Poisoning

Poisoning is a clinical condition caused by exposure to a drug, chemical, natural toxin or gas in an amount that injures the body中毒是因接触药物、化学品、天然毒素或气体并达到损害机体的剂量而导致的临床状态。

It may be acute or chronic, unintentional or intentional, and ranges from mild symptoms to multi-organ failure and death中毒可为急性或慢性、非故意或故意，表现从轻微症状到多器官衰竭与死亡不等。

Diagnosis combines exposure history, toxidrome recognition and targeted laboratory testing, while treatment relies on resuscitation, decontamination, antidotes and enhanced elimination诊断结合暴露史、中毒综合征识别与针对性实验室检查，治疗则依赖复苏、去污染、解毒剂与增强清除。

Terminology and classification

• Poisoning is the toxic effect produced by a substance, whereas overdose means exposure above the therapeutic dose and an adverse drug reaction occurs at a therapeutic dose中毒是物质产生的毒性效应，过量指超过治疗剂量的暴露，而药物不良反应发生在治疗剂量下。^[1]
• Intoxication and toxic exposure are common synonyms, and the route may be ingestion, inhalation, injection, dermal absorption or ocular contact中毒与毒物暴露是常用同义词，暴露途径可为摄入、吸入、注射、皮肤吸收或眼部接触。^[1]
• A toxidrome is a recognisable constellation of signs caused by a class of poisons acting on a specific receptor or enzyme, such as the opioid or antimuscarinic toxidrome中毒综合征是一组由特定受体或酶作用毒物引起的可识别体征组合，例如阿片类或抗胆碱能中毒综合征。^[2]
• ICD-10 codes poisoning by drugs, medicaments and biological substances within T36–T50 and toxic effects of chiefly nonmedicinal substances within T51–T65, with external-cause codes recording intent《国际疾病分类》第十版将药物、药品与生物物质中毒编码于 T36–T50，将主要为非药用物质的中毒效应编码于 T51–T65，并用外因编码记录意图。^[1]
• ICD-11 groups the same clinical territory in the block NE60–NE6Z, covering harmful effects of drugs, medicinal substances, nonmedicinal noxious substances and unspecified substances《国际疾病分类》第十一版将同一临床范围归入 NE60–NE6Z 区块，涵盖药物、药用物质、非药用有害物质与未特指物质的有害效应。^[2]
• Cross-references include MeSH D011041, MONDO:0029000 and Wikidata Q114953, which link poisoning to toxicology, injury-prevention and public-health datasets交叉参照包括 MeSH D011041、MONDO:0029000 与 Wikidata Q114953，将中毒与毒理学、伤害预防及公共卫生数据集关联。^[2]

History

• The first poison control centre in the United States opened in Chicago in 1953, and the American Association of Poison Control Centers was founded in 1958 to coordinate advice and data collection美国首个中毒控制中心于1953年在芝加哥成立，美国中毒控制中心协会于1958年成立，以协调咨询与数据收集。^[3]
• Naloxone was developed in the early 1960s and approved for opioid overdose in 1971, becoming the prototype receptor antagonist used in emergency toxicology纳洛酮于二十世纪六十年代初研发，1971年获批用于阿片类过量，成为急诊毒理学中的原型受体拮抗剂。^[4]
• Fomepizole was approved in 1997 for methanol and ethylene glycol poisoning and later replaced ethanol as the preferred antidote in many centres甲吡唑于1997年获批用于甲醇与乙二醇中毒，后来在许多中心取代乙醇成为首选解毒剂。^[5]
• The American Academy of Clinical Toxicology published practice guidelines for methanol poisoning in 2002, recommending fomepizole, folinic acid, bicarbonate and selective haemodialysis美国临床毒理学会于2002年发布甲醇中毒实践指南，推荐甲吡唑、亚叶酸、碳酸氢钠与选择性血液透析。^[5]
• Intravenous N-acetylcysteine was approved in 2004, standardising treatment for acetaminophen poisoning across hospitals that had previously used oral regimens静脉用乙酰半胱氨酸于2004年获批，使此前采用口服方案的医院在乙酰氨基酚中毒治疗上实现标准化。^[1]
• The EXTRIP workgroup published systematic recommendations from 2012 onward, including lithium in 2015, and its advice now shapes decisions about haemodialysis for dialysable poisonsEXTRIP 工作组自2012年起陆续发表系统推荐，其中包括2015年的锂中毒推荐，其意见现已成为可透析毒物血液净化决策的重要依据。^[6]

