BACKGROUND & AIMS:
BACKGROUND:Although routine administration of pharmacologic sedation or analgesia during mechanical ventilation in preterm neonates is not recommended, its use in clinical practice remains common. Alpha-2 agonists, mainly clonidine and dexmedetomidine, are used as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. Clonidine has not been systematically assessed for use in neonatal sedation during ventilation.
OBJECTIVES:To assess whether clonidine administered to term and preterm newborn infants receiving mechanical ventilation reduces morbidity and mortality rates. To compare the intervention versus placebo, no treatment, and dexmedetomidine; and to assess the safety of clonidine infusion for potential harms.To perform subgroup analyses according to gestational age; birth weight; administration method (infusion or bolus therapy); dose, duration, and route of clonidine administration; and pharmacologic sedation as a co-intervention.
SEARCH METHODS:We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) in the Cochrane Library, MEDLINE via PubMed (1966 to January 10, 2017), Embase (1980 to January 10, 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 10, 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA:We searched for randomized controlled trials, quasi-randomized controlled trials, and cluster trials comparing clonidine versus placebo, no treatment, or dexmedetomidine administered to term and preterm newborns receiving mechanical ventilation via an endotracheal tube.
DATA COLLECTION AND ANALYSIS:For the included trial, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, all-cause death during initial hospitalization, duration of respiratory support, sedation scale, duration of hospital stay) and assessed risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). This review considered primary outcomes of all-cause neonatal death, all-cause death during initial hospitalization, and duration of mechanical ventilation in days.
MAIN RESULTS:One trial, which included 112 infants, met the inclusion criteria for this review. Term newborn infants on mechanical ventilation with the need for continuous analgesia and sedation with fentanyl and midazolam were eligible for enrollment during the first 96 hours of ventilation. Study authors administered clonidine 1 μg/kg/h or placebo on day 4 after intubation.We found no differences between the two groups in all-cause death during hospitalization (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.12 to 3.98). The quality of the evidence supporting these findings is low owing to imprecision of the estimates (one study; few events). The median (interquartile range) duration of mechanical ventilation was 7.1 days (5.7 to 9.1 days) in the clonidine group and 5.8 days (4.9 to 7.9 days) in the placebo group, respectively (P = 0.070). Among secondary outcomes, we found no differences in terms of duration of stay in the intensive care unit. Sedation scale values (COMFORT) and analgesia scores (Hartwig) during the first 72 hours of infusion of study medication were lower in the clonidine group than in the placebo group.
AUTHORS' CONCLUSIONS:At present, evidence is insufficient to show the efficacy and safety of clonidine for sedation and analgesia in term and preterm newborn infants receiving mechanical ventilation.
背景与目标:
背景:尽管不建议早产儿在机械通气期间常规使用药物镇静或镇痛,但其在临床实践中仍很普遍。 Alpha-2激动剂(主要是可乐定和右美托咪定)与阿片类药物和苯二氮卓类药物一起用作辅助(或替代)镇静剂。未对可乐定在通气期间用于新生儿镇静方面进行系统评估。
目的:评估可乐定对接受机械通气的足月和早产儿是否可降低发病率和死亡率。比较介入治疗与安慰剂,未治疗和右美托咪定;根据孕龄进行亚组分析;并评估可乐定输注对潜在危害的安全性。出生体重;给药方法(输注或推注治疗);可乐定的剂量,给药时间和给药途径;和药物镇静作为共同干预。
搜索方法:我们使用Cochrane新生儿审查小组的标准搜索策略通过MedMed(1966年至2017年1月10日)在MEDLINE的Cochrane图书馆中搜索对照试验的Cochrane中央登记册(CENTRAL; 2016年第12期)。 (1980年至2017年1月10日),以及护理和相关健康文献的累积索引(CINAHL; 1982年至2017年1月10日)。我们还搜索了临床试验数据库,会议记录以及检索到的文章的参考文献清单,以进行随机对照试验和准随机试验。
选择标准:我们搜索了比较可乐定与安慰剂,未治疗或右美托咪定经气管插管接受机械通气的足月和早产新生儿的随机对照试验,半随机对照试验和聚类试验。
数据收集和分析:对于纳入的试验,两名评价作者独立提取数据(例如,受试者人数,出生体重,胎龄,首次住院期间的全因死亡,呼吸支持的持续时间,镇静量表,住院时间)和评估偏倚的风险(例如随机性是否足够,致盲,随访是否完整)。该评价考虑了全因新生儿死亡,初次住院期间全因死亡以及几天内的机械通气持续时间的主要结局。
主要结果:一项试验,包括112例婴儿,符合本评价的纳入标准。有机械通气的足月新生儿需要连续镇痛并用芬太尼和咪达唑仑镇静时,可在通气的前96个小时内入组。研究作者在插管后第4天给予可乐定1μg/ kg / h或安慰剂。我们发现两组住院期间全因死亡之间没有差异(风险比[RR] 0.69,95%置信区间[CI] 0.12至3.98)。由于估算的不精确性,支持这些发现的证据质量很低(一项研究;很少发生的事件)。可乐定组机械通气的中位(四分位间距)持续时间分别为7.1天(5.7至9.1天)和安慰剂组为5.8天(4.9至7.9天)(P = 0.070)。在次要结果中,我们发现重症监护病房的住院时间没有差异。可乐定组输注研究药物的前72小时内的镇静标度值(COMFORT)和镇痛评分(Hartwig)低于安慰剂组。
作者的结论:目前,没有足够的证据表明可乐定在接受机械通气的足月和早产儿镇静和镇痛中的有效性和安全性。