■在神经系统受累(中枢神经系统[CNS]疟疾)的疟疾中幸存下来的儿童中有三分之一会出现后遗症。较高的最高温度(Tmax)和癫痫发作是后遗症的危险因素。
■比较使用对乙酰氨基酚和布洛芬的积极退热治疗与仅在38.5°C或更高温度下单独给予对乙酰氨基酚的常规治疗。
这项随机临床试验是在赞比亚的1个三级护理和1个地区医院以及马拉维的一个三级护理中心的住院儿科服务中进行的。包括2至11岁的中枢神经系统疟疾儿童(不包括肌酐>1.2mg/dL的儿童),他们从2019年到2022年注册。数据分析于2022年12月至2023年4月进行。
■积极退热组接受对乙酰氨基酚(30mg/kg负荷,然后15毫克/千克)加布洛芬,10mg/kg,每6小时,无论临床温度为72小时。常规护理组在38.5°C或更高的温度下每6小时根据需要接受15mg/kg对乙酰氨基酚。
■主要结果变量是72小时内的Tmax,随访的总持续时间。次要结果包括癫痫发作和寄生虫清除。
■对553名患者进行了筛查,226(40.9%)不合格,和57(10.3%)下跌。总共256名参与者(n=128/组)的平均(SD)年龄为4.3(2.1)岁;115(45%)为女性,141(55%)为男性。积极退热组的Tmax较低,38.6与39.2°C(差异,-0.62°C;95%CI,-0.82至-0.42;P<.001)并且经历多次或长时间癫痫发作的几率较低,常规护理组10名(8%)vs34名儿童(27%)(比值比[OR],0.26;95%CI,0.12至0.56)。未检测到寄生虫清除时间的组间差异。40名儿童(15%)发生严重不良事件,常规护理组中25例(20%),积极退热组中15例(12%),包括13例死亡(10[8%]和3[2%],分别)。肌酐升高导致常规治疗组的8名儿童(6%)和积极退热组的13名儿童(10%)的研究药物停药(OR,1.74;95%CI,0.63至5.07)。
■这项研究发现,在先前的观察性研究中,积极的解热治疗可将无神经损伤儿童的平均Tmax降低至与Tmax相当的温度水平,并改善急性癫痫发作的结局,而没有寄生虫血症的延长。
■ClinicalTrials.gov标识符:NCT03399318。
UNASSIGNED: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae.
UNASSIGNED: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher.
UNASSIGNED: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023.
UNASSIGNED: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher.
UNASSIGNED: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance.
UNASSIGNED: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07).
UNASSIGNED: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03399318.