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Importance: Opioids administered to treat postsurgical pain are a major contributor to the opioid crisis, leading to chronic use in a considerable proportion of patients. Initiatives promoting opioid-free or opioid-sparing modalities of perioperative pain management have led to reduced opioid administration in the operating room, but this reduction could have unforeseen detrimental effects in terms of postoperative pain outcomes, as the relationship between intraoperative opioid usage and later opioid requirements is not well understood., Objective: To characterize the association between intraoperative opioid usage and postoperative pain and opioid requirements., Design, Setting, and Participants: This retrospective cohort study evaluated electronic health record data from a quaternary care academic medical center (Massachusetts General Hospital) for adult patients who underwent noncardiac surgery with general anesthesia from April 2016 to March 2020. Patients who underwent cesarean surgery, received regional anesthesia, received opioids other than fentanyl or hydromorphone, were admitted to the intensive care unit, or who died intraoperatively were excluded. Statistical models were fitted on the propensity weighted data set to characterize the effect of intraoperative opioid exposures on primary and secondary outcomes. Data were analyzed from December 2021 to October 2022., Exposures: Intraoperative fentanyl and intraoperative hydromorphone average effect site concentration estimated using pharmacokinetic/pharmacodynamic models., Main Outcomes and Measures: The primary study outcomes were the maximal pain score during the postanesthesia care unit (PACU) stay and the cumulative opioid dose, quantified in morphine milligram equivalents (MME), administered during the PACU stay. Medium- and long-term outcomes associated with pain and opioid dependence were also evaluated., Results: The study cohort included a total of 61 249 individuals undergoing surgery (mean [SD] age, 55.44 [17.08] years; 32 778 [53.5%] female). Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. In particular, increased fentanyl administration was associated with lower frequency of uncontrolled pain; a decrease in new chronic pain diagnoses reported at 3 months; fewer opioid prescriptions at 30, 90, and 180 days; and decreased new persistent opioid use, without significant increases in adverse effects., Conclusions and Relevance: Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended outcome of increasing postoperative pain and opioid consumption. Conversely, improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery.

Abstract: Recovery from surgery is quicker in the postpartum period, and this may reflect oxytocin action in the spinal cord. We hypothesized that intrathecal injection of oxytocin would speed recovery from pain and disability after major surgery. Ninety-eight individuals undergoing elective total hip arthroplasty were randomized to receive either intrathecal oxytocin (100 μg) or saline. Participants completed diaries assessing pain and opioid use daily and disability weekly, and they wore an accelerometer beginning 2 weeks before surgery until 8 weeks after. Groups were compared using modelled, adjusted trajectories of these measures. The study was stopped early due to the lack of funding. Ninety patients received intrathecal oxytocin (n = 44) or saline (n = 46) and were included in the analysis. There were no study drug-related adverse effects. Modelled pain trajectory, the primary analysis, did not differ between the groups, either in pain on day of hospital discharge (intercept: -0.1 [95% CI: -0.8 to 0.6], P = 0.746) or in reductions over time (slope: 0.1 pain units per log of time [95% CI: 0-0.2], P = 0.057). In planned secondary analyses, postoperative opioid use ended earlier in the oxytocin group and oxytocin-treated patients walked nearly 1000 more steps daily at 8 weeks ( P < 0.001) and exhibited a clinically meaningful reduction in disability for the first 21 postoperative days ( P = 0.007) compared with saline placebo. Intrathecal oxytocin before hip replacement surgery does not speed recovery from worst daily pain. Secondary analyses suggest that further study of intrathecal oxytocin to speed functional recovery without worsening pain after surgery is warranted., (Copyright © 2022 International Association for the Study of Pain.)

Background: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake., Methods: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed., Results: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups., Conclusion: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD., Competing Interests: The authors have declared that no competing interests exist.

