atmospheric pressure (3.8 mmHg), it would have been feasible to induce anesthesia at a low temperature. However, given the potentially lethal hazards of a light chloroform anesthetic, an adequate and constant depth of anesthesia was essential. The pharmacokinetics of the volatile anesthetic, administered via the open-drop technique in the frigid environment, would have been unfamiliar to the occasional anesthetist. To facilitate vaporization of the chloroform, the team burned penguin skins and seal blubber under overturned lifeboats to increase the ambient temperature from -0.5° to 26.6°C. Chloroform degrades with heat to chlorine and phosgene, but buildup of these poisonous gases did not occur due to venting of the confined space by the stove chimney. The anesthetic went well, and the patient-and all the ship's crew-survived to return home.

Systemic inflammatory response due to chloroform intoxication--an uncommon complication.

Well-known adverse effects of chloroform are drowsiness, nausea, and liver damage. Two cases with an uncommon complication due to chloroform intoxication are presented. In the first case, a general physician, because of nausea and dyspnea, admitted a 34-year-old woman to hospital. She developed a toxic pulmonary edema requiring mechanical ventilation for a few days, and a systemic inflammatory response syndrome (SIRS) with elevated white blood cell counts, a moderate increase of C-reactive protein, and slightly elevated procalcitonin levels. There were inflammatory altered skin areas progressing to necrosis later on. However, bacteria could be detected neither in blood culture nor in urine. Traces of chloroform were determined from a blood sample, which was taken 8 h after admission. Later, the husband confessed to the police having injected her chloroform and put a kerchief soaked with chloroform over her nose and mouth. In the second case, a 50-year-old man ingested chloroform in a suicidal attempt. He was found unconscious in his house and referred to a hospital. In the following days, he developed SIRS without growth of bacteria in multiple blood cultures. He died several days after admission due to multi-organ failure. SIRS in response to chloroform is a rare but severe complication clinically mimicking bacterial-induced sepsis. The mechanisms leading to systemic inflammation after chloroform intoxication are currently unclear. Possibly, chloroform and/or its derivates may interact with pattern recognition receptors and activate the same pro-inflammatory mediators (cytokines, interleukins, prostaglandins, leukotrienes) that cause SIRS in bacterial sepsis.

Poisoning: fact or fiction?

Analytical toxicology is a complex discipline. Simply detecting a poison in a biological sample does not necessarily mean that the individual from whom the sample was obtained had been poisoned. An analysis can prove exposure and perhaps give an indication of the magnitude of exposure, but the results have to be placed in proper context. Even if sampling was ante-mortem an analysis does not necessarily prove the effects that the drug or poison had on the victim immediately before or at the time of sampling. Tolerance is one big issue, the mechanism of exposure (how the drug got into the body) is another, and of course with post-mortem work there are always additional considerations such as site of sample collection and the possibility of post-mortem change in analyte concentration. There are also questions of quality and reliability, and whether a particular analysis and the interpretation placed upon the result are appropriate in a particular case.

Chloroform poisoning--a case report.

Chloroform, a halogenated hydrocarbon, causes central nervous system (CNS) depression, cardiac arrhythmias, hepatotoxicity, and renal failure. We describe a successful outcome in a case of chloroform ingestion with renal and hepatotoxicity with N-acetylcysteine (NAC) administration and hemodialysis support.

Autoerotic Deaths in Hamburg, Germany: Autoerotic accident or death from internal cause in an autoerotic setting? A retrospective study from 2004-2018.

INTRODUCTION: Autoerotic deaths are rare events. The death scene is often bizarre and the death unexpected, thus often requiring forensic autopsies. Our analysis will provide an overview of the expected range of causes and manners of death in cases of autoerotic deaths. METHODS: A retrospective analysis was carried out on all scientific and forensic autopsies and postmortem examinations performed at the Department of Legal Medicine in Hamburg, Germany, over the period of 2004-2018. RESULTS: 25 cases of autoerotic fatalities were identified over this 15-year-period or one to two cases per year, respectively. Autopsies were carried out on 23 of these cases. 16 (64%) of the cases involved autoerotic accidents and 7 (28%) from internal causes of death during an autoerotic act. Two cases had not undergone an autopsy. On average, those who were involved in autoerotic accidents had been younger in age (average age: 37 years) than the individuals who died from internal disease (average age: 61 years). Only one woman was involved. The most common cause of death in autoerotic accidents was strangulation (hanging: 8 cases, ligature strangulation: 1 case), followed by smothering of the respiratory tract (4 cases). Fatal intoxication was diagnosed in three of the cases. Fatalities with natural cause of death solely involved cardiovascular causes of death. CONCLUSIONS: Autoerotic deaths involved a wide range of natural and non-natural causes of death. The reconstruction of such unusual cases and detection of non-natural fatalities requires thorough investigation of the scene of death as well as a postmortem external and internal examination including a chemical toxicological and blood alcohol analysis.

