Skip Navigation LinksHome > June 2005 - Volume 102 - Issue 6 > Effects of Nonsteroidal Antiinflammatory Drugs on Patient-co...
Anesthesiology:
Review Articles

Effects of Nonsteroidal Antiinflammatory Drugs on Patient-controlled Analgesia Morphine Side Effects: Meta-analysis of Randomized Controlled Trials

Marret, Emmanuel M.D.*; Kurdi, Okba M.D.*; Zufferey, Paul M.D.†; Bonnet, Francis M.D.‡
Section Editor(s): Warltier, David C. M.D., Ph.D., Editor

Free Access
Article Outline
Collapse Box

Author Information

Collapse Box

Abstract

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly combined with intravenous morphine patient-controlled analgesia to relieve postoperative pain. NSAIDs have a documented 30–50% sparing effect on morphine consumption. However, most of the studies have not demonstrated a decrease in morphine adverse effects. A meta-analysis of randomized controlled trials was performed to evaluate the risk of morphine adverse effects in patients treated with NSAIDs. Twenty-two prospective, randomized, double-blind studies including 2,307 patients were selected. NSAIDs decreased significantly postoperative nausea and vomiting by 30%, nausea alone by 12%, vomiting alone by 32% and sedation by 29%. A regression analysis yielded findings indicating that morphine consumption was positively correlated with the incidence of nausea and vomiting. Pruritus, urinary retention, and respiratory depression were not significantly decreased by NSAIDs.
OPIOIDS are considered the treatment cornerstone of severe postoperative pain.1 Consequently, in the United States, more than 60% of the patients who have experienced moderate or severe postoperative have received morphine as a postoperative pain therapy.2 Patient-controlled analgesia (PCA) is the most frequent mode of postoperative morphine administration.2 Significantly greater analgesic efficacy and higher patient satisfaction were observed with administration of opioid by PCA, in comparison with as-needed opioid administration.3 Although opioids are highly efficacious, unwanted side effects, such as postoperative nausea and vomiting (PONV), drowsiness, respiratory depression, and gastrointestinal and bladder dysfunction, are frequently observed during opioid PCA.4 Multimodal or balanced analgesia, i.e., the combination of nonopioid analgesics and/or regional analgesic techniques to opioid, have been proposed to decrease morphine consumption and to improve postoperative analgesia after severely painful surgery.5
Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce the opioid analgesic requirement in most of the clinical trials with a 30–50% sparing effect on morphine consumption.6,7 However, most of the studies have not demonstrated a decrease in morphine adverse effects related to the reduction in postoperative morphine requirement. Although morphine adverse events such as PONV have been considered less important by physicians in comparison with other postoperative complications, such as cardiac complications, sepsis, or venous thrombosis, they are costly and are also a major concern for patients.8,9 Patients consider nausea and vomiting as one of the most undesirable postoperative outcomes10 and are ready to pay more than $50 US to avoid them.11 Moreover, PONV delays return to oral feeding, recovery, and hospital discharge.12 Other morphine adverse effects, such as sedation or urinary retention, similarly impair active mobilization and rehabilitation. Although there is no doubt that NSAIDs reduce pain intensity and improve postoperative analgesia, concern remains regarding the real clinical benefit of NSAIDs to reduce adverse effects of opioids in a multimodal analgesic approach.13
Therefore, we performed a meta-analysis to evaluate the effect of NSAIDs in postoperative patients treated with PCA morphine on opioid adverse effects.
Back to Top | Article Outline

Materials and Methods

Identification of the Studies
Two electronic databases were searched via the Internet for studies published between January 1966 and December 2003, PubMed® (MEDLINE/Index Medicus) and the Cochrane Controlled Trials Register published by the Cochrane Library. The Medical Subject Heading terms used for the search were patient controlled analgesia, morphine, and NSAIDs. Supplementary manuscripts were searched by changing the Medical Subject Heading term NSAIDs to celecoxib, rofecoxib, parecoxib, lumiracoxib, or etoricoxib. Additional articles were also retrieved by clicking on hyperlinks and by manually searching reference lists in original published articles, review articles, and correspondence. Four drug companies (Aventis [Paris, France], Pharmacia [Saint-quentin en Yvelines, France], Pfizer [Paris, France], and Abbot [Rungis, France]) were also contacted for research of additional unpublished trials. Only trials published in English were reviewed. For some articles, the authors were contacted for additional information on the results.
Back to Top | Article Outline
Quality Assessment of the Studies
Each study was subjected to a quality assessment by two investigators, who were not blinded to the authors or results. Disagreements between the two investigators were resolved by discussion. In the case of persistent disagreement, a third reviewer helped to reach a consensus after separately reviewing the report. Each article was scored using a five-point scale that evaluates randomization, blinding, and completeness of patient follow-up (Oxford validity scale).14 One point was given if the study was described as randomized. An additional point was given if the randomization method was described and was appropriate (e.g., computer-generated table of random numbers), whereas a point was subtracted if the randomization method was described and inappropriate (e.g., alternate allocation or allocation by date of birth). Similarly, one point was assigned to studies described as double-blind, two points were assigned to studies for which the double-blinding method was described and appropriate (identical placebo, active placebo, double-dummy), and zero points were assigned to studies for which the double-blinding method was described and inappropriate. One point was given if the article specified the numbers of and reasons for withdrawals and dropouts. Thus, the minimum score for a randomized study was 1, and the highest possible score was 5. We included studies with a score of 3 or greater.
Back to Top | Article Outline
Selection Criteria
Criteria for study selection were as follows: randomized, double-blind design; quality assessment score of 3 or greater14; inclusion of adolescents (aged > 12 yr) or adults who underwent major surgery that necessitated morphine administrated by a patient-controlled-analgesia device; NSAID therapy compared to a placebo; report of data on morphine adverse effects such as nausea, vomiting, sedation urinary retention, and respiratory depression; and report of patient satisfaction. We included studies regarding nonselective NSAIDs and selective cyclooxygenase-2 inhibitors.
Criteria for study exclusion were a score of 2 or lower on the three-item Oxford quality five-point scale14; inclusion of children (aged < 12 yr); use of a continuous morphine infusion in addition to PCA; use of a continuous regional analgesia in addition to PCA or other regional techniques exclusively; need for postoperative ventilation during the first 24 h (i.e., cardiac surgery); duration of the study less than 24 h; PCA with an opioid other than morphine (e.g., meperidine, alfentanil, fentanyl, hydromorphone, oxycodone); control group with an NSAID; administration of another nonopioid analgesic in both groups (i.e., acetaminophen, nefopam); and NSAID intrarectal administration.
Back to Top | Article Outline
Outcome Measures
The primary evaluation criterion was the presence of nausea and/or vomiting in the postoperative setting. Three different events were extracted from each trial as mentioned by the authors: nausea, vomiting, and any emetic event. Any emetic event was defined as PONV when authors did not report nausea and vomiting separately in their results section. The regimen of prophylactic antiemetic was also extracted. Other endpoints, such as postoperative urinary retention, sedation defined by the report as sedation or drowsiness, pruritus, apnea, and respiratory depression, were analyzed. Morphine requirement was extracted at 24, 36, and/or 48 h. When trials compared more than two groups, data were extracted in two groups: NSAIDs and control. In dose-ranging studies with a placebo group, we extracted the events of the control group and the highest study-dose group. When authors compared two types of administration with the same dose of NSAIDs (i.e., continuous infusion vs. intermittent or bolus group or preoperative vs. postoperative), patients receiving NSAIDs were pooled and compared to those receiving placebo. Sensitivity analysis was performed to explore the effect of NSAIDs in different procedures, namely peripheral versus pelvic or abdominal surgery, on significant endpoints. Similarly, subgroup analysis for PONV was conducted in groups of patients who did or did not receive opioid intraoperatively and did or did not have reversal of muscle relaxant.
Back to Top | Article Outline
Statistics
When not reported in the article, an intention-to-treat analysis was performed based on the original data. The Mantel-Haenszel–like procedure for relative risk (RR) was used to pool RRs.15 Analyses were performed with WeasyMA software (ClinInfo, Lyon, France) for dichotomous data.16 The RRs (and 95% confidence intervals [CIs]) were calculated, and the results were expressed graphically. All criteria were analyzed separately. In the case that the result of a Q Cochran heterogeneity test was significant (P < 0.1), a random-effects analysis was conducted. For the significant criteria, we computed the number needed to treat (NNT) as the inverse of the difference of the proportion of patients who had any PONV in the NSAID groups and the control groups. CIs of the NNT were constructed by inverting and exchanging the limits of the 95% CI for the RR. The NNT and 95% CI were calculated with the Internet-based program Visual Rx. Relations between morphine requirements and PONV were studied in a weighted linear regression model (Software S-PLUS 2000; MathSoft, Seattle, WA). The model was constructed from aggregated variables. The independent variable was the mean morphine consumption (in milligrams). Dependent variables were the incidence of nausea or vomiting weighted by the inverse variance of the incidence of each trial. All tests were two sided, and P values less than 0.05 were considered statistically significant.
A funnel plot (plot of treatment effect against trial precision) was also created to determine the presence of publication bias and possible other biases (English language, citation, and multiple publication), true heterogeneity, data irregularities, and choice of effect measure in the meta-analysis.17 In the presence of bias that usually leads to an overestimate of the treatment effect, the funnel plot is skewed and asymmetrical. The degree of asymmetry was measured by the Egger test17 using WeasyMA software.16 A P value less than 0.1 was considered statistically significant for asymmetry.17
Back to Top | Article Outline

