Opioid-related Adverse Events Research Articles

Assessment of feasibility of opioid-free anesthesia combined with preoperative thoracic paravertebral block and postoperative intravenous patient-controlled analgesia oxycodone with non-opioid analgesics in the perioperative anesthetic management for video-assisted thoracic surgery.

This study, conducted between December 2015 and March 2018 at a single university hospital, explored the feasibility and safety of opioid-free anesthesia combined with preoperative thoracic paravertebral block (ThPVB) for patients undergoing elective video-assisted thoracoscopic surgery (VATS). The aim was to assess the impact of this approach on postoperative pain levels and opioid consumption. Sixty-four patients scheduled for elective VATS were randomly assigned to either the intervention group, receiving opioid-free anesthesia with ThPVB, or the control group, managed with standard general anesthesia. Postoperatively, both groups received oxycodone patient-controlled analgesia along with non-opioid analgesics. Pain intensity was measured using the Numeric Pain Rating Scale (NRS) and Prince Henry Hospital Pain Score (PHHPS). The total dose of postoperative oxycodone and the occurrence of opioid-related adverse events were recorded during the 24-hour follow-up period. Patients in the intervention group showed significantly lower pain levels at 20 and 24 hours post-procedure ( P = 0.015, P = 0.021, respectively) compared to the control group. Notably, oxycodone consumption at 24 hours was significantly higher in the control group ( p < 0.0001). No serious adverse events were observed during the study period. This study demonstrates the feasibility and safety of opioid-free anesthesia combined with ThPVB for elective VATS. The approach significantly reduces postoperative pain and the need for opioids, supporting its potential as an effective and balanced perioperative anesthetic strategy.

A systematic analysis and data mining of opioid-related adverse events submitted to the FAERS database.

The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.

Novel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review.

Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects. In this review, we discuss the mechanisms of action, findings from preclinical studies and clinical trials, and potential advantages of several novel opioids. The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)-all of which have demonstrated success in the clinical setting when compared to traditional opioids. On the other hand, dinalbuphine sebacate (DNS; semi-synthetic mu partial antagonist and kappa agonist), dual enkephalinase inhibitors (STR-324, PL37, and PL265), and endomorphin-1 analog (CYT-1010) have shown good efficacy in preclinical studies with future plans for clinical trials. Rather than relying solely on mu-opioid receptor agonism to relieve pain and risk opioid-related adverse events (ORAEs), novel opioids make use of alternative mechanisms of action to treat pain while maintaining a safer side-effect profile, such as lower incidence of nausea, vomiting, sedation, and respiratory depression as well as reduced abuse potential.

Assessment of a naloxone distribution plan in a veteran population who experienced an opioid-related overdose event

BackgroundThe Veteran Health Administration prioritizes the distribution of naloxone to veterans diagnosed with opioid use disorder (OUD) to prevent deaths due to opioid-related overdose. The Overdose Education and Naloxone Distribution (OEND) program was created with tools to supplement efforts in identifying veterans at risk of opioid-related adverse events secondary to OUD or other comorbidities and increase access, education, and distribution of naloxone. Utilizing the OEND tool, Veteran Health Indiana (VHI) employed two different distribution initiatives to increase access to naloxone. ObjectiveThe purpose of this study is to assess naloxone distribution efforts at a VA medical center and evaluate outcomes in patients who experienced opioid overdose events before and after the OEND initiatives were implemented. The primary outcome is to assess the distribution of naloxone within the year prior to the documented overdose event before and after the OEND initiatives. Secondary outcomes include assessment of the number of naloxone doses administered during the overdose event, substances involved in the overdose, and distribution of outpatient naloxone prescriptions after the overdose event. MethodsThis study was a retrospective electronic chart review of all patients who experienced an opioid-related overdose event at VHI from March 1, 2019, to March 1, 2022. ResultsOf the 59 opioid-overdose events analyzed, the percentage of patients with a naloxone prescription within 12 months prior to an opioid-overdose event was similar between the pre- and post-OEND initiatives. Within 12 months following the overdose event, naloxone was dispensed to nearly 10% more patients in the post-OEND group compared to the pre-OEND group. ConclusionsThe OEND initiatives increased naloxone distribution amongst patients who ultimately experienced an opioid-related overdose. Additional research is needed to assess if these efforts prevented further overdoses.

