Journal Reading
Presented by 江易穎
Postoperative Ketamine Administration Decreases Morphine Consumption in
Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled
Study
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
BACKGROUND
Tolerance and delayed hyperalgesia from opioid exposure are associated with activation of NMDA receptors in CNS
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Petrenko AB, Yamakura T, Baba H, Shimoji K. The role ofN-methyl-d-aspartate (NMDA) receptors in pain: a review. Anesth Analg 2003;97:1108–16
Woolf CJ, Chong MS. Preemptive analgesia–treating postoperativepain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362–79
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
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
BACKGROUND
optimal dosing and duration
abd op: ketamine intra-op +/- post-op 48 h
postoperative morphine-sparing effect, pain reduction, and side effects
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
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 the
surgical procedure. * 48 h (1 g/6 h) PCA only, lockout 7 min. no limit
1 mg/mL of morphine and 2.5mg/50 mL of DHBP *48 h.
In the PACU, if VAS>40, morphine 3 mg IV q5m
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
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.
RESULTS
81 p’t (27 per group) 4 p’t excluded (protocol violation, not
blinded) 77 (27 CTRL, 27 INTRA and 23 PERI)
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)
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
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
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
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