今日の臨床サポート

アセトアミノフェン中毒

著者: 花木奈央 大阪大学大学院医学研究科 公衆衛生学

監修: 志賀隆 国際医療福祉大学 医学部救急医学/国際医療福祉大学病院 救急医療部

著者校正/監修レビュー済:2022/02/16
参考ガイドライン:
  1. 日本中毒学会:急性中毒の標準治療(2020年1月6日アクセス)
  1. コクランシステマティックレビュー Cochrane Database of Systematic Reviews Interventions for paracetamol (acetaminophen) overdose
患者向け説明資料

概要・推奨   

  1. アセトアミノフェンによる肝障害が悪化する患者は、慢性的にアルコールを摂取している患者、背景に肝疾患を有している患者、偶発的過量服用の患者である。
  1. 摂取量やアセトアミノフェンの血中濃度から肝障害を起こすリスクが高い場合は、解毒薬であるN-アセチルシステインを投与する。
  1. 妊娠時にもRumack-Matthewのノモグラムに従って治療を行うことが勧められている(推奨度1)
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
花木奈央 : 特に申告事項無し[2022年]
監修:志賀隆 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 日本中毒センターに寄せられた相談件数や、血中濃度即時分析可能施設割合など我が国の疫学に関する新たな情報を記載した。
  1. 2020年に出版されたオーストラリアとニュージーランドのガイドラインの内容を反映した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. アセトアミノフェン中毒とは、アセトアミノフェンを大量服薬および誤食したことにより、摂取から数時間以内に胃腸炎、および1~3日後に肝毒性などの症状を生じることである。
  1. 急性薬物中毒の原因物質として、最も頻度の高い薬物の1つである。
  1. 2020年の日本中毒センターに寄せられた相談件数は142件で、解熱鎮痛消炎剤585件の中で最も多かった。
  1. 処方薬以外でも、市販の解熱鎮痛薬、総合感冒薬の70%以上に主成分として含有されており、容易に手に入れることができる。
  1. 自殺目的の大量服薬のほかに、小児の誤食事故が多い。
  1. 毒性代謝物であるN-アセチル-p-キノネミンが、肝では肝細胞の蛋白・核酸と、腎では腎尿細管細胞と共益結合して壊死をもたらす。
問診・診察のポイント  
  1. 中毒を疑った際には「MATTERS」(下表)を意識して問診を行う。

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文献 

Frank F S Daly, Gerald F O'Malley, Kennon Heard, Gregory M Bogdan, Richard C Dart
Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion.
Ann Emerg Med. 2004 Oct;44(4):393-8. doi: 10.1016/j.annemergmed.2004.05.005.
Abstract/Text STUDY OBJECTIVE: Repeated supratherapeutic ingestion of acetaminophen is potentially lethal but poorly described. We provide the first prospective description of the characteristics, course, and outcome of patients with repeated supratherapeutic ingestion of acetaminophen.
METHODS: This was a prospective case series of consecutive patients aged 12 years and older with acetaminophen dosage greater than 4 g per 24 hours referred to our poison center. Acetylcysteine was recommended if serum acetaminophen level exceeded 10 mg/L or aspartate aminotransferase exceeded 50 IU/L. Acetaminophen dosage, demographic factors, treatment, and outcome were recorded using standardized methods. Minimum follow-up was 72 hours.
RESULTS: Of 277 patients eligible, 249 patients were enrolled. At presentation, serum aspartate aminotransferase levels less than 50 IU/L were found in 126 patients, aspartate aminotransferase levels of 50 to 1,000 IU/L were present in 47 patients, and aspartate aminotransferase levels were above 1,000 IU/L in 37 patients. No aspartate aminotransferase data were available for 39 patients. No patient with an aspartate aminotransferase level below 50 IU/L at presentation developed hepatotoxicity (aminotransferase >1,000 IU/L). Seven (15%) patients with aspartate aminotransferase levels of 50 to 1,000 IU/L at presentation subsequently developed hepatotoxicity; 1 patient died. Six (16%) patients with aspartate aminotransferase levels above 1,000 IU/L at presentation died or received liver transplants. Study limitations included recall bias, incomplete patient follow-up, and the assumption that absence of clinical signs indicated insignificant liver injury.
CONCLUSION: Our results suggest that the injury caused by acetaminophen repeated supratherapeutic ingestion is apparent at presentation and related to dose magnitude and duration. All patients who developed hepatotoxicity presented with aspartate aminotransferase above 50 IU/L. Determination of serum aspartate aminotransferase and acetaminophen concentrations may allow early discharge from the emergency department.