Epidemiology

• Unintentional poisoning causes an estimated 193,000 deaths and almost 11 million disability-adjusted life years each year, accounting for about 8 per cent of non-transport unintentional injury deaths非故意中毒每年约造成19.3万例死亡与近1100万伤残调整生命年损失，约占非交通类非故意伤害死亡的8%。^[7]
• About 84 per cent of these deaths occur in low- and middle-income countries, where pesticide availability, weak regulation and limited intensive care amplify risk其中约84%的死亡发生在低中等收入国家，农药可及性、监管薄弱与重症监护资源有限放大了风险。^[7]
• The 2022 National Poison Data System report recorded 2,064,875 human exposures, 50,381 animal exposures and 3,255 human deaths, of which 2,622 were judged related to the exposure2022年国家中毒数据系统报告记录了2,064,875例人类暴露、50,381例动物暴露与3,255例人类死亡，其中2,622例被判定与暴露相关。^[3]
• About 76.4 per cent of 2022 exposures were unintentional, and the leading substance classes were analgesics, household cleaning products, antidepressants, cosmetics and antihistamines2022年约76.4%的暴露为非故意，主要物质类别为镇痛药、家用清洁剂、抗抑郁药、化妆品与抗组胺药。^[3]
• Fatal pesticide self-poisoning caused approximately 110,000 deaths per year between 2010 and 2014, or 13.7 per cent of global suicides, with a sensitivity estimate of 168,000 deaths2010年至2014年间，致死性农药自服每年约造成11万例死亡，占全球自杀的13.7%，敏感性估计可达16.8万例。^[8]
• Carbon monoxide poisoning affects about 50,000 people each year in the United States, has a mortality of 1–3 per cent and leaves 15–40 per cent of survivors with long-term neurocognitive deficits美国每年约5万人发生一氧化碳中毒，病死率为1%至3%，15%至40%的存活者遗留长期神经认知缺陷。^[9]

Pathophysiology

• Most poisons follow a dose-response relationship, and their clinical effect depends on absorbed dose, route, latency, metabolism, distribution and elimination多数毒物遵循剂量-反应关系，其临床效应取决于吸收剂量、途径、潜伏期、代谢、分布与清除。^[1]
• Opioid agonists activate mu receptors and cause miosis, respiratory depression and coma, whereas sympathomimetics produce tachycardia, hypertension, mydriasis, agitation and hyperthermia阿片受体激动剂激活 mu 受体，引起瞳孔缩小、呼吸抑制与昏迷，拟交感物质则导致心动过速、高血压、瞳孔散大、躁动与高热。^[2]
• Antimuscarinic poisons block muscarinic receptors and cause dry flushed skin, mydriasis, delirium, urinary retention and ileus, while cholinergic poisons produce salivation, lacrimation, urination, diarrhoea, bradycardia and bronchorrhoea抗胆碱能毒物阻断毒蕈碱受体，引起皮肤干燥潮红、瞳孔散大、谵妄、尿潴留与肠麻痹，胆碱能毒物则导致流涎、流泪、排尿、腹泻、心动过缓与支气管分泌增多。^[2]
• Serotonergic excess causes clonus, hyperreflexia, hyperthermia and agitation, whereas GABAergic sedatives cause CNS and respiratory depressionnicotinic poisoning causes fasciculations, weakness and paralysis 5-羟色胺过量引起阵挛、反射亢进、高热与躁动，GABA 能镇静剂引起中枢与呼吸抑制，烟碱型中毒则导致肌束颤动、无力与麻痹。^[2]
• Acetaminophen is metabolised to the reactive metabolite NAPQI, which depletes glutathione and binds hepatic proteins, causing centrilobular necrosis once stores are exhausted对乙酰氨基酚代谢为反应性中间产物 NAPQI，后者耗竭谷胱甘肽并与肝蛋白结合，储备耗尽后导致小叶中央坏死。^[1]
• Methanol and ethylene glycol are oxidised by alcohol dehydrogenase to formic acid and glycolic acid, producing metabolic acidosis, visual loss and renal injury, while carbon monoxide and cyanide block mitochondrial respiration甲醇与乙二醇经醇脱氢酶氧化为甲酸与乙醇酸，引起代谢性酸中毒、视力丧失与肾损伤，一氧化碳与氰化物则阻断线粒体呼吸。^[5]

