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Importance: In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately addressing patients' pain. However, there are a lack of prospective, comparative trials evaluating their effectiveness., Objective: To evaluate the effect of a multimodal, opioid-sparing approach to postoperative pain management compared with the current standard of care in patients undergoing arthroscopic shoulder or knee surgery., Design, Setting, and Participants: This randomized clinical trial was performed at 3 clinical sites in Ontario, Canada, and enrolled 200 patients from March 2021 to March 2022 with final follow-up completed in April 2022. Adult patients undergoing outpatient arthroscopic shoulder or knee surgery were followed up for 6 weeks postoperatively., Interventions: The opioid-sparing group (100 participants randomized) received a prescription of naproxen, acetaminophen (paracetamol), and pantoprazole; a limited rescue prescription of hydromorphone; and a patient educational infographic. The control group (100 participants randomized) received the current standard of care determined by the treating surgeon, which consisted of an opioid analgesic., Main Outcomes and Measures: The primary outcome was postoperative oral morphine equivalent (OME) consumption at 6 weeks after surgery. There were 5 secondary outcomes, including pain, patient satisfaction, opioid refills, quantity of OMEs prescribed at the time of hospital discharge, and adverse events at 6 weeks all reported at 6 weeks after surgery., Results: Among the 200 patients who were randomized (mean age, 43 years; 73 women [38%]), 193 patients (97%) completed the trial; 98 of whom were randomized to receive standard care and 95 the opioid-sparing protocol. Patients in the opioid-sparing protocol consumed significantly fewer opioids (median, 0 mg; IQR, 0-8.0 mg) than patients in the control group (median, 40.0 mg; IQR, 7.5-105.0; z = -6.55; P < .001). Of the 5 prespecified secondary end points, 4 showed no significant difference. The mean amount of OMEs prescribed was 341.2 mg (95% CI, 310.2-372.2) in the standard care group and 40.4 mg (95% CI, 39.6-41.2) in the opioid-sparing group (mean difference, 300.8 mg; 95% CI, 269.4-332.3; P < .001). There was no significant difference in adverse events at 6 weeks (2 events [2.1%] in the standard care group vs 3 events [3.2%] in the opioid-sparing group), but more patients reported medication-related adverse effects in the standard care group (32% vs 19%, P = .048)., Conclusions and Relevance: Among patients who underwent arthroscopic knee or shoulder surgery, a multimodal opioid-sparing postoperative pain management protocol, compared with standard opioid prescribing, significantly reduced postoperative opioid consumption over 6 weeks., Trial Registration: ClinicalTrials.gov Identifier: NCT04566250.

Background: Multimodal analgesia, a key component of enhanced recovery after surgery protocols, emphasizes the use of nonopioid analgesics. Preoperative and postoperative gabapentin is often included within multimodal analgesia because it has been shown to reduce postoperative opioid use. However, the role of gabapentin has been questioned because of concerns of adverse effects, particularly in the elderly. In an effort to better understand the specific role of gabapentin within the context of an established enhanced recovery after surgery protocol, the authors studied the prevalence of its adverse effects in patients undergoing abdominal wall reconstruction., Methods: Following institutional review board approval, a retrospective review of a prospectively collected database of 267 consecutive patients who underwent abdominal wall reconstruction performed by a single surgeon was conducted. Demographic variables; operative details; postoperative analgesic use; the presence of dizziness, lightheadedness, or altered mental status; hypotension; negative Richmond Agitation Sedation Scale scores; and postoperative falls were recorded and analyzed according to postoperative gabapentin administration., Results: Two hundred thirteen patients (80 percent) met inclusion criteria, of which 138 (65 percent) received postoperative gabapentin. Postoperative gabapentin use was not associated with dizziness, lightheadedness, or altered mental status; hypotension; negative Richmond Agitation Sedation Scale scores; or falls. Furthermore, even among those aged 65 years or older, postoperative gabapentin use was not significantly associated with these adverse events., Conclusions: In patients undergoing abdominal wall reconstruction, postoperative gabapentin administration was not associated with an increase in adverse effects. Further prospective analysis may better allow the characterization of the adverse effects of perioperative gabapentin., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: The effective therapy to reduce postoperative catheter-related bladder discomfort (CRBD) remained unknown., Objective: We attempted to manage the systematic review and a meta-analysis to clarify the efficacy of dexmedetomidine (DEX) in potential prevention on CRBD., Methods: We performed the meta-analysis on randomized clinical trials (RCTs), and searched the databases from Web of Sciences, Embase and referred Cochrane Library published from October 2016 to September 2020. Data extraction was carefully conducted by 2 authors, respectively. Meta-analysis that was applied synthetically concerns the incidence and severity of CRBD and the treatment effect of DEX on CRBD., Results: We acquired 5 RCTs with interventions of DEX on CRBD. Meta-analysis showed DEX has significantly reduced the incidence and severity of CRBD compared with control at 0 hour (risk ratios [RR] = 0.40, 95% CI = 0.53-0.29, P < .01), 1 hour (RR = 0.44, 95% CI = 0.34-0.57, P < .01), and 2 hours (RR = 0.43, 95% CI = 0.32-0.58, P < .01) and 6 hours (RR = 0.43, 95% CI = 0.29-0.63, P < .01). DEX was also associated with lower incidence of moderate to severe CRBD at 0, 1, and 6 hours after surgery. There were no significant differences in adverse events other than bradycardia, hypotension, and hypertension., Conclusion: The 5 RCTs showed great effectiveness in reducing the incidence and severity of the early and later postoperative CRBD. Meta-analysis showed that DEX interventions were useful in preventing the early and later postoperative CRBD without significant side effects., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Dexmedetomidine is used to reduce opioid consumption in pediatric anesthesia. However, there is conflicting evidence in pediatric adenotonsillectomy literature regarding the total perioperative opioid-sparing effects of dexmedetomidine. The aim of this study was to examine the association between dexmedetomidine and total perioperative opioid consumption in children undergoing adenotonsillectomy., Methods: This was a retrospective cohort study of the children undergoing adenotonsillectomy surgery at Texas Children's Hospital between November 2017 and October 2018. Intraoperative dexmedetomidine was the exposure of interest. The primary outcome was total perioperative opioid consumption calculated as oral morphine equivalents (OME). Secondary outcomes of interest included opioid consumption and pain scores based on presence and absence of obstructive sleep apnea (OSA) and postanesthesia care unit (PACU) duration. We used multivariable linear regression to estimate the association of dexmedetomidine on the outcomes., Results: A total of 941 patients met inclusion criteria, 697 (74.1%) received intraoperative dexmedetomidine. For every 0.1 µg/kg increase in intraoperative dexmedetomidine, the total perioperative OME (mg/kg) decreases by 0.021 mg/kg (95% CI, -0.027 to -0.015; P < .001). Pain scores did not significantly vary by OSA status. PACU duration increased by 1.14 minutes (95% CI, 0.30-1.99; P = .008) for each 0.1 µg/kg of intraoperative dexmedetomidine., Conclusions: Dexmedetomidine is associated with an overall perioperative opioid-sparing effect in children undergoing adenotonsillectomy and a small but statistically significant increase in PACU duration. Additionally, children with OSA did not have reduced perioperative opioid consumption., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: While preoperative gabapentinoids are commonly used in surgical multimodal analgesia protocols, little is known regarding the effects this therapy has on prolonged postsurgical opioid use. In this observational study, we used data from a large integrated health care system to estimate the association between preoperative day-of-surgery gabapentinoids and the risk of prolonged postsurgical opioid use., Methods: We identified adults age ≥65 years undergoing major therapeutic surgical procedures from a large integrated health care system from 2016 to 2019. Exposure to preoperative gabapentinoids on the day of surgery was measured using inpatient medication administration records, and the outcome of prolonged opioid use was measured using outpatient medication orders. We used stabilized inverse probability of treatment-weighted log-binomial regression to estimate risk ratios and 95% confidence intervals (CIs) of prolonged opioid use, comparing patients who received preoperative gabapentinoids to those who did not and adjusting for relevant clinical factors. The main analysis was conducted in the overall surgical population, and a secondary analysis was conducted among procedures where at least 30% of all patients received a preoperative gabapentinoid., Results: Overall, 13,958 surgical patients met inclusion criteria, of whom 21.0% received preoperative gabapentinoids. The observed 90-day risk of prolonged opioid use following surgery was 0.91% (95% CI, 0.77-1.08). Preoperative gabapentinoid administration was not associated with a reduced risk of prolonged opioid use in the main analysis conducted in a broad surgical population (adjusted risk ratio [adjRR], 1.19 [95% CI, 0.67-2.12]) or in the secondary analysis conducted in patients undergoing colorectal resection, hip arthroplasty, knee arthroplasty, or hysterectomy (adjRR, 1.01 [95% CI, 0.30-3.33])., Conclusions: In a large integrated health system, we did not find evidence that preoperative gabapentinoids were associated with reduced risk of prolonged opioid use in patients undergoing a broad range of surgeries., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