PMID 15459622
Richard C Dart, Andrew R Erdman, Kent R Olson, Gwenn Christianson, Anthony S Manoguerra, Peter A Chyka, E Martin Caravati, Paul M Wax, Daniel C Keyes, Alan D Woolf, Elizabeth J Scharman, Lisa L Booze, William G Troutman, American Association of Poison Control Centers
Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management.
Clin Toxicol (Phila). 2006;44(1):1-18.
Abstract/Text The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of acetaminophen. An evidence-based expert consensus process was used to create this guideline. This guideline applies to ingestion of acetaminophen alone and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care. The panel's recommendations follow. These recommendations are provided in chronological order of likely clinical use. The grade of recommendation is provided in parentheses. 1) The initial history obtained by the specialist in poison information should include the patient's age and intent (Grade B), the specific formulation and dose of acetaminophen, the ingestion pattern (single or multiple), duration of ingestion (Grade B), and concomitant medications that might have been ingested (Grade D). 2) Any patient with stated or suspected self-harm or who is the recipient of a potentially malicious administration of acetaminophen should be referred to an emergency department immediately regardless of the amount ingested. This referral should be guided by local poison center procedures (Grade D). 3) Activated charcoal can be considered if local poison center policies support its prehospital use, a toxic dose of acetaminophen has been taken, and fewer than 2 hours have elapsed since the ingestion (Grade A). Gastrointestinal decontamination could be particularly important if acetylcysteine cannot be administered within 8 hours of ingestion. Acute, single, unintentional ingestion of acetaminophen: 1) Any patient with signs consistent with acetaminophen poisoning (e.g., repeated vomiting, abdominal tenderness in the right upper quadrant or mental status changes) should be referred to an emergency department for evaluation (Grade D). 2) Patients less than 6 years of age should be referred to an emergency department if the estimated acute ingestion amount is unknown or is 200 mg/kg or more. Patients can be observed at home if the dose ingested is less than 200 mg/kg (Grade B). 3) Patients 6 years of age or older should be referred to an emergency department if they have ingested at least 10 g or 200 mg/kg (whichever is lower) or when the amount ingested is unknown (Grade D). 4) Patients referred to an emergency department should arrive in time to have a stat serum acetaminophen concentration determined at 4 hours after ingestion or as soon as possible thereafter. If the time of ingestion is unknown, the patient should be referred to an emergency department immediately (Grade D). 5) If the initial contact with the poison center occurs more than 36 hours after the ingestion and the patient is well, the patient does not require further evaluation for acetaminophen toxicity (Grade D). Repeated supratherapeutic ingestion of acetaminophen (RSTI): 1) Patients under 6 years of age should be referred to an emergency department immediately if they have ingested: a) 200 mg/kg or more over a single 24-hour period, or b) 150 mg/kg or more per 24-hour period for the preceding 48 hours, or c) 100 mg/kg or more per 24-hour period for the preceding 72 hours or longer (Grade C). 2) Patients 6 years of age or older should be referred to an emergency department if they have ingested: a) at least 10 g or 200 mg/kg (whichever is less) over a single 24-hour period, or b) at least 6 g or 150 mg/kg (whichever is less) per 24-hour period for the preceding 48 hours or longer. In patients with conditions purported to increase susceptibility to acetaminophen toxicity (alcoholism, isoniazid use, prolonged fasting), the dose of acetaminophen considered as RSTI should be greater than 4 g or 100 mg/kg (whichever is less) per day (Grade D). 3) Gastrointestinal decontamination is not needed (Grade D). Other recommendations: 1) The out-of-hospital management of extended-release acetaminophen or multi-drug combination products containing acetaminophen is the same as an ingestion of acetaminophen alone (Grade D). However, the effects of other drugs might require referral to an emergency department in accordance with the poison center's normal triage criteria. 2) The use of cimetidine as an antidote is not recommended (Grade A).

