OBJECTIVES: To evaluate the evidence for the effectiveness of clonidine, when given as a premedication, in reducing postoperative pain in children less than 18 years of age. We also sought evidence of any clinically significant side effects.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 12, 2012), Ovid MEDLINE (1966 to 21 December 2012) and Ovid EMBASE (1982 to 21 December 2012), as well as reference lists of other relevant articles and online trial registers.

SELECTION CRITERIA: We included all randomized (or quasi-randomized), controlled trials comparing clonidine premedication to placebo, a higher dose of clonidine, or another agent when used for surgical or other invasive procedures in children under the age of 18 years and where pain or a surrogate (principally the need for supplementary analgesia) was reported.

DATA COLLECTION AND ANALYSIS: Two authors independently performed the database search, decided on the inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved any differences between their results by discussion. The data were entered into RevMan 5 for analyses and presentation. Sensitivity analyses were performed, as appropriate, to exclude studies with a high risk of bias.

MAIN RESULTS: We identified 11 trials investigating a total of 742 children in treatment arms relevant to our study question. Risks of bias in the studies were mainly low or unclear, but two studies had aspects of their methodology that had a high risk of bias. Overall, the quality of the evidence from pooled studies was low or had unclear risk of bias. Four trials compared clonidine with a placebo or no treatment, six trials compared clonidine with midazolam, and one trial compared clonidine with fentanyl. There was substantial methodological heterogeneity between trials; the dose and route of clonidine administration varied as did the patient populations, the types of surgery and the outcomes measured. It was therefore difficult to combine the outcomes of some trials for meta-analysis.When clonidine was compared to placebo, pooling studies of low or unclear risk of bias, the need for additional analgesia was reduced when clonidine premedication was given orally at 4 µg/kg (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.11 to 0.51). Only one small trial (15 patients per arm) compared clonidine to midazolam for the same outcome; this also found a reduction in the need for additional postoperative analgesia (RR 0.25, 95% CI 0.09 to 0.71) when clonidine premedication was given orally at 2 or 4 µg/kg compared to oral midazolam at 0.5 mg/kg. A trial comparing oral clonidine at 4 µg/kg with intravenous fentanyl at 3 µg/kg found no statistically significant difference in the need for rescue analgesia (RR 0.89, 95% CI 0.56 to 1.42). When clonidine 4 µg/kg was compared to clonidine 2 µg/kg, there was a statistically significant difference in the number of patients requiring additional analgesia, in favour of the higher dose, as reported by a single, higher-quality trial (RR 0.38, 95% CI 0.23 to 0.65).The effect of clonidine on pain scores was hard to interpret due to differences in study methodology, the doses and route of drug administration, and the pain scale used. However, when given at a dose of 4 µg/kg, clonidine may have reduced analgesia requirements after surgery. There were no significant side effects of clonidine that were reported such as severe hypotension, bradycardia, or excessive sedation requiring intervention. However, several studies used atropine prophylactically with the aim of preventing such adverse effects.

METHODS: Currently available indicators from both household and facility surveys were collated through publicly available global databases and respective survey instruments. We then developed a suite of potential indicators and associated data points for the 45 WHO Essential Interventions spanning preconception to newborn care. Four types of performance indicators were identified (where applicable): process (i.e. coverage) and outcome (i.e. impact) indicators for both screening and treatment/prevention. Indicators were evaluated by an international expert panel against the eRegistries indicator evaluation criteria and further refined based on feedback by the eRegistries technical team.

RESULTS: Of the 45 WHO Essential Interventions, only 16 were addressed in any of the household survey data available. A set of 216 potential indicators was developed. These indicators were generally evaluated favourably by the panel, but difficulties in data ascertainment, including for outcome measures of cause-specific morbidity and mortality, were frequently reported as barriers to the feasibility of indicators. Indicators were refined based on feedback, culminating in the final list of 193 total unique indicators: 93 for preconception and antenatal care; 53 for childbirth and postpartum care; and 47 for newborn and small and ill baby care.