Article, Emergency Medicine

Carbon tetrachloride poisoning from an antique fire extinguisher

Journal logoUnlabelled imageAmerican Journal of Emergency Medicine 38 (2020) 2139-2141

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American Journal of Emergency Medicine

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Carbon tetrachloride poisoning from an antique fire extinguisher

Christopher W. Meaden, MD, MS a,b,?, Gabrielle Procopio, PharmD c, Diane P. Calello, MD a,b, Lewis S. Nelson, MD a,b, Bruce Ruck, PharmD a,b, Amit Gupta, MD c, Jeena E. Jacob, MD, PharmD a,b

a Rutgers New Jersey Medical School, Newark, NJ, United States of America

b New Jersey Poison Information and Education System, Newark, NJ, United States of America

c Hackensack University Medical Center, Hackensack, NJ, United States of America

  1. Introduction

Household exposure to carbon tetrachloride (CCl4) is rare in the United States as it is no longer utilized due to concerns about toxicity. Prior to being phased out of regular use, CCl4 had been used as a compo- nent of fire extinguishers, cleaning agents, degreasing agents, and sol- vents [1]. CCl4 is a volatile liquid that causes hepatotoxicity by oxidative damage after it is activated via CYP2E1 metabolism (with CYP3A contributing at higher concentrations of CCl4) to a trichloromethyl radical [2,3]. Once it is activated to a trichloromethyl radical, it causes a centrilobular pattern of Hepatic injury by creating co- valent bonds with macromolecules within hepatocytes, and causes gen- eration of free radicals and lipid peroxidation [4]. Toxicity from inhaled and ingested routes of exposure have been reported [2].

Recent exposures to carbon tetrachloride are rarely reported in the literature since the use of the product has been largely phased out due to concerns about its hepatotoxicity. However, we must remain cogni- zant that exposure can occur through the acquisition of products that may still contain CCl4. Furthermore, there is little modern guidance as to the treatment for exposed patients that develop signs and symptoms of toxicity. We describe two cases of carbon tetrachloride induced hep- atotoxicity from household exposure. Both cases recovered after treat- ment with N-acetylcysteine (NAC).

  1. Case 1

A 31-year-old male with a past medical history of insulin dependent diabetes mellitus, hypertension, hyperlipidemia, and hypothyroidism presented to the emergency department with vomiting, diarrhea, and fatigue for one day. He denied daily use of alcohol, illicit drug use, and Tobacco use. His Home medications include an Insulin infusion pump and levothyroxine. The day before the onset of his symptoms, both he and his brother were cleaning a poorly ventilated basement of his newly purchased home that was constructed 100 years ago. During their cleaning, they removed an old fire grenade from above the boiler and placed it on a table in the basement. While moving the table, the fire grenade fell and shattered on the concrete floor, spilling its contents. He noted that the spilled contents had an odor and quickly evaporated

* Corresponding author at: Rutgers New Jersey Medical School, Newark, NJ, United States of America.

E-mail address: [email protected] (C.W. Meaden).

within minutes of spilling on the ground. Despite this, both he and his brother, continued to work in the basement for six hours.

When he initially presented for evaluation at the emergency depart- ment, he was given 0.9% normal saline for intravenous (IV) fluid hydra- tion as well as the anti-emetic ondansetron IV. At the time of presentation, his lab work was notable for aspartate aminotransferase : 1243 (U/L), alanine aminotransferase (ALT): 1885 (U/L), total bilirubin level: 1.9 (mg/dl), and International normalized ratio :

1.64. (Table 1) During this presentation, the patient had an Abdominal ultrasound of his right upper quadrant which was notable only for mild hepatomegaly. The patient additionally had an undetectable acet- aminophen concentration as well as a non-reactive hepatitis panel. After feeling improved and able to tolerate fluids orally, the patient was discharged with a plan to repeat his liver function tests as an outpa- tient. The following day, the patient returned for continued complaint of nausea, vomiting and abdominal pain which had returned since being discharged. His vitals in the ED were: heart rate: 66 beats per minute, blood pressure:141/88 mmHg, respiratory rate: 18 breaths per minute, oxygen saturation: 98% on room air, and temperature: 98.1 degrees Fahrenheit. His labs now showed AST: 2982 (U/L), AST: 6390 (U/L), total bilirubin: 2.8 (mg/dl), and INR: 1.64. (Table 1) At the time of this visit the patient recalled the fire grenade that shattered in the basement. An internet query revealed that similar appearing antique fire grenades from the time period his home was built contained carbon tetrachloride. Poison control was contacted at this time.

