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

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Supplementary analgesiaClonidine (any dose) vs placebo or no treatment

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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)

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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

Thank you

Any questions?

lambert@internode.on.net

Women’s and Children’s Hospital, Adelaide

Women’s and Children’s Hospital, Adelaide