This action might not be possible to undo. Are you sure you want to continue?
com ©2010 UpToDate®
Acetaminophen (paracetamol) poisoning in adults: Treatment
Authors: Kennon Heard, MD; Richard Dart, MD, PhD; Section Editor: Stephen J Traub, MD Deputy Editor: Jonathan Grayzel, MD, FAAEM Last literature review version 18.1: January 2010 | This topic last updated: November 4, 2009 INTRODUCTION — Acetaminophen (APAP) poisoning is among the most common causes of medication-related poisoning and death. Acetaminophen poisoning may occur following a single acute ingestion or through the repeated ingestion of supratherapeutic amounts. The management of the acetaminophen-poisoned patient may include stabilization, decontamination, and administration of acetylcysteine, a specific antidote. The duration of acetylcysteine treatment is determined by the type of ingestion and the presence or absence of elevated serum alanine aminotransferase (ALT) concentrations. The treatment of APAP poisoning is reviewed here. The diagnosis of APAP poisoning, both acute and chronic, and the management of hepatic injury or failure are discussed separately. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis" and "Overview of the treatment of acute liver failure".) GENERAL MANAGEMENT — The initial management of acetaminophen poisoning is determined by the patient's presenting symptoms. Most patients who present early (within 24 hours) after an acute acetaminophen ingestion are asymptomatic, while others may require treatment for symptoms related to coingestants. As there are no early symptoms that predict acetaminophen toxicity, poisoning severity following an acute ingestion is quantified by plotting a timed serum acetaminophen concentration on the Rumack-Matthew nomogram (graph 1). Use of the nomogram, as well as risk factors for hepatotoxicity and the diagnosis of both acute and chronic acetaminophen poisoning, are discussed separately. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis".) Patients who present later may manifest symptoms and signs of hepatic injury or failure, such as nausea, vomiting, jaundice, abdominal pain, renal injury, coagulopathy (eg, gastrointestinal bleeding), hepatic encephalopathy, cerebral edema, or hypotension. These patients may require emergent resuscitation, including airway management, intravenous fluids, vasopressors, hemodialysis, or management of cerebral edema. (See "Overview of the treatment of acute liver failure".)
While limited.5 g) are likely to benefit from gastrointestinal decontamination. and that these effects were independent of the time of acetylcysteine administration. Several clinical trials have confirmed these findings: • One randomized trial evaluating decontamination following acetaminophen overdose found that patients treated with AC had a larger decrease in serum acetaminophen concentrations than those treated with gastric lavage or an emesis-inducing drug .) A number of studies using simulated overdose models have shown that AC reduces acetaminophen exposure . • Another retrospective study found that administration of AC to patients who presented over four hours after acetaminophen ingestion was associated with lower peak alanine aminotransferase (ALT) concentrations. 1 g/kg (maximum dose 50 g) by mouth in all patients who present within four hours of a known or suspected acetaminophen ingestion. However. • • A prospective observational study found that patients who received AC prior to A retrospective study of 981 consecutive patients with an acute acetylcysteine were less likely to develop liver injury than those who did not .9] limit the absorption of acetaminophen after simulated overdose and in clinical trials [2.6]. unless there are contraindications to its administration.Techniques used in the resuscitation of adults are discussed separately. (See "Basic airway management in adults" and "Advanced airway management in adults" and "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Use of vasopressors and inotropes" and "Evaluation and management of elevated intracranial pressure in adults". acetaminophen overdose found that patients who received AC within two hours of ingestion were less likely to require acetylcysteine treatment .7] and gastric lavage [8. We suggest treatment with activated charcoal (AC).) GI DECONTAMINATION — Patients who present soon after a potentially toxic ingestion of acetaminophen (single dose ≥7. these therapies appear to be less effective than activated charcoal.4]. A general approach to decontamination of poisoned patients is discussed separately. endotracheal intubation should not be performed solely for the purpose of giving charcoal. Asymptomatic patients who present more than four hours after a reported ingestion are unlikely to benefit from AC. unless endotracheal intubation is performed first. Charcoal should be withheld in patients who are sedated and may not be able to protect their airway. Studies have shown that induced emesis [6. (See "Decontamination of poisoned adults". ANTIDOTE: ACETYLCYSTEINE Effectiveness of acetylcysteine — Acetylcysteine is the accepted antidote for acetaminophen poisoning and is given to all patients at significant risk for hepatotoxicity. this study suggests that administration of AC more than two hours after ingestion may be beneficial . so they are not routinely recommended [2. 2 . However. and we do not recommend routine treatment in these patients.
