Case report: hexachloroethane smoke inhalation: a rare cause of severe hepatic injuries.CONTEXT: We report on two patients, a 23-year-old man and a 24-year-old man, who had chemical pneumonitis and respiratory distress after inhaling hexachloroethane/zinc oxide (HC/ZnO) smoke during military training.
CASE PRESENTATION: The patients had been healthy previously and denied any history of alcohol or drug abuse. Hematologic hematological, hematologic
pertaining to or emanating from blood cells.
total and differential white cell counts, hematocrit estimation, erythrocyte count. tests revealed leukocytosis Leukocytosis Definition
Leukocytosis is a condition characterized by an elevated number of white cells in the blood.
Leukocytosis is a condition that affects all types of white blood cells. with neutrophils predominant. The respiratory conditions of both patients improved after steroid therapy and oxygen support, but deterioration of liver function was found. The laboratory results showed that alanine aminotransferase (ALT) and [gamma]-glutamyl transpeptidase levels were elevated about 1.5-fold the normal limits and that aspartate aminotransferase (AST (AST Computer, Irvine, CA) A PC manufacturer founded in 1980 by Albert Wong, Safi Quershey and Tom Yuen (A, S and T). It offered a complete line of PCs that sold through its dealer channel. ) levels were marginally elevated. The elevation of liver aminotransferase aminotransferase /ami·no·trans·fer·ase/ (-trans´fer-as) transaminase.
n. started from day I and day 2 and peaked from day 18 to day 22. ALT/AST levels then returned to normal in 6 weeks. Common viral hepatitis was ruled out after serologic tests. Abdominal sonography sonography: see ultrasound and physical examination failed to show any specific findings.
DISCUSSION: The hepatotoxic hep·a·to·tox·ic
Damaging or destructive to the liver.
causing liver damage. effect was attributed to inhalation of high-concentration HC/ZnO smoke in an enclosed area, where several hepatotoxicants, including Zn[Cl.sub.2], HC, and chlorinated chlorinated /chlo·ri·nat·ed/ (klor´i-nat?ed) treated or charged with chlorine.
charged with chlorine.
some, e.g. vapors, could have been generated and mixed in the smoke.
RELEVANCE TO CLINICAL PRACTICE. These case reports elaborate the hepatic effects that may occur in addition to pulmonary effects of HC/ZnO smoke.
KEY WORDS: hepatotoxicity hepatotoxicity (hepˑ··tō·t , hexachloroethane hexachloroethane
an anthelmintic used in the treatment of fascioliasis. Poisoning manifested by narcosis, staggering and falling. Fatal cases in cattle have abomasitis and hepatic necrosis. , white smoke, zinc oxide. Environ Health Perspect 114:763-765 (2006). doi: 10.1289/ehp.8635 available via http://dx.doi.org/[Online 24 January 2006]
Hexachloroethane/zinc oxide (HC/ZnO) smoke, also known as white smoke, has many military and civilian applications, such as in training exercises and on the battlefield [Agency for Toxic Substances and Disease Registry The United States Agency for Toxic Substances and Disease Registry, (ATSDR) is an agency for the U.S. Department of Health and Human Services that is directed by a congressional mandate to perform specific functions concerning the effect on public health of hazardous (ATSDR ATSDR Agency for Toxic Substances & Disease Registry ) 1997; Holmes 1999; Zerahn et al. 1999]. Inhalation is the most common route of injury. Documented injuries are predominately pulmonary and range from cough and dyspnea to chemical pneumonitis, pulmonary edema, adult respiratory distress syndrome Adult Respiratory Distress Syndrome Definition
Adult respiratory distress syndrome (ARDS), also called acute respiratory distress syndrome, is a type of lung (pulmonary) failure that may result from any disease that causes large amounts of fluid to , and death (Cullumbine 1957; Greenfield et al. 2002; Hjortso et al. 1988). The toxicity of HC/ZnO smoke results from both the chemical and physical properties of the smoke. The primary component of white smoke is HC/ZnO combined with granular aluminum. Upon burning, several compounds are produced: zinc chloride, 62.5%; ZnO, 9.6%; iron oxide, 10.7%; aluminum oxide, 5.4%; lead oxide, 1%; and chlorinated vapors, 10.8% (DeVaull et al. 1989). The reaction equation is as follows (Cichowicz 1983):
2 Al + [C.sub.2][Cl.sub.6] + 3 ZnO [right arrow] 3 Zn[Cl.sub.2] + [Al.sub.2][O.sub.3] + 2 C + heat.
The reaction is exothermic exothermic /exo·ther·mic/ (-ther´mik) marked or accompanied by evolution of heat; liberating heat or energy.
ex·o·ther·mic or ex·o·ther·mal
1. and self-perpetuating to the right, liberating large amounts of Zn[Cl.sub.2] as a hot vapor. Upon cooling, it nucleates to form an aerosol that rapidly absorbs water from the surrounding atmosphere. Hydrated Zn[Cl.sub.2] particles then scatter light, thereby creating the desired obscurant ob·scur·ant
One who opposes intellectual advancement and political reform.