Results

Table 1
Table 1
Image Tools
One hundred ninety controlled trials were identified by the MEDLINE and the Cochrane Library search. One hundred sixty-eight were excluded for the following reasons: 100 studies considered morphine administration but not by PCA, and/or used opioid other than morphine, and/or had no control group managed without NSAIDs; 32 used regional analgesia/anesthesia; 12 were performed in children; 9 had a quality score lower than 3; 10 reported insufficient clinical data and/or duration of study period less than 24 h; and 5 reported NSAID administration by the rectal route. A manual search of cross-references from the manuscripts and contact with the pharmaceutical companies did not identify additional studies or data. Thus, a total of 22 randomized controlled trials studying intravenous morphine PCA side effects after major surgery were identified by a systematic search of the two databases (table 1).
Back to Top | Article Outline
Study Designs, Patients, and Type of Anesthesia and Surgery
All twenty-two randomized, double-blind studies were published in or after 1991. Most of the studies reported intramuscular or intravenous NSAID administration with a placebo-controlled intramuscular or intravenous saline. Three placebo-controlled comparisons were performed with an active drug administrated per os (ibuprofen for one, rofecoxib and naproxen for two).18–20
Four trials, two with ketorolac21,22 and two with parecoxib,23,24 were dose-ranging studies. In these cases, 30 mg ketorolac every 6 h and 40 mg parecoxib every 12 h were the highest study doses. Two trials compared two modes of NSAID administration (i.e., continuous or intermittent injection) with placebo injection.7,25 In one study, intravenous ketorolac was administrated preoperatively in one group, postoperatively in another group, and compared with a placebo.26 One trial compared two types of NSAIDs administrated preoperatively with a placebo.27 Another compared two types of NSAIDs (tenoxicam vs. piroxicam) with two modes of administration for tenoxicam (intramuscular vs. intravenous) with a placebo.28 One thousand three hundred sixteen patients received NSAID therapy that consisted of intravenous or intramuscular ketorolac (596 patients), intravenous tenoxicam (273 patients), intravenous ketoprofen (93 patients), intravenous parecoxib (82 patients), intravenous dexketoprofen (59 patients), intravenous diclofenac (36 patients), intravenous lysine acetyl salicylate (25 patients), intravenous indomethacin (15 patients), intramuscular tenoxicam (15 patients), intramuscular piroxicam (15 patients), oral ibuprofen (52 patients), oral naproxen (20 patients), or oral rofecoxib (35 patients) (table 1). In the control groups, patients received intravenous saline or placebo tablets. Treatment duration ranged from 24 to 72 h (table 1). Most of the studies demonstrated a significant morphine-sparing effect with NSAIDs (table 1).
The PCA system was programmed to deliver morphine with a bolus dose of 1 mg in 12 trials,7,18,19,22–24,26–32 1.5 mg in 2 trials,21,33 2 mg in 3 trials,20,23,24 2.5 mg in 1 trial,34 5 mg in 1 trial,35 and 0.02 mg/kg in 2 trials.25,36 In one study, the bolus dose was increased in case of inadequate analgesia.7 The lockout intervals were fixed at 2 min,25 5 min,18,27,28,30,32 6 min,7,22–24,36 7 min,33 8 min,21 or 10 min.19,20,26,29,31,34,35 Most of the studies did not fix limitation to the dose of morphine administered. However, 9 studies reported a maximum cumulative dose: 5 mg every hour in 1 study,28 15 mg every 4 h in 1 study,34 20 mg during any 4-h interval in 2 studies,24,33 24 mg every 4 h in 1 study,26 or 30 mg every 4 h in 4 studies.7,21,22,27 The maximum dose could be increased in case of inadequate analgesia in one study.33
Anesthesia was maintained with inhaled agents: halogenates in 19 trials6,18–22,24–27,29–31,33–37 and nitrous oxide in 19 trials.6,18–22,24–31,33–36 Residual muscle relaxation antagonism was described in the methods section in 6 studies.19–21,27,34,35
Back to Top | Article Outline
Postoperative Nausea and Vomiting
Fig. 1
Fig. 1
Image Tools
Fig. 2
Fig. 2
Image Tools
Fig. 3
Fig. 3
Image Tools
Postoperative nausea and vomiting were the most frequently reported morphine adverse effects in 21 trials. Nausea and vomiting were reported indistinctly in 14 trials18–22,25–27,29,30,32–35 (n = 1,343; fig. 1) and separately in 7 trials6,7,23,24,28,31,36 (n = 909; figs. 2 and 3). No prophylactic antiemetic treatment, such as droperidol, dexamethasone, or setron, was used to prevent PONV in any of the 21 trials. Curative antiemetic treatment was reported in only 9 studies. Intravenous metoclopramide, 10 mg, was the most commonly antiemetic treatment used.6,7,18,27,31,32,36 The other curative treatments were alizapride,33 dimenhydrinate,36 and/or droperidol.6
Fig. 4
Fig. 4
Image Tools
In the control group, the incidences of nausea, vomiting, and PONV were 55% (extremes, 16–78%), 21% (extremes, 0–27%), and 30% (extremes, 10–70%), respectively. In the NSAIDs group, the overall incidences of postoperative nausea, vomiting, and PONV were 50% (extremes, 8–66%), 14% (extremes, 0–26%), and 22% (extremes, 0–40%), respectively. NSAIDs reduced the risk of PONV from 30% to 22% (RR, 0.704; 95% CI, 0.590–0.841; P < 0.001; fig. 1). The NNT to prevent one episode of PONV was 12 (95% CI, 9–22). No significant heterogeneity was observed among the six studies that reported postoperative vomiting and nausea separately (figs. 2 and 3). A significant reduction was observed for postoperative vomiting (RR, 0.678; 95% CI, 0.508–0.906; P = 0.008) and also for postoperative nausea (RR, 0.879; 95% CI, 0.785–0.983; P = 0.02). For postoperative vomiting, the NNT value was 15 (95% CI, 10–51), and for postoperative nausea, it was 16 (95% CI, 9–108). A linear relation was documented between the incidence of postoperative nausea (r = 0.61; P = 0.007) and vomiting (r = 0.51; P = 0.02) and morphine consumption in the postoperative period (fig. 4). For each milligram of morphine spared by NSAIDs, the incidences of postoperative nausea and vomiting decreased by 0.9% and 0.3%, respectively.
A subgroup analysis was conducted to explore the effects of NSAIDs on PONV in different procedures. Studies were classified into two groups: orthopedic (peripheral) surgery and pelvic or abdominal surgery. One trial had been conducted in different types of procedures, including orthopedic but also pelvic or abdominal surgery, with no subgroup analysis.33 NSAIDs decreased PONV significantly in the orthopedic subgroup (RR, 0.655; 95% CI, 0.467–0.920; P = 0.01).21,26,29,30 Similarly, NSAIDs were associated with a decrease in PONV after a pelvic or abdominal procedure (RR, 0.684; 95% CI, 0.459–1.020; P = 0.06).18–20,22,25,32,34,35 NSAIDs also decreased PONV in patients in whom reversal neuromuscular block was described in the methods section (RR, 0.546; 95% CI, 0.388–0.770; P < 0.001)19–21,27,34,35 or not described (RR, 0.773; 95% CI, 0.628–0.95; P = 0.01).18,22,25,26,29,30,32,33 Most of the trials studied patients during the first 24 h (table 1). Meta-analysis of these trials showed a significant decrease in PONV (RR, 0.559; 95% CI, 0.434–0.720; P < 0.001),18,20,21,27,30,32,34,35 nausea (RR, 0.883; 95% CI, 0.785–0.994; P = 0.04), or vomiting (RR, 0.719; 95% CI, 0.533–0.970; P = 0.03).6,7,24,28,36
Fig. 5
Fig. 5
Image Tools
A funnel plot of the treatment effect (logarithm RR of PONV or nausea) versus trial precision (inverse of SD) was symmetric and centered around an RR of less than 1.0, suggesting that there is no publication bias or other biases (fig. 5).17 Therefore, there was no evidence of asymmetry and bias in this meta-analysis as shown by the symmetry in the funnel plot for PONV (r = −0.36, intercept [SE] = −0.38 [0.53]; P = 0.49; fig. 4) and nausea (r = −0.36, intercept [SE] = −0.28 [0.69]; P = 0.70; fig. 5).
Back to Top | Article Outline
Sedation
Fig. 6
Fig. 6
Image Tools
Postoperative sedation was reported in 10 studies,6,7,20,26,29,31–35 6 of them including a definition referring to a sedation score. Sedation was measured with a four-point scale in 4 trials26,29,31,34 and with a five-point scale in 2 studies.7,32 Sedation was the second most frequent side effect of intravenous morphine PCA. Among the 570 patients who did not receive NSAIDs, 74 experienced sedation (13%; extremes, 0–41%) The overall incidence of sedation (10%) was significantly less in the 763 patients who were treated with NSAIDs (RR, 0.714; 95% CI, 0.537–0.950; P = 0.02; fig. 6). The NNT to prevent sedation in one patient was 27 (95% CI, 17–154). Another subgroup analysis was conducted to explore the effects of NSAIDs on sedation in different procedures. Two trials included patients scheduled to undergo different procedures (orthopedic, gynecologic, abdominal).7,33 NSAIDs significantly decreased sedation in the orthopedic subgroup (RR, 0.167; 95% CI, 0.031–0.914; P = 0.04)26,29,31 and after pelvic or abdominal surgery (RR, 0.334; 95% CI, 0.175–0.637; P < 0.001).6,20,32,34,35
Back to Top | Article Outline
Pruritus
Pruritus was reported in 10 trials (1,436 patients).6,7,20–24,27,33,34 The overall incidence of pruritus was 9.5% (extremes, 2.0–50.0%) in the control group and 7.8% (extremes, 0.0–42.0%) in the NSAID group. A nonsignificant reduction in the incidence of pruritus was observed in the NSAID group (RR, 0.731; 95% CI, 0.523–1.022; P = 0.07).
Back to Top | Article Outline
Urinary Retention
Only seven trials with a total of 654 patients checked for urinary retention.7,25,29,34–37 Five studies were performed in patients undergoing abdominal surgery, and two were performed in patients undergoing orthopedic surgery. None of the studies selected for the meta-analysis reported systematic bladder catheterization. No specific criteria was used to define urinary retention, and no precise guidelines were used to perform bladder catheterization. The incidence of urinary retention varied from 0 to 20% in the NSAIDs group (mean, 9%) and from 0 to 25% in the control group (mean, 11%). This difference was not significant (RR, 0.807; 95% CI, 0.502–1.297; P = 0.38).
Back to Top | Article Outline
Respiratory Depression
Monitoring of respiratory depression or apnea was reported in eight trials (498 patients).21,26,29,31,32,34–36 Different criteria were used to define respiratory depression. In two trials, it was defined by a respiratory rate less than 10 breaths/min, persistent hypoxemia, pulse oximetry less than 90%, or naloxone administration.26,29 Others considered respiratory depression when the respiratory rate was less than 10 breaths/min21,31,34,35 or less than 8 breaths/min.32 In two studies, respiratory depression was defined by the intravenous injection of naloxone.7,31 One study reported significant episodes of oxygen desaturation defined by a pulse oximetry less than 84% for at least 2 min or less than 90% for at least 10 min in 15% and 17% of patients treated with NSAIDs or placebo, respectively.36 However, no patients required treatment for clinically apparent respiratory depression.36 At least one episode of respiratory depression was documented in only four trials.21,31,32,35 The incidence was not different between the two groups (1.9% in the NSAIDs group vs. 2.5%), and NSAIDs showed no significant effect on the rate of respiratory depression (RR, 0.998; 95% CI, 0.354–2.814; not significant).
Back to Top | Article Outline