PMID 16496488
B S Riggs, A C Bronstein, K Kulig, P G Archer, B H Rumack
Acute acetaminophen overdose during pregnancy.
Obstet Gynecol. 1989 Aug;74(2):247-53.
Abstract/Text During a nationwide acetaminophen overdose study conducted at the Rocky Mountain Poison and Drug Center from 1976-1985, 113 patients entered into the study were reported to be pregnant at the time of the overdose. Follow-up, including appropriate laboratory and pregnancy outcome data, was available in 60 cases. Of these, 19 women overdosed during the first trimester, 22 during the second trimester, and 19 during the third trimester of pregnancy. Of the 24 patients with acetaminophen levels above the acetaminophen overdose nomogram line, ten were treated with N-acetylcysteine within 10 hours post-ingestion; eight delivered normal infants and two had elective abortions. Of ten patients treated with N-acetylcysteine 10-16 hours post-ingestion, five delivered viable infants, two had elective abortions, and three had spontaneous abortions. Of four women treated with N-acetylcysteine 16-24 hours post-ingestion, one mother died, and there was one spontaneous abortion, one stillbirth, one elective abortion, and one delivery. Multiple logistic regression demonstrated a statistically significant correlation between the time to loading dose of N-acetylcysteine and pregnancy outcome, with an increase in the incidence of spontaneous abortion or fetal death when treatment was begun late. We recommend that pregnant women who take an acetaminophen overdose and have a potentially toxic serum level be treated with N-acetylcysteine as early as possible.

PMID 2748061
Lars E Schmidt, Kim Dalhoff, Henrik Enghusen Poulsen
Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity.
Hepatology. 2002 Apr;35(4):876-82. doi: 10.1053/jhep.2002.32148.
Abstract/Text The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were studied, giving special attention to alcohol history, time between overdose and intravenous N-acetylcysteine (NAC) treatment ("time to NAC"), and other data available at the time of admittance. Up until 72 hours after ingestion, time to NAC was the single most important independent risk factor. With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1.78-6.97). Acute alcohol ingestion was an independent protective factor regarding mortality in alcoholic patients (OR, 0.08; 95% CI, 0.01-0.66) but not in nonalcoholic patients (OR, 0.21; 95% CI, 0.03-1.67). Patient age and quantity of acetaminophen were independent risk factors. In conclusion, time to NAC was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due to an increased risk of developing hepatotoxicity should be treated with NAC regardless of risk estimation.

