今日の臨床サポート

薬物中毒

著者: 宮道亮輔 東京慈恵会医科大学 救急医学講座

監修: 箕輪良行 みさと健和病院 救急総合診療研修顧問

著者校正済:2021/12/08
現在監修レビュー中
参考ガイドライン:
  1. 日本中毒学会(編):急性中毒標準診療ガイド, じほう, 2008年.
  1. Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose. 4th edition, Saunders, 2007.
患者向け説明資料

概要・推奨   

  1. 中毒診療の原則は、①医療者の安全確保(避難と除染の判断)、②気道・呼吸・循環・意識状態の評価と安定化、③病歴や身体診察による原因物質の判断、④検査、⑤症状治療(支持療法、吸収の阻害、排泄の促進、拮抗薬・解毒薬)、⑥メンタルヘルスへの対応である(推奨度1)。
  1. 意識障害患者へのcomaカクテル(糖液、サイアミン、ナロキソン、フルマゼニル)投与については、ブドウ糖とサイアミンは経験的投与がお勧めとのことだが、やはりブドウ糖は簡易血糖測定後に投与し、サイアミンはアルコール依存や慢性低栄養状態の患者に投与するのがよいだろう。ナロキソンは麻薬中毒症状のある人のみ、フルマゼニルも治療的鎮静の回復時のみに使用するのがよさそうである(推奨度2)。
  1. 病歴や内服歴を本人から聞くのが基本だが、本人から得る情報は信用できないという調査もある。本人からの情報ももちろん重要であるが、家族や友人、救急隊からの情報を得ることが推奨される(推奨度2)。
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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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
宮道亮輔 : 特に申告事項無し[2021年]
監修:箕輪良行 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、文献的なエビデンスがなくても、教科書に載っていて日常診療に役立つ内容は掲載した。
  1. 中毒診療の原則やトキシドロームなどについて追記した。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 薬物中毒とは、非ステロイド抗炎症薬(NSAIDs)、アセトアミノフェン、抗精神病薬などの薬物を大量服薬および誤食したことにより生じる症状のことである。
  1. 薬物中毒は疑わないと診断できないため、意識障害患者などでは常に念頭に置いて鑑別する。
  1. 詳細な病歴聴取、家族や友人、救急隊からの情報を活用する。
  1. 原因薬物は多岐にわたるため、バイタルサインを含む臨床症状や検査所見を組み合わせて病態を理解することが大切である。
  1. トキシドロームを意識すると臨床診断に有用である。
  1. 原因不明の重症患者では、血液検査(血液ガス、電解質、腎機能、血糖など)や尿検査、心電図、X線撮影などを行う。アニオンギャップや浸透圧ギャップの測定も鑑別に役立つ。
  1. 中毒治療の4原則は、支持療法、吸収の阻害、排泄の促進、拮抗薬解毒薬である。
  1. 重症患者では、各種モニターを実施して、気道・呼吸・循環を安定化するための処置を行う。血液浄化の適用を検討する。
問診・診察のポイント  
 
  1. 原因不明の意識障害患者から、急性中毒患者を見つけ出すことが第一である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: A R Soslow
雑誌名: Ann Emerg Med. 1981 Jan;10(1):18-21.
Abstract/Text A retrospective review of all patients admitted to an urban teaching hospital emergency department with the complaint of overdose, poisoning, or ingestion during a 10-month period was conducted. Analysis of these 82 episodes involving 69 individuals revealed: 1) a preponderance of women in the 20- to 40-year old range; 2) poly-drug character of the ingestion, with alcohol the most common secondary drug; 3) increased utilization of antidepressants and minor tranquilizers and decreased use of barbiturates; 4) non-concordance between drug history of ingested drug and toxicological findings. All patients survived and there was no apparent residual morbidity. Except for one patient requiring hemodialysis and peritoneal dialysis, all patients were treated with aggressive supportive care.

PMID 6109510  Ann Emerg Med. 1981 Jan;10(1):18-21.
著者: N Wright
雑誌名: Clin Toxicol. 1980 May;16(3):381-4. doi: 10.3109/15563658008989963.
Abstract/Text A comparison was made between the history of drugs taken by self-poisoned patients and the drugs detected in the urine from the same patients by laboratory screening procedures. The results coincided exactly in less than half of the patients, and the major tendency was to exaggerate the number of substances taken. It is concluded that drug histories are unreliable and that corroborating evidence should be sought.