Discussion

This systematic review of 22 randomized controlled trials showed that NSAIDs decreased the incidence of postoperative nausea, vomiting, and sedation. Moreover, a significant relation was documented between morphine consumption and the incidence of PONV. The incidence of the other morphine adverse effects (pruritus, urinary retention, respiratory depression) was not significantly reduced by NSAIDs, although there was a trend toward a reduction of the risks in patients treated with NSAIDs in the postoperative period.
Morphine adverse effects are not only frequent but may be considered as a limitation of intravenous morphine PCA. In a review of 32 trials on opioid-based PCA, PONV was reported in 31% of the 252 patients studied.4 In another systematic review on the efficacy of antiemetic treatments used during intravenous PCA, Tramer and Walder38 found an overall 67% incidence of PONV in the control group. Several risk factors of PONV have been documented in addition to postoperative opioid, including a previous history of PONV, nonsmoking status, and/or female sex.39 Other risks factors, such as halogenates, nitrous oxide, neostigmine use, and type of surgery (laparoscopy, breast surgery, or laparotomy), have also been identified.40 In the studies included in this systematic review, patients were anesthetized with halogenates and nitrous oxide, were predominantly women, and could consequently be considered at risk of PONV. The risk of PONV increased with opioid use but also with previous history of PONV, with nonsmoking status, and/or in female compared with male patients.40 Trials included in the current meta-analysis did not distinguish these last three factors, which affected the incidence of PONV. Therefore, the benefit of morphine-sparing effects of NSAIDs could not be stratified in patients with one, two, or three of these risk factors.
Several prospective studies have suggested that NSAIDs were associated with a lesser likelihood of nausea and/or vomiting, but only a few demonstrated a significant reduction.6,7,27,30 Most of the published randomized, controlled, prospective trials were designed to assess the analgesic efficacy of NSAIDs, but the number of patients was usually too small to draw definite conclusions regarding adverse effects. Eleven of the 14 trials that met quality criteria for inclusion in the current meta-analysis yielded a RR of less than 1 for PONV, although the difference was statistically significant in only two trials (fig. 1).27,30 Similarly, only two randomized, double-blind studies showed a significant decrease in postoperative nausea or vomiting (figs. 2 and 3).6,7 However, the study that included the largest population in the current meta-analysis did not find a significant difference in PONV between the NSAID and placebo groups.33 The performance of meta-analysis, which has been developed to increase statistical power for primary or secondary endpoints and also to resolve uncertainty in view of controversial results, was especially appropriate in this setting.
The use of NSAIDs in addition to intravenous morphine PCA is supported by their synergistic interactions.41 Therefore, a multimodal approach has been developed to improve postoperative pain relief by acting on different pain pathways.5 Many randomized studies have demonstrated that a combination of opioid plus NSAIDs decreases morphine requirements and VAS scores. Many authors have considered that reduction in pain intensity or morphine sparing were the primary endpoints and that decreasing morphine adverse effects such as PONV or sedation was a secondary endpoint. However, most of the studies did not confirm a benefit of NSAIDs on morphine adverse effects, probably because of their lack of power. By pooling studies and their secondary endpoints, the current meta-analysis demonstrates the benefit of a multimodal analgesic approach not only on pain control, but also on the incidence of opioid adverse effects.
Sedation has been routinely monitored in many studies because it is an early indicator of respiratory depression.42 Excessive sedation can lead to a discontinuation of PCA or a decrease in morphine consumption. Nevertheless, Paqueron et al.43 noted that 25% of the patients who experienced sedation during morphine titration had visual analog scale scores of greater than 50 mm. Consequently, patients could be sedated despite persistent pain. We observed a significant decrease in postoperative sedation in the NSAIDs group that could be interpreted as the consequence of the decrease in morphine consumption. Decreasing sedation is another way to improve patient compliance to active postoperative care and to hasten recovery. Moreover, sedated patients need especially careful monitoring that could be time-consuming for nurses.
The current systematic review may have some limitations. The quality of trials included in a systematic review may alter the results.44 Moher et al.44 demonstrated that meta-analyses with low-quality trials (Jadad assessment scale score ≤ 2) compared with high-quality trials (assessment scale score > 2) were associated with an increased estimate of benefit of one third. Similarly, trials using inadequate allocation concealment may also have overestimated the benefit of treatment by as much as 37%.44 Moreover, meta-analysis of small trials, i.e., studies with less than 1,000 patients, with inadequate allocation sequence generation or no double blinding can exaggerate the benefit of the treatment in comparison with large trials and contribute to discrepancies.45 Therefore, multiple scales have been proposed to assess the quality of trials included in a meta-analysis and to decrease bias due to the inclusion of low-quality trials. We used the Jadad composite scale to assess quality using factors such as randomization, double blinding, and patient withdrawals.14 Meta-analyses of trials with low quality as evaluated with this scale significantly exaggerate benefits.44 Consequently, all 22 trials selected for our systematic review were double blind and randomized and had an Oxford scale score reflecting high quality. We also limited our meta-analysis to English-language articles. Although the effect of excluding non–English-language trials on the results of a meta-analysis is unclear, in some cases, excluding trials published in other languages may have little effect on summary treatment effects and may actually result in a more conservative estimate of treatment effect.46 In fact, trials published in non-English languages are prone to produce significant results more frequently but also to be lower in terms of methodologic quality. Publication bias and other biases may also exaggerate the benefit of the treatment of meta-analysis in comparison with large trial.17 Consequently, we constructed a funnel plot to test the presence of bias.17 No asymmetry was evident (fig. 5).
The use of antiemetic was different from one study to another, but none of the studies included in the meta-analysis used preventive antiemetic treatment that could have impaired the incidence of PONV. Moreover, most of the studies reported use of metoclopramide that has been documented to be ineffective in the treatment of PONV.47 Numerous scales, such as the visual analog scale (0–100), 11-point numerical rating scale (0–11), or verbal rating scale (none, mild, moderate, severe), are used in the literature to report PONV. Most of the studies included in the current meta-analysis reported PONV as a dichotomous variable. Only one trial reported PONV on a verbal rating scale, and patients of this study were classified into two groups (presence or absence of PONV).20 Nausea is a subjective sensation of the desire to vomit and therefore can be expressed by yes or no or quantified on a visual analog scale. In contrast, vomiting is an objective event that is difficult to quantify on a visual analog scale graded from 0 to 100. Indeed, evaluation of PONV by visual analog scale is considered by some experts to be difficult and prone to bias.48 Therefore, the current meta-analysis explored the effect of NSAIDs only on the presence or absence of postoperative nausea and/or vomiting.
Different types of NSAIDs (nonselective cyclooxygenase inhibitors, such as ketorolac, ketoprofen, naproxen, ibuprofen, or aspirin) and selective cyclooxygenase-2 inhibitors, such as rofecoxib or parecoxib, were included in the current systematic review. All of them inhibit cyclooxygenase-2 expression induced by inflammation or surgery. NSAIDs and selective cyclooxygenase-2 inhibitors comparably decrease postoperative pain intensity.49 Rofecoxib has been recently withdrawn from the market because of an increase in cardiovascular risk.50 This risk was documented for long-term use of the drug. However, one study reported a trend for greater incidence of cardiovascular adverse events in patients taking parecoxib/valdecoxib after coronary artery bypass surgery.51 Coxibs should therefore be used with caution in cardiac patients. Finally, we selected the highest dose of NSAIDs in the dose–response studies.21–24 In these studies, the highest dose was usually associated with the greatest morphine-sparing effect. One may consider that such a decision may favor the benefit of NSAIDs. However, the dose chosen was the one commonly used in the clinical setting or the dose recommended by regulatory agencies.
We decided to exclude studies dedicated to intrarectal administration of NSAIDs because this route is considered uncomfortable by most of the adult patients, especially in the postoperative setting.52 We also did not consider studies where morphine was administrated systematically by subcutaneous or intramuscular injection and studies where continuous infusion was associated with PCA because they were not designed to evaluate a reduction in morphine demand. We also chose to exclude the use of opioids other than morphine to avoid the risk of heterogeneity. In addition, we selected trials where only patients and not nurses or physicians titrated the morphine dose from the PCA system to achieve optimum pain relief. We chose intravenous PCA morphine administration because this technique allowed patients to maintain a balance between acceptable pain control and the occurrence of adverse effects such as PONV. Postoperative nausea and vomiting have been studied mostly in patients who received general anesthesia.53 Most of the patients included in the current systematic review received balanced general anesthesia with halogenates, nitrous oxide, and opioid. Therefore, caution is needed before extrapolating our results to patients receiving regional anesthesia or analgesia.
This current systematic review did not demonstrate a significant reduction in some other morphine adverse effects, such as pruritus, urinary retention, or respiratory depression. These events are less frequent than PONV or sedation or less carefully monitored (pruritus, urinary retention) and consequently less reported.4 Respiratory depression is indeed a rare event, occurring in less than 2% of the cases.4 Although a meta-analysis increases statistical power, it is still limited by the number of events reported by investigators or the incidence of such events.
A significant relation between the incidence of nausea and vomiting and morphine consumption was observed during the postoperative period. Previous studies have documented a correlation between morphine dose and pain relief on one hand, and morphine dose and respiratory depression on the other hand.54 Because respiratory depression has been considered a life-threatening complication, studies have focused on this point. Gal et al.54 demonstrated that intravenous morphine administrated in successive doses of 0.15 mg/kg depressed the slope of the carbon dioxide–response curves, tidal volume, and mean inspiratory flow. Increasing morphine dosage was also associated with a significant increase in threshold and tolerance to experimental pain. Interestingly, the authors noted that patients who received the highest doses of morphine (0.6 mg/kg) exhibited moderate sedation and that four of six reported nausea.54 However, they did not evaluate at each morphine dose the corresponding incidence of sedation and nausea. Morphine side effects were evaluated in more details in a dose–response study of intrathecal morphine administration in human volunteers.55 Bailey et al.55 showed that the incidence of emesis and sedation score were significantly related to the increasing intrathecal morphine dose. Conversely, they did not find a relation between pruritus and urinary retention and intrathecal morphine dose. A dose–response relation was observed between opioid use and the related adverse effects after ambulatory surgery.56 In a randomized, double-blind, placebo-controlled trial that evaluated the use of parecoxib and valdecoxib in ambulatory surgery patients, Zhao et al.56 found that every 3- to 4-mg equivalent dose of morphine increase was associated with one additional clinically significant opioid side effect. Similarly, the current metaregression suggested that a morphine sparing of 10 mg decreases the incidence of nausea by 9% and the incidence of vomiting by 3%. However, the dose–effect relation was documented by a metaregression and may have some limitations. Because trials were not randomized in respect to the dose administered, the relation between morphine dose and nausea and vomiting may also be explained by other factors, such as pain intensity or duration of treatment, even though an attempt was made to limit such bias.57 Morphine consumption was measured during 24–48 h in the different trials included in the current meta-analysis. Nausea and vomiting are usually more frequent during the first 24 h, but morphine requirements are more important during this period of time.40 A subgroup analysis including trials that studied NSAIDs during the first 24 h confirmed the efficacy of NSAIDs to decrease PONV.
In conclusion, the current meta-analysis highlights the benefits of combining NSAIDs and morphine to decrease opioid-related side effects such as PONV and sedation but not pruritus, urinary retention, or respiratory depression.
Back to Top | Article Outline