Outpatient cross-titration to buprenorphine for chronic pain: A retrospective analysis.

To determine the effectiveness and safety of the University of Washington's buprenorphine cross-titration protocol for chronic pain in the outpatient setting. Retrospective chart review was performed on 150 patients transitioned from full µ-opioid agonist therapy to buprenorphine using the University of Washington Medical Center Pain Clinic's cross-titration protocol between September 1, 2020, and December 31, 2021, in an outpatient setting. Primary outcome was to determine the percentage of patients who completed the cross-titration and continued buprenorphine without full µ-opioid agonists 4 weeks after completion. Secondary outcomes included final buprenorphine dose, days needed to complete cross-titration, deviation rates from the protocol, and opioid-related adverse events. Fifteen of 31 (48.4 percent) included patients successfully converted to buprenorphine. Median duration of successful cross-titration was 29 days (interquartile range 19-57). Average end-titration dose for patients on buprenorphine/naloxone sublingual films was 7.9 ± 5.7 mg/day, while for buprenorphine transdermal (TD) patches, it was 11.9 ± 4.8 mcg/h. Morphine equivalent daily dose (MEDD) prior to induction varied widely. All patients transitioned to TD buprenorphine were taking ≤30 mg MEDD. Patients previously taking >120 mg MEDD stabilized on 8-16 mg/day buprenorphine. Most common reasons for cross-titration failure were inadequate pain control and intolerable adverse effects. The University of Washington's buprenorphine cross-titration protocol for chronic pain was successful in about half of included patients undergoing conversion from chronic full µ-opioid agonist therapy and generally well tolerated. Clinical responses were widely variable, and many required slower taper and higher end-titration buprenorphine dose than anticipated. Although protocols provide structure for cross-titration, each course should be monitored closely and individualized.

Analgesic Effect of Intraoperative Intravenous S(+)-Ketamine During Total Knee Arthroplasty Surgery: Study Protocol for a Randomized Controlled Clinical Trial.

Total knee arthroplasty (TKA) is currently the main treatment for end-stage knee disease. The number of cases of TKA in China increased from 53,880 in 2011 to 374,833 in 2019, representing a 5.9-fold increase. Moderate to severe pain often occurs after TKA, which seriously affects postoperative rehabilitation, patient satisfaction, and overall outcome. Multimodal analgesia is considered the ideal solution. Adequate postoperative analgesia can not only reduce pain, opioid consumption, and, consequently, opioid-related adverse events, but can also reduce the length of hospital stay and costs and improve rehabilitation and patient satisfaction. Effective multimodal pain management in the early postoperative period is essential for anesthesiologists. Additional studies have demonstrated that a low-dose intravenous infusion of ketamine can be administered as an adjuvant drug to alleviate acute postoperative pain. Therefore, we aim to appraise the efficacy and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after TKA in older patients. This is a protocol for a randomized, placebo-controlled trial. A total of 144 participants aged 65 years and older undergoing TKA will be randomly allocated into the S(+)-ketamine and placebo groups in a 1:1 ratio. S(+)-ketamine or the placebo will be intravenously administered at 0.3 mg/kg/h during the operation by anesthesiologists. Blinded evaluation by trained investigators will be completed at 2 hours, 24 hours, and 48 hours after surgery. The primary outcome measure will be the numeric rating scale score at rest and movement at 24 hours after surgery. The secondary outcomes will include the numeric rating scale scores at rest and movement at 2 hours and 48 hours after surgery, the number of patients who require additional analgesics during the first 48 hours after operation, the total consumption of opioids or nonsteroid anti-inflammatory drugs during the first 48 hours after operation, and adverse events at 2, 24, and 48 hours after operation. The protocol was registered at Clinical Trials.gov on February 26, 2022. It was performed in accordance with the approved guidelines and regulations of the participating institutions. Recruitment began in April 2022. Data collection is expected to conclude in September 2024. Study completion is expected in December 2024. A randomized, controlled, clinical study was designed to observe the analgesic effect of intraoperative intravenous administration of a lower dose of S(+)-ketamine (0.3 mg/kg/h) in older patients after TKA surgery. The protocol will appraise the efficacy and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after TKA in older patients who may benefit from the administration of S(+)-ketamine. ClinicalTrials.gov NCT05289050; https://clinicaltrials.gov/ct2/show/NCT05289050. DERR1-10.2196/53063.