1. Characterized by opposition to intellectual advancement and political reform.
2. effect (ATSDR 1997; Holmes 1999; Katz et al. 1980). When a smoke grenade is used, the heat causes other chemicals to form, including carbon tetrachloride, tetrachlorethylene tet·ra·chlo·ro·eth·yl·ene also tet·ra·chlor·eth·yl·ene
Noun 1. tetrachlorethylene - anthelmintic agent used against hookworm and other nematodes , hexachlorobenzene, and phosgene phosgene (fŏs`jēn), colorless poison gas, first used during World War I by the Germans (1915). When dispersed in air, the gas has the odor of new-mowed hay. (ATSDR 1997). Medical personnel, military and civilian alike, may be called upon to recognize and treat patients with HC/ZnO smoke injuries. Almost all studies have focused on the pulmonary effects, and little if any information exists on hepatic toxicity. In this article we report two cases of acute hepatic injuries associated with HC/ZnO smoke inhalation.
Patient 1. The first patient, a 23-year-old man with an unremarkable medical and surgical history, was admitted to our hospital because of accidental inhalation of HC/ZnO smoke during military training. The patient had been healthy previously and denied any history of alcohol or drug abuse. This soldier specifically denied any history of smoking or pulmonary disorders. He had been in a tunnel without respiratory protection when a smoke grenade used to simulate battle conditions ignited near the entrance. The tunnel was about 1.75 m x 0.6 m x 360 m (5.74 ft x 1.97 ft x 1,181 ft). The estimated time of exposure to the HC/ZnO smoke was about 3 min. He suffered from lacrimation lacrimation /lac·ri·ma·tion/ (lak?ri-ma´shun) secretion and discharge of tears.
lac·ri·ma·tion or lach·ry·ma·tion
The secretion of tears, especially in excess. , cough, chest tightness, dyspnea, and sore throat at the scene.
On arrival at the hospital, the initial physical examination showed that the patient's blood pressure was 110/70 mmHg, his heart rate was 80 bpm, and his oral temperature was 38.1[degrees]C (100.6[degrees]F). His respirations were shallow but unlabored un·la·bored
1. Done with or requiring little effort; effortless.
2. Not tilled or cultivated. , with a rate of 19/min. Auscultation auscultation
Procedure for detecting certain defects or conditions by listening for normal and abnormal heart, breath, bowel, fetal, and other sounds in the body. The invention of the stethoscope in 1819 improved and expanded this practice, still very useful despite the of the lungs was unremarkable. The cardiac examination revealed a normal S1 and [S.sub.2] without murmur, gallop, rub, or click. Arterial blood gas arterial blood gas Critical care Analysis of arterial blood for O2, CO2, bicarbonate content, and pH, which reflects the functional effectiveness of lung function and to monitor respiratory therapy Ref range pO2 analysis and blood chemistry test values were within the normal ranges except that the alanine aminotransferase (ALT) and [gamma]-glutamyl transpeptidase (GGT GGT
GGT Gammaglutamyltransferase, see there ) levels were elevated about 1.5-fold of normal limits and the aspartate aminotransferase (AST) level was marginally elevated. Leukocytosis with neutrophils predominating was also noted (Table 1). The leukocytosis returned to normal on the 10th day after the event.
He was admitted to the pulmonary ward for observation. Oxygen (6 L/min) was delivered by mask after admission. Exacerbation of his respiratory condition developed on the third day in the hospital. Chest auscultation revealed bilateral basal crackles. Radiography of the chest showed interstitial pulmonary infiltration in both lower lungs. Intravenous hydrocortisone hydrocortisone (hī'drəkôr`tĭzōn'), another name for the steroid hormone cortisol, more especially used to refer to preparations of this hormone used medicinally. (600 mg/day) and a prophylactic antibiotic (ceftazidime 1 g every 8 hr for 5 days) were administered. His respiratory condition improved after steroid therapy. The steroid dose was decreased gradually and discontinued 13 days after initiation. Elevation of liver enzymes was noted during hospitalization. ALT levels increased to 138 U/L U/L Upload
U/L Units/Litre on day 7 and peaked at 625 U/L on day 22 (Figure 1). Serologic investigation was negative for viral hepatitis B and C. No significant abnormal findings were observed on abdominal sonography.