References

1. Practice guidelines for acute pain management in the perioperative setting: A report by the American Society of Anesthesiologists Task Force on Pain Management, Acute Pain Section. Anesthesiology 1995; 82:1071–81

2. Carr DB, Miaskowski C, Dedrick SC, Williams GR: Management of perioperative pain in hospitalized patients: A national survey. J Clin Anesth 1998; 10:77–85

3. Ballantyne JC, Carr DB, Chalmers TC, Dear KB, Angelillo IF, Mosteller F: Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth 1993; 5:182–93

4. Walder B, Schafer M, Henzi I, Tramer MR: Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain: A quantitative systematic review. Acta Anaesthesiol Scand 2001; 45:795–804

5. Kehlet H, Dahl JB: The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg 1993; 77:1048–56

6. Balestrieri P, Simmons G, Hill D, Brown J, Jackson A, Brull SJ, Maneatis TJ, Shefrin A, Bynum L, O’Hara DA: The effect of intravenous ketorolac given intraoperatively versus postoperatively on outcome from gynecologic abdominal surgery. J Clin Anesth 1997; 9:358–64

7. Ready LB, Brown CR, Stahlgren LH, Egan KJ, Ross B, Wild L, Moodie JE, Jones SF, Tommeraasen M, Trierwieler M: Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain: A double-blind, placebo-controlled, multicenter study. Anesthesiology 1994; 80:1277–86

8. Eberhart LH, Morin AM, Wulf H, Geldner G: Patient preferences for immediate postoperative recovery. Br J Anaesth 2002; 89:760–1

9. Hill RP, Lubarsky DA, Phillips-Bute B, Fortney JT, Creed MR, Glass PS, Gan TJ: Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo. Anesthesiology 2000; 92:958–67

10. Macario A, Weinger M, Carney S, Kim A: Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg 1999; 89:652–8

11. Gan T, Sloan F, Dear Gde L, El-Moalem HE, Lubarsky DA: How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesth Analg 2001; 92:393–400

12. Kehlet H, Wilmore DW: Multimodal strategies to improve surgical outcome. Am J Surg 2002; 183:630–41

13. Kehlet H, Dahl JB: Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003; 362:1921–8

14. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17:1–12

15. Greenland S, Robins JM: Estimation of a common effect parameter from sparse follow-up data. Biometrics 1985; 41:55–68

16. Cucherat M, Boissel JP, Leizorovicz A, Haugh MC: EasyMA: A program for the meta-analysis of clinical trials. Comput Methods Programs Biomed 1997; 53:187–90

17. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315:629–34

18. Plummer JL, Owen H, Ilsley AH, Tordoff K: Sustained-release ibuprofen as an adjunct to morphine patient-controlled analgesia. Anesth Analg 1996; 83:92–6

19. Huang JJ, Taguchi A, Hsu H, Andriole GL Jr, Kurz A: Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: A prospective, randomized, double-blinded, placebo-controlled trial. J Clin Anesth 2001; 13:94–7

20. Celik JB, Tuncer S, Reisli R, Sarkilar G, Celik C, Akyurek C: A comparative study of the effect of rofecoxib (a COX 2 inhibitor) and naproxen sodium on analgesic requirements after abdominal hysterectomy. Arch Gynecol Obstet 2003; 268:297–300

21. Reuben SS, Connelly NR, Lurie S, Klatt M, Gibson CS: Dose-response of ketorolac as an adjunct to patient-controlled analgesia morphine in patients after spinal fusion surgery. Anesth Analg 1998; 87:98–102

22. Sevarino FB, Sinatra RS, Paige D, Ning T, Brull SJ, Silverman DG: The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. J Clin Anesth 1992; 4:285–8

23. Malan TP, Marsh G, Hakki SI, Grossman E, Traylor L, Hubbard RC: Parecoxib sodium, a parenteral cyclooxygenase 2 selective inhibitor, improves morphine analgesia and is opioid-sparing following total hip arthroplasty. Anesthesiology 2003; 98:950–6

24. Tang J, Li S, White PF, Chen X, Wender RH, Quon R, Sloninsky A, Naruse R, Kariger R, Webb T, Norel E: Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. Anesthesiology 2002; 96:1305–9

25. Burns JW, Aitken HA, Bullingham RE, McArdle CS, Kenny GN: Double-blind comparison of the morphine sparing effect of continuous and intermittent i. m. administration of ketorolac. Br J Anaesth 1991; 67:235–8