The patient was started on an IV infusion of NAC with a loading dose given over 1 h of 150 mg/kg in 200 mL of 5% dextrose in water (D5W), followed by a four hour infusion of 50 mg/kg in 500 mL of D5W, and then a continuous infusion of 6.25 mL/kg/h. The patient was transferred to a tertiary care hospital for a higher level of hepatology care. When he arrived at the new facility, the patient had a heart rate: 67 beats per minute, blood pressure: 127/92 mmHg, respiratory rate: 20 breaths per minute, oxygen saturation: 96% on room air, and a temperature: 980 F. He was well appearing, non-icteric, and his abdomen was soft, non-tender, and non-distended. The remainder of his physical exam was normal. He was continued on a NAC infusion at 6.25 mL/kg/h for hepatotoxicity.

The patient had improvement of his nausea and vomiting through- out his hospital course, he was kept on the continuous infusion of NAC for 48 h. He was noted to have improvement of his transaminases which decreased from peak levels to AST: 252 (U/L) and ALT: 2726 (U/L) and improvement of his peak INR of 1.7 to 1.3. He was discharged

https://doi.org/10.1016/j.ajem.2020.07.052

0735-6757/(C) 2020

Table 1

Case 1 laboratory data throughout clinical course of aspartate aminotransferase (AST), al- anine aminotransferase (ALT), total bilirubin, and International normalized ratio .

AST (U/L) ALT (U/L) Total Bilirubin (mg/dl) INR Initial Presentation 1243 1885 1.9 1.64

Second ED Visit 2982 6390 2.8 1.7

Hospital Day 1 1584 4499 2.2 1.5

phased out of use in the United States during the twentieth century due to concerns about hepatoxicity. Primary routes of exposure to humans is via inhalation, ingestion, and dermal contact. At room tem- perature it appears as a clear, colorless, heavy liquid with a strong sweet odor [1]. It is a well described hepatotoxin exerting its toxicity through its toxic metabolite, a trichloromethyl free radical; this free rad- ical is created when CCl4 is metabolized largely by the Cytochrome P450 complex isoform 2E1. The radical causes damage through the binding of

Hospital Day 2

Hospital Day 3a

735 3987 1.8 1.4

252 2726 1.3 1.3

intracellular molecules and through the inhibition of cellular processes that includes lipid peroxidation [2]. Toxicity is rarely identified in mod-

Outpatient Day 7 64 742 1.0 1.0

a Represents the day in which the patient was discharged from transplant center to outpatient follow up.

on hospital day 3. The patient never displayed any laboratory findings consistent with an acute kidney injury. A week after discharge, he was noted to have a normal INR, normal total bilirubin level, and a resolving transaminitis. (Table 1).

  1. Case 2

A 24-year-old male, the brother of case 1, with no significant past medical history presented to the emergency department 12 h after his brother’s initial presentation with complaints of abdominal pain, vomiting, and hematemesis. He denied daily alcohol abuse, illicit sub- stance abuse, or tobacco use. His only home medication was over-the- counter ranitidine that he takes as need. He also worked for six hours in the same poorly ventilated basement after the fire grenade shattered. On physical exam he was nontoxic appearing without icterus and had mild upper abdominal tenderness. The remainder of his physical exam- ination was unremarkable. His initial labs were notable for AST: 2174 (U/L), ALT: 2481 (U/L), and INR: 1.29. (Table 2) His acetaminophen con- centration was negative. He had a negative abdominal ultrasound of the right upper quadrant and a non-reactive hepatitis panel.

