Buprenorphine in the Intensive Care Unit: Commentary on the Unanswered Questions.

The removal of the X-waiver in the Mainstreaming Addiction Treatment (MAT) Act of 2023 has substantial implications for buprenorphine prescribing as one of the options to treat opioid use disorder. The purpose of this commentary is to discuss the unanswered questions regarding buprenorphine in the intensive care unit (ICU) including how the passage of the MAT Act will affect ICU providers, which patients should receive buprenorphine, what is the most appropriate route of administration and dose of buprenorphine, what medications interact with buprenorphine, and how can transitions of care be optimized for these patients.

Association between Colonoscopy Sedation Type and Polyp Detection: A Registry-based Cohort Study.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Adenomas and serrated polyps are precursors of colorectal cancer, with serrated polyps being more difficult to detect during colonoscopy. The relationship between propofol use and polyp detection remains unclear. The authors investigated the association of propofol-based versus mild-moderate sedation on adenoma and serrated polyp detection during colonoscopy. METHODS: This retrospective cohort study used observational data from the New Hampshire Colonoscopy Registry. Patients aged greater than 50 yr with screening or surveillance colonoscopies between January 1, 2015, and February 28, 2020, were included. Exclusions were diagnostic examinations, no sedation, missing pathology data, and poor bowel preparation. Multivariate logistic regression was used to evaluate differences in polyp detection between propofol and moderate sedation in the full sample while adjusting for covariates. Propensity score adjustment and clustering at the endoscopist level were used in a restricted sample analysis that included endoscopists and facilities with between 5% and 95% propofol sedation use. RESULTS: A total of 54,063 colonoscopies were analyzed in the full sample and 18,998 in the restricted sample. Serrated polyp prevalence was significantly higher using propofol (9,957 of 29,312; 34.0% [95% CI, 33.4 to 34.5%]) versus moderate sedation (6,066 of 24,751; 24.5% [95% CI, 24.0 to 25.1%]) in the full sample and restricted samples (1,410 of 4,661; 30.3% [95% CI, 28.9 to 31.6%] vs. 3,690 of 14,337; 25.7% [95% CI, 25.0 to 26.5%]). In the full sample multivariate logistic regression, propofol was associated with higher neoplasm (adjusted odds ratio, 1.25 [95% CI, 1.21 to 1.29]), adenoma (odds ratio, 1.07 [95% CI, 1.03 to 1.11]), and serrated polyp detection (odds ratio, 1.51 [95% CI, 1.46 to 1.57]). In the restricted sample using inverse probability of treatment weighted propensity score adjustment and clustering at the endoscopist level, an attenuated but statistically significant effect size was observed for serrated polyps (odds ratio, 1.13 [95% CI, 1.07 to 1.19]), but not for adenomas (odds ratio, 1.00 [95% CI, 0.95 to 1.05]) or any neoplastic lesion (odds ratio, 1.03 [95% CI, 0.98 to 1.08]). CONCLUSIONS: Propofol sedation during colonoscopy may be associated with improved detection of serrated polyps, but not adenomas.

A prospective, randomized trial of liposomal bupivacaine compared to conventional bupivacaine on pain control and postoperative opioid use in adults receiving adductor canal blocks for total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a commonly performed procedure to alleviate pain and improve functional limitations caused by end-stage joint damage. Effective management of postoperative pain following TKA is crucial to the prevention of complications and enhancement of recovery. Adductor canal blocks (ACB) with conventional bupivacaine (CB) provide adequate analgesia after TKA, but carry a risk of rebound pain following block resolution. Liposomal bupivacaine (LB) is an extended-release local anesthetic that can provide up to 72 h of pain relief. The objective of this study was to compare postoperative outcomes between ACBs using LB and CB after TKA. METHODS: This single institution, prospective, randomized, clinical trial enrolled patients scheduled for TKA. Participants were randomized to receive ACB with either LB or CB. Pain scores up to 72 h postoperatively were assessed as the primary outcome. Opioid consumption and length of stay were evaluated as secondary outcomes. RESULTS: A total of 80 patients were enrolled. Demographic and clinical characteristics were similar between the two groups. LB group showed significantly lower cumulative opioid use during the 72 h evaluated (P = 0.016). There were no differences in pain scores or length of stay between the groups. CONCLUSION: The study demonstrated that LB ACBs led to significantly lower opioid consumption in the days following TKA without affecting pain scores or length of stay. This finding has important implications for improving postoperative outcomes and reducing opioid use in TKA patients. Previous studies have reported inconsistent results regarding the benefits of LB, highlighting the need for further research. TRIAL REGISTRATION: This project was retrospectively registered with clinicaltrials.gov ( NCT05635916 ) on 2 December 2022.

