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BMJ Clin Evid. 2007; 2007: 2101.
Published online 2007 December 4.
PMCID: PMC2943815

Paracetamol (acetaminophen) poisoning

Nick Buckley, Consultant Clinical Pharmacologist and Toxicologist# and Michael Eddleston, Wellcome Trust Career Development Fellow#

Abstract

Introduction

Mortality from paracetamol overdose is now about 0.4%, although severe liver damage occurs without treatment in at least half of people with blood paracetamol levels above the UK standard treatment line. In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity; even higher doses may be tolerated by children without causing liver damage.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute paracetamol poisoning? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal (single or multiple dose), gastric lavage, ipecacuanha, liver transplant, methionine, N-acetylcysteine.

Key Points

Paracetamol (acetaminophen) is a common means of self-poisoning in Europe and North America, often taken as an impulsive act of self-harm in young people.

  • Mortality from paracetamol overdose is now about 0.4%, although without treatment, severe liver damage occurs in at least half of people with blood paracetamol levels above the UK standard treatment line.
  • In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity; even higher doses may be tolerated by children without causing liver damage.

Standard treatment of paracetamol overdose is acetylcysteine, which based on animal studies and clinical experience, is widely believed to reduce liver damage and mortality, although few studies have been done.

  • Adverse effects from acetylcysteine include rash, urticaria, vomiting, and anaphylaxis which can, rarely, be fatal.
  • We don't know what the optimal dose, route, and duration of acetylcysteine treatment should be. However, liver damage is less likely to occur if treatment is started within 8 to 10 hours of ingestion.

It is possible that methionine reduces the risk of liver damage and mortality after paracetamol poisoning compared with supportive care, but we don't know for sure.

We don't know whether activated charcoal, gastric lavage, or ipecacuanha reduce the risks of liver damage after paracetamol poisoning.

  • The rapid absorption of paracetamol suggests that a beneficial effect from treatments that reduce gastric absorption is unlikely in many cases.

Liver transplantation may increase survival rates in people with fulminant liver failure after paracetamol poisoning compared with waiting list controls, but long-term outcomes are unknown.

Clinical context

About this condition

Definition

Paracetamol poisoning occurs as a result of either accidental or intentional overdose with paracetamol (acetaminophen).

Incidence/ Prevalence

Paracetamol is the most common drug used for self-poisoning in the UK. It is also a common means of self-poisoning in the rest of Europe, North America, and Australasia. There has been an exponential rise in the number of hospital admissions caused by paracetamol poisoning in England and Wales from 150 in 1968 to a peak of 41,200 in 1989 to 1990, before falling to around 25,000 in 2001 to 2002. Overdoses from paracetamol alone result in an estimated 150 to 200 deaths and 15 to 20 liver transplants each year in England and Wales (data from routinely collected health and coronial statistics). Pack-size restrictions instituted in the UK in 1998 resulted in modest reductions in large overdoses, liver transplants, and deaths in England and Wales. In Scotland, the reduction in admissions and mortality from paracetamol overdose was short lived.

Aetiology/ Risk factors

Most cases in the UK are impulsive acts of self-harm in young people. In one cohort study of 80 people who had overdosed with paracetamol, 42 had obtained the tablets for the specific purpose of taking an overdose, and 33 had obtained them less than 1 hour before the act.

Prognosis

People with blood paracetamol concentrations above the standard treatment line (defined in the UK as a line joining 200 mg/L at 4 hours and 30 mg/L at 15 hours on a semilogarithmic plot) have a poor prognosis without treatment (see figure 1

Figure 1
Nomograms used to determine acetylcysteine or methionine treatment, based on the blood concentrations between 4 hours and 24 hours after ingestion of paracetamol. Published with permission (see text).[6]