PMID 11915034
Robert P Myers, Bing Li, Andrew Fong, Abdel Aziz M Shaheen, Hude Quan
Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004.
BMC Public Health. 2007 Jul 5;7:143. doi: 10.1186/1471-2458-7-143. Epub 2007 Jul 5.
Abstract/Text BACKGROUND: Acetaminophen overdose (AO) is the most common cause of acute liver failure. We examined temporal trends and sociodemographic risk factors for AO in a large Canadian health region.
METHODS: 1,543 patients hospitalized for AO in the Calgary Health Region (population ~1.1 million) between 1995 and 2004 were identified using administrative data.
RESULTS: The age/sex-adjusted hospitalization rate decreased by 41% from 19.6 per 100,000 population in 1995 to 12.1 per 100,000 in 2004 (P < 0.0005). This decline was greater in females than males (46% vs. 29%). Whereas rates fell 46% in individuals under 50 years, a 50% increase was seen in those >/= 50 years. Hospitalization rates for intentional overdoses fell from 16.6 per 100,000 in 1995 to 8.6 per 100,000 in 2004 (2004 vs. 1995: rate ratio [RR] 0.49; P < 0.0005). Accidental overdoses decreased between 1995 and 2002, but increased to above baseline levels by 2004 (2004 vs. 1995: RR 1.24;P < 0.0005). Risk factors for AO included female sex (RR 2.19; P < 0.0005), Aboriginal status (RR 4.04; P < 0.0005), and receipt of social assistance (RR 5.15; P < 0.0005).
CONCLUSION: Hospitalization rates for AO, particularly intentional ingestions, have fallen in our Canadian health region between 1995 and 2004. Young patients, especially females, Aboriginals, and recipients of social assistance, are at highest risk.

PMID 17615056
Marco L A Sivilotti, Mark C Yarema, David N Juurlink, Angela M Good, David W Johnson
A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine.
Ann Emerg Med. 2005 Sep;46(3):263-71. doi: 10.1016/j.annemergmed.2005.04.004.
Abstract/Text STUDY OBJECTIVE: The risk of hepatotoxicity after acute acetaminophen overdose varies with timed serum acetaminophen concentration and delay to treatment. The ability to accurately predict hepatotoxicity is needed to reduce confusion about the optimal treatment regimen for individual patients and the effects of risk modifiers such as ethanol. We quantitatively estimate the risk of hepatotoxicity based on the degree and duration of pretreatment exposure to supratherapeutic concentrations of acetaminophen.
METHODS: We examined all hospitalizations for acute acetaminophen overdose within a retrospective multicenter Canadian registry. We used a previously developed composite measure incorporating timed serum acetaminophen concentration and time to N-acetylcysteine treatment into a single parameter. We then modeled hepatotoxicity on this parameter, as well as age, sex, and ethanol use. Hepatotoxicity was defined as peak aminotransferase level of 1,000 IU/L or greater at 24 hours or longer.
RESULTS: Of 1,270 admitted patients treated mostly with intravenous N-acetylcysteine for less than 24 hours, our model accurately identified the 94 patients who developed hepatotoxicity (discriminatory index 0.93). Hepatotoxicity occurred in none of the 313 patients (95% confidence interval [CI] 0% to 1.0%) above the traditional 150 mug/mL treatment line who were classified as low risk (<1%) using our instrument. After adjustment for severity of exposure, the risk of hepatotoxicity was considerably higher in the absence of coingested ethanol (median hepatotoxic dose 16.5 mmol/L x hour [95% CI 8.74 to 31.0 mmol/L x hour] versus 27.1 mmol/L x hour [95% CI 11.1 to 66.3 mmol/L x hour]), particularly among alcoholics (4.79 mmol/L x hour [95% CI 2.13 to 10.8 mmol/L x hour]).
CONCLUSION: Our risk prediction instrument identifies a large group of low-risk patients for whom 20-hour intravenous N-acetylcysteine therapy is sufficient. Our results suggest that acute and chronic ethanol use dramatically influences acetaminophen toxicity. This work may facilitate the evaluation of individualized treatment strategies for higher-risk patients.