Liposomal bupivacaine in transversus abdominis plane blocks for lower abdominal surgery.

BACKGROUND: Transversus abdominis plane blocks are an established method of postoperative analgesia for abdominopelvic surgeries. Liposomal bupivacaine is an extended-release formulation of bupivacaine providing up to 72 h of analgesia. This study aims to determine if transversus abdominis plane blocks performed with liposomal bupivacaine are associated with reduced opioid consumption and level of pain intensity compared to conventional bupivacaine in patients undergoing lower abdominal surgery. METHODS: This retrospective cohort study was conducted at a single institution between December 2020 and December 2021. After institutional review board approval, we identified patients who underwent lower abdominopelvic surgery with transversus abdominis plane blocks done with liposomal or conventional bupivacaine and collected demographic, clinical, and procedural information for analysis. We compared total opioid consumption over 72-h postoperatively in milligram morphine equivalents (MME), frequency of opioid utilization, and average level of pain intensity between groups. These outcomes were also evaluated after adjusting for covariates. Data were presented as mean ± SD, median [IQR] or frequency (%), as appropriate; p < 0.05 was accepted as significant. RESULTS: A total of 178 patients met inclusion criteria, with 79 patients receiving an admixture of liposomal bupivacaine and conventional bupivacaine and 99 patients receiving conventional bupivacaine. The liposomal bupivacaine group had a median opioid consumption 72-h postoperatively of 47.5 [18-91.8] MME compared to 88 [43.8-160] MME in the conventional bupivacaine group, p = 0.045. Differences in opioid consumption between the groups did not reach statistical significance after adjustment for demographic and clinical characteristics, p = 0.11. There was no significant difference in frequency of opioid use or average pain intensity. CONCLUSION: Transversus abdominis plane blocks using an admixture of liposomal bupivacaine conventional bupivacaine are not associated with decreased opioid consumption or reduced pain up to 72 h following elective abdominopelvic surgery.

Current State of Perioperative Buprenorphine Management-A National Provider Survey.

OBJECTIVES: Buprenorphine maintenance for opioid use disorder (OUD) can present potential challenges for acute postoperative pain management. Provider practice and consistency of buprenorphine management strategies within institutions are unknown. This study aims to identify how providers nationwide manage patients on buprenorphine when they present for elective surgery. METHODS: A prospective survey of anesthesiologists was performed nationwide between November 2021 and March 2022. Survey respondents were selected from academic institutions identified using public databases and were also distributed to online social media platforms where members are required to verify medical licensure and hospital affiliation. Survey results were calculated and interpreted as the percentage rate of response. RESULTS: Survey invitations were sent to 190 institutions and returned 54 responses (28% response rate). An additional 12 completed surveys were obtained from online social media distribution resulting in 66 responses. Only 36% of respondents reported an established protocol for perioperative management of buprenorphine at their institution. Regarding consistency of buprenorphine management within institutions, the majority of respondents endorsed buprenorphine continuation without dose reduction in procedures where minimal pain was anticipated. However, there was a large discrepancy in buprenorphine management for surgeries with moderate-severe pain. Perioperative dosing frequency of buprenorphine was also inconsistent. CONCLUSIONS: The majority of institutions surveyed do not have an established protocol for perioperative buprenorphine management. In addition, there is provider variability in buprenorphine dosing for procedures with moderate-severe pain. This study highlights the need for dissemination of consensus guidelines for buprenorphine management.

