Correspondence
Acute Liver Failure
N Engl J Med 1994; 330:1318-1319May 5, 1994
- Article
To the Editor:
William M. Lee's masterly review of acute liver failure indicts trichloroethylene as a direct liver toxin (Dec. 16 issue)1. This allegation is inconsistent with the fact that trichloroethylene was used for years as an anesthetic and was administered to hundreds of thousands of men, women (including pregnant women), and children, without untoward effects. During the period of this use, trichloroethylene was not thought to cause hepatic injury. The activity of trichloroethylene is quite unlike that of carbon tetrachloride, which predictably produces dose-related hepatic injury.
Lee provides two citations to support his assertion that trichloroethylene and tetrachloroethane “produce hepatic and renal injury”2,3. The report by Ruprah et al.2 deals with carbon tetrachloride, not trichloroethylene. In the other paper,3 Baerg and Kimberg observe, in fact, that “chronic exposure of a variety of experimental animals to trichloroethylene inhalation has produced neither significant dysfunction nor abnormal hepatic histology.” Specifically referring to hepatic necrosis after trichloroethylene anesthesia, Baerg and Kimberg note that “the association has often been obscured by severe intercurrent illness.”
Ignoring the contradictory reports cited in their own article, however, Baerg and Kimberg blame trichloroethylene as exclusively responsible for the injuries observed in the cases they report. The subjects had actually inhaled Carbona, a brand of cleaning fluid. Carbona contains, along with trichloroethylene, up to 56 percent petroleum distillate, an amorphous combination of mostly aliphatic and some aromatic hydrocarbons, which distill at a temperature lower than that of gasoline. As with gasoline, however, inhalation of petroleum distillates can produce an array of symptoms and organ injury4. Moreover, all three of Baerg and Kimberg's subjects abused other chemicals, including model-airplane glues, cocaine, and lysergic acid diethylamide and heroin by injection.
4 ReferencesJohn M.R. Bruner, M.D.
17 School St., Groton, MA 014501
Lee WM . Acute liver failure. N Engl J Med 1993;329:1862-1872
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Ruprah M ,Mant TG ,Flanagan RJ . Acute carbon tetrachloride poisoning in 19 patients: implications for diagnosis and treatment. Lancet 1985;1:1027-1029
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Baerg RD ,Kimberg DV . Centrilobular hepatic necrosis and acute renal failure in “solvent sniffers.” Ann Intern Med 1970;73:713-720
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Nierenberg DW ,Horowitz MB ,Harris KM ,James DH . Mineral spirits inhalation associated with hemolysis, pulmonary edema, and ventricular fibrillation. Arch Intern Med 1991;151:1437-1440
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To the Editor:
Lee states that hyperventilation is of little or no value in the treatment of cerebral edema in patients with fulminant hepatic failure. We strongly disagree.
We used jugular-bulb oximetry to study patients with fulminant hepatic failure.1 Jugular-bulb oximetry, a new cerebral monitoring technique that is now used in the management of severe head injuries, gives an indication of cerebral blood flow at the bedside. In all patients with grade IV encephalopathy, we found a high level of jugular-bulb oxygen saturation, indicating the presence of cerebral hyperemia. The values returned to normal after the initiation of hyperventilation. In only 1 of 10 patients did we find decreased values for jugular-bulb oxygen saturation with the use of mannitol.
Hyperventilation, and not mannitol, must be considered as the first treatment in patients with cerebral edema due to fulminant hepatic failure.
1 ReferencesCathy De Deyne, M.D.
Johan Decruyenaere, M.D.
Francis Colardyn, M.D.
University Hospital, 9000 Gent, BelgiumAuthor/Editor Response
Dr. Lee replies:
To the Editor: Dr. Bruner correctly points out that trichloroethylene was widely used as an anesthetic, and therefore uniform hepatotoxicity attributed to this agent may be questionable. Some experiments in animals have failed to confirm a dramatic, dose-related injury, although other studies are suggestive; differences between species may be important. Despite these inconsistencies, numerous reports appeared in the 1970s and continue to appear concerning injury to the liver and kidneys due to inhalation of trichloroethylene. Higher doses may be required to produce toxicity, such as those that presumably occur in workers during accidental exposures1,2. Alternatively, recurrent exposure over several days may be necessary, as observed in recreational “sniffers,” who seem to become addicted to the substance3. Although there is some evidence of dose-related or cumulative toxicity, the hepatic injury observed may be more idiosyncratic or allergic than uniform, as observed with halothane and other halogenated agents; eosinophilia has been reported in some patients who have inhaled trichloroethylene. In either case, trichloroethylene represents some risk to those heavily or repeatedly exposed to its fumes. In advising physicians or patients about this agent, it may be better to err on the side of caution and overcondemn it than mistakenly to underestimate the risks associated with exposure.
Dr. De Deyne and colleagues mention a new technique for determining oxygen saturation in the jugular bulb, of which I was not aware4. Data concerning this new method are only now becoming available. It may not be wise to equate oxygen saturation at the jugular bulb with the adequacy of cerebral blood flow. Outflow oxygen saturation is the final product of complex changes in cerebral perfusion and oxygen extraction by the edematous brain. Increased brain water, not hyperemia, results in passively decreased brain perfusion. In addition, one could make the interpretation that the higher the venous oxygen saturation, the lower the level of oxygen extraction, possibly because of shunt pathways, as observed in the peripheral circulation.
If the goal of therapy for patients with acute liver failure is to maintain adequate brain-cell oxygenation in the face of a high intracranial ambient pressure, then vasoconstriction may be counterproductive, at least when cerebral perfusion is already marginal. In any case, the only well-controlled study of hyperventilation as the primary method of managing cerebral edema was that of Ede et al.,5 and the result was negative.
Admittedly, mannitol seems a crude method to restore cerebral perfusion, but its use is based on solid clinical experience and study over many years. The limitation of mannitol is its relatively short period of efficacy. If acute hyperventilation were to prove effective, would the benefit last any longer than that observed with mannitol? Until adequate controlled studies are available using this new technique, there seems to be no rationale for a change in management as fundamental as that suggested by Dr. De Deyne and colleagues.
5 ReferencesWilliam M. Lee, M.D.
University of Texas Southwestern Medical School, Dallas, TX 75235-88871
Thiele DL ,Eigenbrodt EH ,Ware AJ . Cirrhosis after repeated trichloroethylene and 1,1,1-trichloroethane exposure. Gastroenterology 1982;83:926-929
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Schattner A ,Malnick SD . Anicteric hepatitis and uveitis in a worker exposed to trichloroethylene. Postgrad Med J 1990;66:730-731
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Clearfield HR . Hepatorenal toxicity from sniffing spot-remover (trichloroethylene). Dig Dis Sci 1970;15:851-856
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Decruyenaere J ,De Deyne C ,Poelaert J . Jugular bulb oximetry as a guide to therapy of hepatic encephalopathy. Eur J Anesth Rel Spec 1993;3:37-375
Ede RJ ,Gimson AE ,Bihari D ,Williams R . Controlled hyperventilation in the prevention of cerebral edema in fulminant hepatic failure. J Hepatol 1986;2:43-51
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