This randomized, controlled study compared the efficacy and safety between oxycodone-paracetamol tablet and celecoxib for postoperative analgesia in patients who underwent arthroscopic knee surgery (AKS). Totally, 232 patients scheduled to undergo AKS were enrolled and were randomly assigned to either the oxycodone-paracetamol (OPT group) or the celecoxib group (CEL group). Pain at rest/motion (based on pain visual analog scale (VAS) score), rescue analgesia consumption, satisfaction level and adverse events were assessed after AKS. Pain VAS score at rest was decreased at 6 h, 12 h post-AKS in the OPT group compared with the CEL group. Similarly, pain VAS score at motion was reduced at 6 h, 12 h, 24 h post-AKS in the OPT group compared to the CEL group. Furthermore, both rescue analgesia rate (14.7% vs. 33.6%) and accumulated pethidine consumption (3.7 ± 8.9 mg vs. 14.0 ± 21.2 mg) were lower in OPT group compared with the CEL group. Patients satisfaction score was either at 24 h, 48 h in OPT group compared with the CEL group. Further subgroup analyses indicated that the effect of oxycodone-paracetamol versus (vs. celecoxib) on post-AKS management was more apparent in the elderly patients and male patients. In addition, the adverse events were well tolerable (including nausea, constipation, vomiting, drowsiness and dizziness) and were of no different between the two groups. In conclusion, oxycodone-paracetamol tablet presents increased analgesic efficacy for acute postoperative pain, with higher patient satisfaction and comparable safety profiles compared with celecoxib in patients underwent AKS., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Postoperative pain is typically treated with multimodal analgesia, using systemic acetaminophen and/or nonsteroidal anti-inflammatory drugs in conjunction with opioids as required. The present study aimed to determine the safety and tolerability of repeated doses of an intravenous fixed-dose combination (FDC) of acetaminophen and ibuprofen., Methods: This multicenter, open-label, single arm, multiple dose study was conducted at 4 centers across New Zealand and the United States between July 2019 and July 2020. Adults (>18 years) requiring multiple doses of parenteral nonopioid analgesics over multiple days following non-laparoscopic general, plastic or orthopedic surgery were eligible. The study drug (acetaminophen 1000 mg+ibuprofen 300 mg) was administered 6-hourly as a 5 min infusion for between 48 h and 5 days. Adverse event data was collected throughout the study, in addition to scheduled vital sign assessments, laboratory tests and electrocardiograms. Participants completed a global evaluation of the FDC at the end of the treatment period., Findings: 232 participants received ≥ 1 dose of the FDC. Most were female (62.1%), White (56.5%) or Black or African American (39.2%), and had undergone orthopedic surgery (85.3%). There was a broad age range (19-87 years), with a mean age of 53.4 years, and 26.3% of participants aged ≥ 65 years. The FDC was safe when used for 48 h to 5 days. Treatment-emergent adverse events (TEAEs) affected 56.0% of participants, the most common were infusion site pain, nausea, infusion site extravasation, constipation, and headache. Minimal changes in vital signs were observed at scheduled timepoints. No clinically significant changes in electrocardiogram assessments occurred. Transient elevations in the hepatic enzymes ALT and AST to < 3 times the upper limit of normal (ULN) affected 10.5% and 9.6% of subjects, elevations to ≥ 3 times the ULN affected 2.6% and 2.2% of subjects, respectively. There were no apparent differences in the safety profile of the FDC in older participants. The FDC was well tolerated; most TEAEs were mild or moderate in severity. Five participants discontinued treatment due to TEAEs, none were considered treatment-related. The FDC was perceived well by study participants; the majority rated their experience as 'excellent' (40.1%) or 'very good' (35.3%)., Implications: The safety profile was comparable to previous studies with no novel safety concerns. The FDC was safe, well tolerated, and perceived positively by participants treated for acute pain between 48 h and 5 days following orthopedic or plastic surgery, supporting a favorable risk benefit profile., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: To evaluate postoperative opioid prescribing patterns in patients undergoing hemodialysis access creation., Methods: Operative logs were reviewed to identify patients undergoing creation of arteriovenous fistula (AVF) or graft (AVG) from September 2016 to January 2018. Immediate postoperative opioid prescriptions were compared for ambulatory patients versus inpatients. Opioid prescriptions at the time of discharge for inpatients were recorded. Rates of opioid prescribing were standardized by conversion to morphine milligram equivalents (MMEs). Opioid use postoperatively and at the time of discharge based on anesthetic technique, general anesthesia versus regional or local anesthesia with sedation were compared. Alternative pain medications administered and pain scores were recorded. Comparisons were made between the percentage of opioid use and doses administered between AVF and AVG patient groups, ambulatory and inpatients, and type of anesthetic technique used. Statistical analysis was performed with chi-square and t-tests., Results: We identified 164 patients undergoing AV access creation but not receiving chronic opioid therapy. A significantly higher percentage of inpatients received opioids in the immediate postoperative period than ambulatory patients (AVF: 72% vs. 19%, P < 0.001; AVG: 62% vs. 25%, P = 0.001). Overall, all AVG patients were more likely to be discharged with an opioid prescription than all AVF patients (37% vs. 8%, P < 0.001). Of AVG patients managed in the ambulatory setting, 48% were discharged with an opioid prescription. The mean total opioid postoperative dose prescribed to inpatients was significantly higher than that prescribed to ambulatory patients for both fistulas (28.73 MMEs vs. 1.27 MMEs, P < 0.001) and grafts (22.11 MMEs vs. 2.16 MMEs, P = 0.005). General anesthesia patient groups were more likely to receive opioids postoperatively than local anesthesia with sedation patients for both AVF (54% vs. 24%, P = 0.027) and AVG creation (61% vs. 17% P < 0.001). Postoperative alternative medication use in the hospital was low with 18% acetaminophen and 1% nonsteroidal anti-inflammatory drug use for AVF patient groups and 24% acetaminophen and 0% nonsteroidal anti-inflammatory drug use for AVG patient groups. The percentage of patients reporting postoperative pain in the recovery room and on the inpatient units was comparable between ambulatory and inpatient settings (AVF: 21% vs. 28%, P = 0.534; AVG: 23% vs. 44%, P = 0.061)., Conclusions: A higher percentage of inpatients undergoing hemodialysis access received opioids when compared with ambulatory patients in the immediate postoperative period. Inpatients were prescribed higher mean doses than ambulatory patients. AVG patient groups were prescribed more opioids than AVF patient groups. Alternative analgesic agent use was low, suggesting an opportunity for improved pain control and opioid reduction. Dialysis access creation represents an opportunity to improve on opioid prescribing patterns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study measured the number of complications after deep inferior epigastric perforator (DIEP) flap reconstruction performed under opioid-free anesthesia (OFA) combined with goal-directed fluid therapy or opioid anesthesia with liberal fluid therapy (OA). This retrospective cohort study consisted of 204 patients who underwent DIEP flap reconstruction at AZSint Jan Brugge between April 2014 and March 2019. Primary outcomes were complications, according to the Clavien-Dindo classification and the length of hospital stay (LOS). The secondary outcomes were flap failure, postoperative nausea and vomiting (PONV), postoperative pain, postoperative opioid consumption, and postoperative skin flap temperature. OFA included a combination of dexmedetomidine, lidocaine, and ketamine without any opioid administered pre- or intraoperatively. OA included a combination of sufentanil and remifentanil. OFA patients received strict goal-directed fluid therapy, whereas OA patients received liberal fluids to maintain perfusion pressure. All patients except 7 (TIVA with remifentanil) received inhalation anesthesia combined with an infusion of propofol. Of the 204 patients, 55 received OFA and 149 received OA. There were no differences in major complications, but fewer minor complications in the OFA group (17.9% vs. 51.4% and P < 0.001). Flap failure occurred in three patients of the OA group. Six patients developed flap thrombosis (five OA patients and one OFA patient). OFA was associated with fewer postoperative opioids, shorter LOS, less PONV, and less pain. In patients without previous nausea, the PONV incidence was higher in the OA group than in the OFA group (12.7% vs. 43.6% and P < 0.001). Patients with previous nausea more frequently required postoperative opioids and had a nausea rate of 60.87%., Competing Interests: Declaration of Competing Interest Harold Mulier: None. Bob De Frene: None. Lara Benmeridja: None. Florian Vanhoorebeeck: None. Bruno Denis: None. Bob Casaer: None. Fabrice Rogge: None. Kris Leleu: None. Jan Mulier: Personal fees, department grants, financial, and nonfinancial support to organize scientific meetings from MSD Merck, GE Healthcare, and Johnson & Johnson outside the submitted work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Ibuprofen and paracetamol (acetaminophen) are very commonly used for analgesia and pain. In 2020, the US FDA gave its first approval of a fixed-dose combination (FDC) of the two drugs in the same tablet for postoperative pain. There has been no quantitative, summative analysis of the FDC effect size measures against postoperative pain in adults. Similar analyses exist, but only in pediatric patients., Objective: This was the first meta-analysis to compare the efficacy and safety outcomes of the ibuprofen/paracetamol FDC against placebo, administered postoperatively, for moderate to severe pain relief in adults., Methods: The MEDLINE, EMBASE, and Cochrane CENTRAL databases, in addition to the grey literature, were searched for clinical trials until April 2020, to identify comparative literature studies of the ibuprofen/paracetamol FDC in acute postoperative pain in adults. No restrictions on doses, formulations (oral, intravenous), and underlying type of surgery were applied. Independent reviewers performed the study selection, data extraction, and the risk-of-bias and quality-of-evidence assessments based on the Cochrane criteria. The outcome measures of interest in the meta-analysis were ≥ 50% pain relief , need for rescue medications, and occurrence of adverse drug events. Statistical analyses using a random-effects model were performed, at a statistical significance of p < 0.05. The RevMan software was used for analysis. A trial sequential analysis (TSA) was conducted to assess how precise and conclusive the meta-analysis outcomes are., Results: Seven double-blind, randomized controlled trials with 2947 participants were included. The FDC dose was at three different levels: 75-100 mg ibuprofen/250 mg paracetamol, 150-200 mg ibuprofen/500 mg paracetamol (FDA-approved dose level), and 292.5-400 mg ibuprofen/975-1000 mg paracetamol. The ≥ 50% pain relief outcome was more achieved with the FDC compared to placebo (risk ratio [RR] 2.60, 95% confidence interval [CI] 2.11-3.20, p < 0.00001), as was the reduced need for rescue medications (RR 0.51, 95% CI 0.37-0.71, p < 0.0001). While inconclusive based on TSA, the FDC was at the highest doses at least as well tolerated as placebo regarding the occurrence of adverse events, including severe, common, and treatment-related adverse events, as well as those that lead to discontinuation, but it was also significantly associated with lower rates of headache and nausea. Subgroup analyses confirmed that the efficacy and safety of the FDC were maintained regardless of doses and formulations. The sensitivity analysis confirmed outcomes against potential publication bias and identified sources of heterogeneity in analyses., Conclusion: The ibuprofen plus paracetamol FDC is conclusively an effective analgesic against placebo in acute postoperative, moderate to severe pain in adults. It is also superiorly well tolerated, including at the higher dose of 292.5-400 mg ibuprofen/975-1000 mg paracetamol; however, safety outcomes were inconclusive. Future studies need to confirm the safety of FDC and its benefits against other marketed analgesics in postoperative pain.