26. Fletcher D, Zetlaoui P, Monin S, Bombart M, Samii K: Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery. Pain 1995; 61:291–7

27. Alexander R, El-Moalem HE, Gan TJ: Comparison of the morphine-sparing effects of diclofenac sodium and ketorolac tromethamine after major orthopedic surgery. J Clin Anesth 2002; 14:187–92

28. De Decker K, Vercauteren M, Hoffmann V, Lasters B, Adriaensen H: Piroxicam versus tenoxicam in spine surgery: A placebo controlled study. Acta Anaesthesiol Belg 2001; 52:265–9

29. Fletcher D, Negre I, Barbin C, Francois A, Carreres C, Falgueirettes C, Barboteu A, Samii K: Postoperative analgesia with i. v. propacetamol and ketoprofen combination after disc surgery. Can J Anaesth 1997; 44:479–85

30. Hanna MH, Elliott KM, Stuart-Taylor ME, Roberts DR, Buggy D, Arthurs GJ: Comparative study of analgesic efficacy and morphine-sparing effect of intramuscular dexketoprofen trometamol with ketoprofen or placebo after major orthopaedic surgery. Br J Clin Pharmacol 2003; 55:126–33

31. Pang W, Mok MS, Ku MC, Huang MH: Patient-controlled analgesia with morphine plus lysine acetyl salicylate. Anesth Analg 1999; 89:995–8

32. Rao AS, Cardosa M, Inbasegaran K: Morphine-sparing effect of ketoprofen after abdominal surgery. Anaesth Intensive Care 2000; 28:22–6

33. Vandermeulen EP, Van Aken H, Scholtes JL, Singelyn F, Buelens A, Haazen L: Intravenous administration of tenoxicam 40 mg for post-operative analgesia: A double-blind, placebo-controlled multicentre study. Eur J Anaesthesiol 1997; 14:250–7

34. Varrassi G, Panella L, Piroli A, Marinangeli F, Varrassi S, Wolman I, Niv D: The effects of perioperative ketorolac infusion on postoperative pain and endocrine-metabolic response. Anesth Analg 1994; 78:514–9

35. Tigerstedt I, Tammisto T, Neuvonen PJ: The efficacy of intravenous indomethacin in prevention of postoperative pain. Acta Anaesthesiol Scand 1991; 35:535–40

36. Etches RC, Warriner CB, Badner N, Buckley DN, Beattie WS, Chan VW, Parsons D, Girard M: Continuous intravenous administration of ketorolac reduces pain and morphine consumption after total hip or knee arthroplasty. Anesth Analg 1995; 81:1175–80

37. Chow GK, Fabrizio MD, Steer T, Potter SR, Jarrett TW, Gelman S, Kavoussi LR: Prospective double-blind study of effect of ketorolac administration after laparoscopic urologic surgery. J Endourol 2001; 15:171–4

38. Tramer MR, Walder B: Efficacy and adverse effects of prophylactic antiemetics during patient-controlled analgesia therapy: A quantitative systematic review. Anesth Analg 1999; 88:1354–61

39. Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N: A simplified risk score for predicting postoperative nausea and vomiting: Conclusions from cross-validations between two centers. Anesthesiology 1999; 91:693–700

40. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramer MR, Watcha M: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003; 97:62–71

41. Fletcher D, Benoist JM, Gautron M, Guilbaud G: Isobolographic analysis of interactions between intravenous morphine, propacetamol, and diclofenac in carrageenin-injected rats. Anesthesiology 1997; 87:317–26

42. Macintyre PE: Safety and efficacy of patient-controlled analgesia. Br J Anaesth 2001; 87:36–46

43. Paqueron X, Lumbroso A, Mergoni P, Aubrun F, Langeron O, Coriat P, Riou B: Is morphine-induced sedation synonymous with analgesia during intravenous morphine titration? Br J Anaesth 2002; 89:697–701

44. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP: Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 1998; 352:609–13

45. Kjaergard LL, Villumsen J, Gluud C: Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001; 135:982–9

46. Juni P, Holenstein F, Sterne J, Bartlett C, Egger M: Direction and impact of language bias in meta-analyses of controlled trials: Empirical study. Int J Epidemiol 2002; 31:115–23

47. Tramer MR: Treatment of postoperative nausea and vomiting. BMJ 2003; 327:762–3

48. Tramer MR: A rational approach to the control of postoperative nausea and vomiting: Evidence from systematic reviews: II. Recommendations for prevention and treatment, and research agenda. Acta Anaesthesiol Scand 2001; 45:14–9

49. Barton SF, Langeland FF, Snabes MC, LeComte D, Kuss ME, Dhadda SS, Hubbard RC: Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery. Anesthesiology 2002; 97:306–14

50. Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med 2004; 351:1709–11

51. Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, Hubbard RC, Hsu PH, Saidman LJ, Mangano DT: Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003; 125:1481–92

52. Vyvyan HA, Hanafiah Z: Patients’ attitudes to rectal drug administration. Anaesthesia 1995; 50:983–4

53. Borgeat A, Ekatodramis G, Schenker CA: Postoperative nausea and vomiting in regional anesthesia: A review. Anesthesiology 2003; 98:530–47

54. Gal TJ, DiFazio CA, Moscicki J: Analgesic and respiratory depressant activity of nalbuphine: A comparison with morphine. Anesthesiology 1982; 57:367–74

55. Bailey PL, Rhondeau S, Schafer PG, Lu JK, Timmins BS, Foster W, Pace NL, Stanley TH: Dose–response pharmacology of intrathecal morphine in human volunteers. Anesthesiology 1993; 79:49–59

56. Zhao SZ, Chung F, Hanna DB, Raymundo AL, Cheung RY, Chen C: Dose-response relationship between opioid use and adverse effects after ambulatory surgery. J Pain Symptom Manage 2004; 28:35–46

57. Thompson SG, Higgins JP: How should meta-regression analyses be undertaken and interpreted? Stat Med 2002; 21:1559–73

∥ Visual Rx. Available at: http://www.nntonline.net/. Accessed June 10, 2004. Cited Here...

Cited By:

This article has been cited 104 time(s).

Pediatric Anesthesia
Early adjuvant use of nonopioids associated with reduced odds of serious postoperative opioid adverse events and need for rescue in children
Voepel-Lewis, T; Wagner, D; Burke, C; Tait, AR; Hemberg, J; Pechlivanidis, E; Malviya, S; Talsma, A
Pediatric Anesthesia, 23(2): 162-169.
10.1111/pan.12026
CrossRef
Journal of Reconstructive Microsurgery
Perioperative Interventions to Reduce Chronic Postsurgical Pain
Carroll, I; Hah, J; Mackey, S; Ottestad, E; Kong, JT; Lahidji, S; Tawfik, V; Younger, J; Curtin, C
Journal of Reconstructive Microsurgery, 29(4): 213-222.
10.1055/s-0032-1329921
CrossRef
Revista Brasileira De Anestesiologia
Pain Management in Burn Patients
de Castro, RJA; Leal, PC; Sakata, RK
Revista Brasileira De Anestesiologia, 63(1): 149-158.

Anaesthesist
Pediatric postoperative quality analysis. Pain and postoperative nausea and vomiting
Balga, I; Konrad, C; Meissner, W
Anaesthesist, 62(9): 707-+.
10.1007/s00101-013-2211-9
CrossRef
Journal of Arthroplasty
Perioperative Administration of Selective Cyclooxygenase-2 Inhibitors for Postoperative Pain Management in Patients After Total Knee Arthroplasty
Lin, J; Zhang, L; Yang, HL
Journal of Arthroplasty, 28(2): 207-213.
10.1016/j.arth.2012.04.008
CrossRef
Journal De Chirurgie
Systemic analgesia for postoperative pain management in the adult
Binhas, M; Marty, J
Journal De Chirurgie, 146(1): 15-23.
10.1016/j.jchir.2009.02.009
CrossRef
Atencion Farmaceutica
Evaluation of Postoperative Analgesia Protocols
Maria, RGJ; Cristina, RN; Carmen, LD; Teresa, BF; Neus, CR; Regine, G; Maria, ML; Roser, CG; Montserrat, OS
Atencion Farmaceutica, 11(4): 211-+.

Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Review article: The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective
Gilron, I
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 53(6): 562-571.

European Journal of Pain
Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat
Dunbar, SA; Karamian, I; Zhang, HH
European Journal of Pain, 11(1): 1-6.
10.1016/j.ejpain.2005.12.007
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Analgesia controlled with patience: towards a better understanding of analgesic self-administration behaviour
Gilron, I
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 55(2): 75-81.

