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Journal Reading

Postoperative Ketamine Administration Decreases Morphine Consumption in Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled Study. Journal Reading. Presented by 江易穎. BACKGROUND. acute tolerance after opioid exposure as early as immediate post-op period

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Journal Reading

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  1. Postoperative Ketamine Administration Decreases Morphine Consumption in Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled Study Journal Reading Presented by 江易穎

  2. BACKGROUND • acute tolerance after opioid exposureas early as immediate post-op period • Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 2000;93:409 –17 • Intra-operative remifentanil might influence pain levels in the immediate post-operative period after major abdominal surgery. Acta Anaesthesiol Scand 2005;49:1464–70

  3. BACKGROUND • Tolerance and delayed hyperalgesia from opioid exposure are associated with activation of NMDA receptors in CNS • Dickenson AH. Spinal cord pharmacology of pain. Br J Anaesth 1995;75:193–200 • Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl-d-aspartate (NMDA) receptors in pain: a review. Anesth Analg 2003;97:1108–16 • Woolf CJ, Chong MS. Preemptive analgesia–treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362–79

  4. BACKGROUND • Ketamine, a NMDA antagonist, prevents experimentally opioid-induced hyperalgesia • ketamine + morphine decreases both pain and morphine consumption postoperatively. • Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand 2005;49:1405–28 • The influence of timing of systemic ketamine administration on postoperative morphine consumption. J Clin Anesth 2005;17:592–7 • Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain 2005; 113:61–70 • Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999;82: 111–25

  5. BACKGROUND • Low-dose ketamine induces a morphine-sparing effect when this administration is limited to the intra-op period or extended to the post-op period • ‘Balanced analgesia’ in the perioperative period: is there a place for ketamine? Pain 2001;92:373–80 • A randomised, controlled study of peri-operative low dose- ketamine in combination with postoperative patient-controlled -ketamine and morphine after radical prostatectomy. Anaesthesia 2004;59:222–8 • The addition of a small-dose ketamine infusion to tramadol for postoperative analgesia: a double-blinded, placebo-controlled, randomized trial after abdominal surgery. Anesth Analg 2007;104:912–7

  6. BACKGROUND • optimal dosing and duration • abd op: ketamine intra-op +/- post-op 48 h • postoperative morphine-sparing effect, pain reduction, and side effects

  7. METHODS • independent ethics committee approval(No. 99H43, CCPPRB of Amiens University, France) • >18 yrmajor abdominal, urologic, or vascular surgery • Excluded: chronic pain, opioid abuse, psychiatric disorders • signed informed consent from each patient

  8. METHODS • Pre-mx: 1 mg/kg of po hydroxyzine 1 h pre-op • Induction: sufentanil 0.5 g/kg, propofol 1.5 mg/kg, and cisatracurium 0.15 mg/kg • Maintained: sufentanil 0.5g/kg/h, desflurane/50% N2O/O2 and cisatracurium. • 1 g of IV paracetamol 30 min before the end of thesurgical procedure. * 48 h (1 g/6 h) • PCA only, lockout 7 min. no limit1 mg/mL of morphine and 2.5mg/50 mL of DHBP *48 h. • In the PACU, if VAS>40, morphine 3 mg IV q5m

  9. METHODS • Prospectively randomized double-blindcomputer-generated opaque envelopes containing the patient number and group assignment. • groups:(1) PERI: intra-op 0.5mg/kg+2ug/kg/min * 48 h(2) INTRA: intra-op 0.5 mg/kg + 2ug/kg/min(3) CTRL: 10 mL N/S + 1mL/h *48 h

  10. METHODS • morphine 50 mg+/-20 in CTRL group / previous data. • 40% difference between PERI and CTRL group for an α-risk of 0.05 and a power of 0.90 • minimum of 66 patients (22 per group) would be • 81 patients (27 per group) • Bonferroni correction for post hoc analysis. Kruskal–Wallis test and Mann–Whitney U-testChi2 with Yates’ correction or Fisher testsP 0.05 was considered significant.

  11. RESULTS • 81 p’t (27 per group) • 4 p’t excluded (protocol violation, not blinded) • 77 (27 CTRL, 27 INTRA and 23 PERI)

  12. RESULTS (P 0.003 by repeated measure analysis of variance). 0.01 0.02 0.05 0.02

  13. RESULTS • Post-op 24 h cumulative morphine dose(1) PERI: median 27 mg, interquartile range[19] (2) INTRA: 48 mg [41.5](3) CTRL: 50 mg [21]PERI<INTRA, CTRL (P=0.008)

  14. RESULTS (P 0.001 by repeated measure analysis of variance) 0.004 0.004 0.0001 0.001 0.0001 0.001

  15. RESULTS

  16. DISCUSSION • lower incidence of nausea • ketamine reduced PONV Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand 2005;49:1405–28 • morphine-sparing effect • morphine PCA with DHBP

  17. DISCUSSION • optimal ketamine dosage? • 0.5 mg/kg IV + 2 ug/kg/mintheoretical plasma concentration 100 ug/mL no significant signs of accumulation. • 7.8 ug/kg/min= psychomimetic effects

  18. DISCUSSION (P 0.003 by repeated measure analysis of variance). 0.01 0.02 0.05 0.02

  19. DISCUSSION (P 0.001 by repeated measure analysis of variance) 0.004 0.004 0.0001 0.001 0.0001 0.001

  20. DISCUSSION • subanesthetic Ketamine: emotional and behavioral • patient’s performance ≠ pain intensity. • N2O enhance ketamine effect on NMDA • timing of ketamine administration • central sensitization: intra-op and also post-op

  21. CONCLUSIONS • Low-dose ketamine improved postoperative analgesia with a significant decrease of morphine consumption when its administration was continued for 48 h postoperatively, with a lower incidence of nausea and with no side effects of ketamine.

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