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acetaminophen gained widespread popularity in the 1960s as a less toxic , analgesic antipyretic agent than aspirin .
ironically , acetaminophen is now the second leading cause of toxic drug ingestions in the united states .
acetaminophen toxicity is thus a real burden on our health care system , and hepatotoxicity due to acetaminophen overdose has become an important problem .
one is the ' garden variety ' , wherein the patients ingested large amounts of acetaminophen with a suicidal intent .
the other pattern is seen in chronic alcoholics who ingest smaller amounts of acetaminophen in an attempt to relieve pain .
some cases of acetaminophen overdose have been described as parasuicidal , where the attempted suicide is more of a gesture than an act of lethal intent .
the aim of our study was to determine the epidemiology of various types of acetaminophen poisoning and analyze their outcome compared with their admission characteristics .
this study was conducted at nassau university medical center ( east meadow , ny , usa ) which represents an urban county hospital .
computer associated search was undertaken of all admission records from january 1996 to april 1999 .
the records of all the patients with a discharge diagnosis of acetaminophen overdose were analyzed .
patients who were not admitted to the hospital after being assessed in the emergency room were excluded from this study .
we included patients who had a history of acetaminophen ingestion reported by either the patient or the family .
we went on to confirm that the patient had substantial acetaminophen ingestion by history , blood acetaminophen level > 10 mg / l , or serum aminotransferase level > 1000
two out of three of these conditions had to be met for a case to be included in our study .
patients who had elevated serum aminotransferase levels but in whom substantial acetaminophen ingestion could not be adequately confirmed were excluded from the study .
chronic alcohol abuse was defined by the diagnostic and statistical manual of mental disorders 4th edition ( dsm - iv ) criteria .
for the patients with accidental acetaminophen ingestion , the triage was based on their clinical condition .
there was a standard management plan for all the patients , as suggested by the national poison control center .
most of the patients were observed for 24 hours in the intensive care unit before being transferred to the medical floor .
the following information was recorded : age ; sex ; race ; acetaminophen dose ; reason for ingestion ; history of alcohol abuse or concurrent intoxication ; time to presentation to the emergency room since ingestion ; and n - acetylcysteine therapy .
the laboratory data included peak acetaminophen level , peak aminotransferase level , prothrombin time , serum bilirubin , and serum creatinine . using the international classification of diseases ninth revision ( icd-9 ) code , the total number of cases of poisonings admitted during the same time period was determined to calculate the prevalence of acetaminophen toxicity .
quantitative data was analyzed using the students unpaired t - test and the mann - whitney rank sum test .
analysis of qualitative data was done using the fisher exact test and the chi - square test .
quantitative data was analyzed using the students unpaired t - test and the mann - whitney rank sum test .
analysis of qualitative data was done using the fisher exact test and the chi - square test .
four patients had to be excluded , because acetaminophen did not appear to be the culprit for their clinical state .
three others were excluded because they presented with another comorbid condition that could have been responsible for their hepatic profile .
of the 93 patients , 80 were classified as suicidal based on psychiatric evaluation , and 13 had accidentally poisoned themselves in an attempt to relieve pain .
the causes of chronic pain in the accidental overdose group were toothache , chronic backache , or headache .
eighty - eight of the 93 patients were admitted to the intensive care unit for first 2448 hours monitoring .
table 1 shows that the patients with suicidal ingestion tended to be younger than the accidental group .
female to male ratio was 2:1 , with a preponderance of whites in both the groups .
it is evident that , although the peak acetaminophen level was higher in the suicidal subgroup ( mean 121.7  97.0 vs 64.5  61.8 mg /
l , p < 0.05 ) , a peak aminotransferase level > 1000 iu / l was seen more frequently in the patients with accidental overdose ( 39% vs 12% , p < 0.05 ) ( table 2 ) .
the renal function was overall unaffected and not significantly different between the two groups ( data not shown ) .
there were only two deaths , both in the accidental group ; one of whom had a history of chronic alcohol abuse .