section on 'Diagnosis'. The two most common protocols are the 20 hour intravenous (IV) protocol  and the 72 hour oral protocol . The key to effective treatment is to start therapy before the onset of alanine aminotransferase (ALT) elevation. We review these protocols immediately below. The approved 20 hour IV dosing regime is complicated and is performed as follows: • • • Administer an initial loading dose of 150 mg/kg IV over 15 to 60 minutes (we Next. When acetylcysteine is administered late following acetaminophen ingestion to patients with evidence of hepatic failure. This is discussed below.) 72 hour oral protocol — The 72 hour oral (PO) dosing protocol for acetylcysteine treatment has been used successfully in the US for more than 30 years. The treatment period is often extended when patients have large ingestions or elevated serum transaminase activity. recommend 60 minutes). Confusion exists about the appropriate route and duration of early acetylcysteine therapy following acute ingestion. presentation. However.) 20 hour IV protocol — The 20 hour intravenous (IV) protocol for acetylcysteine treatment has been used in the United Kingdom since the 1970s. (See 'Duration of treatment' below.25 mg/kg per hour IV. and diagnosis". A discussion of how they are modified based upon clinical circumstances is discussed further on. several studies have described an extremely low incidence of hepatotoxicity following early acetylcysteine administration [10-15]. There are no randomized. 3 . This treatment protocol provides a total of 300 mg/kg over 20 to 21 hours . Finally.Serious hepatotoxicity is uncommon and death extremely rare if acetylcysteine is administered within eight hours following acetaminophen overdose [10-12]. Determination of the risk for hepatotoxicity following either acute or chronic acetaminophen ingestion is discussed separately. administer a dose of 50 mg/kg IV over four hours. it decreases mortality and improves hepatic and cerebral function [16-18]. placebo-controlled trials evaluating the efficacy of acetylcysteine for the prevention of hepatic injury from acetaminophen poisoning (they were considered unethical). It is performed as follows: • Give a loading dose of 140 mg/kg PO.) Although some controversy persists regarding mechanism. administer a 16 hour infusion at 6. most toxicologists believe acetylcysteine prevents acetaminophen-induced hepatic injury by restoring hepatic glutathione stores. This is accomplished by initiating treatment within eight hours of an acute ingestion. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology. (See 'Duration of treatment' below.
most of these subjects are able to tolerate the infusion when it is restarted. Before restarting an infusion in such cases. give a dose of 70 mg/kg PO every four hours for a total of 17 doses. cimetidine (5 mg/kg up to 300 mg).• Next. (See 'Treatment in hepatic failure' below. Patients who experience only flushing do not require intervention and the infusion can be continued. unless more severe signs develop. 4 . Patients who develop urticaria or angioedema should have the infusion stopped and be treated with diphenhydramine (1 mg/kg IV up to 50 mg). Patients who develop hypotension or respiratory symptoms after IV acetylcysteine therapy will generally tolerate oral acetylcysteine. IV administration is favored for patients with any of the following: • • • • Vomiting Contraindications to oral administration (ie. The infusion can be restarted once symptoms resolve. but increases to approximately 40 percent if treatment is delayed beyond 16 hours. In the largest study of oral acetylcysteine.) IV versus oral — There are no head-to-head trials comparing the 20 hour IV and the 72 hour oral treatment protocols in patients treated early after ingestion. Anaphylactoid reaction — Prospective studies suggest that between 10 and 20 percent of patients treated with IV acetylcysteine develop an anaphylactoid reaction [20. and oral ephedrine (0. However. bowel ileus or obstruction.) Adverse reactions — While dosing errors are common during IV acetylcysteine administration . the patient should be pretreated with IV diphenhydramine (1 mg/kg up to 50 mg). no deaths occurred among patients treated before the onset of transaminase elevation . There are several reports describing truncated oral protocols. (See 'Duration of treatment' below. If the patient cannot be treated with oral acetylcysteine.21].5 mg/kg up to 25 mg) . The incidence of hepatotoxicity for patients treated within eight hours of ingestion is less than 10 percent. either the oral or IV route is acceptable. the clinician should consult a medical toxicologist or poison control center for guidance. pancreatitis. The dose does not need to be adjusted if the patient has been treated with activated charcoal. In most patients. The best available data suggest that both routes are effective and differences are minimal. The duration of treatment is discussed further below. Hepatic failure Patients who refuse oral administration bowel injury) Patients with evidence of hepatic failure require IV therapy. significant adverse events stemming from such miscalculations are rare.
