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      A comparison between ketorolac and nefopam as adjuvant analgesics for postoperative patient-controlled analgesia: a randomized, double-blind, prospective study

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          Abstract

          Background

          We compared the analgesic efficacy and side effects of ketorolac and nefopam that were co-administered with fentanyl via intravenous patient-controlled analgesia.

          Methods

          One hundred and sixty patients scheduled for laparoscopic cholecystectomy were randomly assigned to ketorolac (Group K) or nefopam (Group N) groups. The anesthetic regimen was standardized for all patients. The analgesic solution contained fentanyl 600 µg and ketorolac 180 mg in Group K, and fentanyl 600 µg and nefopam 120 mg in Group N. The total volume of analgesic solution was 120 ml. Postoperative analgesic consumption, recovery of pulmonary function, and pain intensities at rest and during the forced expiration were evaluated at postoperative 2, 6, 24, and 48 h. The postoperative side effects of analgesics were recorded.

          Results

          Cumulative postoperative analgesic consumptions at postoperative 48 h were comparable (Group K: 93.4 ± 24.0 ml vs. Group N: 92.9 ± 26.1 ml, P = 0.906) between the groups. Pain scores at rest and during deep breathing were similar at the time of each examination. The recovery of pulmonary function showed no significant differences between the groups. Overall, postoperative nausea and vomiting incidence was higher in Group N compared with Group K (59% vs. 34%, P = 0.015). The other side effects were comparable between both groups.

          Conclusions

          Analgesic efficacies of ketorolac and nefopam that were co-administered with fentanyl for postoperative pain management as adjuvant analgesics were similar. However, postoperative nausea and vomiting incidence was higher in the nefopam-fentanyl combination compared with the ketorolac-fentanyl combination.

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          Most cited references29

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          A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers.

          Recently, two centers have independently developed a risk score for predicting postoperative nausea and vomiting (PONV). This study investigated (1) whether risk scores are valid across centers and (2) whether risk scores based on logistic regression coefficients can be simplified without loss of discriminating power. Adult patients from two centers (Oulu, Finland: n = 520, and Wuerzburg, Germany: n = 2202) received inhalational anesthesia (without antiemetic prophylaxis) for various types of surgery. PONV was defined as nausea or vomiting within 24 h of surgery. Risk scores to estimate the probability of PONV were obtained by fitting logistic regression models. Simplified risk scores were constructed based on the number of risk factors that were found significant in the logistic regression analyses. Original and simplified scores were cross-validated. A combined data set was created to estimate a potential center effect and to construct a final risk score. The discriminating power of each score was assessed using the area under the receiver operating characteristic curves. Risk scores derived from one center were able to predict PONV from the other center (area under the curve = 0.65-0.75). Simplification did not essentially weaken the discriminating power (area under the curve = 0.63-0.73). No center effect could be detected in a combined data set (odds ratio = 1.06, 95% confidence interval = 0.71-1.59). The final score consisted of four predictors: female gender, history of motion sickness (MS) or PONV, nonsmoking, and the use of postoperative opioids. If none, one, two, three, or four of these risk factors were present, the incidences of PONV were 10%, 21%, 39%, 61% and 79%. The risk scores derived from one center proved valid in the other and could be simplified without significant loss of discriminating power. Therefore, it appears that this risk score has broad applicability in predicting PONV in adult patients undergoing inhalational anesthesia for various types of surgery. For patients with at least two out of these four identified predictors a prophylactic antiemetic strategy should be considered.
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            Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review.