The patient was discharged on the 28th hospital day with a decreasing liver enzyme levels. Two weeks later (6 weeks after the accident), the patient's liver function returned to normal. In addition, in serial follow-up studies we failed to find any evidence of HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. (human immunodeficiency virus human immunodeficiency virus
Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans. ) or autoimmune disease for 18 months.
Patient 2. The second patient, a 24-year-old man with an unremarkable medical history, was admitted to our hospital on the same day from the same accident described for patient 1. He had been healthy previously and denied any history of alcohol or drug abuse. He also had dyspnea, cough, chest distress, and a sore throat. Physical examination revealed blood pressure of 120/74 mmHg, heart rate of 84 bpm, and oral temperature of 37.4[degrees]C (99.3[degrees]F). Arterial blood gas analysis and blood chemistry tests were within the normal ranges. Hematologic tests revealed leukocytosis with neutrophils predominant (Table 1). The leukocytosis returned to normal on the 9th day after the event.
Oxygen was given by face mask after admission. Two days later, the patient experienced progressive respiratory distress. Chest auscultation revealed bilateral expiratory wheezes. A chest radiograph radiograph /ra·dio·graph/ (-graf?) the film produced by radiography.
n. revealed diffuse interstitial infiltrates. High-resolution computed tomography high-resolution computed tomography Imaging CT at slice–collimation scan interval widths of ≤ 4 mm, which is narrower than the usual
1-3 cm interval 'slices' obtained in conventional CT imaging. Cf Spiral computed tomography. of the chest showed acute inhalation pneumonitis pneumonitis /pneu·mo·ni·tis/ (noo?mo-ni´tis) inflammation of the lung; see also pneumonia.
hypersensitivity pneumonitis with patchy and small ill-defined nodular nodular
marked with, or resembling, nodules.
see nodular fasciitis (below).
a firm painless nodular swelling, 0. areas of ground-glass opacity over all lung fields. Respiratory supports, including steroid therapy and antibiotic prophylaxis were administered as for patient 1. Three days after treatment, his respiratory condition improved and we began to gradually decrease the steroid.
The AST and ALT concentrations increased to a peak of 92 and 195 U/L, respectively, on day 18 (Figure 1). Serologic tests for hepatitis B and C and abdominal sonography showed no abnormal findings. The ALT level decreased to 95 U/L before discharge on the 27th day. Two weeks after discharge, the patient's liver function returned to normal. In addition, serial follow-up studies failed to find any evidence of HIV or autoimmune disease for 18 months.
[FIGURE 1 OMITTED]
HC/ZnO smoke is used by the military to conceal troops, for crowd dispersal, and occasionally in military and civilian fire-fighting. The acute toxic effects of HC/ZnO smoke on the respiratory tract are primarily attributed to inhalation of hydrated Zn[Cl.sub.2] vapor. The vapor is very corrosive and rapidly damages the respiratory mucosal surface (Cullumbine 1957; Greenfield et al. 2002; Hjortso et al. 1988). To the best of our knowledge, the hepatic effects of HC/ZnO are very limited. Pettila et al. (2000) reported three patients with Zn[Cl.sub.2] inhalation; all three patients had severe acute respiratory distress syndrome acute respiratory distress syndrome
See adult respiratory distress syndrome. (ARDS Ards
District (pop., 2001: 73,244), Northern Ireland. Formerly part of County Down, Ards was established as a district in 1973. Much of its land is devoted to crops and pasture. Newtownards, settled c. 1608 by Scots, is its administrative seat and manufacturing centre. ). Acute exposure causes the elevation of liver enzymes by day 1 or 2, which peaks from day 18 to day 21 and then returns to normal in 6 weeks (Figure 1). The mechanism of hepatotoxicity of HC/ZnO smoke is still unknown. Several compounds, including ZnO, Zn[Cl.sub.2], HC, chlorinated vapors, and medications, may cause hepatic toxicity.