A case of acute toxic hepatitis after suicidal chloroform and dichloromethane ingestion.

Chloroform and dichloromethane are halogenated hydrocarbons that have been used as a potent anesthetic agent or a general industrial solvent. Short-term exposure to chloroform anesthesia and long-term exposure to chloroform and dichloromethane in workplaces can produce adverse health effects, such as hepatitis, cardiac arrhythmia, and carbon monoxide intoxication. Most of the related reports, however, involve the inhalation of such substances by humans. Limited reports are available regarding the adverse clinical effects of these substances in the case of a person's immediate ingestion of them. A 23-year-old man with an altered mental status after attempting suicide through the oral ingestion of unknown chemicals was brought to the emergency department (ED). We identified that the patient was poisoned with chloroform and dichloromethane by analysis of contents of the suspected chemicals in the bottle through gas chromatography. Abnormal liver enzymes were noted on postingestion day 2, and jaundice occurred on postingestion day 3. The radiologic findings from computed tomographic (CT) scanning showed severe fatty infiltration of the liver parenchyma. The patient received supportive cares and was restored to health from hepatic dysfunction and was discharged without complications after 2 weeks of admission.

Hazards of Improper Dispensary: Literature Review and Report of an Accidental Chloroform Injection.

Several clear, transparent solutions are used in endodontics. Inappropriate dispensing methods can lead to accidental injection or accidental irrigation. These accidents can cause permanent tissue damage including damage to the bone, periodontium, nerves, and vasculature. This article reports on the consequences of an accidental chloroform injection. Nonsurgical retreatment of tooth #8 was planned as part of a restorative treatment plan in a 69-year-old woman. The dentist accidentally injected chloroform instead of local anesthesia because chloroform was loaded into the anesthetic syringe. The patient experienced severe pain and swelling and soft tissue necrosis and suffered permanent sensory and motor nerve damage. A review of the literature was performed on accidents caused by improper dispensary, namely accidental injections and accidental irrigations. The data were extracted and summarized. Sodium hypochlorite, chlorhexidine, formalin, formocresol, 1:1000 adrenaline, benzalkonium chloride, and lighter fuel were accidentally injected as an intraoral nerve block or as infiltration injections. Bone and soft tissue necrosis, tooth loss, and sensory nerve damage (anesthesia and paresthesia) were the most common consequences reported. Such disastrous events can be prevented by appropriate labeling and separate dispensing methods for each solution. There is a need for disseminating information on toxicity and biocompatibility of materials/solutions used in endodontics. The authors recommend training dental students and endodontic residents on immediate and long-term therapeutic management of patients when an accidental injection or accidental irrigation occurs.

Chloroform ingestion causing severe gastrointestinal injury, hepatotoxicity and dermatitis confirmed with plasma chloroform concentrations.

CONTEXT: Poisoning due to chloroform ingestion is rare. The classic features of acute chloroform toxicity include central nervous system (CNS) and respiratory depression, and delayed hepatotoxicity. CASE DETAILS: A 30-year-old female ingested 20-30 mL of 99% chloroform solution, which caused rapid loss of consciousness, transient hypotension and severe respiratory depression requiring endotracheal intubation and ventilation. She was alert by 12 h and extubated 16 h post-overdose. At 38-h post-ingestion, her liver function tests started to rise and she was commenced on intravenous acetylcysteine. Her alanine transaminase (1283 U/L), aspartate transaminase (734 U/L) and international normalized ratio (2.3) peaked 67- to 72-h post-ingestion. She also developed severe abdominal pain, vomiting and diarrhoea. An abdominal CT scan was consistent with severe enterocolitis, and an upper gastrointestinal endoscopy showed erosive oesophagitis, severe erosive gastritis and ulceration. She was treated with opioid analgesia, proton pump inhibitors, sucralfate and total parenteral nutrition. Secretions caused a contact dermatitis of her face and back. Nine days post-ingestion she was able to tolerate food. Her liver function tests normalized and the dermatitis resolved. Chloroform was measured using headspace gas chromatograph mass spectrometry, with a peak concentration of 2.00 µg/mL, 4 h 20 min post-ingestion. The concentration-time data fitted a 1-compartment model with elimination half-life 6.5 h. DISCUSSION: In addition to early CNS depression and delayed hepatotoxicity, we report severe gastrointestinal injury and dermatitis with chloroform ingestion. Recovery occurred with good supportive care, acetylcysteine and management of gastrointestinal complications.