PMID 7398227  Clin Toxicol. 1980 May;16(3):381-4. doi: 10.3109/155636・・・
著者: D A Spyker, A Minocha
雑誌名: J Emerg Med. 1988 Mar-Apr;6(2):117-20.
Abstract/Text We recommend a toxicodynamic approach to the management of the poisoned patient. We define the period between ingestion and onset of toxic manifestations (clinical or laboratory) as the preclinical phase, during which the management of the patient necessarily depends solely on the history of ingestion and the predicted toxicity. In the toxic phase during which the patient shows clinical or laboratory evidence of toxicity, the history, clinical status (signs, symptoms, drug levels, laboratory parameters), and toxicodynamics should guide the therapy. In the resolution phase, when the patient shows clinical improvement and declining drug levels, treatment should be based on clinical status. Gastrointestinal decontamination is critical in the first two phases and may be of value during the resolution phase until the body drug burden declines to safe levels. We recommend an aggressive approach to gastrointestinal decontamination, especially in the preclinical phase. With a history of a potentially toxic ingestion of an absorbable drug, an observation period until passage of a charcoal-laden stool should be achieved before discharge of the patient.

PMID 3385172  J Emerg Med. 1988 Mar-Apr;6(2):117-20.
著者: Babak Mokhlesi, Jerrold B Leiken, Patrick Murray, Thomas C Corbridge
雑誌名: Chest. 2003 Feb;123(2):577-92.
Abstract/Text Intensivists are confronted with poisoned patients on a routine basis, with clinical scenarios ranging from known drug overdose or toxic exposure, illicit drug use, suicide attempt, or accidental exposure. In addition, drug toxicity can also manifest in hospitalized patients from inappropriate dosing and drug interactions. In this review article, we describe the epidemiology of poisoning in the United States, review physical examination findings and laboratory data that may aid the intensivist in recognizing a toxidrome (symptom complex of specific poisoning) or specific poisoning, and describe a rational and systematic approach to the poisoned patient. It is important to recognize that there is a paucity of evidence-based information on the management of poisoned patient. However, the most current recommendations by the American Academy of Clinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists will be reviewed. Specific poisonings will be reviewed in the second section of these review articles.

PMID 12576382  Chest. 2003 Feb;123(2):577-92.
著者: K R Olson, P R Pentel, M T Kelley
雑誌名: Med Toxicol. 1987 Jan-Feb;2(1):52-81.
Abstract/Text The rapid diagnosis and immediate intervention required in patients with serious drug overdose or poisoning makes toxicological screening of limited value to the emergency department physician. Instead, a careful clinical evaluation using the history, physical examination, and the more readily available laboratory tests may allow a tentative diagnosis and the initiation of life-saving treatment. Laboratory tests should include serum osmolality, electrolytes, glucose, BUN and an estimation of the anion and osmolar gaps. The ECG can also provide useful information. Clinical findings of important include altered blood pressure, pulse, respiration and body temperature, the presence of coma, agitation, delirium or psychosis, and muscular weakness. An ophthalmological examination is also of importance in the acutely poisoned patient. Oral burns or dysphagia may occur following ingestion of any strongly reactive substance, but the absence of oral burns does not preclude the possibility of oesophageal or stomach injury. Odours and skin colour may also contribute to the diagnosis. Comprehensive toxicology screening may not be immediately available, or may be inaccurate, thus adding little to the information obtained during the initial evaluation of the poisoned patient.

PMID 3547006  Med Toxicol. 1987 Jan-Feb;2(1):52-81.
著者: Timothy B Erickson, Trevonne M Thompson, Jenny J Lu
雑誌名: Emerg Med Clin North Am. 2007 May;25(2):249-81; abstract vii. doi: 10.1016/j.emc.2007.02.004.
Abstract/Text Toxic overdose can present with various clinical signs and symptoms. These may be the only clues to diagnosis when the cause of toxicity is unknown at the time of initial assessment. The prognosis and clinical course of recovery of a patient poisoned by a specific agent depends largely on the quality of care delivered within the first few hours in the emergency setting. Usually the drug or toxin can be quickly identified by a careful history, a directed physical examination, and commonly available laboratory tests. Once the patient has been stabilized, the physician must consider how to minimize the bioavailability of toxin not yet absorbed, which antidotes (if any) to administer, and if other measures to enhance elimination are necessary.