Medications for opioid use disorder prescribed at hospital discharge associated with decreased opioid agonist dispensing in patients with opioid use disorder requiring critical care: A retrospective study.

INTRODUCTION: Buprenorphine is highly effective for the treatment of opioid use disorder (OUD), and, in recent years, the rates of patients maintained on buprenorphine requiring critical care have been steadily increasing. Currently, no unified guidance exists for buprenorphine management during critical illness. Likewise, we do not know if patients maintained on buprenorphine for OUD are prescribed medications for OUD (MOUD) following hospital discharge or if buprenorphine management influences mu opioid agonist dispensing. METHODS: In our cohort of adults over the age of 18 with OUD, receiving buprenorphine formulations in the 3 months preceding their ICU admission, we sought to investigate the relationship between receipt of MOUD and non-MOUD opioid prescribing up to 12 months following hospital discharge. This was a single-center, retrospective cohort study approved by the MaineHealth institutional review board. The study analyzed differences in prescription rates between discharge and subsequent time points using chi square or Fisher's exact test, as appropriate. We performed analyses using SPSS Statistical Software version 28 (IBM SPSS Inc., Armonk, NY) with significance set at p < 0.05. RESULTS: We identified a statistically significant increase in MOUD prescribing 3 months posthospital discharge in patients who received MOUD at time of discharge (87.9 % vs 40 % p = 0.002.) The study found a significant increase in nonbuprenorphine opioid prescribing in patients who did not receive an MOUD prescription at time of discharge (24.2 % vs 70 % p = 0.007). This trend persisted at the 6-month and 12-month time points; however, it did not reach statistical significance. Additionally, the study identified a significant reduction in the incidence of non-MOUD opioid dispensing in patients prescribed MOUD at each time point measured (p = 0.007, p < 0.001. p < 0.001 and p = 0.008 at discharge, 3, 6, and 12 months, respectively). CONCLUSIONS: These findings support continuing buprenorphine dispensing following hospital discharge.

Buprenorphine Continuation During Critical Illness Associated With Decreased Inpatient Opioid Use in Individuals Maintained on Buprenorphine for Opioid Use Disorder in a Retrospective Study.

The number of patients maintained on buprenorphine is steadily increasing. To date, no study has reported buprenorphine management practices for these patients during critical illness, nor its relationship with supplemental full-agonist opioid administration during their hospital stay. In this single-center retrospective study, we have explored the incidence of buprenorphine continuation during critical illness among patients receiving buprenorphine for the treatment of opioid use disorder. Additionally, we investigated the relationship between nonbuprenorphine opioid exposure and buprenorphine administration during the intensive care unit (ICU) and post-ICU phases of care. Our study included adults maintained on buprenorphine for opioid use disorder admitted to the ICU between December 1, 2014, and May 31, 2019. Nonbuprenorphine, full agonist opioid doses were converted to fentanyl equivalents (FEs). Fifty-one (44%) patients received buprenorphine during the ICU phase of care, with an average dose of 8 (8-12) mg/day. During the post-ICU phase of care, 68 (62%) received buprenorphine, with an average dose of 10 (7-14) mg/day. Lack of mechanical ventilation and acetaminophen use were also associated with buprenorphine use. Full agonist opioid use was more frequent on days when buprenorphine was not given (odds ratio [OR], 6.2 [95% CI, 2.3-16.4]; P < .001). Additionally, the average cumulative dose of opioids given on nonbuprenorphine administration days was significantly higher both in the ICU (OR, 1803 [95% CI, 1271-2553] vs OR, 327 [95% CI, 152-708] FEs/day; P < 0.001) and after ICU discharge (OR, 1476 [95% CI, 962-2265] vs OR, 238 [95% CI, 150-377] FEs/day; P < .001). Given these findings, buprenorphine continuation during critical illness should be considered, as it is associated with significantly decreased full agonist opioid use.