Pain Medicine
Intranasal Ketorolac for Postoperative Pain: A Phase 3, Double-blind, Randomized Study
Brown, C; Moodie, J; Bisley, E; Bynum, L
Pain Medicine, 10(6): 1106-1114.
10.1111/j.1526-4637.2009.00647.x
CrossRef
Clinical Pharmacology & Therapeutics
Environmental and genetic factors associated with morphine response in the postoperative period
Coulbault, L; Beaussier, M; Verstuyft, C; Weickmans, H; Dubert, L; Tregouet, D; Descot, C; Parc, Y; Lienhart, A; Jaillon, P; Becquemont, L
Clinical Pharmacology & Therapeutics, 79(4): 316-324.
10.1016/j.clpt.2006.01.007
CrossRef
American Journal of Emergency Medicine
Intravenous morphine titration to treat severe pain in the ED
Lvovschi, V; Aubrun, F; Bonnet, P; Bouchara, A; Bendahou, M; Humbert, B; Hausfater, P; Riou, B
American Journal of Emergency Medicine, 26(6): 676-682.
10.1016/j.ajem.2007.10.025
CrossRef
Journal of Korean Academy of Nursing
The Effects of Preemptive Analgesia of Morphine and Ketorolac on Postoperative Pain, Cortisol, O-2 Saturation and Heart Rate
Seo, YJ; Yoon, H
Journal of Korean Academy of Nursing, 38(5): 720-729.
10.4040/jkan.2008.38.5.720
CrossRef
Anesthesia and Analgesia
The role of the anesthesiologist in fast-track surgery: From multimodal analgesia to perioperative medical care
White, PF; Kehlet, H; Neal, JM; Schricker, T; Carr, DB; Carli, F
Anesthesia and Analgesia, 104(6): 1380-1396.
10.1213/01.ane.0000263034.96885.e1
CrossRef
Acta Anaesthesiologica Scandinavica
Oral naproxen but not oral paracetamol reduces the need for rescue analgesic after adenoidectomy in children
Korpela, R; Silvola, J; Laakso, E; Meretoja, OA
Acta Anaesthesiologica Scandinavica, 51(6): 726-730.
10.1111/j.1399-6576.2007.01319.x
CrossRef
Anaesthesist
Combined analgesics for postoperative pain therapy. Review of effectivity and side-effects
Lange, H; Kranke, R; Steffen, P; Steinfeldt, T; Wulf, H; Eberhart, LHJ
Anaesthesist, 56(): 1001-1016.
10.1007/s00101-007-1232-7
CrossRef
Anaesthesist
Drugs for postoperative analgesia: routine and new aspects. Part1: Non-opioids
Jage, J; Laufenberg-Feldmann, R; Heid, F
Anaesthesist, 57(4): 382-+.
10.1007/s00101-008-1326-x
CrossRef
Anaesthesia
Peri-operative use of paracetamol
Oscier, CD; Milner, QJW
Anaesthesia, 64(1): 65-72.
10.1111/j.1365-2044.2008.05674.x
CrossRef
British Journal of Anaesthesia
Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials
Meylan, N; Elia, N; Lysakowski, C; Tramer, MR
British Journal of Anaesthesia, 102(2): 156-167.
10.1093/bja/aen368
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Brief review: Perioperative management of the patient with chronic non-cancer pain
Hadi, I; Morley-Forster, PK; Dain, S; Horrill, K; Moulin, DE
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 53(): 1190-1199.

Anesthesia and Analgesia
Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety
Tiippana, EM; Hamunen, K; Kontinen, VK; Kalso, E
Anesthesia and Analgesia, 104(6): 1545-1556.
10.1213/01.ane.0000261517.27532.80
CrossRef
Drugs
Pathophysiology and management of opioid-induced pruritus
Ganesh, A; Maxwell, LG
Drugs, 67(): 2323-2333.

Acta Anaesthesiologica Scandinavica
Dexamethasone decreases oxycodone consumption following osteotomy of the first metatarsal bone: a randomized controlled trial in day surgery
Mattila, K; Kontinen, VK; Kalso, E; Hynynen, MJ
Acta Anaesthesiologica Scandinavica, 54(3): 268-276.
10.1111/j.1399-6576.2009.02126.x
CrossRef
Journal of Urology
Fentanyl Sparing Effects of Combined Ketorolac and Acetaminophen for Outpatient Inguinal Hernia Repair in Children
Hong, JY; Han, SW; Kim, WO; Kil, HK
Journal of Urology, 183(4): 1551-1555.
10.1016/j.juro.2009.12.043
CrossRef
Regional Anesthesia and Pain Medicine
Acute post-surgical pain management: A critical appraisal of current practice
Rathmell, JP; Wu, CL; Sinatra, RS; Ballantyne, JC; Ginsberg, B; Gordon, DB; Liu, SS; Perkins, FM; Reuben, SS; Rosenquist, RW; Viscusi, ER
Regional Anesthesia and Pain Medicine, 31(4): 1-41.
10.1016/j.rapm.2006.05.002
CrossRef
Advances in Therapy
Efficacy of thoracic epidural analgesia for laparoscopic cholecystectomy
Erol, DD; Yilmaz, S; Polat, C; Arikan, Y
Advances in Therapy, 25(1): 45-52.
10.1007/s12325-008-0005-2
CrossRef
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
COX-2 Inhibitors for the management of postoperative pain
Schug, SA
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 45(1): 56-60.
10.1055/s-0029-1243379
CrossRef
Anesthesia and Analgesia
The analgesic efficacy of acetaminophen, ketoprofen, or their combination for pediatric surgical patients having soft tissue or orthopedic procedures
Hiller, A; Meretoja, OA; Korpela, R; Piiparinen, S; Taivainen, T
Anesthesia and Analgesia, 102(5): 1365-1371.
10.1213/01.ane.0000204278.71548.bf
CrossRef
Drugs
Recent advances in the pharmacological management of pain
Guindon, J; Walczak, JS; Beaulieu, P
Drugs, 67(): 2121-2133.

Nature Clinical Practice Gastroenterology & Hepatology
Postoperative ileus - an update on preventive techniques
Kehlet, H
Nature Clinical Practice Gastroenterology & Hepatology, 5(): 552-558.
10.1038/ncpgasthep1230
CrossRef
Anasthesiologie & Intensivmedizin
Non-opioid analgesics - indications and contraindications
Schafer, M; Brack, A
Anasthesiologie & Intensivmedizin, 47(): 213-+.

Cochrane Database of Systematic Reviews
Music for pain relief
Cepeda, MS; Carr, DB; Lau, J; Alvarez, H
Cochrane Database of Systematic Reviews, (2): -.
ARTN CD004843.pub2
CrossRef
Anesthesia and Analgesia
Society for ambulatory anesthesia guidelines for the management of postoperative nausea and vomiting
Gan, TJ; Meyer, TA; Apfel, CC; Chung, F; Davis, PJ; Habib, AS; Hooper, VD; Kovac, AL; Kranke, P; Myles, P; Philip, BK; Samsa, G; Sessler, DI; Temo, J; Tramer, MR; Kolk, CV; Watcha, M
Anesthesia and Analgesia, 105(6): 1615-1628.

Minerva Anestesiologica
Comparing the efficacy and safety of continuous epidural analgesia in abdominal and urological. surgery between two oploids with different kinetic properties: morphine and sufentanyl
Delvecchio, L; Bettinelli, S; Klersy, C; Allegri, M; Cavalloro, E; Braschi, A
Minerva Anestesiologica, 74(3): 69-76.

Drug Safety
Drug-induced urinary retention - Incidence, management and prevention
Verhamme, KMC; Sturkenboom, MCJM; Stricker, BHC; Bosch, R
Drug Safety, 31(5): 373-388.

Journal of Neurosurgery-Spine
Nonsteroidal antiinflammatory drugs for postoperative pain management after lumbar spine surgery: a meta-analysis of randomized controlled trials
Jirarattanaphochai, K; Jung, S
Journal of Neurosurgery-Spine, 9(1): 22-31.
10.3171/SPI/2008/9/7/022
CrossRef
Bmc Musculoskeletal Disorders
Perioperative celecoxib administration for pain management after total knee arthroplasty - A randomized, controlled study
Huang, YM; Wang, CM; Wang, CT; Lin, WP; Horng, LC; Jiang, CC
Bmc Musculoskeletal Disorders, 9(): -.
ARTN 77
CrossRef
Journal of Plastic Reconstructive and Aesthetic Surgery
Improving postoperative analgesia for transverse rectus abdominis myocutaneous flap breast reconstruction; the use of a local anaesthetic infusion catheter
Tan, KJ; Farrow, H
Journal of Plastic Reconstructive and Aesthetic Surgery, 62(2): 206-210.
10.1016/j.bjps.2007.10.034
CrossRef
Anesthesia and Analgesia
The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery
Reuben, SS; Buvanendran, A; Kroin, JS; Raghunathan, K
Anesthesia and Analgesia, 103(5): 1271-1277.
10.1213/01.ane.0000237279.08847.2d
CrossRef
European Journal of Pharmacology
Antinociceptive activity of buprenorphine and lumiracoxib in the rat orofacial formalin test: A combination analysis study
Capuano, A; De Corato, A; Treglia, M; Tringali, G; Dello Russo, C; Navarra, P
European Journal of Pharmacology, 605(): 57-62.
10.1016/j.ejphar.2008.12.029
CrossRef
Acta Anaesthesiologica Scandinavica
Open issues in the current pharmacological treatment of pain
Curatolo, M
Acta Anaesthesiologica Scandinavica, 53(): 11-12.

Anesthesia and Analgesia
The Early and Delayed Analgesic Effects of Ketamine After Total Hip Arthroplasty: A Prospective, Randomized, Controlled, Double-Blind Study
Remerand, F; Le Tendre, C; Baud, A; Couvret, C; Pourrat, X; Favard, L; Laffon, M; Fusciardi, J
Anesthesia and Analgesia, 109(6): 1963-1971.
10.1213/ANE.0b013e3181bdc8a0
CrossRef
Health Technology Assessment
Paracetamol and selective and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery:a systematic review
McDaid, C; Maund, E; Rice, S; Wright, K; Jenkins, B; Woolacott, N
Health Technology Assessment, 14(): 1-+.