Check the serum ALT and acetaminophen concentrations as the patient is approaching the end of the protocol (approximately 18 hours after starting treatment). and epinephrine should be available to treat life-threatening reactions. It is reasonable to administer an antiemetic to nauseated patients or patients who have vomited prior to giving oral acetylcysteine. ondansetron) have been suggested as the antiemetics of choice .25 mg/kg per hour and obtain a serum acetaminophen concentration and ALT measurement every 12 hours thereafter. The palatability of acetylcysteine can be improved by diluting it to a 5 percent solution in cola or juice. and drinking through a straw. also measure the international normalized ratio (INR). Treatment can be stopped when the serum acetaminophen concentration is undetectable. using clinical endpoints rather than time to determine duration [25-28]. 5 . Many authors recommend that therapy be tailored to each patient. If the ALT is elevated. If a patient vomits within 60 minutes of an oral dose of acetylcysteine. The current treatment protocols approved by the US Food and Drug Administration are time-based (20 and 72 hours). There is no uniformly accepted definition of "clearly decreasing. Vomiting — Approximately 33 percent of subjects treated with oral acetylcysteine develop nausea and vomiting . controversy persists about the optimal duration of acetylcysteine therapy. Duration of treatment — While the efficacy of IV and oral administration is similar. continue treatment with acetylcysteine at 6.Administer IV or oral acetylcysteine for a minimum of 20 hours (some authors suggest longer treatment when the oral route is used) .Any patient who develops hypotension or respiratory symptoms should be monitored in an ICU setting with airway management capability. the dose should be repeated. covering the cup. There is no convincing evidence that a slower infusion decreases the risk of anaphylactoid reactions. it is clear that the 72 hour protocol is longer than needed for most patients while the 20 hour protocol is not long enough for some others. If the serum ALT is elevated OR if the serum acetaminophen concentration is detectable. We suggest the following approach for three common clinical scenarios based upon the type of ingestion and the clinical status of the patient: • Acute ingestion with treatment started when ALT is NOT elevated or within eight hours of ingestion . Serotonin 5-HT3 receptor antagonists (eg." One conservative definition is a decrease of more than 50 percent from the peak measurement or three consecutive decreasing values. all below 1000 IU/L. the ALT is clearly decreasing or in the normal range. and the INR is less than two. While these protocols are adequate for the vast majority of patients.