Randomised, pragmatic, waitlist controlled trial of cannabis added to prescription opioid support on opioid dose reduction and pain in adults with chronic non-cancer pain: study protocol.

INTRODUCTION: Chronic, non-cancer pain impacts approximately 50 million adults in the USA (20%), approximately 25% of whom receive chronic prescription opioids for pain despite limited empirical efficacy data and strong dose-related risk for opioid use disorder and opioid overdose. Also despite lack of efficacy data, there are many reports of people using cannabis products to manage chronic pain and replace or reduce chronic opioids. Here we describe the protocol for a randomised trial of the effect of cannabis, when added to a behavioural pain management and prescription opioid taper support programme, on opioid utilisation, pain intensity and pain interference. METHODS: This is a pragmatic, single-blind, randomised, wait-list controlled trial that aims to enrol 250 adults taking prescription opioids at stable doses of ≥25 morphine milligram equivalents per day for chronic non-cancer pain who express interest in using cannabis to reduce their pain, their opioid dose or both. All participants will be offered a weekly, 24-session Prescription Opioid Taper Support group behavioural pain management intervention. Participants will be randomly assigned in 1:1 ratio to use cannabis products, primarily from commercial cannabis dispensaries or to abstain from cannabis use for 6 months. Coprimary outcomes are change in prescription monitoring programme-verified opioid dose and change in Pain, Enjoyment, General Activity scale scores. Secondary outcomes include quality of life, depression, anxiety, self-reported opioid dose and opioid and cannabis use disorder symptoms. All other outcomes will be exploratory. We will record adverse events. ETHICS AND DISSEMINATION: This study has ethical approval by the Massachusetts General Brigham Institutional Review Board (#2021P000871). Results will be published in peer-reviewed journals and presented at national conferences. TRIAL REGISTRATION NUMBER: NCT04827992.

A Retrospective Study of Acute Postoperative Pain After Cesarean Delivery in Patients With Opioid Use Disorder Treated With Opioid Agonist Pharmacotherapy.

OBJECTIVE: We aimed to quantify the effect of opioid agonist pharmacotherapy on pain management after cesarean delivery, compared with patients not on these medications. METHODS: Patients undergoing cesarean delivery at our institution between January 2016 and December 2018 were stratified by peripartum use of opioid agonist pharmacotherapy versus no agonist therapy. We compared 24-hour postoperative opioid consumption not including buprenorphine and methadone, in milligram morphine equivalents (MME) (primary outcome), highest pain score on a 0 to 10 numerical rating scale in the first 24 postoperative hours, and postoperative length of stay in hours (secondary outcomes) between groups. These outcomes were also compared after covariate adjustment using logistic regression. RESULTS: We identified 123 patients on opioid agonist pharmacotherapy - in the form of buprenorphine or methadone and 2856 patients not on these medications. The groups differed in demographic characteristics, including age, smoking, and marital status. Opioid consumption during the first 24 postoperative hours (median [interquartile range]) was 99 [75,120] MME for patients on agonist therapy and 30 [0, 64] MME among parturients not taking these medications ( P < 0.001). Highest pain scores during this time were also higher for patients on opioid agonist pharmacotherapy (mean [standard deviation]: 8.2 [1.6] vs 5.5 [2.2], P < 0.001 for the no agonist group). Postoperative length of stay was 73 [68, 77] hours for patients on agonist pharmacotherapy, and 71 [62, 76] hours for parturients taking no agonist ( P < 0.001). All differences remained significant after covariate adjustment. CONCLUSIONS: Parturients on opioid agonist pharmacotherapy have markedly increased opioid utilization and pain severity after cesarean delivery.

Corticosteroid Administration and Impaired Glycemic Control in Mechanically Ventilated COVID-19 Patients.