Opioid-free versus opioid-sparing anaesthesia in ambulatory total hip arthroplasty: a randomised controlled trial

BackgroundEnhanced recovery after surgery pathways are essential for ambulatory surgery. They usually recommend lower intraoperative opioid use to avoid opioid-related adverse effects. This has led to opioid-sparing anaesthesia (OSA) techniques, with the extreme approach of opioid-free anaesthesia (OFA) mostly with dexmedetomidine. As evidence is lacking in day-case primary total hip arthroplasty, this study was performed to assess the potential benefits in postoperative analgesia of OFA over OSA. MethodsIn this single-centre, prospective, triple blind study, we randomly allocated 80 patients undergoing day-case primary THA under general anaesthesia. Patients received a total intravenous anaesthesia with a laryngeal mask and multimodal analgesic regimen with non-opioid analgesics. The OSA group received low dose of sufentanil, and the OFA group received dexmedetomidine The primary outcome was the opioid consumption in the first 24 h in oral morphine equivalents (OME). ResultsThere was no difference in median cumulative OME consumption at 24 h between the OSA and OFA groups (12 [0–25] mg vs 16 [0–30] mg, respectively; P=0.7). Pain scores were similar and low in both groups with comparable walking recovery time. Adverse events were sparse and equivalent in both groups except for dizziness, which was more frequent in the OSA group (P<0.05). ConclusionsIn day-case total hip arthoplasty under general anaesthesia, opioid-free anaesthesia and opioid-sparing anaesthesia both provide early recovery and effective postoperative pain relief. When compared with opioid-sparing anaesthesia, opioid-free anaesthesia does not decrease opioid consumption in the first 24 h. These findings do not suggest any significant benefit from complete intraoperative avoidance of opioids. Clinical trial registrationNCT0507270.

Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis.

Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain. A systematic review and meta-analysis of randomized controlled trials (RCTs). The following data sources were systematically searched: MEDLINE, CENTRAL, and EMBASE (till 02/2021). Adult patients undergoing any surgery. Perioperative use of intravenous ketamine as an additive analgesic drug compared to placebo, no active control treatment, and other additive drugs. Primary outcomes were number of patients with chronic postsurgical pain after 6 months and ketamine related adverse effects. Secondary outcomes were chronic postsurgical pain incidence after 3 and 12 months, chronic postsurgical neuropathic pain incidence, chronic postsurgical moderate to severe pain incidence, intensity of chronic postsurgical pain at rest, and during movement, oral morphine consumption after 3, 6, and 12 months and incidence of opioid-related adverse effects. Thirty-six RCTs were included with a total of 3572 patients. Ketamine compared to placebo may result in no difference in the number of patients with chronic postsurgical pain after 6 months (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.71-1.05; I2 = 34%; 16 studies; low-certainty evidence). Ketamine may reduce the incidence of chronic postsurgical neuropathic pain after 3 months in comparison to placebo (RR 0.78, 95% CI 0.62-0.99, I2 = 31%, seven trials, low-certainty evidence). Ketamine compared to placebo may increase the risk for postoperative nystagmus (RR 9.04, 95% CI 1.15-70.90, I2 30%, two trials, low-certainty evidence) and postoperative visual disturbances (RR 2.29, 95% CI 1.05-4.99, I2 10%, seven trials, low-certainty evidence). There is low-certainty evidence that perioperative ketamine has no effect on chronic postsurgical pain in adult patients. Low-certainty evidence suggests that ketamine compared to placebo may reduce incidence of chronic postsurgical neuropathic pain after 3 months. Questions like ideal dosing, treatment duration and more patient-related outcome measures remain unanswered, which warrants further studies. Prospero CRD42021223625, 07.01.2021.