ZnO has not been reported to cause hepatic damage, whereas Zn[Cl.sub.2], HC, and chlorinated compounds have great potential to induce hepatotoxicity. Among 12 workers with 4-21 years of exposure to ZnO fumes in the production of brass alloys, no liver disease was reported (ATSDR 2003b; Hamdi 1969). Pettila et al. (2000) reported abnormal liver function (ALT of 119, 131, and 2,570 U/L) in three patients; however, because there was no detailed personal history (e.g., transfusion, alcohol consumption) or viral markers, it was difficult to evaluate the potential hepatotoxicity. Marrs et al. (1988) observed a significant increase in the incidence of fatty liver in mice after repeated exposure to Zn[Cl.sub.2] smoke, but the incidence did not increase with the dose, and hepatic toxicity was not observed in the liver of rats and guinea pigs using the same exposure paradigm.
About 5% or less of the compounds in HC/ZnO smoke are released into the air as HC. In one study, Selden et al. (1993) reported that liver function tests Liver Function Tests Definition
Liver function tests, or LFTs, include tests for bilirubin, a breakdown product of hemoglobin, and ammonia, a protein byproduct that is normally converted into urea by the liver before being excreted by the kidneys. were not affected in HC-exposed workers who wore protective clothing. Animal studies have shown that hepatic tissues are moderately vulnerable to HC exposure, especially when exposure occurs by the oral route. Increases in liver weight, increases in serum levels of liver enzymes, centrilobular necrosis, fatty degeneration, hemosiderin-laden macrophages, and hemorrhage were seen in animals exposed to HC [ATSDR 1997; Fowler 1969; Gorzinski 1985; National Toxicology Program National Toxicology Program Environment A program that conducts toxicologic tests on substances frequently found at the EPA's National Priorities List sites, which have the greatest potential for human exposure (NTP (Network Time Protocol) A TCP/IP protocol used to synchronize the real time clock in computers, network devices and other electronic equipment that is time sensitive. It is also used to maintain the correct time in NTP-based wall and desk clocks. ) 1989; Weeks et al. 1979]. In these studies, effects on the liver and kidneys were mild with inhalation exposure and more pronounced with oral exposure. In a study of acute and intermediate-duration inhalation exposure, the only effect noted by Weeks et al. (1979) after 6 weeks of exposure to 260 ppm HC was an increase in liver weight in rats and guinea pigs but not in quail.
About 10% of HC/ZnO smoke is composed of chlorinated compounds (Holmes 1999; Katz et al. 1980; National Research Council 1997). The chlorinated compounds include tetrachloromethane (i.e., carbon tetrachloride, C[Cl.sub.4]), tetrachloroethylene tetrachloroethylene /tet·ra·chlo·ro·eth·y·lene/ (tet?rah-klor?o-eth´i-len) a moderately toxic chlorinated hydrocarbon used as a dry-cleaning solvent and for other industrial uses. , and hexachlorobenzene. C[Cl.sub.4] has long been known to be a powerful hepatotoxic agent in humans and animals. The principal clinical signs of liver injury in humans who inhale C[Cl.sub.4] are a swollen and tender liver, elevated levels of hepatic enzymes in serum, elevated serum bilirubin Bilirubin
The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase. levels and the appearance of jaundice, and decreased serum levels of proteins such as albumin and fibrinogen Fibrinogen
The major clot-forming substrate in the blood plasma of vertebrates. Though fibrinogen represents a small fraction of plasma proteins (normal human plasma has a fibrinogen content of 2–4 mg/ml of a total of 70 mg protein/ml), its conversion (ATSDR 2003a). Liver necrosis was reported in one fatal case involving an alcoholic patient who was exposed to 250 ppm for 15 min (Norwood et al. 1950). High C[Cl.sub.4] vapor concentration might have produced liver injury in our patients. However, we could not identify any right upper quadrant right upper quadrant Physical exam The abdominal region that contains the liver, duodenum and head of pancreas tenderness or liver enlargement in either of our patients.
Toxicant- or drug-induced liver injury is a potential complication of nearly every medication (Lee 1995). We needed to rule out the possibility that the observed hepatic toxicity was due to therapeutic drugs. For our cases, we prescribed acetaminophen for fever, steroids, antibiotics, bambuterol, aminophylline aminophylline /am·i·noph·yl·line/ (am?i-nof´i-lin) a salt of theophylline, used as a bronchodilator and as an antidote to dipyridamole toxicity.
n. , ipratropium, mucolytics for pulmonary symptoms, and a mild sedative for sleeping. The three potential hepatic toxicants are acetaminophen, steroids, and antibiotics; however, acetaminophen taken at recommended doses (0.5-3 g daily) is relatively safe (Norris 2000). One of our cases took < 0.5 mg/day for 2 days, and the other never took it.
