Opioid Agonist to Buprenorphine Cross-titration During Pregnancy: A Case Report.

BACKGROUND: We present a case report of a first-trimester pregnant individual with chronic pain on chronic opioid therapy who successfully cross-titrated from full-µ agonist opioid to buprenorphine without causing significant withdrawal symptoms. CASE PRESENTATION: A 37-year-old gravida 1, para 0 woman with chronic pain on opioid therapy successfully completed a 6-week cross-titration from 120 morphine equivalent dose to buprenorphine in her first trimester without affecting pain scores, functional capacity, withdrawal symptoms except for mild nausea and insomnia, or adverse perinatal outcomes. After increasing her buprenorphine in the second trimester, at 38 weeks, she bore a healthy neonate without eliciting signs of neonatal abstinence syndrome while on a stable buprenorphine dose. CONCLUSIONS: The American College of Obstetricians and Gynecologists and the American Society of Addiction Medicine agree that pregnant patients with chronic pain should avoid or minimize opioids. For patients on chronic opioid therapy unable to minimize opioid use during pregnancy, it is unclear whether to continue their chronic opioid therapy or transition to other medications, including buprenorphine. This case demonstrated how one pregnant person with chronic pain on opioid therapy but not meeting diagnostic criteria for opioid use disorder safely transitioned from full-µ agonist opioids to buprenorphine without precipitating withdrawal or adverse perinatal outcomes. Cross-titration could be similarly performed for a pregnant patient with untreated opioid use disorder. In addition, the used cross-titration schedule and the rationale are provided.

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

OBJECTIVE: To determine the effectiveness and safety of the University of Washington's buprenorphine cross-titration protocol for chronic pain in the outpatient setting. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Postoperative respiratory depression in patients on sublingual buprenorphine: a retrospective cohort study for comparison between postoperative continuation and discontinuation of buprenorphine.

BACKGROUND: We tested the hypothesis that patients who continued buprenorphine postoperatively experience postoperative respiratory depression less frequently than those who discontinued buprenorphine. METHODS: This is a retrospective cohort study of patients who were on buprenorphine preoperatively. The primary outcome was postoperative respiratory depression as defined by respiratory rate < 10/minute, oxygen saturation (SpO2) < 90%, or requirement of naloxone for 48 h postoperatively. The secondary outcome was the composite of postoperative respiratory complications. The associations between postoperative buprenorphine continuation and respiratory depression and respiratory complications were estimated using separate multivariable logistic regression models, including demographic, intraoperative characteristics, and preoperative buprenorphine dose as covariates. RESULTS: Postoperative buprenorphine continuation was not associated with postoperative respiratory depression (adjusted odds ratio (OR), 1.11, 95% confidence interval (CI), 0.61 to 1.99, P=0.72). In subanalysis stratified by the preoperative buprenorphine dose, buprenorphine continuation was not associated with postoperative respiratory depression either when preoperative buprenorphine dose was high (≥16 mg daily) or low (<16 mg daily). Postoperative buprenorphine continuation was associated with lower incidence of postoperative respiratory complications (adjusted OR, 0.43, 95% CI, 0.21 to 0.86, P=0.02). CONCLUSIONS: Continuing buprenorphine was not associated with respiratory depression, but it was associated with a lower incidence of respiratory complications.

Comparison of PACU length of stay and opioid requirements of patients maintained on buprenorphine or methadone for opioid use disorder.