n - acetylcysteine therapy was given to 62% of the patients in the accidental group , compared to 73% in the suicidal overdose group .
the hospital stay was higher in the accidental overdose group ( mean 6.4  6.1 days vs 3.9  2.7 days , p < 0.01 ) .
this study did not take the dose of acetaminophen ingested into consideration due to several reasons .
accurate dose estimations could not be made in the accidental group because many of these patients had inadvertent ingestion of acetaminophen in more than one form over several days .
the other problem we faced was that some patients in the accidental group were unaware of the presence of acetaminophen in some over - the - counter drugs .
about 40% of the patients in the suicidal group could not give an accurate history about the dose of acetaminophen ingested .
a substantial number of patients in the suicidal group were drowsy and sedated due to other concomitant ingestions . moreover , most of the studies in the literature fail to demonstrate any clear - cut , direct relationship between acetaminophen dose and hepatotoxicity .
low acetaminophen levels ( < 10 mg / l ) were found in 38% patients in the accidental group , compared to 10% in the suicidal overdose group . this is probably because these patients presented late , and they had ingested small doses over a prolonged period . surprisingly , the morbidity and mortality were higher in the accidental overdose group than the suicidal group ( 15% vs 0% , p < 0.05 ) .
first , these patients present late and sometimes the diagnosis is delayed , both of which hinder optimal antidotal treatment .
the second reason could be the increased chronic alcohol use among the accidental group ( 39% vs 12% , p < 0.05 ) .
however , the data on the amount of alcohol , duration of intake , or interval between intake of alcohol and acetaminophen are subject to recall bias , withholding of information by the patient , or non - responsive state of the patient on presentation . the presumed basis for the potentiation of acetaminophen - induced hepatotoxicity by chronic ethanol ingestion has been amply discussed .
elegant studies performed in the early 1970s   established that acetaminophen , taken in therapeutic doses , is metabolized by the liver through two pathways .
most of the drug ( 8090% ) is conjugated with either glucuronic acid or sulphates , yielding the nontoxic conjugates that are excreted by the kidney . a small proportion ( 5% )
this metabo - lite is rendered nontoxic by conjugation with glutathione to form mercapturic acid and related conjugates that are also excreted in the urine .
if the drug is taken in excessive doses , an augmented amount is converted by cytochrome p-450 to the highly reactive , toxic intermediate metabolite .
it then may reach a level that overwhelms the protective mechanism of glutathione conjugation and ultimately , through covalent binding to hepatocyte proteins , leads to hepatocellular necrosis .
therapeutic doses of acetaminophen have the potential of producing liver damage if they are associated with circumstances that enhance the activity of the p-450 system leading to increased production of toxic metabolite , or that interfere with the protective mechanism by depleting the available glu - tathione .
ethanol can potentiate damage due to both of these reasons . in the present study 6/9 ( 66% )
patients in the accidental overdose group and 7/55 ( 13% ) in the suicidal overdose group presented to the emergency room more than 24 hours after the overdose .
n - acetylcysteine therapy was given to 62% of the patients in the accidental group , compared to 73% patients in the suicidal group .
treatment with n - acetylcysteine has been very successful in preventing or ameliorating hepatic injury after suicidal acetaminophen overdose .
however , the benefit of n - acetylcysteine in the syndrome of acetaminophen injury as a therapeutic misadventure is not clearly defined .
the final outcome in the case of accidental overdose is dependent on a multitude of factors , and thus a large number of cases will be required for multivariate analysis to identify the role of n - acetylcys - teine . as the efficacy of n - acetylcysteine as an antidote decreases after eight hours
, the treatment must be started immediately following all potentially toxic doses of acetaminophen ( > 10 g ) .
however , a large retrospective trial indicated that n - acetylcysteine therapy decreased the incidence of hepatotoxicity when administered up to 24 hours post overdose .
patients , who have an increased susceptibility to acetaminophen toxicity , particularly alcoholics , should be considered for n - acetylcysteine therapy at plasma levels that are half of those indicated in the standard graph .