Intravenous NAC was initiated after consultation with hepatology and poison control. He was given an initial dose of 150 mg/kg in 200 mL of 5% dextrose in water (D5W), followed by a four-hour infusion of 50 mg/kg in 500 mL of D5W, and then a continuous infusion of 6.25 mL/kg/h. Peak AST and ALT were 4345 (U/L) and 4782 (U/L) respectively, and INR was 1.56. (Table 2) His symptoms of nausea, vomiting, and ab- dominal pain improved throughout his hospital course. The patient did not develop laboratory evidence of acute kidney injury throughout his hospitalization. He was continued on NAC until his transaminases de- creased below 1000 (U/L) and was discharged to outpatient follow up on hospital day 6. Eleven days after discharge, his AST was 25 (U/L) and his ALT was 89 (U/L); the INR was not repeated on this visit.

  1. Discussion

CCl4 is a volatile liquid that was used as a fire extinguishing agent, solvent, cleaner, and degreaser in both industry and the home. It was

Table 2

Case 2 laboratory data throughout clinical course of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and International normalized ratio .

ern clinical practice in the United States.

Patients who develop carbon tetrachloride toxicity may present with vague symptoms, and a challenging diagnosis if there is no re- ported history of exposure. They may complain of fatigue, headache, nausea, vomiting, and depressed mental status. Laboratory analysis may reveal evidence of hepatotoxicity as well as an acute kidney failure. Clinical toxicity may occur with exposure to as little as five milliliters of CCl4. Toxicity is dependent upon the patient, route, dose, and duration of exposure [2].

The cases described presented with non-specific symptoms and a transaminitis that was initially unexplained. Since CCl4 is rarely used, it is less likely to be on the differential diagnosis of most clinicians. This led to multiple emergency department visits by the cases described and a Delay in diagnosis and therapy. Although these patients had a pos- itive outcome, this may not have been the case. This emphasizes the need to obtain a thorough history and consider hepatotoxicity from less common sources.

NAC is an amino acid analog readily used as an antidote in Poisoned patients, most notably acetaminophen induced hepatotoxicity. It has been suggested that NAC may aid in detoxification of the metabolic in- termediates created during CCl4 metabolism that are responsible for he- patocellular damage [5-9]. Although there is no established protocol for the use of NAC in this setting, prior reports extrapolated a protocol for administration of NAC in Acetaminophen toxicity [5]. A review of pub- lished literature shows that NAC is relatively safe; however, it is associ- ated with dose-related vomiting and rate-related anaphylactoid reactions (most commonly dermal reactions) when administered intra- venously. These symptoms are mitigated by temporarily stopping or slowing the infusion if the reaction occurs [10-13].

Limitations of this report include lack of confirmed CCl4 serum con- centrations and laboratory confirmation of the product contained in the fire grenade. Despite this, the customary use of CCl4 in fire grenades from the time period the home was built, the shared exposure, tempo- rality, and clinical course of both cases make CCl4 induced hepatotoxic- ity most likely.

  1. Conclusion

Although rarely encountered in contemporary medical practice, exposure to carbon tetrachloride and other similar haloalkanes should be considered on the differential diagnosis in the setting of unex- plained Hepatic dysfunction. A thorough history during patient en- counters including industrial and household exposures should be obtained. The outcomes of the described cases concur with prior re- ports of CCl4 hepatotoxicity that suggest treatment with NAC is bene- ficial. We would continue to recommend the use of NAC in the

AST (U/L)

ALT (U/L)

Total Bilirubin (mg/dl)

INR

treatment of acute CCl4 hepatotoxicity given potential benefit and minimal risk of harm.

Initial Presentation 2174 2481 1.5 1.29

Hospital Day 1 3104 4463 1.2 1.41

Hospital Day 2 2305 4302 1.2 1.3

Hospital Day 3 303 2211 0.5 1.12

Hospital Day 4 186 1787 0.7 1.09

Hospital Day 5a 123 1349 0.5 1.04

Outpatient Day 11 25 89 0.4 Not performed

a Represents the day in which the patient was discharged from hospital to outpatient follow up.

Declaration of Competing Interest

None of the authors have any affiliations with or involvement in any organization or entity with any financial interest, or non- financial interest in the subject matter or materials discussed in this manuscript.

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