PMID 17482020  Emerg Med Clin North Am. 2007 May;25(2):249-81; abstrac・・・
著者: K A Sporer
雑誌名: Ann Intern Med. 1999 Apr 6;130(7):584-90.
Abstract/Text Acute heroin overdose is a common daily experience in the urban and suburban United States and accounts for many preventable deaths. Heroin acts as a pro-drug that allows rapid and complete central nervous system absorption; this accounts for the drug's euphoric and toxic effects. The heroin overdose syndrome (sensitivity for diagnosing heroin overdose, 92%; specificity, 76%) consists of abnormal mental status, substantially decreased respiration, and miotic pupils. The response of naloxone does not improve the sensitivity of this diagnosis. Most overdoses occur at home in the company of others and are more common in the setting of other drugs. Heroin-related deaths are strongly associated with use of alcohol or other drugs. Patients with clinically significant respiratory compromise need treatment, which includes airway management and intravenous or subcutaneous naloxone. Hospital observation for several hours is necessary for recurrence of hypoventilation or other complications. About 3% to 7% of treated patients require hospital admission for pneumonia, noncardiogenic pulmonary edema, or other complications. Methadone maintenance is an effective preventive measure, and others strategies should be studied.

PMID 10189329  Ann Intern Med. 1999 Apr 6;130(7):584-90.
著者: R S Hoffman, L R Goldfrank
雑誌名: JAMA. 1995 Aug 16;274(7):562-9.
Abstract/Text OBJECTIVE: In the assessment and management of the potentially poisoned patient with altered consciousness, the most consequential and controversial interventions occur during the first 5 minutes of care. In this review article, the risks and benefits of standard diagnostic and therapeutic interventions are presented to guide clinicians through this critical period of decision making.
DATA SOURCES: Data for discussion were obtained from a search of English-language publications referenced on MEDLINE for the years 1966 to 1994. Older literature was included when pertinent. Search terms included poisoning, overdose, toxicity, naloxone, glucose, thiamine, and flumazenil.
STUDY SELECTION: Only large trials were used for determinations of diagnostic utility and efficacy. Small trials, case series, and case reports were reviewed extensively for adverse effects.
DATA EXTRACTION AND SYNTHESIS: Trials were reviewed for overall methodology, inclusion and exclusion criteria, sources of bias, and outcome.
CONCLUSION: Analysis favors empirical administration of hypertonic dextrose and thiamine hydrochloride to patients with altered consciousness. Although rapid reagent test strips can be used to guide this therapy, they are not infallible, and they fail to recognize clinical hypoglycemia that may occur without numerical hypoglycemia. Administration of naloxone hydrochloride should be reserved for patients with signs and symptoms of opioid intoxication. Flumazenil is best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose.

PMID 7629986  JAMA. 1995 Aug 16;274(7):562-9.
著者: J R Hoffman, D L Schriger, J S Luo
雑誌名: Ann Emerg Med. 1991 Mar;20(3):246-52.
Abstract/Text STUDY OBJECTIVE: To determine whether clinical criteria (respirations of 12 or less, mitotic pupils, and circumstantial evidence of opiate abuse) could predict response to naloxone in patients with acute alteration of mental status (AMS) and to evaluate whether such criteria predict a final diagnosis of presence or absence of opiate overdose as accurately as response to naloxone.
CASES AND SETTING: Seven hundred thirty patients with AMS who received naloxone for diagnostic or therapeutic purposes at the discretion of two large, urban, paramedic base teaching hospitals.
METHODS: We reviewed paramedic run sheets and audiotapes on all 730 patients as well as available hospital records of all patients who demonstrated any response to naloxone to determine whether overdose was responsible for their clinical presentations. We also reviewed hospital records for a selected sample of naloxone nonresponders.
MAIN RESULTS AND CONCLUSION: Only 25 patients (3.4%) demonstrated a complete response to naloxone, whereas 32 (4.4%) manifested a partial or equivocal response. Nineteen of 25 complete responders (76%), two of 26 partial responders (8%) (with known final diagnosis), and four of 195 non-responders (2%) (with known final diagnosis) were ultimately diagnosed as having overdosed. Respirations of 12 or less or the presence of any one of the three clinical findings as a group were each highly sensitive in predicting response to naloxone, and at least as sensitive as response to naloxone in predicting a diagnosis of opiate overdose. Selective administration of naloxone for AMS would have decreased the use of this drug by 75% to 90% while still administering it to virtually all naloxone responders who had a final diagnosis of opiate overdose.