British Journal of Anaesthesia
Effects of a loading dose of morphine before i.v. morphine titration for postoperative pain relief: a randomized, double-blind, placebo-control study
Aubrun, F; Amour, J; Rosenthal, D; Coriat, P; Riou, B
British Journal of Anaesthesia, 98(1): 124-130.
10.1093/bja/ael284
CrossRef
Annales Francaises D Anesthesie Et De Reanimation
Perioperative anti-inflammatory drug use: which evidences for their utility and safety?
Marret, E; Bonnet, F
Annales Francaises D Anesthesie Et De Reanimation, 26(6): 535-539.
10.1016/j.annfar.2007.03.014
CrossRef
Anesthesia and Analgesia
The prolonged postoperative analgesic effect when dexamethasone is added to a nonsteroidal antiinflammatory drug (rofecoxib) before breast surgery
Kjetil, H; Sem, TK; Ellen, S; Johan, R
Anesthesia and Analgesia, 105(2): 481-486.
10.1213/01.ane.0000267261.6l444.69
CrossRef
Regional Anesthesia and Pain Medicine
Dyloject, a novel injectable diclofenac formulation, offers greater safety and efficacy than voltarol for postoperative dental pain
Leeson, RM; Harrison, S; Ernst, CC; Hamilton, DA; Mermelstein, FH; Gawarecki, DG; Moshman, M; Carr, DB
Regional Anesthesia and Pain Medicine, 32(4): 303-310.
10.1016/j.rapm.2006.07.010
CrossRef
Methods and Findings in Experimental and Clinical Pharmacology
Efficacy of Oral Paracetamol and Ketoprofen for Pain Management after Major Orthopedic Surgery
Karvonen, S; Salomaki, T; Olkkola, KT
Methods and Findings in Experimental and Clinical Pharmacology, 30(9): 703-706.
10.1358/mf.2008.30.9.1316919
CrossRef
Burns
The management of pain in the burns unit
Richardson, P; Mustard, L
Burns, 35(7): 921-936.
10.1016/j.burns.2009.03.003
CrossRef
Clinical Drug Investigation
Perioperative Use of Nonsteroidal Anti-Inflammatory Drugs Results of a UK Regional Audit
Allen, SC; Ravindran, D
Clinical Drug Investigation, 29(): 703-711.

Anesthesia and Analgesia
A Randomized, Double-Blind, Controlled Trial of Perioperative Administration of Gabapentin, Meloxicam and Their Combination for Spontaneous and Movement-Evoked Pain After Ambulatory Laparoscopic Cholecystectomy
Gilron, I; Orr, E; Tu, DS; Mercer, CD; Bond, D
Anesthesia and Analgesia, 108(2): 623-630.
10.1213/ane.0b013e318193cd1b
CrossRef
Pain
Intravenous morphine titration in immediate postoperative pain management: Population kinetic-pharmacodynamic and logistic regression analysis
Hammoud, HA; Simon, N; Urien, S; Riou, B; Lechat, P; Aubrun, F
Pain, 144(): 139-146.
10.1016/j.pain.2009.03.029
CrossRef
Anesthesia and Analgesia
Update on acute pain management
Rowlingson, JC
Anesthesia and Analgesia, (): 95-106.

Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
New aspects in postoperative pain therapy
Brack, A; Bottiger, BW; Schafer, M
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 41(3): 184-192.
10.1055/s-2006-925141
CrossRef
Cochrane Database of Systematic Reviews
Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain
Hudcova, J; McNicol, E; Quah, C; Lau, J; Carr, DB
Cochrane Database of Systematic Reviews, (4): -.
ARTN CD003348
CrossRef
Chirurgische Gastroenterologie
Pain therapy
Schwenk, W; Eypasch, E; Meissner, W; Simanski, C; Wiebalck, A
Chirurgische Gastroenterologie, 23(1): 60-63.
10.1159/000097470
CrossRef
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Non-opioid strategies for acute pain management
Beaulieu, P
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 54(6): 481-485.

Acta Anaesthesiologica Scandinavica
Perioperative management of patients on chronic opioids
Kontinen, V
Acta Anaesthesiologica Scandinavica, 51(): 69-70.

European Journal of Pain
Postoperative analgesia and early rehabilitation after total knee replacement: A comparison of continuous low-dose intravenous ketamine versus nefopam
Aveline, C; Gautier, JF; Vautier, P; Cognet, F; Le Hetet, H; Attali, JY; Leconte, V; Leborgne, P; Bonnet, F
European Journal of Pain, 13(6): 613-619.
10.1016/j.ejpain.2008.08.003
CrossRef
Anaesthesist
Concepts for perioperative pain therapy. A critical stocktaking
Reichl, S; Pogatzki-Zahn, E
Anaesthesist, 58(9): 914-+.
10.1007/s00101-009-1589-x
CrossRef
Critical Care
Bench-to-bedside review: Routine postoperative use of the nasogastric tube - utility or futility?
Tanguy, M; Seguin, P; Malledant, Y
Critical Care, 11(1): -.
ARTN 201
CrossRef
Current Opinion in Investigational Drugs
Multimodal analgesia: Its role in preventing postoperative pain
White, PF
Current Opinion in Investigational Drugs, 9(1): 76-82.

Anesthesia and Analgesia
Risk factors for postoperative nausea and vomiting
Gan, TJ
Anesthesia and Analgesia, 102(6): 1884-1898.
10.1213/01.ANE.0000219597.16143.4D
CrossRef
Annales Francaises D Anesthesie Et De Reanimation
Systemic analgesia adapted to the children's condition
Johr, M; Berger, TM; Ruesch, S
Annales Francaises D Anesthesie Et De Reanimation, 26(6): 546-553.
10.1016/j.annfar.2007.03.022
CrossRef
Orthopade
New and evidence-based aspects of postoperative pain therapy
Volk, T
Orthopade, 37(): 953-+.
10.1007/s00132-008-1331-4
CrossRef
Orthopade
Pain therapy for the lower extremities
Simanski, CJP
Orthopade, 37(): 959-+.
10.1007/s00132-008-1337-y
CrossRef
Chest
Pain Management Principles in the Critically Ill
Erstad, BL; Puntillo, K; Gilbert, HC; Grap, MJ; Li, D; Medina, J; Mularski, RA; Pasero, C; Varkey, B; Sessler, CN
Chest, 135(4): 1075-1086.
10.1378/chest.08-2264
CrossRef
Pediatric Surgery International
Systemic postoperative pain management following minimally invasive pectus excavatum repair in children and adolescents: a retrospective comparison of intravenous patient-controlled analgesia and continuous infusion with morphine
Rugyte, DC; Kilda, A; Karbonskiene, A; Barauskas, V
Pediatric Surgery International, 26(7): 665-669.
10.1007/s00383-010-2619-0
CrossRef
Anesthesia and Analgesia
Effect of postoperative analgesia on major postoperative complications: A systematic update of the evidence
Liu, SS; Wu, CL
Anesthesia and Analgesia, 104(3): 689-702.
10.1213/01.ane.0000255040.71600.41
CrossRef
Acta Anaesthesiologica Scandinavica
Physiology of pain
Werner, MU
Acta Anaesthesiologica Scandinavica, 51(): 56-58.

British Journal of Surgery
Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery
Marret, E; Rolin, M; Beaussier, M; Bonnet, F
British Journal of Surgery, 95(): 1331-1338.
10.1002/bjs.6375
CrossRef
Presse Medicale
Rehabilitation after abdominal surgery
Bonnet, F; Szymkiewicz, O; Marret, E; Houry, S
Presse Medicale, 35(6): 1016-1022.