all below 1000 IU/L. Our approach is based upon a few case reports where patients had toxic acetaminophen concentrations at the end of the 20 hour IV treatment protocol [25-27]. except the final infusion rate (6." One conservative definition is a decrease of more than 50 percent from the peak measurement or three consecutive decreasing values. After 11 hours of treatment check the serum ALT activity and acetaminophen concentration. Patients who develop hepatic encephalopathy are treated as described immediately below.) Monitoring during treatment — If acetylcysteine therapy is initiated within eight hours of ingestion (ie. 6 . However. continue treatment with acetylcysteine at 6. one major guideline recommends no additional testing at the end of treatment . • Evidence of hepatic injury following either acute or repeated ingestion . (See "Overview of the treatment of acute liver failure". the ALT is clearly decreasing or in the normal range. There is no uniformly accepted definition of "clearly decreasing. and the INR is less than two. Additional supportive therapies for patients with acute hepatic failure are started as indicated. If the ALT is elevated.• Repeated ingestion with treatment started when ALT is NOT elevated . before ALT elevation). AND the serum acetaminophen concentration is undetectable. also measure the patient's INR. so all patients should receive IV therapy. Treatment can be stopped when the serum acetaminophen concentration is undetectable. all below 1000 IU/L. There are no studies of oral acetylcysteine in hepatic failure. as some patients will develop liver injury during the treatment period. Treatment in hepatic failure — If a patient develops hepatic failure (hepatic failure is differentiated from hepatic injury by the onset of encephalopathy). we suggest measuring the ALT prior to stopping acetylcysteine and continuing treatment if the ALT is abnormal. We also suggest remeasuring the serum acetaminophen concentration prior to stopping acetylcysteine to verify that the level is undetectable." One conservative definition is a decrease of more than 50 percent from the peak measurement or three consecutive decreasing values. There is no uniformly accepted definition of "clearly decreasing.Administer IV or oral acetylcysteine for a minimum of 12 hours .25 mg/kg per hour) is continued until the patient receives a liver transplant OR the hepatic encephalopathy resolves [2.25 mg/kg per hour and obtain a serum acetaminophen concentration and ALT measurement every 12 hours thereafter. IV acetylcysteine decreases mortality and improves hepatic microcirculatory function. If the serum ALT is elevated OR if the serum acetaminophen concentration is detectable. the INR is less than two. The dosing protocol is the same as the 20 hour regimen used for the prevention of hepatic injury.16] and the INR is less than two .Administer IV or oral acetylcysteine until the ALT is clearly decreasing.6.
but none is considered standard care in humans [42-45]. then the serum bicarbonate. Closer monitoring (eg.Other guidelines recommend measuring serum acetaminophen. glucose. While this treatment was useful in animal models. the safety and efficacy of acetylcysteine leaves no role for dialysis in the management of acetaminophen poisoning if acetylcysteine is available. ADDITIONAL RESOURCES — The management of acetaminophen toxicity can sometimes be complex and clinicians can benefit from expert guidance. SUMMARY AND RECOMMENDATIONS 7 . or access the World Health Organization's list of international poison centers (www. cardiac monitor) may be indicated based upon the patient's clinical condition if a significant coingestion is known or suspected or other problems arise. and dimercaprol [13. To obtain emergent consultation with a medical toxicologist.int/ipcs/poisons/centre/directory/en). ICU admission. More frequent testing does not allow enough time to detect clinically meaningful trends. occur between 4 and 20 hours post ingestion. international normalized ratio (INR). Indications for extracorporeal removal — Although acetaminophen is cleared by hemodialysis [48.46. call the United States Poison Control Network at 1800-222-1222 1-800-222-1222 . Extracorporeal removal may be useful for lowering serum acetaminophen concentrations if acetylcysteine is not available.47].5). and resolve as treatment is continued .who. INR >1. and serum creatinine at the end of treatment and continuing treatment if any value is abnormal . If the patient develops an ALT greater than 1000 IU/L. Older studies evaluated therapies such as methionine. The ALT is used to monitor the degree of hepatic injury and the other tests are used to determine the need for liver transplant . Hemodialysis should never be considered an alternative to acetylcysteine therapy. an inhibitor of acetaminophen metabolism [36-40]. Other substances have also been evaluated in animal models. but there are no systematic studies to evaluate the effectiveness of this treatment. cysteamine. Side effects — Both therapeutic serum concentrations of acetylcysteine and high concentrations of acetaminophen can elevate the INR. The most commonly cited is cimetidine. or encephalopathy. We suggest measuring the ALT and INR every 12 hours for any patient who develops ALT elevation. OTHER TREATMENTS Cimetidine and other medications — Several other treatments have been suggested as possible adjuncts for the prevention of acetaminophen-induced liver injury.5).49]. and creatinine should also be measured every 12 hours. it had no effect in a clinical trial where patients were treated with acetylcysteine . coagulopathy (ie. These elevations are usually mild (INR should not be greater than 1. but these treatments were limited by adverse effects and play no role in current management. serum bicarbonate.