). In one cohort study of 57 untreated people with blood concentrations above this line, 33/57 (58%) developed severe liver damage and 3/57 (5%) died. People with a history of chronic alcohol misuse, use of enzyme inducing drugs, eating disorders, or multiple paracetamol overdoses may be at risk of liver damage with blood concentrations below this line. In the USA, a lower line is used as an indication for treatment, but we found no data relating this line to prognostic outcomes. More recently, a modified nomogram specifically designed to estimate prognosis (not need for treatment) has been developed by modelling data from a large cohort. This takes into account time to initiation of acetylcysteine treatment, and the effect of alcohol use. However, it has not yet been validated, and is not widely used. Reversible renal injury occurs in some people, most commonly (but not always) in association with hepatic injury. Dose effect: The dose ingested also indicates the risk of hepatotoxicity. One case series showed that people ingesting less than 125 mg/kg had no significant hepatotoxicity, with a sharp dose-dependent rise for higher doses. The threshold for toxicity after acute ingestion may be higher in children, where a single dose of less than 200 mg/kg has not been reported to lead to death and rarely causes hepatotoxicity. The higher threshold for toxicity in children may relate to different metabolic pathways or their larger relative liver size. For people who present later than 24 hours, or an unknown time after ingestion, several other prognostic indicators have been proposed, including prothrombin time, and abnormal liver function tests. These have not been validated prospectively. Slow release preparations: Pharmacokinetic studies of small overdoses of slow-release paracetamol formulations in healthy volunteers showed that peak plasma concentrations usually still occur within 4 hours, and the apparent half-life is the same as or only slightly longer than that of conventional paracetamol preparations. The bioavailability was not increased. The nomogram has not specifically been validated for these formulations. However, only a small proportion of cases of slow release preparation ingestion have resulted in initial non-toxic levels and subsequent toxic levels on the usual nomograms. In just one case, with other risk factors, the use of the nomogram led to treatment being ceased, and this may have contributed to a fatal outcome. Children and repeated supra-therapeutic doses: There are reports of major dosing errors leading to severe hepatotoxicity in children. Of more concern are other cases of apparent toxicity with repeated doses only slightly above the current maximum recommended doses (around 75 mg/kg/day). There are possibly additional risk factors in these cases, but these have not been established.

Aims of intervention

To prevent liver failure, liver transplantation, or death, with minimal adverse effects.

Outcomes

Mortality, hepatotoxicity (most commonly defined by the objective criterion of blood aspartate aminotransferase greater than 1000 U/L), liver failure (includes liver transplantation [with the exception of our option on liver transplant]).

Methods

Clinical Evidence search and appraisal March 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to March 2007, Embase 1980 to March 2007, and The Cochrane Library (all databases) 2007, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — all databases, Turning Research into Practice (TRIP), and NICE. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, including non-blinded or "open" studies, and containing at least 20 individuals of whom more than 80% were followed up. The minimum length of follow-up required to include studies was one week. We also did a search for observational studies on all the interventions. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table
GRADE Evaluation of interventions for Paracetamol (acetaminophen) poisoning.

Glossary

Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low-quality evidence
Any estimate of effect is very uncertain.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Nick Buckley, Canberra Hospital, Canberra, Australia.

Michael Eddleston, Centre for Tropical Medicine, University of Oxford, Oxford, UK.

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2007; 2007: 2101.
Published online 2007 December 4.

Acetylcysteine

Summary

Standard treatment of paracetamol overdose is acetylcysteine, which based on animal studies and clinical experience, is widely believed to reduce liver damage and mortality, although few studies have been done.

Adverse effects from acetylcysteine include rash, urticaria, vomiting, and anaphylaxis which can, rarely, be fatal.

We don't know what the optimal dose, route, and duration of acetylcysteine treatment should be. However, liver damage is less likely to occur if treatment is started within 8 to 10 hours of ingestion.

We found no direct information from RCTs comparing different regimens of acetylcysteine or acetylcysteine compared with methionine in the treatment of people with paracetamol poisoning.

Benefits and harms

Acetylcysteine versus no treatment:

RCTs comparing acetylcysteine versus no treatment are now likely to be considered unethical.

Acetylcysteine versus placebo:

We found one systematic review (search date 2001), which identified one small RCT. We also found ten studies reporting on adverse effects of acetylcysteine.

Mortality

Acetylcysteine compared with placebo Acetylcysteine may be more effective at reducing mortality in people with established paracetamol-induced liver failure and receiving conventional intensive liver care compared with placebo after 21 days (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Mortality

RCT
50 people with established paracetamol-induced liver failure
In review
Mortality 21 days
13/25 (52%) with acetylcysteine (150 mg/kg over 15 minutes, 50 mg/kg over 4 hours, and then 100 mg/kg diluted in 5% dextrose over 16 hours)
20/25 (80%) with placebo (5% dextrose)

ARR 28%
95% CI 3% to 53%
P = 0.037
Possible bias due to sealed envelope allocation; for full details, see further information on studies
Effect size not calculatedacetylcysteine

Hepatotoxicity

No data from the following reference on this outcome.

Liver failure

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
50 people with established paracetamol-induced liver failure
In review
Adverse effects
with acetylcysteine (150 mg/kg over 15 minutes, 50 mg/kg over 4 hours, and then 100 mg/kg diluted in 5% dextrose over 16 hours)
with placebo (5% dextrose)
Population details not reported Adverse effects
with acetylcysteine
Treatment-related mortality
Population details not reported Treatment-related mortality
with acetylcysteine
Vomiting
Population details not reported Vomiting
with oral acetylcysteine

Acetylcysteine versus methionine:

See option on methionine.

