1. A systematic review of the analgesic efficacy and adverse effects of epidural morphine versus parenteral morphine after caesarean section Carmen KM Chan 1 Sui Cheung Yu 1, Anna Lee 2 1.Department of Anaesthesiology, Pain Medicine and Operating Services, United Christian Hospital, Hong Kong 2.Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong

2. Caesarean section and pain relief Epidural morphine Better than intermittent parenteral opioids Parenteral morphine IV PCA good practice NICE: CG 13 (2004) ASA: Practice Guidelines (2007) ANZCA & FPM: Acute Pain Management Scientific Evidence (2010)

3. Objectives Compare: epidural versus parenteral morphine for pain relief after caesarean section efficacy side effects systematic review meta-analysis RCT

4. Pre-determined search strategy and selection criteria Caesarean section Morphine RCT Epidural MeSH, keywords: CENTRAL Medline EMBASE Exclude: Labour analgesia Sustained-release EM

5. Quality assessment of the studies Sequence generation Allocation concealment Blinding Incomplete outcome data Selective outcome reporting Other sources of bias Cochrane Handbook for Systematic Reviews of Interventions (2008) Domain based approach

6. Outcomes VAS (0-10) 12 hours VAS (0-10) 24 hours Mean total morphine usage in first 24 hours No. of patients requiring supplementary analgesics in first 24 hours Incidence of side effects: Vomiting Pruritus Respiratory depression Urinary retention Patient satisfaction Primary Secondary

7. Data extraction and analysis Data extraction RevMan Available case analysis Random effects modelling Continuous WMD ± 95% CI Dichotomous OR ± 95% CI

8. Results Database and reference search 538 Included: 12 trials 1427 patients Excluded: 526 reports

9. Quality of the trials was variable

10. Epidural morphine lower VAS 12 hours Pan 1994 Rapp-Zingraff 1997 Heterogeneity: Tau 2 =0.03; Chi 2 =1.74, df=1 (P=0.19); I 2 =43% Favours EMFavours PM -2 -402 4 WMD -1.39 [-1.75, -1.02] (P<0.001)

11. No difference in VAS at 24 hours Pan 1994 Rapp-Zingraff 1997 Heterogeneity: Tau 2 =0.46; Chi 2 =4.37, df=1 (P=0.04); I 2 =77% Favours EMFavours PM -2 -402 4 WMD -0.54 [-1.60, 0.51] (P=0.31)

12. Less morphine (mg) usage in 24 hours 0-50-10050100 Favours EMFavours PM WMD -30.02 [-38.82, -20.22] (P<0.001) Cohen 1983 Coombs 1982 Eisenach 1988 Youngstrom 1982 Heterogeneity: Tau 2 =60.72; Chi 2 =8.75, df=3 (P=0.03); I 2 =66%

13. Less supplementary analgesics and more pruritus Supplementary analgesics (3 trials) 1 Pruritus (11 trials) 2 1 Heterogeneity: Tau 2 =0.00; Chi 2 =1.90, df=2 (P=0.39); I 2 =0% 2 Heterogeneity: Tau 2 =0.58; Chi 2 =27.18, df=10 (P=0.002); I 2 =63% 1 0.1 10 OR 0.30 [0.12, 0.73] P=0.008 1 0.1 10 OR 6.07 [3.10, 11.86] P<0.001

14. Other secondary outcomes Inadequate data Vomiting Respiratory depression Urinary retention Patient satisfaction Outcome measures too heterogeneous

15. Summary Benefits: Epidural morphine gives better analgesia in the first 12 hours Less morphine and supplementary analgesics inferring better analgesia at 24 hours Harm: More pruritus Implication for clinical practice: ?optimal dose

16. A systematic review of the analgesic efficacy and adverse effects of epidural morphine versus parenteral morphine after caesarean section Carmen KM Chan 1 Sui Cheung Yu 1, Anna Lee 2 1.Department of Anaesthesiology, Pain Medicine and Operating Services, United Christian Hospital, Hong Kong 2.Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong

17. Limitations Publication bias is possible Quality of the primary studies was poor (?studies with all domain rated yes) Other side effects not included Patient satisfaction too heterogeneous

18. Similar findings with recent SR EM decreased pain scores and postoperative morphine request during the first 24 hours EM increased incidence of pruritus (RR 2.7; 95% CI, 2.1–3.6) and nausea (RR 2.0; 95% CI, 1.2–3.3). Bonnet MP, Mignon A, et al. European Journal of Pain (2010)