) • Acetylcysteine may be given intravenously (IV). Determination of the risk for hepatotoxicity following either acute or chronic acetaminophen ingestion is discussed separately. unless there are contraindications to its administration (Grade 2B). (See 'GI decontamination' above. pancreatitis. Patients who present later may manifest symptoms and signs of hepatic injury.) • Patients who present soon after a potentially toxic ingestion of acetaminophen (single dose ≥7. presentation.Vomiting .) • IV administration of acetylcysteine is favored for patients who present acutely following an ingestion and have any of the following: • • • . Risk factors for hepatotoxicity following acetaminophen ingestion. poisoning severity in acute ingestion is quantified by plotting a timed serum acetaminophen concentration on the Rumack-Matthew nomogram (graph 1). Patients who present within 24 hours after an acute ingestion are generally asymptomatic. section on 'Diagnosis'. presentation. . and diagnosis". The key to effective treatment is to start therapy before the onset of alanine aminotransferase (ALT) elevation.Contraindications to oral administration (ie. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology.• The initial management of acetaminophen poisoning is determined by the patient's presenting symptoms. There are no early symptoms that predict acetaminophen toxicity. In the text. Each protocol and its indications are described in the text. we describe a treatment approach for three common clinical scenarios based upon the type of ingestion and the clinical status of the patient.5 g) are likely to benefit from gastrointestinal decontamination. (See 'Duration of treatment' above. • We tailor acetylcysteine therapy to the patient. bowel ileus or obstruction.) 8 . and the use of the nomogram are discussed separately.) • We recommend treatment with acetylcysteine for all patients with acetaminophen poisoning at significant risk for hepatotoxicity (Grade 1A). We suggest treatment with activated charcoal. the diagnosis of acetaminophen ingestion. using a 20 hour protocol. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology. and diagnosis". or orally.Patients who refuse oral administration bowel injury) In addition. using a 72 hour protocol. using clinical endpoints rather than time to determine treatment duration. 1 g/kg (maximum dose 50 g) by mouth in all patients who present within four hours of a known or suspected acetaminophen ingestion. patients with evidence of hepatic failure require IV therapy. (See '20 hour IV protocol' above and '72 hour oral protocol' above and 'IV versus oral' above. This is accomplished by initiating treatment within eight hours of an acute ingestion.
C. J Toxicol Clin Toxicol 1999. Bangh. TJ. Ann Emerg Med 1994. Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population. Dove. REFERENCES 1. AF. Cochrane Database Syst Rev 2006. 7:148. Smilkstein. 30:1. :CD003328. (See 'Anaphylactoid reaction' above and 'Additional resources' above. Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. Gastric lavage for liquid poisons. SA. 35:435. Position paper: gastric lavage. LF. MK. Management depends upon the severity of the reaction and is described in the text. Klein-Schwartz. Grande. (See 'Monitoring during treatment' above. MJ. Buckley. BH. 42:933. Ann Emerg Med 1991. Rumack. Tenenbein. Arch Intern Med 1981. Bond. the dose should be repeated. Serotonin 5-HT3 receptor antagonists (eg. GR. Interventions for paracetamol (acetaminophen) overdose. Kulig. et al. J Emerg Med 2006. (See 'Vomiting' above. Sitar. RK. 20:1058. Krenzelok. 6. DS. Brok. 319:1557. 2. Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. Ann Emerg Med 1993. R. Gluud. GL. et al. Prescott. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. 10. A comparison of the efficacy of gastric lavage. Buckley. Kulig. HA. Green. 9 . O'Connell. Linden. 141:386. 5. Grierson.) Use of UpToDate is subject to the Subscription and License Agreement. MJ. Arch Emerg Med 1990. If the patient vomits within 60 minutes of an oral dose of acetylcysteine. 4. 9. Spiller. 37:753. Knapp.) • Between 10 and 20 percent of patients treated with IV acetylcysteine develop an anaphylactoid reaction. N Engl J Med 1988. Dawson. Position paper: Ipecac syrup. DL. EP. W. 7. Ann Emerg Med 2000. J. Krenzelok. M. GA. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Smilkstein. C. 11. Greene. Analysis of the national multicenter study (1976 to 1985). In the case of severe reactions (eg. HA. We also suggest remeasuring the serum acetaminophen concentration prior to stopping acetylcysteine to verify that the level is undetectable. Spiller.) • Approximately 33 percent of subjects treated with oral acetylcysteine develop nausea and vomiting. KW. Whyte. ipecacuanha and activated charcoal in the emergency management of paracetamol overdose. as some patients will develop liver injury during the treatment period. Requa. 12.• We routinely measure the ALT prior to stopping acetylcysteine and continue treatment if the ALT is abnormal. ML. R. 22:1403. Winter. EP. IM. Bronstein. respiratory difficulty). ondansetron) are useful antiemetics. 8. et al. the infusion should be stopped and the clinician should obtain guidance from a medical toxicologist or poison control center. AC. 3. 23:519. J Toxicol Clin Toxicol 2004. N. Vale. AH. J Toxicol Clin Toxicol 2004. NA. JA. Underhill. K. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. 42:133.