OBJECTIVE: Recent clinical trials confirmed the corticosteroid dexamethasone as an effective treatment for patients with COVID-19 requiring mechanical ventilation. However, limited attention has been given to potential adverse effects of corticosteroid therapy. The objective of this study was to determine the association between corticosteroid administration and impaired glycemic control among COVID-19 patients requiring mechanical ventilation and/or veno-venous extracorporeal membrane oxygenation. DESIGN: Multicenter retrospective cohort study between March 9 and May 17, 2020. The primary outcome was days spent with at least 1 episode of blood glucose either >180 mg/dL or <80 mg/dL within the first 28 days of admission. SETTING: Twelve hospitals in a United States health system. PATIENTS: Adults diagnosed with COVID-19 requiring invasive mechanical ventilation and/or veno-venous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 292 mechanically ventilated patients. We fitted a quantile regression model to assess the association between steroid administration ≥320 mg methylprednisolone (equivalent to 60 mg dexamethasone) and impaired glycemic control. Sixty-six patients (22.6%) died within 28 days of intensive care unit admission. Seventy-one patients (24.3%) received a cumulative dose of least 320 mg methylprednisolone equivalents. After adjustment for gender, history of diabetes mellitus, chronic liver disease, sequential organ failure assessment score on intensive care unit day 1, and length of stay, administration of ≥320 mg methylprednisolone equivalent was associated with 4 additional days spent with glucose either <80 mg/dL or >180 mg/dL (B = 4.00, 95% CI = 2.15-5.85, P < .001). CONCLUSIONS: In this cohort study of 292 mechanically ventilated COVID-19 patients, we found an association between corticosteroid administration and higher incidence of both hyperglycemia and hypoglycemia.

Pain Management Considerations in Patients With Opioid Use Disorder Requiring Critical Care.

The opioid epidemic has resulted in increased opioid-related critical care admissions, presenting challenges in acute pain management. Limited guidance exists in the management of critically ill patients with opioid use disorder (OUD). This narrative review provides the intensive care unit clinician with guidance and treatment options, including nonopioid analgesia, for patients receiving medications for OUD and for patients actively misusing opioids. Verification and continuation of the patient's outpatient medications for OUD regimen, specifically buprenorphine and methadone formulations; assessment of pain and opioid withdrawal; and treatment of acute pain with nonopioid analgesia, nonpharmacologic strategies, and short-acting opioids as needed, are all essential to adequate management of acute pain in patients with OUD. A multidisciplinary approach to treatment and discharge planning in patients with OUD may be beneficial to engage patients with OUD early in their hospital stay to prevent withdrawal, stabilize their OUD, and reduce the risk of unplanned discharge and other associated morbidity.

A prospective, randomized trial of the effect of buprenorphine continuation versus dose reduction on pain control and post-operative opioid use.

INTRODUCTION: An increasing number of individuals are taking buprenorphine for management of opioid use disorder (OUD). Pain control can be challenging when these patients develop acute pain requiring supplemental analgesia. Buprenorphine's pharmacokinetic profile can render supplemental opioid-based analgesia ineffective. There is limited guidance on the optimal management of buprenorphine when acute pain is anticipated. Although there is growing acceptance that the risk of OUD relapse with buprenorphine discontinuation overshadows the risks of increased opioid utilization and difficult pain control with buprenorphine continuation, perioperative courses comparing buprenorphine dose reduction and full dose buprenorphine continuation have yet to be investigated. Here, we describe the protocol for our randomized controlled, prospective trial investigating the effect of buprenorphine continuation compared to buprenorphine dose reduction on pain control, post-operative opioid use, and OUD symptom management in patients on buprenorphine scheduled for elective surgery. METHODS AND ANALYSIS: This is a single institution, randomized trial that aims to enroll 80 adults using 12 mg buprenorphine or greater for treatment of OUD, scheduled for elective surgery. Participants will be randomly assigned to receive 8mg of buprenorphine on the day of surgery onwards until postsurgical pain subsides or to have their buprenorphine formulation continued at full dose perioperatively. Primary outcome will be a clinically significant difference in pain scores 24 hours following surgery. Secondary outcomes will be opioid consumption at 24, 48, and 72 hours postoperatively, opioid dispensing up to 30 days following surgery, changes in mood and withdrawal symptoms, opioid cravings, relapse of opioid misuse, and continued use of buprenorphine treatment postoperatively.