PMID 1996818  Ann Emerg Med. 1991 Mar;20(3):246-52.
著者: G Randall Bond
雑誌名: Ann Emerg Med. 2002 Mar;39(3):273-86.
Abstract/Text Gastrointestinal decontamination has been practiced for hundreds of years; however, only in the past few years have data emerged that demonstrate a clinical benefit in some patients. Because most potentially toxic ingestions involve agents that are not toxic in the quantity consumed, the exact circumstances in which decontamination is beneficial and which methods are most beneficial in those circumstances remain important topics of research. Maximum benefit from decontamination is expected in patients who present soon after the ingestion. Unfortunately, many overdose patients present at least 2 hours after taking a medication, when most of the toxin has been absorbed or has moved well into the intestine, beyond the expected reach of gastrointestinal decontamination. Decontamination probably does not contribute to the outcome of many such patients, especially those without symptoms. However, if absorption has been delayed or gastrointestinal motility has been slowed, activated charcoal may reduce the final amount absorbed. The use of activated charcoal in these cases may be beneficial and is associated with few complications. Therefore, administration of activated charcoal is recommended as soon as possible after emergency department presentation, unless the agent and quantity are known to be nontoxic, the agent is known not to adsorb to activated charcoal, or the delay has been so long that absorption is probably complete. The use of gastric emptying in addition to activated charcoal has generated intense debate. Several large comparative studies have failed to demonstrate a benefit of gastric emptying before activated charcoal. Because complications of such 2-step decontamination include a higher rate of intubation, aspiration, and ICU admission, gastric emptying in addition to activated charcoal cannot be considered the routine approach to patients. However, there are several infrequent circumstances in which the data are inadequate to accurately assess the potential benefit of gastric emptying in addition to activated charcoal: symptomatic patients presenting in the first hour after ingestion, symptomatic patients who have ingested agents that slow gastrointestinal motility, patients taking sustained release medications, and those taking massive or life-threatening amounts of medication. These circumstances represent only a small subset of ingestions. In the absence of convincing data about benefit or lack of benefit of gastric emptying for these patients, individual physicians must act on a personal valuation: Is it better to use a treatment that might have some benefit but definitely has some risk or not to use a treatment that has any risk unless there is proven benefit?

PMID 11867980  Ann Emerg Med. 2002 Mar;39(3):273-86.
著者: K S Merigian, M Woodard, J R Hedges, J R Roberts, R Stuebing, M C Rashkin
雑誌名: Am J Emerg Med. 1990 Nov;8(6):479-83. doi: 10.1016/0735-6757(90)90146-q.
Abstract/Text The authors prospectively studied the effect of gastric emptying (GE) and activated charcoal (AC) upon clinical outcome in acutely self-poisoned patients. Presumed overdose patients (n = 808) were treated using an alternate day protocol based on a 10-question cognitive function examination and presenting vital sign parameters. Asymptomatic patients (n = 451) did not receive GE. AC was administered to asymptomatic patients only on even days. GE in the remaining symptomatic patients (n = 357) was performed only on even days. On emptying days, alert patients had ipecac-induced emesis while obtunded patients received gastric lavage. AC therapy followed gastric emptying. On nonemptying days, symptomatic patients were treated only with AC. No clinical deterioration occurred in the asymptomatic patients treated without GE. AC use did not alter outcome measures in asymptomatic patients. GE procedures in symptomatic patients did not significantly alter the length of stay in the emergency department, mean length of time intubated, or mean length of stay in the intensive care unit. Gastric lavage was associated with a higher prevalence of medical intensive care unit admissions (P = .0001) and aspiration pneumonia (P = .0001). The data support the management of selected acute overdose patients without GE and fail to show a benefit from AC in asymptomatic overdose patients.

PMID 1977400  Am J Emerg Med. 1990 Nov;8(6):479-83. doi: 10.1016/0735・・・

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