IM. The use of oral methionine. Keays. Ther Drug Monit 2000. 34. Dawson. 29. 335:1572. Hoffman. IM. Thomas. et al. Ann Emerg Med 2007. Rumack. 26. Management of anaphylactoid reactions to intravenous Nacetylcysteine. Ann Emerg Med 1998. 31:710. RJ. 10 . 32. Amara. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. L. et al. :. JA. 303:1026. Koch. Heard. LS. A 20-hour treatment for acute acetaminophen overdose. Buckley. 30. BD. Rumack. Hepatotoxicity despite early administration of intravenous N-acetylcysteine for acute acetaminophen overdose. Smith. 31. Patient-tailored acetylcysteine administration. 16:34. 50:272. B. S. 22:742. 16. Acetaminophen overdose with altered acetaminophen pharmacokinetics and hepatotoxicity associated with premature cessation of intravenous N-acetylcysteine therapy. Ballantyne. JA. 34:163. BH. Keays. Acetaminophen overdose. Peterson. et al. GG. Harrison. et al. Daly. 662 cases with evaluation of oral acetylcysteine treatment. PM. A. MA. The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning. Gimson. Vale. Gaudreault. 21. Howland. 44:393. P. S. Williams. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. 33. Fountain. Wallace. Bailey. 22. 141:394. RC. PI. DK. W. SR. 25. Whyte. Harrison. Yip. J Toxicol Clin Toxicol 1996. et al. McEwen. Meredith. 50:280. 18. RC. F. EA. Frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose. B. Prescott. Med J Aust 1989. Ann Emerg Med 2007. Med Clin North Am 2008. Klein-Schwartz. Med J Aust 2008. 42:1333. RS. FF. Hayes. The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine. Cantrell. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. A. BH. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. 20. L. Henry. PM. 150:329. Dart. Ann Emerg Med 2005. K. DP. O'Malley.13. et al. Arch Intern Med 1981. Murray. GP. Clark. AH. R. AE. 324:1852. Betten. W. Wendon. Kerr. 19:202. Dawson. TJ. R. 17. Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII. N Engl J Med 1991. 188:296. 24. N Engl J Med 2003. Whyte. Bray. R. et al. Chen. Hayes. J. 141:380. Ann Pharmacother 2008. et al. SW. JS. Nelson. 2:432. MA. Acute liver failure including acetaminophen overdose. R. BMJ 1991. Treatment of acetaminophen poisoning. A prospective evaluation of shortened course oral N-acetylcysteine for the treatment of acute acetaminophen poisoning. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. IA. Wendon. Reith. 14. Acad Emerg Med 2009. J. Lancet 1990. Emerg Med J 2002. Arch Intern Med 1981. Paracetamol overdose: an evidence based flowchart to guide management. CI. 19. 42:766. Development of Hepatic Failure Despite Use of Intravenous Acetylcysteine After a Massive Ingestion of Acetaminophen and Diphenhydramine. DM. 23. NA. PM. LF. RC. Bailey. DA. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Park. Schwartz. Sarmiento. JA. GF. Lancet 1977. Crit Care Med 2003. McGuigan. Doyon. 35. 15. et al. 28. Dart. FF. 27. BD. Ann Pharmacother 2008. Ann Emerg Med 2004. SC. 45:402. Amre. 348:2471. 31:299. Doyon. AL. FL. Klein-Schwartz. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Ann Emerg Med 2008. Jones. KF. Daly. Dargan. Harrison. Goulding. et al. 92:761. Guidelines for the management of paracetamol poisoning in Australia and New Zealand--explanation and elaboration. Fontana. RF. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial.