Ultrasound-guided supraclavicular vs. retroclavicular block of the brachial plexus: comparison of ipsilateral diaphragmatic function: A randomised clinical trial.

BACKGROUND: The ultrasound-guided retroclavicular block (RCB) is a recently described alternative approach to brachial plexus blockade at the level of the cords. Although more distal blockade of the brachial plexus is thought to be associated with a lower incidence of phrenic nerve block, the impact of RCB on ipsilateral diaphragmatic function has not been formally investigated. OBJECTIVE: To compare the effects of supraclavicular and retroclavicular brachial plexus block on diaphragmatic function. SETTING: A single tertiary hospital, study period from December 2017 to May 2019. DESIGN: Double-blinded, randomised study. PATIENTS: A total of 40 patients undergoing upper extremity surgery below the axilla. Exclusion criteria included significant pulmonary disease, BMI more than 40 and contra-indication to peripheral nerve block. INTERVENTIONS: Patients were randomised to supraclavicular or retroclavicular brachial plexus block with ropivacaine 0.5%. OUTCOME MEASURES: Phrenic block was assessed by measuring changes in diaphragmatic excursion using M-mode ultrasound, and maximum inspiratory volume on incentive spirometry from baseline, at 15 and 30 min postblock, and postoperatively. Comparative assessment of block characteristics included timing and distribution of sensory and motor block onset in the upper extremity, and scanning and block performance times. RESULTS: The incidence of phrenic block in the supraclavicular group was higher by ultrasound imaging (70 vs. 15%) and also by pulmonary function testing (55 vs. 5%), with both diaphragmatic excursion and maximum inspiratory volume decreasing to a greater extent after supraclavicular block (SCB) compared with RCB at 15, 30 min and postoperative time points (repeated measures analysis of variance, P < 0.001). There was no difference in timing and extent of distal arm block, but suprascapular and axillary nerves were more consistently blocked after SCB than after RCB. CONCLUSION: The current study confirms the hypothesis that a RCB is significantly less likely to affect ipsilateral diaphragmatic function than a SCB. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02631122.

Perioperative Continuation of Buprenorphine at Low-Moderate Doses Was Associated with Lower Postoperative Pain Scores and Decreased Outpatient Opioid Dispensing Compared with Buprenorphine Discontinuation.

OBJECTIVE: An increasing number of individuals are prescribed buprenorphine as medication-assisted treatment for opioid use disorder. Our institution developed guidelines for perioperative buprenorphine continuation with an algorithm for dose reduction based upon the surgical procedure and patient's maintenance dose. The objective of this study was to compare the effects of buprenorphine continuation with those of discontinuation on postoperative pain scores and outpatient opioid dispensing. DESIGN: Retrospective observational study. SUBJECTS: Surgical patients on buprenorphine from March 2018 to October 2018. Patients on buprenorphine for chronic pain and those with minor procedures were excluded from analysis. METHODS: We compared postoperative outpatient opioid dispensing and postanesthesia care unit (PACU) pain scores in patients where buprenorphine was continued compared with held perioperatively, collecting single surgical subspecialty prescriber data on outpatient full mu-opioid agonist prescriptions dispensed, converted into mean morphine equivalents. Buprenorphine formulations were not included in our morphine milligram equivalents (MME) total. RESULTS: There were 55 patients total (38 cont. vs 17 held). There was no difference in postoperative buprenorphine treatment adherence (91% cont. vs 88% held, P = 0.324). The number of opioid prescriptions dispensed was significantly higher with buprenorphine discontinuation (53% cont. vs 82% held, P = 0.011), as was MME dispensed (mean of 229 cont. vs mean of 521 held, P = 0.033). PACU pain scores were higher with buprenorphine discontinuation (mean 2.9 cont. vs mean 7.6 held, P < 0.001). CONCLUSIONS: There was a significant reduction in opioid prescriptions filled, MME dispensed, and PACU pain scores in patients where buprenorphine was continued vs held perioperatively. We provide evidence to support that buprenorphine can be continued perioperatively and that continuation is associated with decreased postoperative pain and decreased outpatient opioid dispensing. These results contribute to the existing literature supporting the perioperative continuation of buprenorphine.