Purpose: Pain is a frequent finding in surgical and trauma patients, and effective pain control remains a common challenge in the hospital setting. Opioids have traditionally been the foundation of pain management; however, these agents are associated with various adverse effects and risks of dependence and diversion., Summary: In response to the rising national opioid epidemic and the various risks associated with opioid use, multimodal pain management through use of nonopioid analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, α 2 agonists, N-methyl-d-aspartate (NMDA) receptor antagonists, skeletal muscle relaxants, sodium channel blockers, and local anesthetics has gained popularity recently. Multimodal analgesia has synergistic therapeutic effects and can decrease adverse effects by enabling use of lower doses of each agent in the multimodal regimen. This review discusses properties of the various nonopioid analgesics and encourages pharmacists to play an active role in the selection, initiation, and dose-titration of multimodal analgesia. The choice of nonopioid agents should be based on patient comorbidities, hemodynamic stability, and the agents' respective adverse effect profiles. A multidisciplinary plan for management of pain should be formulated during transitions of care and is an area of opportunity for pharmacists to improve patient care., Conclusion: Multimodal analgesia effectively treats pain while decreasing adverse effects. There is mounting evidence to support use of this strategy to decrease opioid use. As medication experts, pharmacists can play a key role in the selection, initiation, and dose-titration of analgesic agents based on patient-specific factors., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To alleviate pain after tonsillectomy (TE) with escalating gradual treatment protocols in a prospective trial., Materials & Methods: Following TE, 83 consecutive adult patients were treated with two different four-staged escalating analgesic protocols. Metamizole served as basic medication in protocol 1 (PT1; n = 44), whereas with protocol 2 (PT2; n = 39) ibuprofen was applied as baseline analgesic. Both protocols were escalated according to the patient´s needs to metamizole and ibuprofen vice versa and additional weak to strong opioids. The primary efficacy endpoint was defined as the minimum and maximum pain as well as pain on ambulation (NRS, 0-10). Secondary endpoints comprised analgesic score, patient satisfaction and treatment-related side-effects., Results: Both patient groups exhibited similar demographic characteristics (PT1: Ø 28.8 years; 64% ♀ and PT2: Ø 26.6 years; 56% ♀). Maximum pain (6.7 ± 1.9 vs. 7.6 ± 1.6, t (81)  = -2.254, p = 0.027) and pain on ambulation (5.0 ± 1.8 vs. 5.8 ± 1.8, t (81)  = -2.114, p = 0.038) were significantly higher with PT2. 68.2% of patients with PT1 needed an escalation of analgesic treatment compared to 100% with PT2 (p < 0.001). The opioid consumption was also significantly higher with PT2 (43.2% vs. 71.8%, p < 0.001). There were no significant differences regarding functional impairments, side-effects and patient satisfaction (7.0 ± 2.0 vs. 7.4 ± 2.4, t (79)  = -0.897, p = 0.373)., Conclusion: Both treatment protocols yielded in a high degree of patient satisfaction but dissatisfactory pain relief following TE. Metamizole can be recommended as a basic medication allowing for improved pain relief. Reported pain intensities were independent of the amount of opioid intake. Further research is mandatory to standardize and improve analgesic treatment after TE., Competing Interests: Declaration of Competing Interests There was no financial support, no funding and no conflict of interest during the preparation of this article. This material has never been published and is not currently under evaluation in any other peer-reviewed publication., (Copyright © 2020. Published by Elsevier B.V.)

Background: Limiting harm from postoperative pain treatment is important. However, long-term follow-up from acute pain trials are rare. The aim of the study was to provide long-term follow-up data regarding harm from the "Paracetamol and Ibuprofen in Combination" (PANSAID) trial., Methods: In this preplanned long-term follow-up study from the PANSAID trial, we used data from Danish national health registries (the Danish National Patient Registry and the Danish Civil Registration System) in addition to the 90-day follow-up in the original trial. The primary outcome was 1-year proportion of patients with one or more serious adverse events., Results: One-year follow-up was complete for 551 patients (99%). We found three additional patients with one or more serious adverse events in the 1-year follow-up compared with the 90-day follow-up. The relative risk of having one or more serious adverse event when randomized to ibuprofen compared with paracetamol was 1.40 (95% CI: 0.84-2.33, P = .20)., Conclusion: We found no statistically significant difference in 1-year serious adverse events between patients randomized to ibuprofen compared with paracetamol in patients having planned primary total hip arthroplasty. There were few additional events from the 90-day follow-up to the 1-year follow-up., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background and Aims: Postoperative pain can cause serious adverse reactions that severely affect postoperative outcome. The present study evaluated the effect of dexmedetomidine (DEX) added to sufentanil in intravenous patient-controlled analgesia (PCA) on the relief of pain and inflammatory responses during postoperative recovery of patients undergoing a combined thoracoscopic-laparoscopic esophagectomy (TLE)., Methods: Sixty patients undergoing TLE were randomly allocated to receive 1 μg/ml of sufentanil alone (Group S) or 1 μg/ml of sufentanil plus 2.5 μg/ml of DEX (Group D) for postoperative intravenous (IV) PCA. Postoperative pain relief, cumulative PCA requirements, inflammatory marker levels, delirium and recovery were assessed., Results: A joint DEX and sufentanil regimen significantly reduced the area under the curve of numerical rating scores for pain at rest (NRSR) and coughing (NRSC) at 1-48 h postoperatively (P = 0.000) that were associated with lower PCA-delivered cumulative sufentanil consumption and less PCA frequency until 48 h postoperatively (P < 0.05 and P < 0.0001, respectively). The simultaneous administration of DEX and sufentanil significantly reduced plasma IL-6 and TNF-α concentrations and increased IL-10 level (P < 0.0001, P = 0.0003 and P = 0.0345, respectively), accompanied by better postoperative delirium categories and health statuses of patients (P = 0.024 and P < 0.05, respectively). There was no hypotension, bradycardia, respiratory depression or oversedation in Group D., Conclusion: Patients receiving DEX in addition to IV PCA sufentanil for TLE exhibited better postoperative analgesia, fewer inflammatory responses and lower postoperative delirium categories and better health statuses., (© 2020 The Author(s).)

What Is Known and Objective: Adenotonsillectomies are common surgical procedures performed under general anaesthesia in childhood. Post-operative pain and agitation are complications associated with this procedure. We compared the effects of dexmedetomidine and tramadol on post-operative pain, agitation, haemodynamic parameters, and extubation quality in patients undergoing an adenotonsillectomy using sevoflurane as an anaesthetic agent., Methods: Sixty paediatric patients who had undergone an adenotonsillectomy were included in this study. The patients were randomized into two groups that received either dexmedetomidine (n = 30) or tramadol (n = 30). Haemodynamic variables, extubation time, post-operative pain, agitation and adverse events were recorded for all patients. Post-operative pain was assessed with the pain point system scale (PPSS), and agitation was assessed using the Riker Sedation-Agitation Scale (SAS)., Results: Patients in the dexmedetomidine group had significantly lower heart rates than the tramadol group. In addition, patients in the dexmedetomidine group had significantly lower post-operative PPSS and Riker SAS scores than patients in the tramadol group. Not breathing, cough-bucking and desaturation after extubation occurred less frequently in patients who received dexmedetomidine than in patients who received tramadol. However, the time to extubation was significantly longer for patients who received dexmedetomidine., What Is New and Conclusion: Our study demonstrated that dexmedetomidine was more effective than tramadol for mitigating post-operative pain and agitation in paediatric patients following an adenotonsillectomy with sevoflurane. Although dexmedetomidine was associated with a longer time to extubation, it was also associated with fewer complications following extubation compared with tramadol., (© 2019 John Wiley & Sons Ltd.)

Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (<2 years of age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain management for at least 24 hours were enrolled. Subjects were randomly assigned to receive intravenous acetaminophen low dose, intravenous acetaminophen high dose, or placebo. A population PK model of intravenous acetaminophen was updated by combining 581 samples from the current study of 158 neonate and infant subjects with results from a previously developed model. The individual predicted-versus-observed concentrations plots showed that the structural PK model fit the blood and plasma acetaminophen concentration-versus-time profiles in the active and placebo groups. Terminal elimination half-life was prolonged in neonates and younger infants and in intermediate and older infants similar to values in adults. When compared with placebo, total rescue opioid consumption was similar and significantly fewer intravenous acetaminophen patients prematurely discontinued because of treatment-emergent adverse events (P < .01). For intravenous acetaminophen, neonates receiving 12.5 mg/kg every 6 hours had PK profiles similar to younger, intermediate, and older infants, adolescents, and adults weighing <50 kg receiving 15 mg/kg every 6 hours and adults ≥ 50 kg receiving 1000 mg every 6 hours., (© 2019 Mallinckrodt. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

Background: To help control opioid overprescription, we conducted a large institutional, 3-site initiative to provide discharge prescribing guidelines for different procedures. Our aim is to refine institutional guidelines for parathyroidectomy., Methods: Patients undergoing parathyroidectomy completed a 28-question survey about opioid consumption. Discharge opioid prescription amounts were converted into morphine milligram equivalents (MMEs) and reported as median and interquartile range (IQR). Consumption was dichotomized into top quartile MME users (Q4) versus standard users (Q1, Q3). Univariate analysis compared opioid consumption., Results: A total of 91 patients were included; 90% were opioid-naive. While the median prescribed was 75 (IQR 75, 150) MME, the median consumed was 0 (IQR 0, 20). Top users reported higher pain scores [median (IQR): 2 (2, 4)] compared to standard users [1 (0, 3), P = 0.01]. However, there was no difference in opioid consumption between unilateral neck exploration, bilateral exploration, or thyroidectomy and parathyroidectomy, P = 0.11. There was no difference in opioid consumption by age, sex, or BMI (all P > 0.05). Of those receiving a prescription, 94.6% had left-over opioids at the time of survey, resulting in 82% of prescribed opioids being unused., Conclusions: Over half of patients undergoing parathyroidectomy did not consume any opioid, and very few needed more than 2 d of opioid. Moreover, most patients did not dispose the unused opioids, which put these pills at risk of diversion and misuse. Surgical approach did not change consumption, illustrating that these guidelines are applicable to thyroidectomy given the similarity between techniques. We recommend prescribing nonopioid analgesics for patients undergoing parathyroidectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In patients undergoing total knee arthroplasty under spinal anesthesia, we compared the postoperative analgesic effect of intraoperative sedation with dexmedetomidine versus propofol. We hypothesized that sedation with dexmedetomidine would result in lower postoperative opioid analgesic consumption than with propofol., Methods: Forty-eight patients were enrolled and randomly assigned to either a dexmedetomidine group (n = 24), which received a loading dose of 1 μg/kg dexmedetomidine over 10 minutes, followed by a continuous infusion of 0.1-0.5 μg·kg·hour, or a propofol group (n = 24), which received a continuous infusion of propofol via a target-controlled infusion to maintain the effect-site concentration within a range of 0.5-2.0 μg/mL. The drug infusion rate was determined according to the sedation level, targeting a modified observer's assessment of alertness/sedation score of 3 or 4. The cumulative amounts of fentanyl administered via intravenous patient-controlled analgesia were recorded at 24 and 48 hours postoperatively (primary outcome). The postoperative numerical rating scale for pain was assessed at 6, 12, 24, and 48 hours (secondary outcome). The postoperative use of additional rescue analgesic (ketoprofen) and antiemetic drugs was also compared between the 2 groups at 24 and 48 hours., Results: Dexmedetomidine significantly reduced postoperative fentanyl consumption (median [interquartile range]) during 0-24 hours (45 [30-71] vs 150 [49-248] μg, P = .004; median difference = -105 μg [99.98% CI, 210-7.5]), 24-48 hours (90 [45-143] vs 188 [75-266] μg, P = .005; median difference = -98 μg [99.98% CI, 195-45]), and 0-48 hours (135 [68-195] vs 360 [146-480] μg, P = .003; median difference = -225 μg [99.98% CI, 405-7.5]). The numerical rating scale (median [interquartile range]) was lower at 6 hours (1 [0-2] vs 2 [1-3], P = .003), 12 hours (1 [1-2] vs 3 [2-3], P < .001), 24 hours (1 [1-2] vs 3 [2-3], P < .001), and 48 hours (2 [2-3] vs 3 [3-4], P < .001) after surgery in the dexmedetomidine group compared to the propofol group. No significant intergroup differences were observed in the amount of rescue analgesics and antiemetics at 24 hours (P = .155 and P = .482) and 48 hours (P = .082 and P = .153) after surgery., Conclusions: Intraoperative dexmedetomidine sedation was associated with a small but clinically important reduction in postoperative opioid use after total knee arthroplasty.