An unusual autoerotic fatality associated with chloroform inhalation.

We report the death of a young male attributed to chloroform poisoning during autoerotic asphyxia. He was found lying on the floor of his apartment, prone on a piece of foam and a towel. His eyes were bound with a towel, his lower face and nose were almost entirely covered with duct tape surrounding a rubber hose in his mouth. The other end of the hose was loosely sitting inside an open bottle which was in a box beside him. He was bound-up by an intricate system of ropes, handles, and rods, ending with a noose around his neck. Toxicology testing indicated chloroform concentrations of 18.1 mg/L in femoral blood and 1.5 mg/L in urine. Chloroform was measured by headspace gas chromatography with flame-ionization detection using 1,1,1-trichloroethane as the internal standard. The cause of death was recorded as "chloroform toxicity" with "autoerotic asphyxia" as a contributing factor, and the manner of death was "accidental".

Associations of cancer mortality with halomethanes in drinking water.

Associations between site- and sex-specific county cancer mortality rates and levels of trihalomethanes (THM's) in drinking water were examined after adjustment of rates for the influence of multiple socioeconomic, industrial, and demographic factors. U.S. counties with sampled supplies were grouped by percent of the county population receiving water from the supply, as well as by region of the country. For two sites (bladder and lung), county rates were also adjusted for the activity level in specific high-risk industries. Positive correlations with THM levels were observed for several cancers, including bladder and brain cancers in both sexes, and non-Hodgkin's lymphoma and kidney cancer in males. Stomach cancer in females showed a negative association. Bladder cancer mortality rates showed the strongest and most consistent association with a THM exposure index, after control for differences in social class, ethnic group, urban versus rural residence, region of the United States, and industrialization of the county. These ecologic associations suggested that further evaluation in analytic investigations is warranted.

Diagnostic radiopacity and hepatotoxicity following chloroform ingestion: a case report.

BACKGROUND: Diagnostic imaging can help in the management of toxicologic emergencies. The authors report on a patient who presented to the emergency department with coma and suppressed respirations after ingestion of an unknown substance. METHODS: Ingestion of chloroform with radiopaque material in the bowel on abdominal radiograph was documented. The patient was treated with haemoperfusion, activated charcoal, and laxatives to decrease the toxicities. RESULTS: Hepatotoxicity occurred on post-ingestion day 3 and elevation of liver enzymes reached peak levels on post-ingestion day 5. The patient received N-acetylsystein and supportive care during hospitalisation. The patient improved from hepatic dysfunction and was discharged without complication on post-ingestion day 11. CONCLUSION: Radiographic studies in toxicology may confirm a diagnosis and assist in therapeutic intervention.

"Experimentation" with chloroform.

A young patient presented with unconsciousness, cardiac arrhythmias, arterial hypotension, and mild intravascular hemolysis after intentional inhalation of chloroform. After the initial complications had resolved, nausea, loss of appetite, and mild transitory jaundice developed. Chloroform-associated hepatotoxicity was biochemically and histologically documented. Facilitating factors included long-term moderate alcohol consumption and an initial episode of arterial hypoxemia. Chloroform inhalation for recreational purposes is probably uncommon. Yet, because of its delayed onset, chloroform poisoning should be considered in acute liver disease without a clear antecedent cause.

Changes in cytochrome P450 molecular species in rat liver in chloroform intoxication.