PMID 16126138
Angela L Chiew, Christian Gluud, Jesper Brok, Nick A Buckley
Interventions for paracetamol (acetaminophen) overdose.
Cochrane Database Syst Rev. 2018 Feb 23;2:CD003328. doi: 10.1002/14651858.CD003328.pub3. Epub 2018 Feb 23.
Abstract/Text BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites.
OBJECTIVES: To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose.
SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews.
SELECTION CRITERIA: Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of benefits and underestimation of harms). We used Trial Sequential Analysis to control risks of random errors (i.e. play of chance) and GRADE to assess the quality of the evidence and constructed 'Summary of findings' tables using GRADE software.
MAIN RESULTS: We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). Extracorporeal interventions included charcoal haemoperfusion compared with conventional treatment (supportive care including gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16 participants. The mean cumulative amount of paracetamol removed was 1.4 g. One participant from the haemoperfusion group who had ingested 135 g of paracetamol, died. There were no deaths in the conventional treatment group. Accordingly, we found no benefit of charcoal haemoperfusion (very low quality of evidence). Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine was unproven. One small trial (low quality evidence) found that acetylcysteine may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The most recent randomised clinical trials studied different acetylcysteine regimens, with the primary outcome being adverse events. It was unclear which acetylcysteine treatment protocol offered the best efficacy, as most trials were underpowered to look at this outcome. One trial showed that a modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose was associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen (low quality of evidence). All Trial Sequential Analyses showed lack of sufficient power. Children were not included in the majority of trials. Hence, the evidence pertains only to adults.
AUTHORS' CONCLUSIONS: These results highlight the paucity of randomised clinical trials comparing different interventions for paracetamol overdose and their routes of administration and the low or very low level quality of the evidence that is available. Evidence from a single trial found activated charcoal seemed the best choice to reduce absorption of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best efficacy. Current management of paracetamol poisoning worldwide involves the administration of intravenous or oral acetylcysteine which is based mainly on observational studies. Results from these observational studies indicate that treatment with acetylcysteine seems to result in a decrease in morbidity and mortality, However, further evidence from randomised clinical trials comparing different treatments are needed.

PMID 29473717
Daniel J B Marks, Paul I Dargan, John R H Archer, Charlotte L Davies, Alison M Dines, David M Wood, Shaun L Greene
Outcomes from massive paracetamol overdose: a retrospective observational study.
Br J Clin Pharmacol. 2017 Jun;83(6):1263-1272. doi: 10.1111/bcp.13214. Epub 2017 Jan 25.
Abstract/Text LINKED ARTICLE: This article is commented on by Bateman DN and Dear JW. Should we treat very large paracetamol overdose differently? Br J Clin Pharmacol 2017; 83: 1163-5. https://doi.org/10.1111/bcp.13279 AIMS: Treatment of paracetamol (acetaminophen) overdose with acetylcysteine is standardized, with dose determined only by patient weight. The validity of this approach for massive overdoses has been questioned. We systematically compared outcomes in massive and non-massive overdoses, to guide whether alternative treatment strategies should be considered, and whether the ratio between measured timed paracetamol concentrations (APAPpl ) and treatment nomogram thresholds at those time points (APAPt ) provides a useful assessment tool.
METHODS: This is a retrospective observational study of all patients (n = 545) between 2005 and 2013 admitted to a tertiary care toxicology service with acute non-staggered paracetamol overdose. Massive overdoses were defined as extrapolated 4-h plasma paracetamol concentrations >250 mg l-1 , or reported ingestions ≥30 g. Outcomes (liver injury, coagulopathy and kidney injury) were assessed in relation to reported dose and APAPpl :APAPt ratio (based on a treatment line through 100 mg l-1 at 4 h), and time to acetylcysteine.
RESULTS: Ingestions of ≥30 g paracetamol correlated with higher peak serum aminotransferase (r = 0.212, P < 0.0001) and creatinine (r = 0.138, P = 0.002) concentrations. Acute liver injury, hepatotoxicity and coagulopathy were more frequent with APAPpl :APAPt  ≥ 3 with odds ratios (OR) and 95% confidence intervals (CI) of 9.19 (5.04-16.68), 35.95 (8.80-158.1) and 8.34 (4.43-15.84), respectively (P < 0.0001). Heightened risk persisted in patients receiving acetylcysteine within 8 h of overdose.
CONCLUSION: Patients presenting following massive paracetamol overdose are at higher risk of organ injury, even when acetylcysteine is administered early. Enhanced therapeutic strategies should be considered in those who have an APAPpl :APAPt  ≥ 3. Novel biomarkers of incipient liver injury and abbreviated acetylcysteine regimens require validation in this patient cohort.