Purpose of Review: To explore the data for and against the use of the various components of multimodal analgesia in cranial neurosurgery., Recent Findings: Postcraniotomy pain is a challenging clinical problem in that analgesia must be accomplished without affecting neurologic function (i.e. 'losing the neurologic exam'). The traditional approach with low-dose opioids is often insufficient and can cause well recognized side effects. Newer multimodal analgesic approaches have proven beneficial in a variety of other surgical patient populations. The combined use of multiple nonopioid analgesics offers the promise of improved pain control and reduced opioid administration, while preserving the clinical neurologic exam. Specifically, acetaminophen and gabapentinoids should be considered for craniotomy patients, both preoperatively and postoperatively. The gabapentinoids have the added benefit of reduced nausea. Scalp blocks have moderate quality evidence supporting their use over incisional infiltration alone, with analgesia that extends into the postoperative period. Intraoperative dexmedetomidine reduces postoperative opioid requirements with the added benefit of reduced postcraniotomy hypertension. Methocarbamol, NSAIDs [both nonspecific cyclooxygenase (COX) 1 and 2 inhibitors and specific COX-2 inhibitors], ketamine, and intravenous lidocaine require further data regarding safety and efficacy in craniotomy patients., Summary: Opioids are the mainstay for treating acute postcraniotomy pain but should be minimized. The evidence to support a multimodal approach is growing; neuroanesthesiologists and neurosurgeons should seek to incorporate multimodal analgesia into the perioperative care of craniotomy patients. Preoperative and postoperative gabapentin and acetaminophen, intraoperative dexmedetomidine, and scalp blocks over incisional infiltration have the most data for benefit, with good safety profiles. Further research is needed to define the safety, efficacy, and dosing parameters for NSAIDs including COX-2 inhibitors, methocarbamol, ketamine, and intravenous lidocaine in cranial neurosurgery.

With the growing opioid epidemic, plastic surgeons are being encouraged to transition away from reliance on postoperative opioids. However, many plastic surgeons hesitate to use nonopioid analgesics such as nonsteroidal antiinflammatory drugs and local anesthetic blocks because of concerns about their safety, particularly bleeding. The goal of this systematic review is to assess the validity of risks associated with nonopioid analgesic alternatives. A comprehensive literature search of the PubMed and MEDLINE databases was conducted regarding the safety of opioid alternatives in plastic surgery. Inclusion and exclusion criteria yielded 34 relevant articles. A systematic review was performed because of the variation between study indications, interventions, and complications. Thirty-four articles were reviewed that analyzed the safety of ibuprofen, ketorolac, celecoxib, intravenous acetaminophen, ketamine, gabapentin, liposomal bupivacaine, and local and continuous nerve blocks after plastic surgery procedures. There were no articles that showed statistically significant bleeding associated with ibuprofen, celecoxib, or ketorolac. Similarly, acetaminophen administered intravenously, ketamine, gabapentin, and liposomal bupivacaine did not have any significant increased risk of adverse events. Nerve and infusion blocks have a low risk of pneumothorax. Limitations of this study include small sample sizes, different dosing and control groups, and more than one medication being studied. Larger studies of nonopioid analgesics would therefore be valuable and may strengthen the conclusions of this review. As a preliminary investigation, this review showed that several opioid alternatives have a potential role in postoperative analgesia. Plastic surgeons have the responsibility to lead the reduction of postoperative opioid use by further developing multimodal analgesia.

Background:  Dexmedetomidine (DEX) is a highly selective α-2 agonist with many desirable effects including analgesia, improvement of hemodynamic stability, and potential myocardial and renal protection. The aim of this study was to investigate the effect of DEX on patients undergoing off-pump coronary artery bypass (OPCAB) grafting with regard to less pain medication, earlier extubation, faster transfer to normal ward, and cardiac protection., Patients and Methods:  From January 2012 to March 2015, 464 patients receiving OPCAB were included for retrospective analysis. After propensity matching (1:1), two groups (DEX vs. propofol, n  = 129) could be compared. Continuous and categorical variables were reported as mean ± standard deviation or percentages, and compared with the chi-square test and the Mann-Whitney's test, respectively., Results:  In the DEX group, less use of pain medication in the initial phase at intensive care unit was observed. During the first 2 hours, DEX patients received more nicomorphine (DEX 8 ± 3.2 mg vs. propofol 6 ± 4 mg, p  < 0.001), while in the following 2 hours, the pain medication was significantly reduced (DEX 3.2 ± 2.8 mg vs. propofol 4.7 ± 3.3 mg, p  < 0.001). Remifentanil was stopped considerably earlier (DEX 238 ± 209 minutes vs. propofol 353 ± 266 minutes, p  < 0.001). DEX led to earlier extubation (DEX 208 ± 106 minutes vs. propofol 307 ± 230 minutes, p  < 0.001) and less postoperative atrial fibrillation (AF) ( p  = 0.01)., Conclusion:  Early postoperative DEX application supports the fast-track strategy in patients after OPCAB through enabling rapid extubation, effective pain control, and reduced occurrence of new-onset AF. We are confident to give precedence to DEX over propofol as the new routine medication during postoperative patient transfer., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The morbidity of knee arthritis is increasing among aged people and total knee arthroplasty has been its mainstream treatment to date. Postoperative rehabilitation is an important part of the procedure. However, the intense pain during the functional exercise involved has always been a challenge for both patients and health care professionals. The aim of this study is to test the analgesic effect of a mixture of nitrous oxide/oxygeb (1:1) inhalation for patients who are doing functional exercise 1 month after total knee arthroplasty., Methods/design: This double-blind, randomized, placebo-controlled study will be implemented in the Rehabilitation Department in the General Hospital of Ningxia Medical University. Patients aged between 50 and 75 years who underwent a primary unilateral total knee arthroplasty are eligible for inclusion. The key exclusion criteria include: epilepsy, pulmonary embolism, intestinal obstruction, aerothorax. The treatment group (A) will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesics), and the control group (B) will receive oxygen plus conventional treatment (no analgesics). Patients, physicians, therapists, and data collectors are all blind to the experiment. Assessments will be taken immediately after functional exercise begins (T0), 5 min (T1) after functional exercise begins, and 5 min after functional exercise has finished (T2). Patients will be randomly allocated between a treatment group (A) and a control group (B) in a ratio of 1:1. Primary outcome, including pain severity in the procedure, will be taken for each group. Secondary outcomes include blood pressure, heart rate, oxygen saturation, side effects, knee joint range of motion, Knee Society Score (KSS), rescue analgesia need, and satisfaction from both therapists and patients., Discussion: This study will focus on exploring a fast and efficient analgesic for patients who are doing functional exercise after total knee arthroplasty. Our previous studies suggested that the prefixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burn-dressing pain and breakthrough cancer pain. The results of this study should provide a more in-depth insight into the effects of this analgesic method. If this treatment proves successful, it could be implemented widely for patients doing functional exercise in the rehabilitation department., Trial Registration: ChiCTR-INR-17012891 . Registered on 6 October 2017.

Importance: Ibuprofen is an effective analgesic after tonsillectomy alone or tonsillectomy with adenoidectomy, but concerns remain about whether it increases postoperative hemorrhage., Objective: To investigate the effect of ibuprofen compared with acetaminophen on posttonsillectomy bleeding (PTB) requiring surgical intervention in children., Design, Setting, and Participants: A multicenter, randomized, double-blind noninferiority trial was conducted at 4 tertiary medical centers (Massachusetts Eye and Ear Infirmary, Boston; Naval Medical Center, San Diego, California; Naval Medical Center, Portsmouth, Virginia; Madigan Army Medical Center, Tacoma, Washington). A total of 1832 children were assessed for eligibility (presence of sleep-disordered breathing or obstructive sleep apnea, adenotonsillar hypertrophy, or infectious tonsillitis undergoing extracapsular tonsillectomy by electrocautery). Of these, 1091 were excluded because they did not meet eligibility criteria (n = 681) or refused to participate (n = 410); thus, 741 children aged 2 to 18 years undergoing tonsillectomy alone or tonsillectomy with adenoidectomy were enrolled between May 3, 2012, and January 20, 2017., Interventions: Participants were randomized to receive ibuprofen, 10 mg/kg (n = 372), or acetaminophen, 15 mg/kg (n = 369), every 6 hours for the first 9 postoperative days., Main Outcomes and Measures: Rate and severity of posttonsillectomy bleeding were recorded using a postoperative bleeding severity scale: type 1 (bleeds that were observed at home or evaluated in the emergency department without further intervention), type 2 (bleeds that required readmission for observation), and type 3 (bleeds that required a return to the operating room for control of hemorrhage). Type 3 bleeding was the main outcome measure. The noninferiority margin was set at 3%, and modified intention-to-treat analysis was used., Results: Of the 741 children enrolled, 688 children (92.8%) (median [interquartile range] age, 5 [4] years; 366 boys [53.2%]) received the study medication and were included in a modified intention-to-treat analysis. The rate of bleeding requiring operative intervention was 1.2% in the acetaminophen group and 2.9% in the ibuprofen group (difference, 1.7%; 97.5% CI upper limit, 3.8%; P = .12 for noninferiority). There were no significant adverse events or deaths., Conclusions and Relevance: This study could not exclude a higher rate of severe bleeding in children receiving ibuprofen after tonsillectomy alone or tonsillectomy with adenoidectomy. This finding should be considered when selecting a postoperative analgesic regimen. Further studies are needed to understand if bleeding risk is affected when ibuprofen is used for a shorter duration or in combination with acetaminophen for postoperative analgesia., Trial Registration: ClinicalTrials.gov identifier: NCT01605903.