            Non-opioid analgesics, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), or cyclo-oxygenase 2 (COX-2) inhibitors are often given along with morphine as part of multimodal analgesia after major surgery. We have undertaken a systematic review and a mixed treatment comparison (MTC) analysis in order to determine explicitly which class of non-opioid analgesic, paracetamol, NSAIDs, or COX-2 inhibitors is the most effective in reducing morphine consumption and morphine-related adverse effects. Sixty relevant studies were identified. The MTC found that when paracetamol, NSAIDs, or COX-2 inhibitors were added to patient-controlled analgesia (PCA) morphine, there was a statistically significant reduction in morphine consumption: paracetamol [mean difference (MD) -6.34 mg; 95% credibility interval (CrI) -9.02, -3.65], NSAIDs (MD -10.18; 95% CrI -11.65, -8.72), and COX-2 inhibitors (MD -10.92; 95% CrI -12.77, -9.08). There was a significant reduction in nausea and postoperative nausea and vomiting with NSAIDs compared with placebo (odds ratio 0.70; 95% CrI 0.53, 0.88) but not for paracetamol or COX-2 inhibitors, nor for NSAIDs compared with paracetamol or COX-2 inhibitors. There was no statistically significant difference in sedation between any intervention and comparator. On the basis of six trials (n=695), 2.4% of participants receiving an NSAID experienced surgical-related bleeding compared with 0.4% with placebo. The MTC found that there is a decrease in 24 h morphine consumption when paracetamol, NSAID, or COX-2 inhibitors are given in addition to PCA morphine after surgery, with no clear difference between them. Similarly, the benefits in terms of reduction in morphine-related adverse effects do not strongly favour one of the three non-opioid analgesics.
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              Nefopam for the prevention of postoperative pain: quantitative systematic review.

              Nefopam, a centrally acting analgesic, has been used in the surgical setting in many countries since the mid-1970s. However, clinical trials provide contflicting results for its analgesic potency. We performed a systematic search (multiple databases, bibliographies, any language, to January 2008) for randomized, placebo-controlled trials of nefopam for the prevention of postoperative pain. Data were combined using classic methods of meta-analyses and were expressed as weighted mean difference (WMD), relative risk (RR), and number needed to treat/harm (NNT/H) with 95% confidence interval (CI). Nine trials (847 adult patients, 359 received nefopam) were included. Nefopam (cumulative doses, 20-160 mg) was given orally or i.v., as single or multiple doses, or as a continuous infusion. Compared with placebo, cumulative 24 h morphine consumption was decreased with nefopam: WMD -13 mg (95% CI -17.9 to -8.15). Pain intensity at 24 h was also decreased: on a 100 mm visual analogue scale, WMD -11.5 mm (95% CI -15.1 to -7.85). The incidence of tachycardia was increased with nefopam (RR 3.12, 95% CI 1.11-8.79; NNH 7), as was the incidence of sweating (RR 4.92, 95% CI 2.0-12.1; NNH 13). There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients. The analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs. However, dose responsiveness and adverse effect profile remain unclear, and the role of nefopam as part of multimodal analgesia needs to be established. Data in children are lacking.
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                Author and article information

                Journal
                Korean J Anesthesiol
                Korean J Anesthesiol
                KJAE
                Korean Journal of Anesthesiology
                The Korean Society of Anesthesiologists
                2005-6419
                2005-7563
                December 2017
                28 April 2017
                : 70
                : 6
                : 612-618
                Affiliations
                Department of Anesthesiology and Pain Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Korea.
                Author notes
                Corresponding author: Seonghoon Ko, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Chonbuk National University Medical School and Hospital, 20, Gunji-ro, Deokjin-gu, Jeonju 54907, Korea. Tel: 82-63-250-1979, Fax: 82-63-250-1240, shko@ 123456jbnu.ac.kr
                Author information
                https://orcid.org/0000-0002-6672-4576
                https://orcid.org/0000-0003-2742-9985
                Article
                10.4097/kjae.2017.70.6.612
                5716819
                29225744
                a6dc1312-8d98-4fe8-a5b0-5d737d3b7c3f
                Copyright © The Korean Society of Anesthesiologists, 2017

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 February 2017
                : 24 March 2017
                : 29 March 2017
                Categories
                Clinical Research Article

                Anesthesiology & Pain management
                ketorolac,nefopam,patient-controlled analgesia,postoperative pain

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