LF. Cimetidine as adjunctive treatment for acetaminophen overdose. Deng. J Int Med Res 1981. Kucukardali. Peterson. NJ. KV Jr. 43. Park. CD. Comparison of the therapeutic efficacy of 4methylpyrazole and N-acetylcysteine on acetaminophen (paracetamol) hepatotoxicity in rats. Marbury. J. FS. CS. TC. Janco. Chen. MC. HV. 47. Gastroenterology 1983. 39. Han. Mitchell. WJ. et al. Lesna. Steele. Burkhart. Kulig. Sutherland. 15:1829. 45. 77:1273. Avant. LH.36. 81:1052. KV Jr. CC. prospective controlled trial of early therapy. Aleksunes. Qaw. GZ. 44. Speeg. Zhonghua Yi Xue Za Zhi (Taipei) 1999. Arch Pharm Res 2009. Hemodialysis of acetaminophen in uremic patients. CO. Lin. et al. Lee. Y. Methionine and cysteamine in paracetamol (acetaminophen) overdose. Al-Ali. 42. Toxicology 1997. NM. World J Gastroenterol 2009. KW. et al. X. Speeg. KV Jr. Schenker. AN. PL. 49. Abdul-Cader. 32:221. 73:383. SA. 40. J Clin Invest 1984. Prevention of acetaminophen and cocaine hepatotoxicity in mice by cimetidine treatment. Sun. Wu. MC. 3:263. FJ. Al-Mustafa. Klaassen. Maldonado. FY. BH. Hum Exp Toxicol 1995. Selective inhibition of acetaminophen oxidation and toxicity by cimetidine and other histamine H2-receptor antagonists in vivo and in vitro in the rat and in man. 62:907. 41. JF. 18:78. MC. Gastroenterology 1981. Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression. Z. methionine. GR. Additive protection of cimetidine and Nacetylcysteine treatment against acetaminophen-induced hepatic necrosis in the rat. 121:223. GR. Wang. LM. 85:122. Hamlyn. ML. GRAPHICS Severity of acetaminophen intoxication 11 . Hemodialysis as adjunctive therapy for severe acetaminophen poisoning: a case report. Cinan. ZH. Lindemann. Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf2-independent processes. Biochem Pharmacol 2009. S. Speeg. Acar. AL. J Pharmacol Exp Ther 1985. S. et al. Mitchell. Chen. 37. 48. Record. Schenker. et al. Cysteamine. Antioxidative and hepatoprotective effects of magnolol on acetaminophen-induced liver damage in rats. 46. RG. Int J Artif Organs 1980. 38. 2:109. Rumack. Knodell. Tsai. Yang. KK. N. 14:299. Lancet 1976. Cimetidine protects against acetaminophen hepatotoxicity in rats. Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol. Mitchell. and penicillamine in the treatment of paracetamol poisoning. 234:550. 9:226. CK. Prescott. Curr Med Res Opin 2002. M. U. Liu. YH. AK. Reisman.
and the risk of hepatic toxicity. Inc. 55:873.30. Adapted from Rumack.83. © 2010 UpToDate.18-6FF8814DCB-6] Licensed to: UpToDate Individual Web – Do Quoc Huy 12 . the time after drug ingestion. Pediatrics 1975. H. A relatively low level (such as 10 µg/mL) is safe soon after ingestion. Relationship between plasma acetaminophen concentration (in µg/mL or µmol/L). BH.com-123. The thick diagonal line of possible hepatic toxicity represents a 25 percent likelihood of disease.Matthews. | Subscription and License Agreement |Support Tag: [ecapp1002p.utd. but associated with appreciable risk at 24 hours since it reflects a high initial load which has now distributed into the tissues. All rights reserved.