Objective: To describe pain assessment, the pattern of analgesic and sedative drug use, and adverse drug reactions in a neonatal intensive care unit (NICU) during the postsurgery phase., Method: Demographic characteristics, pain scores, and drug use were extracted and analyzed from electronic patient medical files for infants after surgery, admitted consecutively between January 2012 and June 2013., Result: One hundred and sixty-eight infants were included. Acute (DAN score) and prolonged (EDIN score) pain assessment scores were used in 79% and 64% of infants, respectively, on the 1st day. This percentage decreased over the 7 days following surgery. The weekly average scores postsurgery were 2/15 (±2.2) for the EDIN score and 1.6/10 (±2.0) for the DAN score. The rates of pain control were 88% for the EDIN and 72% for the DAN. The most prescribed opiate drug was fentanyl (98 patients; 58%) with an average dose of 1.8 (±0.6) μg/kg/h. Midazolam was used in 95 patients (56%), with an average dose of 35 (±14) μg/kg/h. A bolus was administered in 7% (±7.4) of the total dose for fentanyl and 8% (±9.3) for midazolam. Similar doses were used in term and preterm neonates. Of 118 patients receiving fentanyl and/or midazolam, 40% presented urinary retention, 28% a weaning syndrome. Paracetamol (155 patients; 92%) and nalbuphine (55 patients; 33%) were the other medications most often prescribed., Conclusion: The off-label use of fentanyl and midazolam was necessary to treat pain after surgery. Pain assessment should be conducted for all neonates in order to optimize their treatment. Research on analgesic and sedative medicine in vulnerable neonates seems necessary to standardize practices and reduce adverse drug reactions., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background and objectives: The combination of non-steroidal anti-inflammatory drugs and paracetamol is widely used for pediatric postoperative pain management, although the evidence of superiority of a combination over either drug alone is insufficient. We aimed to find out if intravenous (i.v.) paracetamol in a dose of 60 mg kg - 1 24 h - ¹, given in addition to i.v. ketoprofen (4.5 mg kg - 1 24 h - ¹), improves analgesia, physical recovery, and satisfaction with postoperative well-being in children and adolescents following moderate and major general surgery. Materials and Methods: Fifty-four patients were randomized to receive either i.v. paracetamol or normal saline as a placebo in adjunct to i.v. ketoprofen. For rescue analgesia in patients after moderate surgery, i.v. tramadol (2 mg kg - ¹ up two doses in 24 h), and for children after major surgery, i.v. morphine-patient-controlled analgesia (PCA) were available. The main outcome measure was the amount of opioid consumed during the first 24 h after surgery. Pain level at 1 and over 24 h, time until the resumption of normal oral fluid intake, spontaneous urination after surgery, and satisfaction with postoperative well-being were also assessed. Results: Fifty-one patients (26 in the placebo group and 25 in the paracetamol group) were studied. There was no difference in required rescue tramadol doses ( n = 11 in each group) or 24-h morphine consumption (mean difference (95% CI): 0.06 (⁻0.17; 0.29) or pain scores between placebo and paracetamol groups. In patients given morphine-PCA, time to normal fluid intake was faster in the paracetamol than the placebo subgroup: median difference (95% CI): 7.5 (1.3; 13.7) h, p = 0.02. Parental satisfaction score was higher in the paracetamol than the placebo group (mean difference: ⁻1.3 (⁻2.5; ⁻0.06), p = 0.04). Conclusions : There were no obvious benefits to opioid requirement or analgesia of adding regular intravenous paracetamol to intravenous ketoprofen in used doses. However, intravenous paracetamol may contribute to faster recovery of normal functions and higher satisfaction with postoperative well-being., Competing Interests: The authors declare no conflict of interest.

Objective: Acute pain control after cranial surgery is challenging. Prior research has shown that patients experience inadequate pain control post-craniotomy. The use of oral medications is sometimes delayed because of postoperative nausea, and the use of narcotics can impair the evaluation of brain function and thus are used judiciously. Few nonnarcotic intravenous (IV) analgesics exist. The authors present the results of the first prospective study evaluating the use of IV acetaminophen in patients after elective craniotomy., Methods: The authors conducted a randomized, double-blinded, placebo-controlled investigation. Adults undergoing elective, supratentorial craniotomies between September 2013 and June 2015 were randomized into two groups. The experimental group received 1000 mg/100 ml IV acetaminophen every 8 hours for 48 hours. The placebo group received 100 ml of 0.9% normal saline on the same schedule. Both groups were also treated with a standardized pain control algorithm. The study was powered to detect a 30% difference in the primary outcome measures: narcotic consumption (morphine equivalents, ME) at 24 and 48 hours after surgery. Patient-reported pain scores immediately postoperatively and 48 hours after surgery were also recorded., Results: A total of 204 patients completed the trial. No significant differences were found in narcotic consumption between groups at either time point (in the treatment and placebo groups, respectively, at 24 hours: 84.3 ME [95% CI 70.2–98.4] and 85.5 ME [95% CI 73–97.9]; and at 48 hours: 123.5 ME [95% CI 102.9–144.2] and 134.2 ME [95% CI 112.1–156.3]). The difference in improvement in patient-reported pain scores between the treatment and placebo groups was significant (p < 0.001)., Conclusions: Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population.

Importance: Multimodal postoperative analgesia is widely used but lacks evidence of benefit., Objective: Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens., Design, Setting, and Participants: Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018., Interventions: Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS-PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery., Main Outcomes and Measures: Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P < .0042; minimal clinically important difference, 10 mg), and proportion of patients with 1 or more serious adverse events (SAEs) within 90 days (multiplicity-adjusted thresholds for statistical significance, P < .025)., Results: Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM + IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM + IBU. The median difference in morphine consumption between the PCM + IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P < .001); for the PCM-alone group vs HS-PCM + IBU, 8 mg (99.6% CI, -1 to 14; P = .001); and for the PCM + IBU group vs IBU alone, 6 mg (99.6% CI, -2 to 16; P = .002). The difference in morphine consumption was not statistically significant for the PCM + IBU group vs HS-PCM + IBU (8 mg [99.6% CI, -2 to 16]; P = .005) or for the PCM-alone group vs IBU alone (10 mg [99.6% CI, -2 to 16]; P = .004) after adjustment for multiple comparisons and 2 co-primary outcomes. There was no significant difference between the IBU-alone group vs HS-PCM + IBU (2 mg [99.6% CI, -10 to 7]; P = .81). The proportion of patients with SAEs in groups receiving IBU was 15%, and in the PCM-alone group, was 11%. The relative risk of SAE was 1.44 (97.5% CI, 0.79 to 2.64; P = .18)., Conclusions and Relevance: Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia., Trial Registration: ClinicalTrials.gov Identifier: NCT02571361.

Introduction: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is most commonly implanted under general anesthesia (GA), due to the intraoperative discomfort associated with tunneling and dissection. Postoperative pain can be substantial and is often managed with opioids. There is a growing interest in transitioning away from the routine use of GA during S-ICD implantation, while also controlling perioperative discomfort without the use of narcotics. As such, we assessed the feasibility of a multimodal analgesia regimen that included regional anesthesia techniques in patients undergoing S-ICD implantation., Methods and Results: Twenty patients received truncal plane block (TBL) immediately before S-ICD implantation. The first 10 patients were implanted under general anesthesia (GA + TBL), and the next 10 patients were implanted under deep sedation (DS + TBL). Additionally, the DS + TBL patients were also prescribed a structured regimen of nonopioid analgesics in the perioperative period. Opioid consumption was calculated as milligram morphine equivalents (MME). In-hospital opioid consumption was significantly lower in the patients implanted with DS + TBL (MME = 0) as compared with patients receiving GA + TBL (MME = 60; P = 0.004)., Conclusions: Subcutaneous ICD implantation with anesthesia-delivered DS and a multimodal anesthetic regimen that includes TBL is feasible and associated with significantly less perioperative opioid consumption., (© 2018 Wiley Periodicals, Inc.)

Background: Pain following tonsillectomy is often poorly managed in the home setting. Multimodal analgesia with acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs offers superior analgesia over monotherapy but may be difficult for caregivers to manage. A fixed-dose combination oral suspension product containing paracetamol and ibuprofen has been developed to facilitate pediatric dosing., Aims: The aims of this study are to determine the analgesic effectiveness, pharmacokinetics, and safety of the fixed-dose combination at two doses in the pediatric population., Methods: In this prospective, multicenter, randomized, single-blind, parallel group trial, 251 children aged 2-12 years undergoing day-stay (adeno)tonsillectomy were randomized to two dose groups of the fixed-dose combination. A doubled loading dose was given preoperatively, followed by treatment for up to 11 days (Higher dose: paracetamol 15 mg/kg + ibuprofen 4.5 mg/kg, Lower dose: paracetamol 12 mg/kg + ibuprofen 3.6 mg/kg). Blood samples were collected for pharmacokinetic analysis for up to 6 hours after the loading dose. The analgesic effectiveness was examined on the first day after surgery using both Parents Postoperative Pain Measurement and modified Wong-Baker Faces pain scales. Rescue medication consumption was recorded throughout the study., Results: Differences in maximum plasma concentration (C max ) and total exposure (AUC 0→t ) between the treatment groups for both analytes were consistent with a 25% increase in dose; there was no difference in time to peak concentration (T max ). On the first postoperative day, there was no difference in pain scores or rescue medication use between treatment groups (approximately 30% in both groups). The combination was well tolerated by both groups. The most common adverse events were vomiting and nausea. The incidence of postoperative bleeding was 4.4%., Conclusion: The shallow dose-response relationship and good tolerability of the fixed-dose combination over an extended study period supports the utility of both doses of the fixed-dose combination in the home setting., (© 2018 John Wiley & Sons Ltd.)