Clinical features

• Common early features include nausea, vomiting, abdominal pain, dizziness, altered mental status, tachycardia, hypotension and metabolic acidosis, but none is specific to a single poison常见早期表现包括恶心、呕吐、腹痛、头晕、意识改变、心动过速、低血压与代谢性酸中毒，但均非某一毒物特异。^[1]
• The opioid toxidrome combines miosis, respiratory depression and CNS depression, and the antimuscarinic toxidrome combines dry skin, flushing, mydriasis and delirium阿片类中毒综合征表现为瞳孔缩小、呼吸抑制与中枢抑制，抗胆碱能中毒综合征则表现为皮肤干燥、潮红、瞳孔散大与谵妄。^[2]
• Organophosphate poisoning produces the cholinergic syndrome with bradycardia, bronchorrhoea, miosis, sweating and fasciculations, and severe cases develop respiratory failure有机磷中毒产生胆碱能综合征，表现为心动过缓、支气管分泌增多、瞳孔缩小、出汗与肌束颤动，重症可发生呼吸衰竭。^[2]
• Carbon monoxide poisoning causes headache, dizziness, syncope, chest pain and coma, and delayed leukoencephalopathy may appear days to weeks after apparent recovery一氧化碳中毒引起头痛、头晕、晕厥、胸痛与昏迷，迟发性脑白质病可在看似恢复后数日至数周出现。^[9]
• Serious complications include aspiration pneumonitis, acute respiratory distress syndrome, acute kidney injury, rhabdomyolysis, hepatic failure, arrhythmia, cardiac arrest and hypoxic brain injury严重并发症包括误吸性肺炎、急性呼吸窘迫综合征、急性肾损伤、横纹肌溶解、肝衰竭、心律失常、心脏骤停与缺氧性脑损伤。^[1]
• Children, older adults, pregnant patients and people with cardiorespiratory or renal disease are at higher risk of severe outcomes at lower exposure doses儿童、老年人、孕妇以及合并心肺或肾脏疾病者在较低暴露剂量下即面临更高的重症风险。^[3]

Diagnosis

• Assessment begins with a structured history of substances, dose, route, time, co-ingestants, intent and access to medications, supplemented by a full examination and repeated vital signs评估始于结构化病史，包括物质、剂量、途径、时间、共同摄入、意图与药物可及性，并辅以完整体格检查与反复生命体征监测。^[1]
• A 12-lead ECG is essential because QRS widening suggests sodium-channel blockade by tricyclic antidepressants and QT prolongation predicts arrhythmic risk十二导联心电图至关重要，因为 QRS 增宽提示三环类抗抑郁药阻断钠通道，QT 延长预示心律失常风险。^[1]
• Targeted tests include acetaminophen and salicylate concentrations, blood gas, electrolytes, renal and liver function, creatine kinase, lactate and, when indicated, specific drug levels针对性检查包括对乙酰氨基酚与水杨酸浓度、血气、电解质、肝肾功能、肌酸激酶、乳酸，以及必要时的特定药物浓度。^[1]
• An elevated anion gap suggests poisoning by methanol, ethylene glycol, salicylate or other organic acids, and an osmolal gap supports toxic alcohol exposure before metabolism is complete阴离子间隙升高提示甲醇、乙二醇、水杨酸或其他有机酸中毒，渗透压间隙则支持代谢尚未完成的毒性醇类暴露。^[5]
• Carboxyhaemoglobin measurement by multi-wavelength co-oximetry is required for suspected carbon monoxide poisoning, because standard pulse oximetry cannot distinguish carboxyhaemoglobin from oxyhaemoglobin疑似一氧化碳中毒需用多波长血氧分析仪测定碳氧血红蛋白，因为标准脉搏血氧饱和度无法区分碳氧血红蛋白与氧合血红蛋白。^[9]
• The differential diagnosis includes stroke, sepsis, hypoglycaemia, seizure, alcohol withdrawal, serotonin syndrome, neuroleptic malignant syndrome, psychiatric illness and metabolic disorders鉴别诊断包括卒中、脓毒症、低血糖、癫痫发作、酒精戒断、5-羟色胺综合征、抗精神病药恶性综合征、精神疾病与代谢性疾病。^[2]

