Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit

Cochrane Review by Ng E, Taddio A, Ohlsson A

This record should be cited as: Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002052. DOI: 10.1002/14651858.CD002052.

ABSTRACT

Title

Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit

Background

Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short acting benzodiazepine that is increasingly used in neonatal intensive care units (NICU). However, its effectiveness as a sedative in neonates has not been systematically evaluated.

Objectives

To determine whether intravenous midazolam infusion is an effective sedative, as evaluated by behavioural and/or physiologic measurements, for critically ill neonates undergoing intensive care and to assess clinically significant short and long-term adverse effects associated with its use.

Search strategy

We performed the literature search according to the Cochrane Neonatal Review Group search strategy. Randomized and quasirandomized controlled trials of intravenous midazolam use in neonates were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2009),MEDLINE (1985 to 2009), EMBASE (1980 to 2009), CINAHL (1981 to 2009), reference lists of published studies, personal files, and abstracts published in Pediatric Research from 1990 to 2009.

Selection criteria

Randomized and quasi-randomized controlled trials of intravenous midazolam infusion in infants less than or equal to 28 days of age for sedation were selected for review.

Data collection and analysis

Data regarding the primary outcome of level of sedation were abstracted. Secondary outcomes such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), death, length of NICU stay, and adverse effects associated with midazolam were assessed. When appropriate, meta-analyses were performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (95% CI) for categorical variables and weighted mean difference (WMD) for continuous variables.

Main results

Three trials were included in the review. Using different sedation scales, each study showed a statistically significantly higher sedation level in the midazolam group compared to the placebo group. However, since none of the sedation scales used have been validated in preterm infants, the effectiveness of midazolam in this population could not be ascertained. One study showed a statistically significant higher incidence of adverse neurologic events (death, grade III-IV IVH, PVL), and meta-analysis of data from two studies showed a statistically significant longer duration of NICU stay in the midazolam group compared to the placebo group.

Authors' conclusions

There are insufficient data to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.

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