Steroid therapy is a standard treatment of ARDS and is applied universally. A thorough search of the literature revealed only a few case reports of suspected corticosteroid-induced hepatomegaly hepatomegaly /hep·a·to·meg·a·ly/ (hep?ah-to-meg´ah-le) enlargement of the liver.
The abnormal enlargement of the liver. Also called megalohepatia. (Nanki et al. 1999). Based on limited data, it is difficult to justify any correlation between corticosteroid use and the hepatitis seen in our patients.
Elevations in liver enzymes and bilirubin have occurred during treatment with ceftazidime. The incidence appears similar to that with other cephalosporins Cephalosporins Definition
Cephalosporins are medicines that kill bacteria or prevent their growth.
Cephalosporins are used to treat infections in different parts of the body—the ears, nose, throat, lungs, sinuses, and (Meyers 1985). In most cases, liver enzyme elevations have been transient, with levels returning to normal after withdrawal of treatment. Our patients received a 5-day course of ceftazidime for prophylaxis. However, continued deterioration of liver function was observed after ceftazidime was discontinued.
The diagnosis of toxicant-induced liver injury is often obscured by difficulty in determining the precise timing of toxicant ingestion and lack of specific symptoms (Lee 1995; Norris 2000). Central to the diagnosis is a thorough history, including drug exposure and occupational hazards with exposure to chemicals. In addition, the changes of liver enzymes may represent progression on underlying disease, a complication of the underlying disease, or an unrelated episode, such as sepsis or shock (Norris 2000). Confirmation of the diagnosis by a toxicant rechallenge is reliable but rarely justifiable (Lee 1995; Maria et al. 1997; Norris 2000). However, given that these two individuals inhaled the same gas, it is more likely that the effects were due to either the chemicals in the smoke or a combination of the chemicals in the smoke and the drugs, rather than the drugs alone.
The main treatment for toxicant-induced hepatotoxicity is the withdrawal or removal of the agent, supportive care, and alleviation of the symptoms (Lee 1995; Norris 2000). In our cases, there was no treatment beyond what was done for the respiratory effects.
Inhalation of HC/ZnO smoke may have hepatic effects in addition to the effect of pulmonary distress. The hepatotoxic effect in our patients was attributed to inhalation of high-concentration HC/ZnO smoke in an enclosed area, where several compounds including Zn[Cl.sub.2], HC, and chlorinated vapors may have been generated and mixed in the smoke.
Received 7 September 2005; accepted 23 January 2006.
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War materiel, especially weapons and ammunition. Often used in the plural.
tr.v. mu·ni·tioned, mu·ni·tion·ing, mu·ni·tions
To supply with munitions. and Chemical Command, U.S. Army Aberdeen Proving Ground Aberdeen Proving Ground (APG) is a United States Army facility located near Aberdeen, Maryland (in Harford County).
The Army's oldest active proving ground, it was established on October 20, 1917, six months after the United States entered World War I. .
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Ching-Hui Loh, (1) Yaw-Wen Chang, (1) Saou-Hsing Liou, (2,3) Jun-Hei Chang, (1) and Hong-I Chen (4,5)
(1) Department of Family Medicine and Community Health, Tri-Service General Hospital The Tri-Service General Hospital (Chinese: 三軍總醫院; Pinyin: Sānjūn Zǒngyīyuàn; abbreviation TSGH) is a medical center in Taipei, Republic of China. , National Defense Medical Center, Taipei, Taiwan, ROC; (2) Department of Public Health, National Defense Medical Center, Neihu, Taipei, Taiwan, ROC, (3) Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Kaohsiung, Taiwan, ROC; (4) Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; (5) Medical Bureau, Department of National Defense, Taipei, Taiwan, ROC
Address correspondence to H.-I. Chen, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Rd., Sec. 2, Neihu 114, Taipei, Taiwan, ROC. Telephone: 886-2-8792-3100. Fax: 886-2-8792-7057. E-mail: firstname.lastname@example.org
The authors declare they have no competing financial interests.
Table 1. Characteristics and biochemical data of patients 1 and 2 at 4 hr after the event. Normal range Patient 1 Patient 2 for males Age (years) 23 24 Body weight (kg) 64.5 67 Body massindex 19 21 18-24 (kg/[m.sup.2]) White blood cell 21,900 17,100 4,500-11,000 (L/[mm.sup.3]) Neutrophils (%) 93 91 40-70 Lymphocytes (%) 3.8 3.4 19-48 ALT (U/L) 60 24 <41 AST (U/L) 47 31 <37 ALP (U/L) 176 123 40-129 GGT (U/L) 61 25 9-40 ALP, alkaline phosphatase.