Further information on studies

Allocation was concealed but treatment was not blinded. The RCT used a sealed-envelope method to allocate people to treatment, which is considered less effective at concealing allocation than a centralised computer allocation process, and may have increased the risk of bias. There were differences between the groups in prognostic variables (prothrombin time, coma grade) and other treatments, but a possible confounding effect could not be assessed adequately because of the small size of the study.

Adverse effects reported were predominantly rash, urticaria, and occasionally more serious anaphylactoid reactions occurring with the initial “loading” dose. In most or all cases in the studies identified, adverse effects responded to temporary stopping of infusions and symptomatic treatment, and did not recur when treatment recommenced. Adverse reactions were more common in people with asthma and those who had non-toxic paracetamol concentrations. Oral acetylcysteine can also cause hypersensitivity and anaphylactoid reactions.

Comment

Widespread adoption of intravenous acetylcysteine for paracetamol poisoning coincided with a marked drop in overall case fatality ratio from around 3% in the early 1970s to 0.4% in the 1980s. There are clear animal data, observational evidence, and clinical experience that the introduction of acetylcysteine has dramatically changed the natural history of paracetamol poisoning favourably. The optimal dose, route, and duration of treatment are unknown, and assessment by RCTs is required. One observational study evaluated the effects of intravenous acetylcysteine in people presenting early to hospital. It found that people treated within 10 hours of ingestion were less likely to develop liver damage than were untreated historical controls (1/62 [2%] with treated people v 33/57 [58%] with untreated people).

Early versus delayed treatment:

Pooled analysis of case series and one additional case series suggested that overall hepatotoxicity was worse if treatment was delayed beyond 8 to 10 hours.

Oral versus intravenous treatment:

We found no RCTs. Pooled analysis of case series comparing oral versus intravenous administration of acetylcysteine, and two subsequent observational studies comparing different protocols for intravenous and oral acetylcysteine, did not find marked differences in outcomes between groups, but these findings require confirmation by RCTs.

Duration of infusion:

We found one RCT (223 people, 180 [81%] evaluated; allocation by slips of paper in a closed box) comparing rates of drug-related adverse events with intravenous acetylcysteine infusion over 60 minutes versus infusion over the standard 15 minutes. It found limited evidence of no significant difference between groups (drug-related adverse events: 49/109 [45%] with 15 minutes v 27/71 [38%] with 60 minutes; mean difference +7, 95% CI −8 to +22), although methodological problems make it difficult to draw any reliable conclusions from these results, and properly conducted RCTs are required. The RCT used a sealed-envelope method to allocate people to treatment, which is considered less effective at concealing allocation than a centralised computer allocation process, and may have increased the risk of bias. Groups were not comparable at baseline, and the 15-minute group was much larger that the 60-minute group (109 people in the 15-minute group v 71 people in the 60-minute group).

Substantive changes

No new evidence

2007; 2007: 2101.
Published online 2007 December 4.

Methionine

Summary

It is possible that methionine reduces the risk of liver damage and mortality after paracetamol poisoning compared with supportive care, but we don't know for sure.

We found no direct information from RCTs about methionine compared with acetylcysteine in the treatment of people with paracetamol poisoning.

Benefits and harms

Methionine versus usual care:

We found one systematic review (search date 2001), which identified one small RCT.

Mortality

Methionine compared with usual care Methionine may be no more effective at reducing mortality in people with paracetamol poisoning compared with supportive care (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Mortality

RCT
3-armed trial
40 people with blood concentrations of paracetamol above the UK standard treatment line (see figure 1 )
In review
Mortality
0/13 (0%) with methionine (2.5 g 4-hourly for 4 doses)
1/13 (8%) with usual care

Reported as not significant
P value not reported
Possible bias due to sealed envelope allocation; for full details, see further information about studies
Not significant

Hepatotoxicity

Methionine compared with supportive care Methionine may be more effective at reducing hepatotoxicity in people with paracetamol poisoning compared with supportive care (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Hepatic necrosis

RCT
3-armed trial
40 people with blood concentrations of paracetamol above the UK standard treatment line (see figure 1 )
In review
Grade III hepatic necrosis
0/9 (0%) with methionine (2.5 g 4-hourly for 4 doses)
6/10 (60%) with usual care