in addition , patients with accidental overdose acquired over a number of hours should be still considered for treatment , because in these cases plasma levels are unreliable in predicting hepatotoxicity .
our study also showed that , although patients with suicidal overdose had higher peak acetaminophen levels than the accidental overdose group , the peak aminotransferase level ( > 1000
iu / l ) was more often seen in the accidental overdose group ( 39% vs 12% , p < 0.05 ) .
the suicidal overdose patients with high levels of liver enzymes more often had a history of chronic alcohol abuse and they presented late .
even when acute hepatic failure develops because of suicidal overdose of acetaminophen , these patients have a good prognosis in terms of liver transplantation and death . .
in fact , none of our patients in the suicidal overdose group died or had to be referred for transplantation .
in contrast to this , in the accidental overdose group 2/13 patients developed fulminant hepatic failure leading to hepatic coma and ultimately to death . thus peak acetaminophen levels correlate poorly with hepatic dysfunction , morbidity and mortality .
there are numerous studies which have shown that the total cost of treating a patient in the intensive care unit in the us is approximately $ 25,00035,000 per day .
it is a tradition in many hospitals in the country to admit patients with acetaminophen overdose to critical care units . in our study , out of the 80 patients in the suicidal group , 75
were admitted to the intensive care unit , whereas all the 13 patients in the accidental overdose group were admitted to this unit .
because of their benign clinical course , we recommend that patients with suicidal acetaminophen overdose can be safely managed on the medical floors unless there is a history of chronic alcohol abuse or other concomitant poisonings . in our hospital
in summary , acetaminophen poisoning continues to remain a significant reason for hospital admissions among young adults .
the admission of the patients to the intensive care unit or ward should be determined by the degree of derangement of their clinical parameters .
patients with suicidal overdose and no history of chronic alcohol use do not need be admitted to the intensive care unit .
this excludes patients for whom there is any doubt about the history of chronic alcohol abuse and those who have accidentally poisoned themselves .
these are the patients who have an unfavorable clinical course and should be monitored in a critical care setting .
characteristics of patients with acetaminophen overdose clinical variables seen in the suicidal and accidental overdose groups
introductionacetaminophen toxicity , which can lead to hepatotoxicity , is a burden on our health care system and contributes significantly to intensive care unit admissions and cost of hospitalization . 
 the aim of our study was to determine the epidemiology of various types of acetaminophen poisoning and analyze their outcome compared with their admission characteristics.methodswe identified 93 consecutive patients , hospitalized for acetaminophen toxicity over a 52-month period from 1996 to 1999 in our urban county hospital . 
 retrospective case - control analysis was carried out using the data obtained from the medical records.resultsacetaminophen accounted for 7.5% of all cases of poisoning admitted during this period . of the 93 patients , 80 were classified as suicidal and 13 
 had accidentally poisoned themselves in an attempt to relieve pain . 
 the ratio of females to males was found to be 2:1 . 
 of the 93 patients studied , 88 were admitted to the intensive care unit for initial 2448 hours of monitoring . 
 peak acetaminophen levels were higher in the suicidal overdose group ( mean 121.7  97.0 mg / l vs 64.5  61.8 mg / l , p < 0.05 ) than in the accidental group . in spite of this , peak aminotransferase levels > 1000 iu / l were more often seen in the latter ( 39% vs 12% , p < 0.05 ) . 
 hepatic coma and death were seen more often in the accidental overdose group ( 15% vs 0% , p < 0.05 ) . 
 interestingly chronic alcohol abuse was also more frequent in the accidental overdose category ( 39% vs 18% , p = 0.05).discussionalthough the peak acetaminophen level in the suicidal group was significantly higher , cases of therapeutic misadventure had higher rates of morbidity and mortality . 
 peak acetaminophen levels correlate poorly with hepatic dysfunction , morbidity and mortality.conclusionwe recommend that the patients with suicidal acetaminophen overdose , without any concomitant poisoning , can safely managed on the medical floors .