Perioperative Management of Buprenorphine: Solving the Conundrum.

OBJECTIVE: There is no consensus on the optimal perioperative management of patients on buprenorphine (BUP) for opioid use disorder (OUD). This article will review the available literature on BUP and the analgesic efficacy of BUP combined with full mu-opioid agonists and discuss the conflicting management strategies in the context of acute pain and our institution's protocol for the periprocedural management of BUP. METHODS: We searched published data on BUP periprocedural management from inception through March 2018 without language restrictions. Study selection included publications reporting outcomes on perioperative pain management in OUD patients maintained on BUP. RESULTS: Our search resulted in four case reports supporting periprocedural discontinuation of BUP and two case series, one secondary observational study, one prospective matched cohort study, and four retrospective cohort studies supporting periprocedural continuation of BUP. No clinical trials were identified. CONCLUSIONS: Maintaining BUP perioperatively does not lead to worsened clinical outcomes. Patients can receive adequate pain control from mu-opioid agonists while maintained on BUP. Based upon available evidence, we recommend continuing BUP at a reduced dose when indicated to avoid withdrawal symptoms and to facilitate the analgesic efficacy of mu-opioid agonists administered in combination for acute postoperative pain.

Opioid Use Disorders: Perioperative Management of a Special Population.

Opioid-related overdose deaths have reached epidemic levels within the last decade. The efforts to prevent, identify, and treat opioid use disorders (OUDs) mostly focus on the outpatient setting. Despite their frequent overrepresentation, less is known about the inpatient management of patients with OUDs. Specifically, the perioperative phase is a very vulnerable time for patients with OUDs, and little has been studied on the optimal management of acute pain in these patients. The preoperative evaluation should aim to identify those with OUDs and assess factors that may interfere with OUD treatment and pain management. Efforts should be made to provide education and assistance to patients and their support systems. For those who are actively struggling with opioid use, the perioperative phase can be an opportunity for engagement and to initiate treatment. Buprenorphine, methadone, and naltrexone medication treatment for OUD and opioid tolerance complicate perioperative pain management. A multidisciplinary team approach is crucial to provide clinically balanced pain relief without jeopardizing the patient's recovery. This article reviews the existing literature on the perioperative management of patients with OUDs and provides clinical suggestions for the optimal care of this patient population.

PARP cleavage, DNA fragmentation, and pyknosis during excitotoxin-induced neuronal death.

Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear enzyme activated by DNA breaks and serves a role in DNA repair through the formation of polymers (poly(ADP)ribosylation) at sites of DNA damage. PARP-1 is activated by DNA damage in neurons of the hippocampus and cerebral cortex following excessive exposure to glutamate receptor agonists such as NMDA or kainic acid. In addition, recent studies suggest that degradation of PARP-1 occurs in cells that undergo apoptotic versus nonapoptotic forms of cell death. To investigate this process further, we examined the spatiotemporal aspects of excitotoxic injury in the rodent visual cortex by making focal intracerebral injections of kainic acid. These injections resulted in DNA damage, PARP-1 activation, and neuronal cell death over a 5-day period. Rapid neuronal cell injury assessed by Fluoro-Jade staining appeared within hours, but increased TUNEL staining occurred only after 24 h. A dramatic increase in caspase-3 activity, as well as an increase in the number of neurons containing active caspase-3, peaked 2 days after injury. Last, increased PARP-1 immunoreactivity and PARP-1 cleavage reached peak levels 2 to 3 days after delivering the excitotoxin. These findings suggest that increased caspase-3 activity may regulate the degradation of PARP-1 in subsets of cortical neurons during excitotoxic cell death.