Annales Francaises D Anesthesie Et De Reanimation
Risk factors for renal dysfunction after total hip arthrosplasty
Aveline, C; Leroux, A; Vautier, P; Cognet, F; Le Hetet, H; Bonnet, F
Annales Francaises D Anesthesie Et De Reanimation, 28(9): 728-734.
10.1016/j.annfar.2009.07.077
CrossRef
Anesthesia and Analgesia
Opiate-induced nausea and vomiting: What is the challenge?
Redmond, M; Glass, P
Anesthesia and Analgesia, 101(5): 1341-1342.
10.1213/01.ANE.0000181329.07214.D8
CrossRef
Anaesthesist
Anesthesia and analgesia in addicts
Jage, J; Heid, F
Anaesthesist, 55(6): 611-+.
10.1007/s00101-006-1012-9
CrossRef
Arthroscopy-the Journal of Arthroscopic and Related Surgery
Analgesic efficacy of Perioperative celecoxib in ambulatory arthroscopic knee surgery: A double-blind, placebo-controlled study
Ekman, EF; Wahba, M; Ancona, F
Arthroscopy-the Journal of Arthroscopic and Related Surgery, 22(6): 635-642.
10.1016/j.arthro.2006.03.012
CrossRef
Journal of Palliative Medicine
Palliative care for the older adult
Kapo, J; Morrison, LJ; Liao, S
Journal of Palliative Medicine, 10(1): 185-209.
10.1089/jpm.2006.9989
CrossRef
Brazilian Journal of Otorhinolaryngology
Intravenous paracetamol and dipyrone for postoperative analgesia after day-case tonsillectomy in children: a prospective, randomized, double blind, placebo controlled study
Kocum, AI; Sener, M; Caliskan, E; Bozdogan, N; Micozkadioglu, D; Yilmaz, I; Aribogan, A
Brazilian Journal of Otorhinolaryngology, 79(1): 89-94.
10.5935/1808-8694.20130015
CrossRef
Journal of Vascular and Interventional Radiology
Comparison of the Efficacy of Dexmedetomidine plus Fentanyl Patient-controlled Analgesia with Fentanyl Patient-controlled Analgesia for Pain Control in Uterine Artery Embolization for Symptomatic Fibroid Tumors or Adenomyosis: A Prospective, Randomized Study
Kim, SY; Chang, CH; Lee, JS; Kim, YJ; Kim, MD; Han, DW
Journal of Vascular and Interventional Radiology, 24(6): 779-786.
10.1016/j.jvir.2013.02.034
CrossRef
Pain Medicine
Safety of a Novel Parenteral Formulation of Diclofenac after Major Orthopedic or Abdominal/Pelvic Surgery in a Population Including Anticoagulated, Elderly or Renally Insufficient Patients: An Open-Label, Multiday, Repeated Dose Clinical Trial
Chelly, JE; Singla, SK; Melson, TI; Lacouture, PG; Paadre, S; Carr, DB
Pain Medicine, 14(5): 749-761.
10.1111/pme.12076
CrossRef
Pain
Intravenous acetaminophen reduces postoperative nausea and vomiting: A systematic review and meta-analysis
Apfel, CC; Turan, A; Souza, K; Pergolizzi, J; Hornuss, C
Pain, 154(5): 677-689.
10.1016/j.pain.2012.12.025
CrossRef
Journal of Anesthesia
Adding pregabalin to a multimodal analgesic regimen does not reduce pain scores following cosmetic surgery: a randomized trial
Chaparro, LE; Clarke, H; Valdes, PA; Mira, M; Duque, L; Mitsakakis, N
Journal of Anesthesia, 26(6): 829-835.
10.1007/s00540-012-1447-x
CrossRef
British Journal of Anaesthesia
Effect of ketamine as an adjunct to intravenous patient-controlled analgesia, in patients at high risk of postoperative nausea and vomiting undergoing lumbar spinal surgery
Song, JW; Shim, JK; Song, Y; Yang, SY; Park, SJ; Kwak, YL
British Journal of Anaesthesia, 111(4): 630-635.
10.1093/bja/aet192
CrossRef
Expert Review of Neurotherapeutics
Room for improvement: unmet needs in postoperative pain management
Pogatzki-Zahn, EM; Schnabel, A; Zahn, PK
Expert Review of Neurotherapeutics, 12(5): 587-600.
10.1586/ERN.12.30
CrossRef
Journal of Critical Care
Prescribing nonopioids in mechanically ventilated critically ill patients
Payen, JF; Genty, C; Mimoz, O; Mantz, J; Bosson, JL; Chanques, G
Journal of Critical Care, 28(4): -.
ARTN 534.e7
CrossRef
Anesthesiology
Intravenous Lidocaine Infusion Facilitates Acute Rehabilitation after Laparoscopic Colectomy
Kaba, A; Laurent, SR; Detroz, BJ; Sessler, DI; Durieux, ME; Lamy, ML; Joris, JL
Anesthesiology, 106(1): 11-18.

PDF (503)
Anesthesiology
Improving Postoperative Pain Management: What Are the Unresolved Issues?
White, PF; Kehlet, H
Anesthesiology, 112(1): 220-225.
10.1097/ALN.0b013e3181c6316e
PDF (588) | CrossRef
Anesthesiology
Postsurgical Safety of Opioid-sparing Cyclooxygenase-2 Inhibitors
Babul, N; Sloan, P; Lipman, AG
Anesthesiology, 104(2): 375.

PDF (530)
Anesthesiology
Postsurgical Safety of Opioid-sparing Cyclooxygenase-2 Inhibitors
Marret, E; Bonnet, F
Anesthesiology, 104(2): 376.

PDF (530)
Anesthesiology
Analgesic Treatment after Laparoscopic Cholecystectomy: A Critical Assessment of the Evidence
Bisgaard, T
Anesthesiology, 104(4): 835-846.

PDF (371)
Anesthesiology
Postoperative Opioid Sparing to Hasten Recovery: What Are the Issues?
Kehlet, H
Anesthesiology, 102(6): 1083-1085.

PDF (229)
Anesthesiology
Postoperative Analgesic Effects of Continuous Wound Infiltration with Diclofenac after Elective Cesarean Delivery
Lavand'homme, PM; Roelants, F; Waterloos, H; De Kock, MF
Anesthesiology, 106(6): 1220-1225.
10.1097/01.anes.0000267606.17387.1d
PDF (326) | CrossRef
Anesthesiology
Comparison of Morphine, Ketorolac, and Their Combination for Postoperative Pain: Results from a Large, Randomized, Double-blind Trial
Silva, C; Morales, O; Cepeda, MS; Carr, DB; Miranda, N; Diaz, A
Anesthesiology, 103(6): 1225-1232.

PDF (391)
Anesthesiology
Does Multimodal Analgesia with Acetaminophen, Nonsteroidal Antiinflammatory Drugs, or Selective Cyclooxygenase-2 Inhibitors and Patient-controlled Analgesia Morphine Offer Advantages over Morphine Alone?: Meta-analyses of Randomized Trials
Elia, N; Lysakowski, C; Tramèr, MR
Anesthesiology, 103(6): 1296-1304.

PDF (777)
Anesthesiology
Extended-release Epidural Morphine Formulation Data Far from Clear
Viscusi, ER
Anesthesiology, 103(6): 1318-1319.

PDF (409)
Anesthesiology
Susceptibility to Fraud in Systematic Reviews: Lessons from the Reuben Case
Marret, E; Elia, N; Dahl, JB; McQuay, HJ; Møiniche, S; Moore, RA; Straube, S; Tramèr, MR
Anesthesiology, 111(6): 1279-1289.
10.1097/ALN.0b013e3181c14c3d
PDF (367) | CrossRef
The Clinical Journal of Pain
Long-term Continuous Subcutaneous Infusion of Ketoprofen Combined With Morphine: A Safe and Effective Approach to Cancer Pain
Moselli, NM; Cruto, M; Massucco, P; Savojardo, M; Debernardi, F
The Clinical Journal of Pain, 26(4): 267-274.
10.1097/AJP.0b013e3181c20221
PDF (277) | CrossRef
European Journal of Anaesthesiology (EJA)
Effect of a low‐dose ketamine regimen on pain, mood, cognitive function and memory after major gynaecological surgery: a randomized, double‐blind, placebo‐controlled trial
Riou, B; Aubrun, F; Gaillat, C; Rosenthal, D; Dupuis, M; Mottet, P; Marchetti, F; Coriat, P
European Journal of Anaesthesiology (EJA), 25(2): 97-105.
10.1017/S0265021507002566
PDF (133) | CrossRef
European Journal of Anaesthesiology (EJA)
An opioid-free anaesthetic using nerve blocks enhances rapid recovery after minor hand surgery in children
De Windt, AC; Asehnoune, K; Roquilly, A; Guillaud, C; Le Roux, C; Pinaud, M; Lejus, C
European Journal of Anaesthesiology (EJA), 27(6): 521-525.
10.1097/EJA.0b013e3283349d68
PDF (166) | CrossRef
European Journal of Anaesthesiology (EJA)
Comparison of a bupivacaine peripheral nerve block and systemic ketoprofen on peripheral inflammation and hyperalgesia in rats
Combettes, E; Benhamou, D; Mazoit, J; Beloeil, H
European Journal of Anaesthesiology (EJA), 27(7): 642-647.
10.1097/EJA.0b013e3283366590
PDF (233) | CrossRef
European Journal of Anaesthesiology (EJA)
A survey of postoperative epidural and intravenous analgesia in Greece
Tzavellas, P; Papilas, K; Grigoropoulou, I; Zolindaki, C; Kouki, P; Chrona, H; Kostopanagiotou, G
European Journal of Anaesthesiology (EJA), 24(11): 942-950.
10.1017/S0265021507001160
PDF (92) | CrossRef
Journal of Neurosurgical Anesthesiology
United Kingdom and Ireland Survey of the Use of Nonsteroidal Anti-inflammatory Drugs After Intracranial Surgery
Sebastian, J; Hunt, K
Journal of Neurosurgical Anesthesiology, 18(4): 267.
10.1097/01.ana.0000211009.71398.f6
PDF (68) | CrossRef
Spine
Effect of Parecoxib on Postoperative Pain After Lumbar Spine Surgery: A Bicenter, Randomized, Double-Blinded, Placebo-Controlled Trial
Jirarattanaphochai, K; Thienthong, S; Sriraj, W; Jung, S; Pulnitiporn, A; Lertsinudom, S; Foocharoen, T
Spine, 33(2): 132-139.
10.1097/BRS.0b013e3181604529
PDF (343) | CrossRef
Back to Top | Article Outline

© 2005 American Society of Anesthesiologists, Inc.

Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Login

Article Tools

Images

Share