Background: Having entered the US market relatively recently, the perioperative role of intravenous acetaminophen (ivAPAP) remains to be established for several surgeries. Using national data, we therefore assessed current utilization and whether it reduces inpatient opioid prescription and opioid-related side effects in a procedure with relatively high opioid utilization., Methods: Patients undergoing a lumbar/lumbosacral spinal fusion (n = 117,269; 2011-2014) were retrospectively identified in a nationwide database and categorized by the amount and timing of ivAPAP administration (1 or >1 dose on postoperative day [POD] 0, 1, or 1+). Multivariable models measured associations between ivAPAP utilization categories and opioid prescription and perioperative complications; odds ratios (or % change) and 95% confidence intervals are reported., Results: Overall, ivAPAP was used in 18.9% (n = 22,208) of cases of which 1 dose on POD 0 was the most common (73.6%; n = 16,335). After covariate adjustment, use of ivAPAP on POD 0 and 1 was associated with minimal changes in opioid prescription, length and cost of hospitalization particularly favoring >1 ivAPAP dose with a modestly (-5.2%, confidence interval, -7.2% to -3.1%; P < .0001) decreased length of stay. Use of ivAPAP did not coincide with a consistent pattern of significantly reduced odds for complications. In comparison, the most commonly used nonopioid analgesic, pregabalin/gabapentin, did demonstrate reduced opioid prescription combined with lower complication risk., Conclusions: We could not show that perioperative ivAPAP reduces inpatient opioid prescription with subsequent reduced odds for adverse outcomes. It remains to be determined if and under what circumstances ivAPAP has a meaningful clinical role in everyday practice.

Objective: Total knee arthroplasty (TKA) is an established surgical technique and is the standard treatment for degenerative knee joint diseases. However, severe pain after TKA makes it difficult for many patients to perform early postoperative rehabilitation and functional exercise, which might result in subsequent unsatisfactory recovery of knee joint function and great reduction in patients' satisfaction and quality of life. Orthopaedic surgeons have tried a large variety of analgesics and analgesic modes to relieve patients' pain after TKA. There are many analgesic regimens available in clinical practice but all have some deficiencies. Parecoxib sodium, a highly selective inhibitor of cyclooxygenase-2 (COX-2), can reduce the synthesis of peripheral prostaglandin to exert the effect of analgesia, and relieve inflammation and prevent central sensitization through inhibition of peripheral and central COX-2 expression. In addition, it can be used as a preemptive analgesic without affecting platelet aggregation. However, there does seem to be conflicting evidence in the current research as to whether parecoxib sodium can be used successfully as a preemptive analgesic; the effect of preemptive analgesia with parecoxib sodium in multimodal analgesia is still controversial. This research investigated the effects of parecoxib sodium in a preemptive multimodal analgesic regimen., Methods: Eighty-eight patients were randomized into two groups. The experimental group received parecoxib (46 patients) and the control group received saline (42 patients), administered 30 min before the initiation of the surgical procedure. A patient-controlled analgesia (PCA) pump was applied within 48 h after surgery. The visual analogue scale (VAS), drug consumption through the PCA pump, use of salvaging analgesia, range of motion (ROM) of the knee joints, and postoperative complications were observed., Results: The VAS score in the post-anesthesia care unit (PACU) of the parecoxib group was significantly lower than that of the control group (P = 0.039). There was no significant difference in the demographic profiles, duration of operation, hemorrhage in surgery, postoperative hemorrhage, postoperative drainage, VAS at different time points, function of knee joints, length of hospital stay, use of salvaging analgesia, and postoperative drug consumption through the PCA between the two groups (P > 0.05)., Conclusion: In preemptive multimodal analgesia regimens, parecoxib sodium can significantly decrease the VAS score in the short term, relieve pain shortly after surgery, and does not increase the incidence of complications. Parecoxib sodium is a safe and effective drug in the perioperative analgesic management for TKA., (© 2018 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Dexmedetomidine (DEX) improves postoperative pain scores and prolongs the duration of blockage when combined with local anesthetics (LAs) for neuraxial and brachial plexus block; however, there is little information about the effectiveness of DEX as an adjuvant to LAs in paravertebral block (PVB). Therefore, a systematic review and meta-analysis were performed to evaluate the safety and efficacy of DEX combined with LAs in PVB., Method: An electronic database search from inception date to February 2018 was performed. Randomized controlled trials (RCTs) comparing DEX as an adjuvant to LAs with LAs alone for PVB in adult patients were included. Postoperative pain scores, duration of analgesia, cumulative perioperative analgesic consumption, and adverse events were analyzed., Result: We identified 7 trials enrolling 350 patients and found that DEX reduced pain scores at rest by standardized mean differences (SMD) -0.86 cm (95% confidence interval [CI] [-1.55, -0.17], P = .01) and SMD -0.93 cm (95% CI [-1.41, -0.26], P =.008) at postoperative 12 hours and 24 hours, respectively. DEX reduced pain scores while dynamic by SMD -1.63 cm (95% CI [-2.92, -0.34], P =.01) and SMD -1.78 cm (95% CI [-2.66, -0.90], P =.007) for postoperative 12 hours and 24 hours, respectively. DEX extended the duration of analgesia by weighted mean differences (WMD) 201.53 minutes (95% CI [33.45, 369.61], P =.02); and reduced cumulative postoperative analgesic consumption by WMD -7.71 mg (95% CI [-10.64, -4.78], P <.001) and WMD -45.64 mg (95% CI [-69.76, -21.53], P < .001) for 24 hours morphine and 48 hours tramadol subgroups, respectively. DEX also increased the odds of hypotension by odds ratio (OR) 4.40 (95% CI [1.37, 14.17], P = .01); however, there was no statistically significant difference for intraoperative fentanyl consumption and the incidence of the bradycardia., Conclusions: DEX combined with LAs in PVB significantly improved postoperative pain scores, prolonged the duration of analgesia, reduced postoperative analgesic consumption, and increased the odds of hypotension. However, we cannot neglect the heterogeneity of the included RCTs. More large-scale prospective studies are needed to further clarify the above conclusions., Systematic Review Registration: PROSPERO registration number CRD42018090251.

Objective: To compare the outcomes of hysterectomy patients who received standard pain management including IV acetaminophen (IV APAP) versus oral APAP., Methods: We performed a retrospective analysis of the Premier Database (January 2012 to September 2015) comparing hysterectomy patients who received postoperative pain management including IV APAP to those who received oral APAP starting on the day of surgery and continuing up to the third post-operative day, with no exclusions based on additional pain management. We compared the groups on length of stay (LOS), hospitalization costs, and average daily morphine equivalent dose (MED). The quarterly rate of IV APAP use for all hospitalizations by hospital was used as an instrumental variable in two-stage least squares regressions also adjusting for patient demographics, clinical risk factors, and hospital characteristics., Results: We identified 22,828 hysterectomy patients including 14,811 (65%) who had received IV APAP. Study subjects averaged 50 and 52 years of age, respectively in the IV APAP and oral APAP cohorts and were predominantly non-Hispanic Caucasians (≥60% in both cohorts). Instrumental variable models found IV APAP associated with 0.8 days shorter hospitalization (95% CI: -0.92 to -0.68, p<0.0001) and $2,449 lower hospitalization costs (95% CI: -$2,902 to -$1,996, p<0.0001). Average daily MED trended lower without statistical significance (-1.41 mg, 95% CI: -3.43 mg to 0.61 mg, p = 0.17)., Conclusions: Compared to oral APAP, managing post-hysterectomy pain with IV APAP is associated with shorter LOS and lower total hospitalization costs., Competing Interests: We also want to openly declare the following competing interests. RNH has received grants and consulting fees from Mallinckrodt Pharmaceuticals. ATP and BL are former employees of Mallinckrodt Pharmaceuticals. EAB and GJW are employees of Mallinckrodt Pharmaceuticals. RDU has served as a consultant for Mallinckrodt Pharmaceuticals and has received grant support for an unrelated study. Additionally, IV acetaminophen is commercialized by Mallinckrodt Pharmaceuticals. These competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials. However, access to the data set used in this analysis is restricted based on a commercial license with Premier and thus cannot be shared.

Objective: Evaluate post-tonsillectomy outcomes in children discharged with ibuprofen versus those without., Methods: This was a retrospective review of children who underwent tonsillectomy ± adenoidectomy from 2012 to 2016 at a tertiary care children's hospital. Main outcome measures included bleed rates, ER visits, and nurse phone calls., Results: Seven hundred and seventy-three patients were included; 504 had ibuprofen at discharge (ID) and 269 did not (NID). There were significant differences in mean age, 6.7 years in the ID group years versus 8.6 for the NID group (P < 0.001). Indication for surgery was sleep apnea in 70.5% of ID patients and 44.0% of NID patients (P < 0.001). Post-tonsillectomy bleeds occurred in 8.7% in the ID group and 5.9% of the NID group (P = 0.168). Other outcome measures revealed no significant differences between the two groups. There was no significant difference in the outcome measures between patients with sleep apnea or recurrent tonsillitis. Age was important; 12.1% of children 9-18 years versus 4.8% in children 3.1-6 years (P = 0.006) had post-tonsillectomy bleeding. For children 9-18 years old, 16.7% in the ID group bled versus 7.5% in the NID group (P = 0.039). Logistical regression revealed that age contributed to post-op bleeding, and ibuprofen contributed to number of ER visits., Conclusion: Ibuprofen is associated with significantly elevated post-tonsillectomy bleeding in older children, further research is needed and other analgesics should be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study evaluated the efficacy and safety of dexmedetomidine in intravenous patient-controlled analgesia (PCA) after cesarean delivery. This multicenter study enrolled 208 subjects who were scheduled for selective cesarean delivery from 9 research centers. Patients received 0.5 ug/kg dexmedetomidine (study group) or normal saline (control group) after delivery and an intravenous PCA pump after surgery (100 μg sufentanil +300 μg dexmedetomidine for the study group, 100 μg sufentanil for the control group, background infusion: 1 ml/h, bolus dose: 2 ml and lock time: 8 min). The sufentanil consumption, pain scores, rescue analgesia, sedation scores, analgesic satisfaction, the incidence of postoperative nausea and vomiting (PONV) and the first passage of flatus were recorded within 24 h after surgery. The sufentanil consumption in the study group was significantly lower than that in the control group (p = 0.004). Compared with the control group, the study group had lower pain scores (p < 0.01), higher analgesic satisfaction degree [p < 0.001, odd ratio 4.28 and 95% CI (2.46, 7.46)], less requirement of rescue analgesia (p = 0.003), lower incidence of PONV (p = 0.005 and p < 0.001, respectively), and shorter time to first passage of flatus (p = 0.007). Dexmedetomidine added to sufentanil intravenous PCA significantly enhanced the analgesic effects, improved analgesic satisfaction, and had the potential benefits of reducing PONV and the recovery of intestinal functions after cesarean section.

