toxicity from chloroform can include central nervous system depression , cardiac arrhythmias , hepatic injury , and hepatic cancer .
most cases of chloroform toxicity are the result of inhalational exposures , and very few reports involve oral ingestions . since this route of exposure is exceedingly rare , information regarding the clinical course and management dilemmas of chloroform ingestions is limited .
we describe the successful treatment of an acute chloroform ingestion with intravenously administered n - acetylcysteine ( nac ) despite having one of the highest reported serum chloroform levels in a survivor .
a 19-year - old african - american man was found unconscious in his car with a suicide note and a half - empty bottle of chloroform he had ordered on the internet from overseas ( fig .  1 ) .
he was brought to the emergency department obtunded and required immediate endotracheal intubation and mechanical ventilation .
it was later determined that he had drank about 75  ml of the chloroform prior to his being discovered .
his initial vital signs included a heart rate of 75  beats / min and a blood pressure of 113/60  mm hg ; he was mechanically ventilated at a rate of 16  breaths / min with an oxygen saturation of 100% on 100% fio2 .
the patient had an ecg performed , which did not reveal any signs of ischemia with a qrs of 86  ms and qt of 408  ms .
blood drawn on arrival revealed a glucose of 135  mg / dl , ast of 18  iu / l , alt of 10 
iu / l , total bilirubin of 1.3  mg / dl , and direct bilirubin of 0.1  mg / dl ; pt was 13.6  s ( inr 1.16 ) and had normal serum electrolytes , bun , and creatinine .
his admission serum ethanol concentration was 15  mg / dl , and serum salicylate and acetaminophen concentrations were undetectable .
fig .  1a half - empty bottle of chloroform a half - empty bottle of chloroform the poison center was notified by ems upon finding the patient with bottle of chloroform , allowing us to evaluate the patient at bedside upon arrival in the emergency department . in light of chloroform s hepatotoxicity , therapy with nac was recommended .
the patient was treated with intravenously administered nac 150  mg / kg over 1  h , followed by 50  mg / kg over 4  h , and then was started on an intravenous drip at a rate of 6.25  mg  kg  h. on the evening of the second hospital day , the patient had regained consciousness and was successfully extubated . prior to extubation ,
the patient completed 21  h of intravenously administered nac finishing the infusion the pharmacy had prepared .
because the patient was still intubated when the first infusion of nac was completed , the decision was made to continue nac at 6.25  mg  kg  h. we had planned on stopping the intravenously administered nac when the second pre - mixed infusion was finished ; however , on hospital day 3 , his total bilirubin began to rise although his ast and alt remained normal . since information on the clinical course of chloroform ingestions is limited , we continued nac therapy . on hospital day 4 , his serum ast and alt began to rise .
his total serum bilirubin and pt both peaked on hospital day 4 at 16.3  mg / dl and 21.3  s ( inr 2.25 ) , respectively ( fig .  2 ) . on hospital day 5 , his ast and alt had peaked at 224 and 583 
at that time , his total serum bilirubin had fallen to 4.1  mg / dl , and his pt had declined to 17.7  s ( inr 1.87 ) . the following day ,
his serum bilirubin , ast , and alt all began to decline , and intravenously administered nac therapy was stopped . by hospital
day 8 , the patient s ast had fallen to 47  iu / l , his alt had fallen to 231 
iu / l , his total serum bilirubin was 1.1  mg / dl , and his pt had normalized .
his serum chloroform concentration on admission was later determined to be 91  g / ml . 
 fig . 
like all halogenated hydrocarbons , chloroform exerts its anesthetic effects through activation of the gabaa receptor , causing an influx of chloride ions , hyper - polarizing the neuron and thereby clinically inducing sedation .
most fatalities are believed to be the result of anoxia secondary to deep sedation and impairment of airway reflexes and respiratory drive [ 1 , 3 ] . other observed effects of these agents can include sensitization of the myocardium to catecholamines , ventricular arrhythmias , and delayed hepatotoxicity resulting from free radical damage to the centrilobular hepatocytes [ 1 , 3 ] . besides the above clinical findings , oral exposure to chloroform can also cause direct irritation of the oral , esophageal , and gastro - intestinal mucosa .