© 2016 The British Pharmacological Society.
PMID 28002875
Norio Otani, Toru Hifumi, Takeshi Kitamoto, Kentaro Kobayashi, Nobuaki Nakaya, Joji Tomioka
Current state of drug analysis in Japanese emergency departments: a nationwide survey.
Acute Med Surg. 2020 Jan-Dec;7(1):e566. doi: 10.1002/ams2.566. Epub 2020 Oct 15.
Abstract/Text Aim: In 1999, the Japanese Society for Clinical Toxicology proposed 15 toxicants that would be useful for analysis: methanol, barbiturates, benzodiazepines, bromovalerylurea, tricyclic acid, acetaminophen, salicylic acid, theophylline, organic phosphorus pesticides, carbamate pesticides, glufosinate, paraquat, arsenic, cyanide, and methamphetamine. We aimed to reveal the current state of drug analysis for acute poisoning in the emergency department of Japanese hospitals.
Methods: From 1 April, 2017, we undertook a questionnaire survey in the emergency departments of 546 hospitals designated as educational institutions for emergency physicians.
Results: Responses were obtained from 246 hospitals (45.1%). Among drug abuse screening kits for qualitative testing, 80.9% used the Triage Drugs of Abuse Panel and 7.3% used Instant-View M-1. Analytical results have always been immediately obtained by 2.8% of facilities for methanol, 19.5% for barbiturates, 2.4% for benzodiazepines, 0.8% for bromovalerylurea, 1.2% for tricyclic acid, 12.2% for acetaminophen, 4.1% for salicylic acid, 44.3% for theophylline, 2.0% for organic phosphorus pesticides, 1.6% for carbamate pesticides, 1.2% for glufosinate, 2.4% for paraquat, 0.8% for arsenic, 1.2% for cyanide, and 1.2% for methamphetamine.
Conclusion: In the treatment of acute poisoning, drug analysis is important for both clinical judgment and academic verification. However, many of the 15 toxicants proposed to be useful for analysis in 1999 are not yet immediately analyzed in the emergency department of Japanese hospitals. Furthermore, it is necessary to develop inexpensive testing systems and to provide insurance points for testing so that analysis can be carried out by emergency departments.

© 2020 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.
PMID 33088578
Angela L Chiew, David Reith, Adam Pomerleau, Anselm Wong, Katherine Z Isoardi, Jessamine Soderstrom, Nicholas A Buckley
Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand.
Med J Aust. 2020 Mar;212(4):175-183. doi: 10.5694/mja2.50428. Epub 2019 Dec 1.
Abstract/Text INTRODUCTION: Paracetamol is a common agent taken in deliberate self-poisoning and in accidental overdose in adults and children. Paracetamol poisoning is the commonest cause of severe acute liver injury. Since the publication of the previous guidelines in 2015, several studies have changed practice. A working group of experts in the area, with representation from all Poisons Information Centres of Australia and New Zealand, were brought together to produce an updated evidence-based guidance.
MAIN RECOMMENDATIONS (UNCHANGED FROM PREVIOUS GUIDELINES): The optimal management of most patients with paracetamol overdose is usually straightforward. Patients who present early should be given activated charcoal. Patients at risk of hepatotoxicity should receive intravenous acetylcysteine. The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion. Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions.
MAJOR CHANGES IN MANAGEMENT IN THE GUIDELINES: The new guidelines recommend a two-bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h). This has similar efficacy but significantly reduced adverse reactions compared with the previous three-bag regimen. Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine. All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine. Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine.

© 2019 AMPCo Pty Ltd.
PMID 31786822

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