Background: Adjuvant perineural dexmedetomidine can be used to prolong the analgesic effect of interscalene brachial plexus block (ISB). We investigated the optimal dose of dexmedetomidine in ISB for postoperative analgesia in patients undergoing arthroscopic shoulder surgery., Methods: One hundred patients scheduled for elective shoulder arthroscopic surgery were enrolled in this randomized, double-blind study. Ultrasound-guided ISB was performed before general anesthesia using 22 mL of ropivacaine 0.5% combined with 1, 1.5, or 2 μg/kg of dexmedetomidine (group D1, D2, and D3, respectively) or with normal saline as a control (group R, n = 25 per group). The primary outcome was the duration of analgesia (DOA), numeric pain rating scale (NRS), and consumption of additional analgesics during 36 h after ISB. Secondary outcome included durations of motor and sensory block (DOM and DOS), hemodynamic variables and sedation and dyspnea scores., Results: Ninety-seven patients completed the study. The DOS, DOM, and DOA were significantly longer in the dexmedetomidine groups than in group R. The DOA was significantly longer in group D3 than in groups D1 (P = .026) and D2 (P = .039). The DOA was 808.13 ± 179.97, 1032.60 ± 288.14, 1042.04 ± 188.13, and 1223.96 ± 238.06 min in groups R, D1, D2, and D3, respectively. The NRS score was significantly higher in group R than in the dexmedetomidine groups 12 h after ISB (P < .001) and significantly lower in group D3 than in the other groups 18 h after ISB (P = .02). The incidence of hypotension was higher in groups D2 and D3 than in group R during surgery (P = .008 and P = .011, respectively). There were no significant differences in consumption of rescue analgesics, sedation, and dyspnea scores between the study groups., Conclusion: Perineural dexmedetomidine 2 μg/kg could be the optimal dose in ISB for arthroscopic shoulder surgery in that it provides an adequate DOA. However, this dose was associated with increased risk of hypotension.

Background and Objectives: Carpal tunnel syndrome is a frequent cause of neuropathic pain of the upper limb. Surgery is often proposed in second-line treatment, leading to an expected decrease in analgesic drug consumption. The main objective of this study was to investigate the variations in analgesic drug prescriptions, with a special focus on constant or increasing prescription patterns, before and after surgery for carpal tunnel syndrome., Methods: We designed a retrospective cohort study of French beneficiaries from the health insurance system in Midi-Pyrénées area. All patients undergoing carpel tunnel surgery during a specified period were identified and included. Definition of increased or constant prescription of analgesics was based on the comparison of the accumulated defined daily doses received by months and a difference between early preoperative (2 months before) and late postoperative period (2-12 months after surgery) superior to a -3.5 margin. We performed 4 multivariate logistic regression models to identify factors associated with increased or constant analgesic drug prescription patterns (for all analgesics, opioid, antineuropathic, nonopioid drugs)., Results: Among the 3665 patients included, 3255 (89%) received at least 1 analgesic drug during the late postoperative period (39% [n = 1426] for opioids and 15% [n = 563] for antineuropathic drugs). Prescription of analgesic, opioid, or antineuropathic drugs was maintained or increased in the late postoperative period in 11%, 5%, and 3% of the population, respectively. High levels of preoperative pain and female sex were associated with an increase in opioid use, whereas inpatient surgery (vs ambulatory surgery), high levels of preoperative pain, and psychiatric disorders were found to be associated with an increase in antineuropathic drug use., Conclusions: This study revealed that approximately 3% to 5% of patients undergoing carpal tunnel surgery had persistent and even increased use of opioid or antineuropathic drugs more than 2 months after surgery, in relation with possible chronic postoperative pain. Considering the incidence of carpal tunnel syndrome, the risks associated with persistent opioid use in this population should be further monitored.

There is an epidemic of opioid use, abuse, and misuse in the United States, which results in significant morbidity and mortality. It may be difficult to reduce perioperative opioid use given known acute surgical trauma and resultant pain; however, the discrete and often limited nature of postoperative pain also may make management easier in part by utilizing nonopioid modalities, such as regional anesthesia/analgesia, and multimodal analgesia, which may decrease the need for powerful opioids. This article reviews the relevant literature describing the use of adjunct medications, regional anesthesia and analgesic techniques, and regional block additives in the context of providing adequate pain control while lessening opioid use.

Background: The United States is in the midst of an opioid epidemic, and opioid use disorder often begins with a prescription for acute pain. The perioperative period represents an important opportunity to prevent chronic opioid use, and recently there has been a paradigm shift toward implementation of enhanced recovery after surgery (ERAS) protocols that promote opioid-free and multimodal analgesia. The objective of this study was to assess the impact of an ERAS intervention for colorectal surgery on discharge opioid prescribing practices., Methods: We conducted a historical-prospective quality improvement study of an ERAS protocol implemented for patients undergoing colorectal surgery with a focus on the opioid-free and multimodal analgesia components of the pathway. We compared patients undergoing colorectal surgery 1 year before implementation (June 15, 2015, to June 14, 2016) and 1 year after implementation (June 15, 2016, to June 14, 2017)., Results: Before the ERAS intervention, opioids at discharge were not significantly increasing (1% per month; 95% confidence interval [CI], -1% to 3%; P = .199). Immediately after the ERAS intervention, opioid prescriptions were not significantly lower (13%; 95% CI, -30% to 3%; P = .110). After the intervention, the rate of opioid prescriptions at discharge did not decrease significantly 1% (95% CI, -3% to 1%) compared to the pre-period rate (P = .399). Subgroup analysis showed that in patients with a combination of low discharge pain scores, no preoperative opioid use, and low morphine milligram equivalents consumption before discharge, the rate of discharge opioid prescription was 72% (95% CI, 61%-83%)., Conclusions: This study is the first to report discharge opioid prescribing practices in an ERAS setting. Although an ERAS intervention for colorectal surgery led to an increase in opioid-free anesthesia and multimodal analgesia, we did not observe an impact on discharge opioid prescribing practices. The majority of patients were discharged with an opioid prescription, including those with a combination of low discharge pain scores, no preoperative opioid use, and low morphine milligram equivalents consumption before discharge. This observation in the setting of an ERAS pathway that promotes multimodal analgesia suggests that our findings are very likely to also be observed in non-ERAS settings and offers an opportunity to modify opioid prescribing practices on discharge after surgery. For opioid-free anesthesia and multimodal analgesia to influence the opioid epidemic, the dose and quantity of the opioids prescribed should be modified based on the information gathered by in-hospital pain scores and opioid use as well as pain history before admission.

Background: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results., Methods/design: The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively., Discussion: PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination of paracetamol and ibuprofen used in a perioperative setting., Trial Registration: ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015.

Background: Dexmedetomidine showed some potential in pain control in patients undergoing knee arthroscopy. We conducted a systematic review and meta-analysis to explore the efficacy of dexmedetomidine in patients undergoing knee arthroscopy., Methods: We searched the randomized controlled trials (RCTs) assessing the effect of dexmedetomidine on knee arthroscopy in PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases. The primary outcome was pain scores. Meta-analysis was performed using the random-effect model., Results: Five RCTs were included. Overall, compared with control intervention in patients with knee arthroscopy, dexmedetomidine intervention could significantly reduce the pain scores [Std. mean difference = -0.84; 95% confidence interval (95% CI) = -1.24 to -0.44; P < .0001] and postoperative diclofenac sodium consumption (Std. mean difference = -1.76; 95% CI = -3.32 to -0.21; P = .03), improve duration of analgesic effect (Std. mean difference = 1.78; 95% CI = 0.56-3.00; P = .004), but showed no influence on hypotension [risk ratio (RR) = 0.93; 95% CI = 0.14-5.92; P = .94], bradycardia (RR = 4.93; 95% CI = 0.91-26.58; P = .06), nausea, and vomiting (RR = 1.96; 95% CI = 0.31-12.58; P = .48)., Conclusion: Dexmedetomidine intervention was able to significantly reduce the pain scores and postoperative diclofenac sodium consumption, and improve duration of analgesic effect in patients undergoing knee arthroscopy, but had no influence on hypotension, bradycardia, nausea, and vomiting.

Background: Thoracic outlet decompression (TOD) is associated with significant postoperative pain often leading to hospital length of stay out of proportion to the risk profile of the operation. We seek to describe the improvement in hospital length of stay and patient pain control with an improved multiagent pain management regimen., Methods: We retrospectively reviewed the hospital length of stay, medication regimen/usage, operative details, and operative indications for all patients undergoing TOD from January 2012 through June 2015. During early experience, single-agent narcotic therapy was the mainstay of postoperatively pain control. Since 2014, we have adopted a regimen consisting of narcotic patient controlled analgesia, oral narcotics, and scheduled ibuprofen and valium, which is transitioned to oral narcotics/valium upon discharge. Operative approach (supraclavicular, infraclavicular, transaxial, or paraclavicular) was determined by patient anatomy and indication for procedure (neurogenic/arterial thoracic outlet syndrome or arteriovenous access dysfunction)., Results: Seventy-four patients were treated with TOD over the study period: 36 (49.3%) for neurogenic thoracic outlet syndrome, 23 (31.5%) for venous thoracic outlet syndrome, and 15 (19.2%) for arteriovenous access dysfunction. Prior to 2014, the mean length of stay was 4 days with a median pain score of 6. Since 2014, the mean length of stay was 2.6 (P = 0.04) with a median pain score of 4 (P = 0.005). There was no statistically significant difference in the indication for operation or operative approach between the two periods., Conclusions: Since adoption of a multiagent pain management regimen to include scheduled NSAIDs and benzodiazepines, we have reduced the mean pain score experienced by our patients as well as the hospital length of stay., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Control of emergence hypertension and pain is important after craniotomy for monitoring the neurological status. This prospective double-blinded study investigated the hemodynamics after a single bolus of dexmedetomidine (DEX) infusion administered to the patient undergoing craniotomy under general anesthesia, and its effect on emergence hypertension and postsurgical pain., Methods: Adult patients scheduled for elective surgery for supratentorial tumors were randomized to receive a 10-minute intraoperative DEX infusion of 0.4 μg/kg (small dose, n=43) or 0.8 μg/kg (medium dose, n=46), or normal saline (vehicle control, n=45), ∼60 minutes before the end of anesthesia., Results: A transient increase in the blood pressure associated with DEX was observed; 53.5% and 91.3% of the patients in the small-dose and the medium-dose groups, respectively, required treatment. Emergence mean arterial pressure and heart rates were significantly lower in the DEX groups compared with the control group. Incidence rates of postoperative hypertension in the small-dose (16.3%) and the medium-dose groups (15.2%) were significantly lower relative to that of the control group (35.6%). Patients who received DEX had a lower Verbal Numerical Rating Scale (VNRS) score in the neurosurgical ICU than the control group, and postsurgical pain (VNRS≥4) was lower in the medium-dose group (41.3%) than in the control group (71.1%). No shivering was observed in the medium-dose group, which was significantly less than that of the other 2 groups., Conclusions: An intraoperative bolus of DEX risks a transient increase in mean arterial pressure, but controls emergence hypertension effectively. Dose-related reductions in postsurgical pain and shivering were observed.

