Blake K V, Bailey D, Zientek G M, Hendeles L
College of Pharmacy, Division of Pediatric Pharmacology/Toxicology, University of Florida, Gainesville.
Clin Pharm. 1988 May;7(5):391-7.
A case of long-term acetaminophen overdosage in a six-year-old child, which contributed to her death despite optimal medical management including oral acetylcysteine therapy, is reported. Acetaminophen 325 mg every six hours was prescribed for fever associated with measles. Believing that acetaminophen was nontoxic, the child's mother progressively increased the dose over three days, first in response to fever and subsequently for abdominal pain probably secondary to unrecognized acetaminophen toxicity. On admission to the hospital, the patient's serum acetaminophen concentration was 163 micrograms/mL (11 hours after the last dose); subsequently, the acetaminophen half-life was determined to be 15 hours. A course of oral acetylcysteine therapy (a loading dose of 140 mg/kg as the sodium salt followed by 70 mg/kg every four hours for 17 doses) was begun. Hepatic and renal failure developed within two days, followed by the onset of seizures, and brain death occurred on the 11th day. Autopsy findings consistent with acetaminophen toxicity included centrilobular hepatic and renal tubular necrosis. Aspergillis fumigatus and Cryptococcus neoformans isolates from pulmonary abscesses and bronchopulmonary lymph nodes, respectively, were an unexpected finding. However, in the absence of acetaminophen overdosage, death would have been unlikely. Cryptococcal lymphadenitis was believed to have been the initial febrile illness that was treated with supratherapeutic doses of acetaminophen. Fatalities in children from a single overdose of acetaminophen have been rare, and there is only one previous report of a fatality after long-term administration of multiple excessive doses. The lethal outcome in this case illustrates the need to educate the public on the potential toxicity of nonprescription medications.
报告了一例6岁儿童长期过量服用对乙酰氨基酚的病例,尽管采取了包括口服乙酰半胱氨酸治疗在内的最佳医疗措施,该儿童仍不幸死亡。患儿因麻疹发热,医生开具了每6小时服用325毫克对乙酰氨基酚的处方。患儿母亲认为对乙酰氨基酚无毒,在三天内逐渐增加剂量,起初是为了应对发热,后来是因为可能由未被识别的对乙酰氨基酚毒性引起的腹痛。入院时,患者血清对乙酰氨基酚浓度为163微克/毫升(最后一剂后11小时);随后,对乙酰氨基酚的半衰期被确定为15小时。开始了一个疗程的口服乙酰半胱氨酸治疗(以钠盐形式给予140毫克/千克的负荷剂量,随后每4小时给予70毫克/千克,共17剂)。两天内出现肝肾功能衰竭,随后发生癫痫发作,第11天出现脑死亡。尸检结果与对乙酰氨基酚毒性相符,包括小叶中心性肝坏死和肾小管坏死。分别从肺脓肿和支气管肺淋巴结分离出烟曲霉和新型隐球菌,这是一个意外发现。然而,如果没有过量服用对乙酰氨基酚,死亡不太可能发生。据信,隐球菌性淋巴结炎是最初的发热疾病,患儿接受了超治疗剂量的对乙酰氨基酚治疗。单次过量服用对乙酰氨基酚导致儿童死亡的情况很少见,之前仅有一例长期多次过量服用后死亡的报告。该病例的致命结局表明有必要对公众进行非处方药潜在毒性的教育。