The effect of CHCl3 on the composition of hepatic microsomal cytochrome P450 species was compared with that of CCl4 in rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (3MC). The administration of CHCl3 hardly affected cytochrome P450 content in non-treated rat liver, but caused a similar degree of depletion in the content as observed after CCl4 administration in PB-pretreated rats. In the pretreatment with 3MC, the administration of CHCl3 brought about a marked decrease in the content to 24% of control after 12 hr, while CCl4 reduced the content only to one-half of control. It was demonstrated by SDS-polyacrylamide gel electrophoresis and Whatman DE-52 anion-exchange chromatography that 3MC-induced P450 species decreased with CHCl3, while it was affected little by CCl4 treatment. The activity of benzo[a]pyrene hydroxylase was altered together with the change in the content of cytochrome P450 species. The administration of CHCl3 to PB-pretreated rats caused the depletion in PB-induced P450. These findings indicate that cytochrome P450 species induced with 3MC as well as PB are highly susceptible to CHCl3 intoxication, whereas the administration of CCl4 depletes the PB-induced species without affecting the 3MC-induced species.

Individual serum bile acids as early indicators of carbon tetrachloride- and chloroform-induced liver injury.

Individual serum bile acids (SBA) are emerging as potentially useful early indicators of liver injury. This study was undertaken to compare the usefulness of individual SBA with the routinely used assays for detecting the effects of the hepatotoxicants carbon tetrachloride (CCl4) and chloroform (CHCl3). Serum samples were assayed for liver injury by determination of alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP), bilirubin and total bile acid (by enzymatic kit). These results were compared with levels of individual SBA measured by high performance liquid chromatography (HPLC). Liver samples from CCl4-treated rats were taken for light and electron microscopic examination. The highest dose for each chemical caused increases in serum ALT and AST but not ALP. Chloroform at the highest dose increased bilirubin. Total SBA levels as assayed by the kit were elevated in response to CCl4 and CHCl3 at doses below which serum enzymes and bilirubin were increased. Some individual SBA were increased at a still lower dose for each of these two chlorinated solvents. At the lowest dose of CCl4 tested no consistent light microscopic or ultrastructural changes were found. At all the higher doses periacinar cells displayed typical accumulation of lipid droplets and degranulation and dilation of rough endoplasmic reticulum. The extent of the ultrastructural changes were dose-dependent. Thus individual SBA assayed by HPLC may be considered as a very sensitive indicator of liver injury induced by the classical hepatotoxicants carbon tetrachloride and chloroform.

Studies on the composition of gases in the post-mortem body: animal experiments and two autopsy cases.

The composition of gases was measured in a cadaver, particularly in the stomach, using gas chromatography. High concentrations of carbon dioxide (CO2) and hydrogen (H2) and a low concentration of methane (CH4) were found. At an environmental temperature of 25 degrees C, the concentrations of CO2 and H2 were approximately 80% and 10%, respectively, at an advanced stage of putrefaction, while at an environmental temperature of 15 degrees C the concentrations were approximately 60% and 35%, respectively. These gases were not produced until the fourth day at 15 degrees C, but after that the volume of gases was greater than that produced at 25 degrees C, the cadaver becoming greatly enlarged. Oxygen (O2) in air injected into a body disappeared during putrefaction. This study revealed that H2 was the main component of inflammable gas in a dead body. The mechanisms of production of the gases are also discussed.

Multiple homicides as a result of chloroform poisoning: case report and experimental study.

Two cases (involving five murder victims) of multiple homicide by inhalational chloroform intoxication are reported. In the discussion of the findings the valence of toxicological analyses is underlined with regard to the possibility of forcible external suffocation due to occlusion of the respiratory orifices by means of a chloroform-soaked soft covering. In addition storage experiments were performed at +4, +20 and -20 degrees C with cadaver blood mixed with chloroform. The optimal solution for avoiding volatile losses was stored in glass tubes with ground glass stoppers. In cases of unclear death in which involvement of volatile substances is suspected it is, therefore, advisable to preserve an additional blood sample at -20 degrees C in glass tubes that are only opened for the analysis of volatile substances.

Estimated worst case trihalomethane body burden of a child using a swimming pool.

The amount of trihalomethane (as chloroform) absorbed over a three-hour period by a six-year-old boy when using a chlorinated freshwater swimming pool containing 500 microgram/liter of trihalomethanes, has been estimated to be 2.82 mg.