Preemptive analgesia debate refuses to go away
ESRA Academy. Schug S. Mar 7, 2017; 170352
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This study confirms the role of COX–2 inhibitors as an important component of multimodal analgesia in the postoperative setting, here specifically after total knee replacement. The opioidsparing effect in the range of 30% is in line with multiple previous reports, and while the study presented here did not use PCA to determine opioid consumption, the findings are in line with PCA-based studies.
Regrettably, pain scores were not reported in any detail; in particular, it would have been interesting to see pain scores on movement, as here NSAIDs offer a further benefit in the setting of orthopaedic surgery.
In addition, the study attempted to address again the issue of a preemptive effect of NSAIDs. In doing so it followed the classical definition of preemptive analgesia, i.e. preoperative treatment is more effective than the identical treatment administered after surgery. The results of this study show a minor advantage of administration of the COX–2 inhibitor 1 hour before surgery versus in the recovery room. However, the difference was small (44 versus 52 mg morphine over 48 hours) and not significant in the Tukey’s multiple comparisons test used throughout the table of results (P = 0.133), but only significant in a t-test with Welch’s correction (P = 0.02). Overall this small study with some limitations is not sufficient to reverse previous conclusions on the lack of a preemptive effect of NSAIDs on postoperative pain (1). However, the study shows the importance of the role of NSAIDs as one component of multimodal analgesia. The use of the COX–2 inhibitor etoricoxib was safe in the setting of total knee joint replacement with no relevant difference in adverse outcomes in this small study. While blood loss was not addressed as a potential complication, a previous meta–analysis in the setting of this operation has already confirmed the lack of an effect of COX–2 inhibitors on blood loss, thereby addressing a major concern of many orthopaedic surgeons (2).

1. White PF, Kehlet H, Liu S. Perioperative analgesia: what do we still know? Anesth Analg 2009; 108(5): 1364–7.
2. Lin J, Zhang L, Yang H. Perioperative administration of selective cyclooxygenase-2 inhibitors for postoperative pain management in patients after total knee arthroplasty. J Arthroplasty 2013; 28(2): 207–13.


Optimal postoperative analgesia is a challenge for the anaesthesiologist, with the ideal combination of methods, drugs, doses and timing of administration still the subject of research. The COX-2 inhibitors are a class of NSAIDs that may provide useful perioperative analgesia but the optimal timing of administration has not been elucidated.


We hypothesised that etoricoxib given 1 h before total knee arthroplasty under spinal anaesthesia will decrease the cumulative dose of intravenous and subcutaneous morphine required to maintain pain intensity of 3 or less on a 10-point numerical rating scale (NRS) during the first postoperative 48 h compared with the same dose of etoricoxib given after surgery.


Randomised, double-blind, placebo-controlled trial.


University hospital, between January and September, 2014.


Overall, 165 patients scheduled for total knee arthroplasty under spinal anaesthesia.


The patients were randomised into one of three groups: the ETORICOX-PREOP group received etoricoxib 120 mg orally 1 h before surgery, one placebo pill at the end of surgery and a further 120 mg etoricoxib after 24 h; the ETORICOX-POSTOP group received one placebo pill 1 h before surgery and etoricoxib 120 mg at the end of surgery and after 24 h. The PLACEBO group received one placebo pill 1 h before surgery, one at end of surgery and a third after 24 h.


The primary outcome measure was the cumulative dose of intravenous and subcutaneous morphine required during the first postoperative 48 h to maintain a 10-point numerical pain rating scale value of 3 or less. Secondary outcomes measures were duration of analgesia from initiation of spinal anaesthesia until the first analgesic requirement and the side-effects of the treatment.


The quantity of morphine over the first postoperative 48 h required by the ETORICOX-PREOP group (44 ± 16 mg) and the ETORICOX-POSTOP group (52 ± 23 mg) were both significantly less than the PLACEBO group (71 ± 20 mg) (P = 0.001), demonstrating a morphine-sparing effect of etoricoxib of the order of 30%; the difference between the PRE vs. POST groups was statistically significant (P = 0.02), favouring a preemptive analgesic effect. Also, there was evidence of a longer time to first analgesia compared with PLACEBO in the PREOP group (P = 0.02) but no significant difference between PREOP and POSTOP groups (P = 0.30). There was no difference in side-effects among the three study groups and there were no serious adverse effects of etoricoxib.


Preemptive administration of etoricoxib 120 mg orally in patients undergoing total knee arthroplasty under spinal anaesthesia is superior to postoperative administration of the same dose in terms of its morphine-sparing effect during the first postoperative 48 h, but not in prolonging the time to first analgesia, and is associated with a similar incidence of side-effects.

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