Perioperative celecoxib administration for pain management after total knee arthroplasty – A randomized, controlled study

<p>Abstract</p> <p>Background</p> <p>Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty.</p> <p>Methods</p> <p>This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed.</p> <p>Results</p> <p>Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 ± 1.68 vs. 3.43 ± 1.50, p = 0.03) and 72 hrs (1.78 ± 1.66 vs. 3.17 ± 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8° ± 17.3° vs. 25.8° ± 11.5°, p = 0.01 (day 1); 60.7° ± 18.1° vs. 45.0° ± 17.3°, p = 0.004 (day 2); 77.7° ± 15.1° vs. 64.3° ± 16.9°, p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions.</p> <p>Conclusion</p> <p>Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00598234</p

Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room. For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief

Effect of valdecoxib pretreatment on pain and secondary hyperalgesia: a randomized controlled trial in healthy volunteers [ISRCTN05282752, NCT00260325]

BACKGROUND: Induction of the COX-2 isoenzyme appears to play a major role in the genesis of central sensitization after nociceptive stimulation. This study aimed to investigate the efficacy of a single, oral dose of the specific COX-2 inhibitor-valdecoxib in attenuating the central sensitization – induced secondary hyperalgesia in a heat/capsaicin pain model in healthy volunteers. METHODS: The study was a randomized, double blind, placebo controlled, crossover, single dose efficacy trial using 20 healthy volunteers. Two hours following placebo or 40 mg, PO valdecoxib, participants underwent skin sensitization with heat/capsaicin, as well as supra-threshold pain and re-kindling measurements according to an established, validated pain model. Subjects rated pain intensity and unpleasantness on a visual analog scale and the area of secondary hyperalgesia was serially mapped. RESULTS: The area of secondary hyperalgesia produced after 40 mg of valdecoxib was no different than that after placebo. Furthermore, there were no significantly relevant differences when volunteers were treated with valdecoxib or placebo in relation to either cold- or hot pain threshold or the intensity of pain after supra-threshold, thermal pain stimulation. CONCLUSION: We demonstrated that a single, oral dose of valdecoxib when does not attenuate secondary hyperalgesia induced by heat/capsaicin in a cutaneous sensitization pain model in healthy volunteers

Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.</p> <p>Methods</p> <p>We conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery), and former users (SSRI prescription more than 30 days before initial breast cancer surgery). We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR) of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders.</p> <p>Results</p> <p>389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI) = 1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3).</p> <p>Conclusions</p> <p>Current use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.</p