P <0.05
Possible bias due to sealed envelope allocation; for full details, see further information about studies
Effect size not calculatedmethionine
Liver enzyme levels

RCT
3-armed trial
40 people with blood concentrations of paracetamol above the UK standard treatment line (see figure 1 )
In review
Peak aspartate aminotransferase greater than 1000 U
1/13 (8%) with methionine (2.5 g 4-hourly for 4 doses)
8/13 (62%) with usual care

RR 0.13
95% CI 0.02 to 0.86
NNT 2
95% CI 2 to 6
Large effect sizemethionine

Liver failure

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
3-armed trial
40 people with blood concentrations of paracetamol above the UK standard treatment line (see figure 1 )
In review
Adverse effects
with methionine (2.5 g 4-hourly for 4 doses)
with usual care

No data from the following reference on this outcome.

Methionine versus acetylcysteine:

We found two systematic reviews (search dates 2003 and 2005), which identified no RCTs.

Further information on studies

Bias The RCT used a sealed-envelope method to allocate people to treatment, which is considered less effective at concealing allocation than a centralised computer allocation process, and may have increased the risk of bias. Interpretation of liver biopsy results Only 27/40 (68%) of people had a liver biopsy, and an intention-to-treat analysis was not possible.

Comment

None.

Substantive changes

No new evidence

2007; 2007: 2101.
Published online 2007 December 4.

Activated charcoal (single or multiple dose)

Summary

We don't know whether activated charcoal reduces the risks of liver damage after paracetamol poisoning.

The rapid absorption of paracetamol suggests that a beneficial effect from treatments that reduce gastric absorption is unlikely in many cases.

Benefits and harms

Activated charcoal (single or multiple dose):

We found one systematic review (search date 2005), which found no RCTs that specifically examined clinical outcomes after paracetamol poisoning. The review found no large study of complications of activated charcoal in people poisoned by paracetamol. We found three studies assessing adverse effects of activated charcoal.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

Non-systematic review
Population details not reported Adverse effects
with activated charcoal
Vomiting

RCT
327 people with medicinal poisoning, 89/327 (27%) with paracetamol poisoning Vomiting
15% with activated charcoal
14% with no gastrointestinal decontamination
Absolute numbers not reported

Significance not assessed
Aspiration

RCT
327 people with medicinal poisoning, 89/327 (27%) with paracetamol poisoning Aspiration
<1% with activated charcoal
<1% with no gastrointestinal decontamination
Absolute numbers not reported

Significance not assessed
878 people treated with multiple-dose activated charcoal Pulmonary aspiration
6/878 (0.6%), 95% CI 0.1% to 1.1% with activated charcoal

Further information on studies

None.

Comment

Single-dose activated charcoal:

The systematic review included simulated overdose studies in volunteers, and found that activated charcoal given within 2 hours of paracetamol ingestion decreased absorption by a variable amount, and that this amount diminished with time. One cohort study in 450 consecutive people who had taken 10 g or more of paracetamol found that those who had been given activated charcoal were significantly less likely to have high-risk blood paracetamol concentrations than those who had not been given activated charcoal (OR 0.36, 95% CI 0.23 to 0.58). The effect was seen only in those treated within 2 hours, and the study was not large enough to assess the effect of many potential confounders. One non-systematic review of activated charcoal in all forms of poisoning found no evidence that activated charcoal improved outcome in poisoned people.

Multiple-dose activated charcoal:

The review found no studies of simulated overdose that evaluated multiple-dose regimens in paracetamol poisoning. One non-systematic review of case series and reports of multiple-dose regimens in all forms of poisoning found no evidence that multiple-dose regimens improved outcomes in poisoned people. The rapid absorption and short half-life of paracetamol suggest that a beneficial effect is unlikely.

Substantive changes

Activated charcoal One RCT added; categorisation (Unknown effectiveness) unchanged but harms data enhanced.

2007; 2007: 2101.
Published online 2007 December 4.

Gastric lavage

Summary

We don't know whether gastric lavage reduces the risks of liver damage after paracetamol poisoning.

The rapid absorption of paracetamol suggests that a beneficial effect from treatments that reduce gastric absorption is unlikely in many cases.