Analysis of Opioid-Related Adverse Events in Japan Using FAERS Database.

Adverse events associated with opioid use in palliative care have been extensively studied. However, predicting the occurrence of adverse events based on the specific opioid used remains difficult. This study aimed to comprehensively analyze the adverse events related to µ-opioid receptor stimulation of opioids approved in Japan and investigate the tendencies of adverse event occurrence among different opioids. We utilized the FDA Adverse Event Reporting System database to extract reported adverse events for opioids approved in Japan. Cluster analysis was performed on reporting odds ratios (RORs) of adverse event names among opioids to visualize relationships between opioids and adverse events, facilitating a comparative study of their classifications. We calculated the RORs of adverse events for the target opioids. Cluster analysis based on these RORs resulted in five broad clusters based on the reported adverse events: i.e., strong opioids, weak opioids, loperamide, tapentadol, and remifentanil. This study provides a comprehensive classification of the association between μ-opioid-receptor-stimulating opioids and adverse events.

Effectiveness of Intravenous Non-Opioid Analgesics for Postoperative Pain Management of in Patients Undergoing Hip Surgery: A Systematic Review and Meta-Analysis.

Background and Objectives: Intravenous (IV) non-opioid analgesics (NOAs) have been extensively investigated as a multimodal analgesic strategy for the management of acute pain after hip surgery. This pair-wise meta-analysis examined IV NOA effects following hip surgery. Materials and Methods: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of IV NOA for postoperative pain management following hip surgery up to 7 June 2023. We compared in-admission opioid use, postoperative VAS (visual analogue scale) score, hospital stay duration, and opioid-related adverse events between IV NOA and control groups. Results: Seven studies were included with a total of 953 patients who underwent hip surgery. Of these, 478 underwent IV NOA treatment, and 475 did not. The IV NOA groups had lower opioid use within 24-h following hip surgery (SMD, -0.48; 95% CI, -0.66 to -0.30; p < 0.01), lower VAS score (SMD, -0.47; 95% CI, -0.79 to -0.16; p < 0.01), shorter hospital stay (SMD, -0.28; 95% CI, -0.44 to -0.12; p < 0.01), and lower incidence of nausea and vomiting (OR, 0.32; 95% CI, 0.15 to 0.67; p < 0.01) compared with the control groups. Conclusions: This meta-analysis demonstrated that IV NOA administration following hip surgery may have more favorable postoperative outcomes than those in control groups.

Postoperative opioid-induced respiratory depression or oversedation requiring naloxone treatment in a community hospital: a case series

Background Postoperative opioid-induced respiratory depression and oversedation can lead to fatal events and increase perioperative mortality. In reports from major academic centers, naloxone administration has been used as a proxy for severe opioid overdose. Herein, we studied the incidence, clinical characteristics, and outcomes of postoperative naloxone use in a mid-size community hospital. Methods This was a retrospective review of adult patients who received naloxone within 48 postoperative hours between July 9, 2017, and May 31, 2022. Results During the study timeframe, a total of 23,362 surgical procedures were performed and a total of 19 patients received naloxone (8 in the recovery room, 11 on hospital wards), with an incidence of 8.1 [95% confidence interval 4.9–12.7] per 10,000 anesthetics. In 12 cases (63%), naloxone was indicated for oversedation, and in 7 cases (37%), for opioid-induced respiratory depression. All patients received naloxone within the first 24 postoperative hours. While all patients survived the opioid-related adverse event, 2 patients were intubated, 1 developed stress-induced cardiomyopathy, and 5 required intensive care unit admission. Conclusion The rate of early postoperative opioid-induced respiratory depression or oversedation in our community hospital was low; however, these patients often require a substantial escalation of medical management.

Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications

BACKGROUND: Optimal intrathecal dosing regimens for hydromorphone are not well established for analgesia after abdominal surgery. OBJECTIVES: We reviewed intrathecal hydromorphone doses and complications because dosing variability has been observed among anesthesiologists. We hypothesized that increasing doses of intrathecal hydromorphone would be associated with improved postoperative analgesia, but with increased rates of opioid-related adverse events. STUDY DESIGN: Retrospective analysis. SETTING: A high-volume academic referral center in the United States. METHODS: A retrospective study was conducted of adults undergoing abdominal surgery under general anesthesia supplemented preoperatively with intrathecal hydromorphone for postoperative analgesia from May 5, 2018, through May 31, 2021. Patients were categorized into 3 hydromorphone dosing groups: low-dose (50-100 µg), middle-dose (101-199 µg), and high-dose (200-300 µg). Multivariable logistic regression models were used to assess rates of severe postoperative pain, severe opioid-related adverse events, oversedation, and pruritus in the postanesthesia care unit (PACU) and within 24 hours after PACU discharge. RESULTS: Of 1,846 patients identified, 1,235 (66.9%) were in the low-dose group; 321 (17.3%), middle-dose group; and 290 (15.7%), high-dose group. Patients receiving the 2 higher doses had more extensive procedures. An unadjusted analysis showed differing rates of severe pain in the PACU by group: 306 (24.8%) in the low-dose, 73 (22.7%) middle-dose, and 45 (15.5%) in the high-dose group (P = 0.003); these differences, however, were no longer significant after an adjusted analysis (P = 0.34). Ten severe opioid-related events occurred; all were recognized in the PACU. Five events each occurred in the low-dose and high-dose groups versus none in the middle-dose group (P = 0.02). No other differences were identified with adjusted analyses. LIMITATIONS: Limitations of our study include its retrospective design and its conduct at a single center, along with the apparent, but difficult to characterize, treatment biases in hydromorphone dosing. CONCLUSIONS: No dose response was observed between intrathecal hydromorphone dose and postoperative analgesia, a finding that may reflect treatment bias. Higher rates of severe opioid-related events were detected for patients receiving high-dose hydromorphone in the PACU, but all other safety outcomes were similar between dosing regimens. KEY WORDS: Drug-related side effects, opioid analgesics, outcome assessment, postoperative pain, spinal injections

Tapentadol Versus Oxycodone for Opioid-Related Adverse Drug Events and Clinical Outcomes After Inpatient Surgery

Oxycodone is a commonly prescribed opioid for postoperative pain. However, there has been a marked increase in the use of tapentadol over the previous decade due to a perceived superior safety profile of tapentadol compared to oxycodone. There is limited real-world evidence on the safety of tapentadol compared to oxycodone after surgery. The primary objective was to examine the impact of tapentadol compared to oxycodone use on the incidence of opioid-related adverse drug events after surgery. Data for adult surgical patients receiving tapentadol or oxycodone during hospitalization between January 1, 2018, and December 31, 2021, were collected from electronic medical records of 3 tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events. Patients receiving tapentadol or oxycodone were matched using nearest-neighbour propensity score matching. In the matched cohorts (n = 1,530 vs n = 2,775; mean [standard deviation] age 62.3 [17.0] years vs 61.9 [standard deviation 17.9] years; 43% vs 45% male for the tapentadol vs oxycodone groups, respectively), patients given tapentadol experienced a similar incidence of adverse events overall (14.4%, 220/1,530 vs 12.6%, 349/2,775; P = .100; 95% CI −.35% to 3.95%). Secondary outcomes included an increased risk of delirium (2.7%, 41/1,530 vs 1.3%, 37/2,775), arrhythmias (3.4%, 52/1,530 vs 2.2%, 62/2,775), and length of hospital stay (5 [range 1–201] vs 4 [range 1–226] days) compared with oxycodone use. Further real-world studies are warranted to determine the impact of tapentadol use on a broad range of patient outcomes. PerspectiveThis study provides an early signal that tapentadol use may be associated with an increased risk of some adverse events and a longer length of stay. Further research is needed to examine the impact of tapentadol use on a broad range of patient outcomes in clinical practice settings.

Opioid Prescription in Patients With Chronic Kidney Disease: A Systematic Review of Comparing Safety and Efficacy of Opioid Use in Chronic Kidney Disease Patients.

Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the severity of renal insufficiency; this will determine treatment options at the beginning and throughout the management of pain in CKD patients. The dosage of hydrophilic drugs and drugs with active metabolites should be adjusted according to the severity of CKD, and the process of treatment should be monitored by modifying drug dosages as necessary for background and breakthrough pain. Patients with CKD may benefit from opioid analgesics that are lipophilic, such as methadone, fentanyl, and buprenorphine, as the first line; however, fentanyl is inappropriate for patients undergoing hemodialysis. Opioid prescription in CKD patients is the subject of this systematic review, which aims to compare their safety and efficacy. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Using three databases (PubMed, ScienceDirect, and Google Scholar), we collected and reviewed articles, including literature reviews, randomized control trials (RCTs), and systematic reviews published between 1980 and 2022, to enable us to gather enough valuable data on this rare topic. After applying appropriate filters, a total of 109 results were obtained. They were further screened and subjected to quality assessment tools, which finally yielded 11 studies included in this systematic review. This consisted of two RCTs, two systematic reviews, and seven narrative reviews. This review focused on the safety and appropriate use of opioids in patients with CKD. The accumulation of morphine and codeine metabolites may result in neurotoxic side effects. Hydromorphone and oxycodone are considered safe to administer but require careful adjustments in dosage. Common comorbidities among patients with CKD may amplify opioid-related adverse effects.

Multimodal Analgesia in Pediatric Cancer Pain Management: A Retrospective Single-Center Study.

Objectives A multimodal approach to pain management, including potential interventional techniques, is suggested to achieve adequate pain control. This study discusses the techniques and medications employed to manage pain in pediatric oncology patients. Methodology This study included 90 patients under 18 years of age who underwent pain management in the algology clinic between 2002 and 2020. From the algology follow-up records, the following data were recorded: demographic information, follow-up time, cancer diagnosis and stage, cause and location of pain, systems involved, duration and intensity of pain, analgesic and adjuvant drugs prescribed, routes and duration of drug administration, complications, interventional procedures if performed, "pain intensity" scores prior to and following treatment, and daily and total analgesic consumption of the patients. Results The mean age was 11.4±4.1 years (min-max: 2-17). Leukemia and lymphoma were the most frequently diagnosed (30%). Of the 31 features identified in the staging, 27 (87.1%) were stage 4 at admission. The causes of pain in children were neoplasms in 81.2% (n = 73). At admission, 72.3% (n = 65) had severe pain for at least a month. It was determined that 90% (n = 81) of the patients were using opioids and 28.9% (n = 26) were using dual opioids. The mean tramadol dose was 129.0±97.9 mg/day (12-380 mg/day), and the mean morphine dose was 14.8±11.3 mg/day (1-52 mg/day). The mean transdermal fentanyl dose was 33.2±21.6 µgr/h (12-75 µgr/h). Adjuvant therapy was administered in 25.6% (n = 24) of the patients. Epidural catheterization was performed on 6.6% (n = 6) of the patients. The mean initial pain scores were 5.2±1.7, which decreased to 1.5±0.7 with a significant difference (p < 0.001). In the study, 93% (n = 84) of the patients had no pain management complications noted. Conclusions The pain level that pediatric cancer patients endure critically influences their and their family's quality of life. The fact that opioid-related adverse effects associated with pediatric pain management occur far less frequently than previously thought may help prevent opiophobia. Effective and safe analgesia can be provided with multimodal analgesia to manage pediatric cancer pain.

Naloxone co-prescriptions for surgery patients prescribed opioids: A retrospective cohort study