Background: Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs)., Methods: We performed a pre-specified analysis of 145 735 adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used., Results: PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses [median: 3.85; inter-quartile range (IQR): 3.42-4.50 μg kg -1 , quartile 4 (Q4)], low intraoperative fentanyl dose [median: 0.80, IQR: 0.00-1.14 μg kg -1 , quartile 1 (Q1)] was significantly associated with lower odds of PRCs [Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75-0.84; P<0.001; adjusted absolute risk difference (aARD) -1.7%]. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD -6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD -2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD -3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75-0.89, P<0.001)., Conclusions: Intraoperative low-dose fentanyl (about 60-120 μg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups., Clinical Trial Registration: NCT03198208., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Although racial/ethnic and sex disparities have been examined in health care generally and pain management more specifically, the combined influence of these sociodemographic factors together has not been well documented. The aim of this study was to examine the association between administration of opioid analgesics in the emergency department (ED) and interaction of race/ethnicity and sex., Methods: We conducted a retrospective cohort study using 2010-2014 Center for Disease Control-National Hospital Ambulatory Medical Care Survey data for patients 12-55 years of age presenting to EDs with a primary diagnosis of appendicitis or gallbladder disease as defined by International Classification of Diseases, Ninth Revision codes. The primary outcome was the receipt of opioid analgesic medications. Secondary outcomes included: receipt of nonopioids, receipt of antiemetic medications, wait time to see a provider, and length of visit in the ED. The association between sex and analgesic receipt within Caucasian non-Hispanic and non-Caucasian groups was evaluated adjusting for pain score on presentation, patient age, emergent status, number of comorbidities, time of visit (month, day of the week, standard versus nonstandard working hours, year), and US region., Results: After exclusions, a weighted sample of 553 ED visits was identified, representing 2,622,926 unique visits. The sample population was comprised of 1,858,035 (70.8%) females and 1,535,794 (58.6%) Caucasian non-Hispanics. No interaction was found in adjusted sampling-weighted model between sex and race/ethnicity on the odds of receiving opioids (P = .74). There was no difference in opioid administration to males as compared to females (odds ratio [OR] = 0.96, 95% CI, 0.87-1.06; P = .42) or to non-Caucasians as compared to Caucasians (OR = 0.99, 95% CI, 0.89-1.10; P = .84). In adjusted weighted models, non-Caucasian males, 123,121/239,457 (51.4%) did not differ from Caucasian non-Hispanic males, 317,427/525,434 (60.4%), on odds of receiving opioids, aOR = 0.88, 95% CI, 0.39-1.99; P = .75. Non-Caucasian females, 547,709/847,675 (64.6%) also did not differ from Caucasian females, 621,638/1,010,360 (61.5%), on odds of receiving opioids, aOR = 1.01, 95% CI, 0.53-1.90; P = .98. Across both sexes, non-Caucasians did not differ from Caucasians on receipt of nonopioid analgesics or antiemetics. Neither wait time to see a provider nor the length of the hospital visit was significantly different between sexes or race/ethnicities., Conclusions: Based on National Hospital Ambulatory Medical Care Survey data from 2010 to 2014, there is no statistically significant interaction between race/ethnicity and sex for administration of opioid analgesia to people presenting to the ED with appendicitis or gallbladder disease. These results suggest that the joint effect of patient race/ethnicity and sex may not manifest in disparities in opioid management.

Background: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission., Methods: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors., Results: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors., Conclusions: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery., Methods: We conducted a survey at six academic medical centers in the United States from September 2014 to March 2016. Women who had undergone a cesarean delivery were contacted by phone 2 weeks after discharge and participated in a structured interview about the opioid prescription they received on discharge and their oral opioid intake while at home., Results: A total of 720 women were enrolled; of these, 615 (85.4%) filled an opioid prescription. The median number of dispensed opioid tablets was 40 (interquartile range 30-40), the median number consumed was 20 (interquartile range 8-30), and leftover was 15 (interquartile range 3-26). Of those with leftover opioids, 95.3% had not disposed of the excess medication at the time of the interview. There was an association between a larger number of tablets dispensed and the number consumed independent of patient characteristics. The amount of opioids dispensed did not correlate with patient satisfaction, pain control, or the need to refill the opioid prescription., Conclusion: The amount of opioid prescribed after cesarean delivery generally exceeds the amount consumed by a significant margin, leading to substantial amounts of leftover opioid medication. Lower opioid prescription correlates with lower consumption without a concomitant increase in pain scores or satisfaction.