Background: This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions., Objectives: To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level., Search Methods: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries., Selection Criteria: Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain., Data Collection and Analysis: Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE, and created 'Summary of findings' tables., Main Results: This updated review included 24 studies; six additional studies added 1001 participants involved in comparisons of ketoprofen or dexketoprofen and placebo, with a 12% increase in participants taking ketoprofen and a 65% increase for dexketoprofen. Most participants (70%) were women. Dental studies typically involved young participants (mean age 20 to 30 years); other types of surgery involved older participants (mean age 37 to 68 years). Overall, we judged the studies at high risk of bias only for small size, which can lead to an overestimation of benefit.Ketoprofen doses ranged between 6.5 mg and 150 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual ketoprofen oral dose of 50 mg was 57%, compared to 23% with placebo, giving an NNT of 2.9 (95% CI 2.4 to 3.7) (RR 2.5, 95% CI 2.0 to 3.1; 594 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 1.8) than other surgery (NNT 4.2). The proportion of participants using rescue medication within six hours was lower with ketoprofen (32%) than with placebo (75%), giving a number needed to treat to prevent use of rescue medication (NNTp) of 2.3 (95% CI 1.8 to 3.1); 263 participants; 4 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with ketoprofen (18%) and placebo (11%) (RR 1.6, 95% CI 0.98 to 2.8; 342 participants; 5 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence).Dexketoprofen doses ranged between 5 mg and 100 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual dexketoprofen oral dose of 20 mg or 25 mg was 52%, compared to 27% with placebo, giving an NNT of 4.1 (95% CI 3.3 to 5.2) (RR 2.0, 95% CI 1.6 to 2.2; 1177 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 2.7) than other surgery (NNT 5.7). The proportion of participants using rescue medication within six hours was lower with dexketoprofen (47%) than placebo (69%), giving an NNTp of 4.7 (95% CI 3.3 to 8.0); 445 participants; 5 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with dexketoprofen (14%) and placebo (10%) (RR 1.4, 95% CI 0.89 to 2.2; 536 participants, 6 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence)., Authors' Conclusions: Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 2.9 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 for 50 mg dose). Dexketoprofen is also effective with an NNT of 4.1 in the dose range 10 mg to 25 mg. Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual. Both drugs were well tolerated in single doses.

Objective: A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy of pregabalin for the management of postoperative pain in patients undergoing primary total knee arthroplasty (TKA) and primary total hip arthroplasty (THA)., Method: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for related articles using search strategy. RevMan 5.3 software was selected to conduct the meta-analysis., Results: Seven RCTs were included in our meta-analysis. There were significant differences in visual analogue scale (VAS) at 24 and 48 h with rest, knee flexion degree, mean morphine consumption, and postoperative side effects (nausea, vomiting, pruritus, and dizziness) when comparing the pregabalin group to the placebo group after TKA and THA. However, the differences in VAS at 72 h with rest and at 24 h on movement were not significant between the two groups., Conclusions: Pregabalin was found to improve pain control at 24 and 48 h with rest, reduce morphine consumption, improve the knee flexion degree, decrease the incident rate of nausea, vomiting, and pruritus, and increase the incident rate of dizziness after TKA and THA but could not improve the pain control at 72 h with rest. In summary, the use of pregabalin may be a valuable asset in pain management within the first 48 h after TKA and THA. However, future studies regarding doses and pregabalin medication are required.

Background and Objectives: Dexmedetomidine has been thought to be an effective adjuvant to local anesthetics in brachial plexus blockade. We sought to clarify the uncertainty that still exists as to its true efficacy., Methods: A meta-analysis of randomized controlled trials was conducted to assess the ability of dexmedetomidine to prolong the duration and hasten the onset of motor and sensory blockade when used as an adjuvant to local anesthesia for brachial plexus blockade versus using local anesthesia alone (control). A search strategy was created to identify eligible articles in MEDLINE, EMBASE, and The Cochrane Library. The methodological quality for each included study was evaluated using the Cochrane Tool for Risk of Bias., Results: Eighteen randomized controlled trials were included in this meta-analysis (n = 1092 patients). The addition of dexmedetomidine significantly reduced sensory block time onset time by 3.19 minutes (95% confidence interval [CI], -4.60 to -1.78 minutes; I = 95%; P < 0.00001), prolonged sensory block duration by 261.41 minutes (95% CI, 145.20-377.61 minutes; I = 100%; P < 0.0001), reduced the onset of motor blockade by 2.92 minutes (95% CI, -4.37 to -1.46 minutes; I = 96%, P < 0.0001), and prolonged motor block duration by 200.90 minutes (CI, 99.24-302.56 minutes; I = 99%; P = 0.0001) as compared with control. Dexmedetomidine also significantly prolonged the duration of analgesia by 289.31 minutes (95% CI, 185.97-392.64 minutes; I = 99%; P < 0.00001). Significantly more patients experienced intraoperative bradycardia with dexmedetomidine (risk difference [RD], 0.06; 95% CI, 0.00-0.11; I = 72%; P = 0.03); however, there was no difference in the incidence of intraoperative hypotension (RD, 0.01; 95% CI, -0.02 to 0.04; I = 3%; P = 0.45). It is important to note that all studies reported that intraoperative bradycardia was either transient in nature or reversible, when needed, with the administration of intravenous atropine., Conclusions: Dexmedetomidine has the ability to hasten the onset and prolong the duration of blockade when used as an adjuvant to local anesthesia for brachial plexus blockade. Considering an analgesic effect to be either decreased pain, a longer duration of analgesic block, or decreased opioid consumption, the addition of dexmedetomidine to local anesthetics for brachial plexus blockade was found to significantly improve analgesia in all 18 included studies. However, patients receiving dexmedetomidine should be continuously monitored for the potentially harmful but reversible adverse effect of intraoperative bradycardia., Level of Evidence: Therapeutic, level I.

Intraoperative dexemdetomidine (DEX) with or without loading dose is well-established to improve postoperative pain control in patient-controlled analgesia (PCA). This study was designed to compare the pro-analgesia effect between the 2 in patients received general anesthesia.Seventy patients shceduced abdominal surgery under general anesthesia were randomly assigned into 3 groups which were maintained using propofol/remifentanil/Ringer solution (PRR), propofol/remifentanil/dexmedetomidine with (PRDw) or without (PRDo) a loading dose of dexmedetomidine before induction.PRDw/o patients displayed a greater Romsay sedation score measured immediately after surgery. When compared with PRR patients, those from the PRDw/o group had an increased time to first request of postoperative morphine and decreased 24 hours total morphine consumption. No significant difference was observed between patients from the PRDw and PRDo groups with respect to these parameters.The present study suggests that the administration of a DEX loading dose does not affect the pro-analgesic effect of intraoperative use of DEX on morphine-based PCA.

Background: Morphine, and analgesics other than morphine (AOM), are commonly used to treat postoperative pain after major surgery. However, which AOM provides the best efficacy-safety profile remains unclear., Methods: Randomized trials of any AOM alone or any combination of AOM compared with placebo or another AOM in adults undergoing major surgery and receiving morphine patient-controlled analgesia were included in a network meta-analysis. The outcomes were morphine consumption, pain, incidence of nausea, vomiting at 24 h and severe adverse effects., Results: 135 trials (13,287 patients) assessing 14 AOM alone or in combination were included. For all outcomes, comparisons with placebo were over-represented. Few trials assessed combinations of two AOM and none the combination of three or more. Network meta-analysis found morphine consumption reduction was greatest with the combination of two AOM (acetaminophen + nefopam, acetaminophen + NSAID, and tramadol + metamizol): -23.9 (95% CI -40;-7.7), -22.8 (-31.5;-14) and -19.8 (35.4;-4.2) mg per 24 h, respectively. For AOM used alone, morphine consumption reduction was greatest with α-2 agonists, NSAIDs, and COX-2 inhibitors. When considering the risk of nausea, NSAIDs, corticosteroids and α-2 agonists used alone were the most efficacious (OR 0.7 [95% CI: 0.6-0.8], 0.36 [0.18-0.79], 0.41 [0.15-.64], respectively). The paucity of severe adverse effects data did not allow assessment of efficacy-safety balance., Conclusions: A combination of aetaminophen with either an NSAID or nefopam was superior to most AOM used alone, in reducing morphine consumption. Efficacy was best with three AOM used alone (α-2 agonists, NSAIDs and COX-2 inhibitors) and least with tramadol and acetaminophen. There is insufficient trial data reporting adverse events., Clinical Trial Registration: PROSPERO: CRD42013003912., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To evaluate postoperative pain management (POPM) practices by anesthesiologists caring for patients with chronic kidney disease (CKD)., Design: Prospective one-time survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR)., Setting: A self-administered online questionnaire was distributed to members of SFAR nationally., Participants: Three hundred seven SFAR members participated in the study., Intervention: Close-ended questions concerned: standard test used to assess renal function, analgesic agent selection and dose adjustment based on the CKD functional stage, and the availability of standard operating procedures., Main Outcomes Measures: The primary end-point was to identify the most frequently prescribed analgesics in case of CKD, variations in practice based on different stages of CKD, and drug dosing adjustments. The secondary end-point was to identify the most commonly used tests to evaluate kidney function., Results: The most commonly used postoperative analgesics were paracetamol (acetaminophen) and morphine. The most commonly used opioid was morphine, relative to oxycodone and sufentanil. Modification of diet in renal disease (MDRD) and Cockcroft equations were used by 39 and 40 percent of anesthesiologists, respectively, to measure kidney function. Six percent of anesthesiologists declared following standard operating procedures for POPM in patients with CKD., Conclusions: There is considerable variability in POPM practices for patients with all stages of CKD. Morphine is favored even in end-stage renal disease. Departments of anesthesiology are insufficiently involved in drafting standard operating procedures.