BackgroundSurgeon-prescribed opioids contribute to 11% of prescription drug overdoses in the United States (US). With prescription opioids involved in 24% of all opioid-related overdose deaths in 2020, the US Centers for Disease Control and Prevention (CDC) recommends naloxone co-prescribing to patients at high-risk of overdose and death as a harm reduction strategy. We sought to 1) examine naloxone co-prescribing rates to surgical patients (using common post-surgical prescribing amounts) and those with potential risk factors for opioid-related overdoses or adverse events, and 2) identify the factors associated with patients receiving naloxone co-prescriptions. MethodsWe conducted a single-institution, retrospective study using the electronic medical records of all patients undergoing surgery at an academic institution between August 2020 and May 2021. We included post-surgical adults prescribed opioids that were sent to a pharmacy in our health system. The primary outcome was the percentage of co-prescribed naloxone in patients prescribed opioids. ResultsThe overall naloxone co-prescription rate was low (1.7%). Only 14.6% of patients prescribed ≥350 morphine milligram equivalents (MME, equivalent to 46.7 oxycodone 5 mg tablets) and 8.6% of patients using illicit drugs were co-prescribed naloxone. On multivariable analysis, patients who were prescribed >350 MME, used illicit drugs or tobacco, underwent an elective or emergent general surgery procedure, self-identified as Hispanic, or had ASA scores of 2-4 were more likely to receive a naloxone co-prescription. ConclusionsNaloxone co-prescribing after surgery remains low, even for high-risk patients. Harm reduction strategies such as naloxone, safe storage, and disposal of leftover opioids could reduce surgeons’ iatrogenic contributions to the worsening US opioid crisis.

The Efficacy of Fascia Iliaca Block for Pain Control after Total Hip Arthroplasty

Abstract Background Total hip arthroplasty (THA) are common surgical procedures for treatment of the degenerative disorders and traumatic diseases. However, a majority of patients often experience moderate to severe postoperative pain after THA. Postoperative pain control has a significant impact on earlier ambulation, initiation of physiotherapy, and better functional recovery. In addition, effective pain control would lower the length of hospital stay and the risk of thrombotic events which improves patients’ satisfaction. Aim of the Study To assess the efficacy and safety of FICB compared with standard multimodal analgesia in patients undergoing THA. Patients and Methods Ninety adult patients scheduled for total hip arthroplasty (THA), under spinal anesthesia were included in this study. The patients' age was ranging from 18 to 65 years and with the American Society of Anesthesiologists (ASA) Class II and III. Patients were included in the study, and were divided into two groups (n = 42; each); group FICB and control group. Results At PACU arrival there is no difference between two groups as two groups were recovering from anesthesia then facia illiaca block group showed the best response as regard as pain control post operatively for 12 hours postoperative then there is no statistical difference between two groups. There was statistically significant difference between groups as regard as visual analog score. As regard to total dose of morphine used in each group, facia illiaca block scientifically used less amount of morphine than control group (P &amp;lt; 0.001). Conclusion Fascia iliaca compartment block is effective for pain relief during the early post-operative period after total hip arthroplasty. Meanwhile, it can reduce the cumulative morphine consumption and the risk of opioid-related adverse effects.

Risk Factors for Opioid-Related Adverse Drug Events Among Older Adults After Hospitalization for Major Orthopedic Procedures.

Older adults undergoing orthopedic procedures are commonly discharged from the hospital on opioids, but risk factors for postdischarge opioid-related adverse drug events (ORADEs) have not been previously examined. We aimed to identify risk factors for ORADEs after hospital discharge following orthopedic procedures. This is a retrospective cohort study of a national sample of Medicare beneficiaries 65 years or older, who underwent major orthopedic surgery during hospitalization in 2016 and had an opioid fill within 2 days of discharge. We excluded beneficiaries with hospice claims and those admitted from or discharged to a facility. We used billing codes and medication claims to define potential ORADEs requiring a hospital revisit within 30 days of discharge. Among 30,514 hospitalizations with a major orthopedic procedure (89.7% arthroplasty, 5.6% treatment of fracture of dislocation, 4.7% other) and an opioid claim, a potential ORADE requiring hospital revisit occurred in 750 (2.5%). Independent risk factors included age of 80 years or older (hazard ratio [HR], 1.65; 95% confidence interval, 1.38-1.97), female sex (HR, 1.34 [1.16-1.56]), and clinical conditions, including heart failure (HR, 1.34 [1.10-1.62]), respiratory illness (HR, 1.23 [1.03-1.46]), kidney disease (HR, 1.23 [1.04-1.47]), dementia/delirium (HR, 1.63 [1.26-2.10]), anxiety disorder (HR, 1.42 [1.18-1.71]), and musculoskeletal/nervous system injuries (HR, 1.54 [1.24-1.90]). Prior opioid use, coprescribed sedating medications, and opioid prescription characteristics were not associated with ORADEs after adjustment for patient characteristics. Potential ORADEs occurred in 2.5% of older adults discharged with opioids after orthopedic surgery. These risk factors can inform clinician decision making, conversations with older adults, and targeting of harm reduction strategies.

