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.


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


METHODS
We performed a literature search according to the Cochrane Neonatal Review Group search strategy. Randomised and quasi-randomised controlled trials of intravenous midazolam use in neonates were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2012), MEDLINE (1985 to 2012), EMBASE (1980 to 2012), CINAHL (1981 to 2012), reference lists of published studies, personal files, and abstracts published in The Pediatric Academic Societies Meeting Abstract Archives from 1990 to 2011.


METHODS
Randomised and quasi-randomised controlled trials of intravenous midazolam infusion in infants aged 28 days or less for sedation were selected for review.


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


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 neurological events (death, grade III or 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.


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.
Aubrey andMarla Dan ProgramforHigh RiskMothers and Babies, SunnybrookHealth Sciences Centre, Toronto, Canada. eugene.ng@sunnybrook.ca.
Eugene
E
Ng
Anna
A
Taddio
Arne
A
Ohlsson
D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007363:Intensive Care Units, Neonatal; D015931:Intensive Care, Neonatal; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic
D006993:Hypnotics and Sedatives; D008874:Midazolam