associated symptoms include chest pain , abdominal pain , nausea , and vomiting . if aspirated , chloroform can also cause symptoms of acute pneumonitis and acute lung injury .
intravenously administered nac therapy is commonly used for intubated patients in our institution . after the decision to use intravenously administered nac , we had limited information on ingestions of chloroform to predict the duration of hepatotoxicity .
his significant elevation of bilirubin on day 4 was surprising given that fact that his transaminases had just started to rise .
the nac regimen used in this case was the identical protocol used in acetaminophen toxicity . due to continued abnormalities with his liver function testing , we continued the regimen of 6.25  mg  kg  h of intravenously administered nac therapy through hospital day 6 until the hepatotoxicity had clearly improved .
case reports of oral ingestions of chloroform have been previously described [ 1 , 3 - 5 ] . other than the direct mucosal irritant effects described above , oral chloroform toxicity is believed similar to that of inhaled chloroform [ 1 , 3 , 4 ] .
these previous case reports demonstrated average blood concentrations in fatal chloroform poisonings to have ranged between 33 and 64  g / ml .
these levels are significantly lower than that of our patient who went on to have a complete recovery [ 1 , 6 ] .
the utilization of nac for chloroform - induced hepatotoxicity has demonstrated successful outcomes in cases with mild hepatotoxicity [ 5 , 7 ] . however , none of these previous cases utilized the intravenous formulation of nac . because chloroform is believed to cause hepatic damage by free radical injury and nac is known to replete glutathione and scavenge free radicals ,
it is logical that both formulations of nac may decrease hepatic injury secondary to chloroform exposure [ 8 , 9 ] .
a recent report describes a case of both chloroform and dichloromethane ingestion who survived without nac therapy . in this case ,
chloroform levels were not reported , but liver function tests peaked with an ast of 1,617  iu / l and alt of 2,677  iu /
additionally , the total bilirubin peaked at 7  mg / dl , and they report that liver function tests took 4  weeks to return within normal limits . without knowing the chloroform level and further clinical information , it is difficult to quantify the effects of nac therapy .
however , our patient presented with a chloroform level well above reports of previous fatalities , and his ast and alt peaked at only 224 and 583 
iu / l , respectively . considering that nac therapy has such low risk and high theoretical benefit , it should be considered for use in chloroform and other halogenated hydrocarbon - induced hepatotoxicity . in summary ,
chloroform can cause injury resulting in central nervous system depression , respiratory depression , direct mucosal irritation , myocardial sensitization , and hepatotoxicity .
aggressive treatment with supportive care , with emphasis on protecting the airway and ventilation , as well as the use of nac therapy to treat hepatic injury , can result in complete recovery even with significant elevated chloroform levels .
 chloroform , a halogenated hydrocarbon , causes central nervous system depression , cardiac arrhythmias , and hepatotoxicity . 
 we describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered n - acetylcysteine ( nac ) . 
 a 19-year - old man attempting suicide ingested approximately 75 ml of chloroform . 
 he was unresponsive and intubated upon arrival . 
 intravenously administered nac was started after initial stabilization was complete . 
 his vital signs were normal . 
 admission laboratory values revealed normal serum electrolytes , ast , alt , pt , bun , creatinine , and bilirubin . 
 serum ethanol level was 15  mg / dl , and aspirin and acetaminophen were undetectable . 
 the patient was extubated but developed liver function abnormalities with a peak ast of 224  
 iu / l , alt of 583  iu / l , and bilirubin level reaching 16.3  mg / dl . 
 nac was continued through hospital day 6 . 
 serum chloroform level obtained on admission was 91  g / ml . the patient was discharged to psychiatry without known sequelae and normal liver function tests . 
 the average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64  g / ml , significantly lower than our patient . 
 the toxicity is believed to be similar in both inhalation and ingestion routes of exposure , with mortality predominantly resulting from anoxia secondary to central nervous system depression . 
 hepatocellular toxicity is thought to result from free radical - induced oxidative damage . 
 previous reports describe survival after treatment with orally administered nac , we report the first use of intravenously administered nac for chloroform ingestion 
 . acute oral ingestion of chloroform is extremely rare . 
 our case illustrates that with appropriate supportive care , patients can recover from chloroform ingestion , and intravenously administered nac may be of benefit in such cases . 