Benefits and harms

Gastric lavage:

We found one systematic review (search date 2001), which found no RCTs or cohort studies that reported clinical outcomes. The review found no large study of complications of gastric lavage in people poisoned by paracetamol. We found one RCT assessing adverse effects of gastric emptying.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
876 people with acute oral overdose of a variety of drugs; 136/876 (16%) with paracetamol poisoning Complication rates
13% with gastric emptying plus charcoal
8% with charcoal alone
Absolute numbers not reported

P = 0.43
Results may not be generalisable to people undergoing gastric lavage: see further information on studies
Not significant

Further information on studies

Harms with any method of gastric emptying plus charcoal included aspiration 17/459 (3.7%), diarrhoea (3 people), ileus (3 people), arrhythmia during vomiting (2 people), dystonia from metoclopramide given for vomiting (1 person), and haematemesis (2 people). These harms results may not generalise to gastric lavage for paracetamol poisoning, as about 50% of people were treated with ipecacuanha, and only 16% of the study population had paracetamol poisoning.

Comment

The systematic review included studies of simulated overdose in human volunteers, and found that gastric lavage carried out within 1 hour removed a variable number of paracetamol tablets and that the number removed diminished with time. One cohort study (described previously, see comment under activated charcoal) found that those given activated charcoal were significantly less likely to have high-risk blood paracetamol concentrations than those not given activated charcoal (OR 0.36, 95% CI 0.23 to 0.58). The addition of gastric lavage to activated charcoal regimens did not further decrease the risk (OR 1.12, 95% CI 0.57 to 2.20). One non-systematic review of gastric lavage in all forms of poisoning found no evidence that gastric lavage improved outcome in poisoned people.

Substantive changes

No new evidence

2007; 2007: 2101.
Published online 2007 December 4.

Ipecacuanha

Summary

We don't know whether ipecacuanha reduces the risks of liver damage after paracetamol poisoning.

The rapid absorption of paracetamol suggests that a beneficial effect from treatments that reduce gastric absorption is unlikely in many cases.

Benefits and harms

Ipecacuanha:

We found one systematic review (search date 2001), which found no RCTs examining the clinical effects of ipecacuanha in people with paracetamol poisoning. The review found no large study of complications of ipecacuanha in people poisoned by paracetamol. We found one RCT assessing adverse effects of gastric emptying.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
876 people with acute oral overdose of a variety of drugs; 136/876 (16%) with paracetamol poisoning Complication rates
13% with gastric emptying plus charcoal
8% with charcoal alone
Absolute numbers not reported

P = 0.43
Results may not be generalisable to people receiving ipecacuanha: see further information on studies
Not significant

Further information on studies

Harms with any method of gastric emptying plus charcoal-included aspiration 17/459 (3.7%), diarrhoea (3 people), ileus (3 people), arrhythmia during vomiting (2 people), dystonia from metoclopramide given for vomiting (1 person), and haematemesis (2 people). These harms results may not generalise to ipecacuanha for paracetamol poisoning, as about 50% of people were treated with gastric lavage, and only 16% of the study population had paracetamol poisoning.

Comment

Human simulated overdose studies suggest that ipecacuanha given within 1 hour could reduce paracetamol absorption but no studies have shown a change in clinical outcome. One non-systematic review of ipecacuanha in all forms of poisoning found no evidence that ipecacuanha improved outcome in poisoned people.

Clinical guide:

Administration of ipecacuanha may delay the administration of activated charcoal and oral antidotes.

Substantive changes

No new evidence

2007; 2007: 2101.
Published online 2007 December 4.

Liver transplant

Summary

Liver transplantation may increase survival rates in people with fulminant liver failure after paracetamol poisoning compared with waiting list controls, but long-term outcomes are unknown.

Benefits and harms

Liver transplant:

We found one systematic review (search date 2005), which found no RCTs assessing clinical outcomes of liver transplant in people with fulminant hepatic failure after paracetamol poisoning. Here, we report the largest study identified by the review that assessed complications of liver transplantation in people poisoned by paracetamol.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects
44 people with orthotopic liver transplant
In review
Adverse effects
with liver transplant

Further information on studies

None.

Comment

Short-term outcomes:

The systematic review identified two cohort studies, in people who met the “Kings College” transplant criteria, but who had not had a transplant. Results suggested that liver transplant increased short-term survival rates compared with waiting-list (mean 1 year survival rates: 60–70% with transplant v 20–25% with waiting list), and that waiting list survival rates varied widely (0–66%). The highest reported survival rate (35/53 [66%]) found by the review came from a recent multicentre cohort study in the USA and may partly reflect improvements in supportive care since the King's criteria were first suggested. A systematic review of other criteria for transplant found that most criteria have similar (or worse) sensitivity and specificity to the King's criteria. Criteria might be improved with stricter definitions, and need to be prospectively validated in a setting of current best supportive care.

Long-term outcomes:

The systematic review found no long-term studies of outcomes after liver transplant. Long-term adverse effects may occur from immunosuppressants after liver transplant.

Substantive changes


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