EEG-derived pain threshold index-guided versus standard care during propofol-remifentanil anesthesia: A randomized controlled trial

PurposeThe pain threshold index (PTI), a novel index of nociception based on spontaneous EEG wavelet analysis, has been reported to provide reliable accuracy for predicting postoperative pain and hemodynamic reactivity. The present study is aimed to investigate whether PTI-guided analgesia reduces the pain intensity and rate of remedial analgesia in the post-anesthesia care unit (PACU). MethodsA total of 122 females undergoing elective gynecologic surgeries had been randomized to receive either PTI-guided analgesia (PTI group) or standard clinical care (control group). Remifentanil administration in the PTI group was guided by PTI to maintain the value between 40 and 65, while that in the control group was guided by hemodynamic changes. The primary outcome was remedial analgesia rate in the PACU. The postoperative pain scores, intraoperative remifentanil requirements, opioid-related adverse events and perioperative serum stress hormone concentrations between the two groups were also compared. FindingsIt was found that 23 of 58 patients (40%) in the control group and 8 of 58 patients (14%) in the PTI group needed remedial analgesia. The relative risk of receiving remedial analgesia was 2.88 (95% CI, 1.40–5.89, P = 0.002) in the control group. Sufentanil consumption in the PACU (μg) was lower in the PTI group (P = 0.002) than in the control group. Remifentanil and propofol consumption, opioid-related adverse events between these two groups were comparable. ImplicationsPTI-guided analgesia during gynaecologic operations resulted in 25.87% less remedial analgesia. However, studies with different PTI thresholds and larger, more diverse populations should be conducted to further demonstrate the clinical effectiveness of PTI.

Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial

Opioid analgesics are commonly used for acute low back pain and neck pain, but supporting efficacy data are scarce. We aimed to investigate the efficacy and safety of a judicious short course of an opioid analgesic for acute low back pain and neck pain. OPAL was a triple-blinded, placebo-controlled randomised trial that recruited adults (aged ≥18 years) presenting to one of 157 primary care or emergency department sites in Sydney, NSW, Australia, with 12 weeks or less of low back or neck pain (or both) of at least moderate pain severity. Participants were randomly assigned (1:1) using statistician-generated randomly permuted blocks to guideline-recommended care plus an opioid (oxycodone-naloxone, up to 20 mg oxycodone per day orally) or guideline-recommended care and an identical placebo, for up to 6 weeks. The primary outcome was pain severity at 6 weeks measured with the pain severity subscale of the Brief Pain Inventory (10-point scale), analysed in all eligible participants who provided at least one post-randomisation pain score, by use of a repeated measures linear mixed model. Safety was analysed in all randomly assigned eligible participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000775516). Between Feb 29, 2016, and March 10, 2022, 347 participants were recruited (174 to the opioid group and 173 to the placebo group). 170 (49%) of 346 participants were female and 176 (51%) were male. 33 (19%) of 174 participants in the opioid group and 25 (15%) of 172 in the placebo group had discontinued from the trial by week 6, due to loss to follow-up and participant withdrawals. 151 participants in the opioid group and 159 in the placebo group were included in the primary analysis. Mean pain score at 6 weeks was 2·78 (SE 0·20) in the opioid group versus 2·25 (0·19) in the placebo group (adjusted mean difference 0·53, 95% CI -0·00 to 1·07, p=0·051). 61 (35%) of 174 participants in the opioid group reported at least one adverse event versus 51 (30%) of 172 in the placebo group (p=0·30), but more people in the opioid group reported opioid-related adverse events (eg, 13 [7·5%] of 174 participants in the opioid group reported constipation vs six [3·5%] of 173 in the placebo group). Opioids should not be recommended for acute non-specific low back pain or neck pain given that we found no significant difference in pain severity compared with placebo. This finding calls for a change in the frequent use of opioids for these conditions. National Health and Medical Research Council, University of Sydney Faculty of Medicine and Health, and SafeWork SA.