Management

• Initial management follows the ABCDE approach with airway protection, oxygenation, ventilation, circulatory support and correction of hypoglycaemia, seizures and hyperthermia初始处理遵循 ABCDE 方法，包括气道保护、氧合、通气、循环支持以及低血糖、癫痫与高热的纠正。^[1]
• Dermal and ocular exposure require immediate removal of contaminated clothing and copious irrigation, while inhalation exposure requires removal from the source and supplemental oxygen皮肤与眼部暴露需立即脱去污染衣物并大量冲洗，吸入暴露则需脱离污染源并给予补充氧气。^[1]
• Activated charcoal may reduce absorption if given within about one hour of ingestion in a patient with a protected airway, but it is contraindicated for corrosives, hydrocarbons and unprotected vomiting在摄入约一小时内有气道保护的患者中，活性炭可减少吸收，但腐蚀性物质、烃类与无气道保护的呕吐患者禁用。^[1]
• Naloxone reverses opioid-induced respiratory depression, N-acetylcysteine replenishes glutathione in acetaminophen poisoning, and fomepizole blocks alcohol dehydrogenase in toxic alcohol poisoning纳洛酮逆转阿片类所致呼吸抑制，乙酰半胱氨酸在对乙酰氨基酚中毒中补充谷胱甘肽，甲吡唑在毒性醇类中毒中阻断醇脱氢酶。^[4]
• Sodium bicarbonate is used for tricyclic-induced sodium-channel blockade and for alkalinisation in salicylate poisoning, while atropine and pralidoxime treat organophosphate poisoning碳酸氢钠用于三环类药物所致钠通道阻滞及水杨酸中毒的碱化治疗，阿托品与解磷定用于有机磷中毒。^[1]
• Hydroxocobalamin binds cyanide, digoxin immune Fab neutralises digoxin, and intravenous lipid emulsion is reserved for severe cardiotoxicity from lipophilic drugs羟钴胺结合氰化物，地高辛免疫 Fab 中和地高辛，静脉脂肪乳剂则保留用于亲脂性药物所致严重心脏毒性。^[1]
• Haemodialysis is recommended for severe methanol, ethylene glycol, lithium and salicylate poisoning, and EXTRIP provides substance-specific thresholds and stop criteria血液透析推荐用于严重甲醇、乙二醇、锂与水杨酸中毒，EXTRIP 提供了各物质的特异性阈值与停止标准。^[6]
• Prevention includes child-resistant packaging, safe storage, carbon monoxide detectors, poison-centre access, naloxone distribution and restriction of highly toxic pesticides预防包括儿童安全包装、安全储存、一氧化碳报警器、中毒中心可及性、纳洛酮分发以及高毒农药的限制。^[8]

Research and controversies

• New evidence suggests that fomepizole may have indications beyond toxic alcohols, including acetaminophen poisoning, while L-carnitine and naloxone are being studied for broader uses新证据提示甲吡唑可能具有超出毒性醇类的适应证，包括对乙酰氨基酚中毒，而左卡尼汀与纳洛酮正在研究更广泛的用途。^[4]
• Engineered haemoglobin-like CO scavengers are being developed as the first specific antidotes for carbon monoxide poisoning, which currently relies on oxygen and supportive care工程化类血红蛋白一氧化碳清除剂正在研发，作为一氧化碳中毒的首个特异性解毒剂，目前治疗仍依赖氧气与支持治疗。^[10]
• Better bedside and laboratory tools are needed to distinguish overlapping toxidromes and to detect co-ingestions that alter prognosis and antidote choice需要更好的床旁与实验室工具来区分重叠的中毒综合征，并识别会改变预后与解毒剂选择的共同摄入。^[2]
• Pesticide regulation, lethal-means restriction and improved access to mental health care are the interventions with the strongest evidence for reducing fatal self-poisoning农药管制、致死手段限制与精神卫生服务可及性改善，是减少致死性自服中毒证据最强的干预措施。^[8]

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