Women’s and Children’s Hospital, Adelaide
Clonidine premedication for postoperative analgesia in children: a meta-analysis
Dr Paul Lambert Dr Nick KnightANZCA-HKCA CSM, May 14th 2011
Women’s and Children’s Hospital, Adelaide
Rationale for reviewClonidine premedication in children
• Postoperative pain• A problem in search of a solution
• Premedication• ? Analgesic efficacy postoperatively• Has a number of other objectives• May have adverse effects• Clonidine may be useful for postoperative
analgesia
• No systematic review, specifically of clonidine's analgesic efficacy, to date
Women’s and Children’s Hospital, Adelaide
Clonidine: Background• α-adrenergic agonist
• Preferential α2 activity
• Useful/desirable characteristics• Analgesic• Sedative• Anxiolytic• Administered via a variety of routes
• Side-effects• Hypotension• Bradycardia• Excessive sedation
Women’s and Children’s Hospital, Adelaide
Clonidine premedication reviewStudy aims
To determine the effects of clonidine premedication, in children, on
postoperative pain
Women’s and Children’s Hospital, Adelaide
Clonidine premedication reviewPrimary Outcomes
•Incidence of analgesia use in • recovery unit• postoperative period
•Incidence of sedation requiring intervention
Women’s and Children’s Hospital, Adelaide
Clonidine premedicationSecondary outcomes
•Analgesia outcomes• Pain-free in PACU• Requiring opioid• Pain scores• Time to first analgesic dose
•Adverse effects• Hypotension or bradycardia• PONV• Shivering• Agitation or confusion• HDU or ICU admission
Women’s and Children’s Hospital, Adelaide
Literature Search•Electronic databases
• Medline, EMBASE, CENTRAL
•Bibliographies of retrieved studies
•Search strategy• Fields
- clinical trials- clonidine- paediatric anaesthesia - pain and other postoperative complications
Women’s and Children’s Hospital, Adelaide
Study (Number of patients) Comparison
Georgiou 1999 (60)Hackmann 2003 (39)Mikawa 1996 (90)Nishina 2000 (125)
Placebo or no treatment
Reimer 1998 (36) Fentanyl
Bergendahl 2004 (100)Cao 2009 (45)Fazi 2001 (134)Kuvaki 1999 (40)Schmidt 2007 (60)
Midazolam
Clonidine premedication: Included studies
Women’s and Children’s Hospital, Adelaide
Description of Studies
• Heterogeneity• Types of comparisons•Dose and route of clonidine•Comparator
• Type of surgery• Outcome measure• Risk of bias
• Primary Outcome Measure• Additional analgesia requirement: Only one study (Riemer 1999) explicitly separates
analgesia use in recovery unit from use on ward
Women’s and Children’s Hospital, Adelaide
Supplementary analgesiaClonidine (any dose) vs placebo or no treatment
Women’s and Children’s Hospital, Adelaide
Supplementary analgesiaLow or high dose clonidine vs placebo or no treatment
Women’s and Children’s Hospital, Adelaide
Clonidine can replace opioid • Reimer 1998
(clonidine 4 µg/kg vs. fentanyl 3 µg/kg):•No difference in opioid requirement
postoperatively (RR 0.89 [0.56-1.42])
• Hackmann 2003 (clonidine 4µg/kg vs. placebo):
•No difference in additional analgesia requirements postoperatively, but more fentanyl given to placebo group intraoperatively
Women’s and Children’s Hospital, Adelaide
Supplementary analgesiaClonidine 4 µg/kg vs midazolam 0.5 mg/kg
Women’s and Children’s Hospital, Adelaide
Study Clonidine dose (µg/kg)Midazolam dose (mg/kg) Route Outcome measures Favours
Bergendahl 2004 5 0.3 Rectal OPS Clonidine
Cao 2009 2, 4 0.5 Oral Analgesia use Clonidine
Fazi 2001 4 0.5 OralCHEOPSTime to first analgesia
Midazolam
Kuvaki 1999 2.5 0.5 Rectal Pain score parental rating Neither
Schmidt 2003 4 0.5 Oral VAS or VNRSNo. pain free Clonidine
Clonidine vs midazolam
Women’s and Children’s Hospital, Adelaide
Adverse effects
•No study reported excessive (hazardous) sedation
•Low incidence of • Bradycardia• Hypotension(Note: Bergendahl 2004, Georgiou 1999,
Kuvaki 1998, Mikawa 1996, Nishina 2000 all gave atropine prophylaxis)
Women’s and Children’s Hospital, Adelaide
Study limitations
• Heterogeneity between studies
• Inverse correlation of pain scores with sedation scores – are we looking at analgesia or sedation?
Women’s and Children’s Hospital, Adelaide
Implications for practice
•Clonidine premedication at adequate dose does appear to lower analgesia requirements postoperatively in children
•Low incidence of serious side-effects
Women’s and Children’s Hospital, Adelaide
Future work• Either small studies, each tailored to
a particular type of surgery…
• …or a large trial with subgroup analysis
• Multiple outcome measures
Women’s and Children’s Hospital, Adelaide
Acknowledgements•Formal project supervisor• Allan M Cyna
•Co-investigators• Philippa Middleton• Nicholas Knight
•Other assistance• T. Hackmann• B. Kuvaki• E. Reimer• A. Schmidt
• Cochrane Collaboration
Women’s and Children’s Hospital, Adelaide
Women’s and Children’s Hospital, Adelaide