OBJECTIVES: Literature supporting best practice of perioperative buprenorphine management for opioid use disorder is evolving with more recent studies trending toward maintenance of home dose. To guide treatment protocols at our institution, we evaluated patients taking medication for opioid use disorder (MOUD) undergoing similar surgeries. Patients were maintained on either their outpatient buprenorphine or methadone. PATIENTS AND PARTICIPANTS: Data were collected on 46 patients maintained on buprenorphine MOUD who underwent surgery. A subset of these patients (n = 24) was compared with 24 patients maintained on methadone MOUD, matched on surgical procedure, admission date, age, and sex. DESIGN: This is a retrospective matched control study. SETTING: An academic, tertiary, Level 1 trauma center. MAIN OUTCOME MEASURES: Primary outcomes were post-operative opioid use and post-anesthesia care unit (PACU) length of stay. RESULTS: No significant differences in demographic characteristics, physical status, comorbid psychiatric diagnoses, or illicit substance use history were observed between patient groups. A higher proportion of patients taking methadone was admitted due to infection (41.7 percent vs 16.7 percent, p = 0.031) and underwent nonelective surgery (75.0 percent vs 45.8 percent, p = 0.039). No significant differences were observed between patients taking buprenorphine versus methadone with respect to PACU length of stay, post-operative opioid consumption, time-to-transition to oral opioids, or discharge opioid prescriptions. Patients taking buprenorphine were more likely to receive intravenous lidocaine (25.0 percent vs 0.0 percent, p = 0.031) and ketamine (83.3 percent vs 54.2 percent, p = 0.039). CONCLUSION: Findings from this study support accumulating evidence that patients should be maintained on buprenorphine MOUD throughout the perioperative period.

Comparison Between Preoperative Methadone and Buprenorphine Use on Postoperative Opioid Requirement: A Retrospective Cohort Study.

OBJECTIVES: Buprenorphine is a partial agonist at mu-opioid receptors and competes for these receptors with other opioids in vitro. Whether patients on buprenorphine maintenance require high doses of opioid analgesics to attain adequate postoperative pain control has not been determined. We evaluated differences in acute postoperative opioid consumption and pain burden between patients taking buprenorphine and those taking methadone preoperatively. MATERIALS AND METHODS: A retrospective review of medical records of 928 patients, of whom 195 were on buprenorphine and 733 were on methadone preoperatively, was performed. Among methadone and buprenorphine patients, 615 and 89, respectively, continued to receive the medications postoperatively. Buprenorphine patients were compared with methadone patients for the first 48 hours postoperatively with regard to acute opioid dose requirements (morphine milligram equivalents [MME] above their baseline buprenorphine and methadone doses) and time-weighted average (TWA) pain scores (using targeted maximum likelihood estimation). RESULTS: Opioid dose requirements for 48 hours postoperatively were 150 (22 to 297) (median [interquartile range]) and 220 [90 to 360] MME for buprenorphine and methadone patients, respectively. Preoperative buprenorphine was associated with a 59.9% lower postoperative MME (95% confidence interval: 46.6%-69.8%, P<0.0001) compared with methadone. Postoperative TWA pain scores for the first 48 hours were 5.0±2.7 (mean±SD), and 5.4±2.3 for buprenorphine and methadone patients, respectively. Preoperative buprenorphine was associated with a 0.37-point lower TWA pain score (95% confidence interval: 0.14-0.61, P=0.002) compared with methadone. DISCUSSION: Preoperative buprenorphine use was associated with >50% reduction in postoperative opioid dose requirement and a statistically significant, though clinically unimportant, reduction in acute pain burden in comparison to methadone. The study is limited by several important factors such as the exclusion of patients requiring intravenous patient-controlled analgesia, small number of patients were on higher dose of buprenorphine, and a large percentage of methadone patients were not on a stable dose of methadone yet.

Postoperative Pain and Opioid Dose Requirements in Patients on Sublingual Buprenorphine: A Retrospective Cohort Study for Comparison Between Postoperative Continuation and Discontinuation of Buprenorphine.

OBJECTIVE: To test the hypothesis that patients who continued buprenorphine postoperatively experience less severe pain and require a smaller dose of opioids than those who discontinued buprenorphine. MATERIALS AND METHODS: This is a retrospective cohort study of surgical patients who were on buprenorphine preoperatively. Using our previous study's data as pilot data, we selected the covariates to be included in 2 regression models with postoperative time-weighted average pain score and opioid dose requirements in morphine milligram equivalents during 48 hours after surgery as the outcomes. Both contained preoperative daily buprenorphine dose, whether buprenorphine was continued postoperatively, and the preoperative daily dose-by-postoperative continuation interaction as predictors. Precision variables were identified by exhaustive search of perioperative parameters with the exposure variables (preoperative daily dose, postoperative continuation, and their interaction) included in the regression model. The model selected by using the pilot data was estimated again using the new data extracted for this study to make inference about the effect of the 2 exposures (postoperative buprenorphine continuation and preoperative daily buprenorphine dose) and their interaction on the outcomes. RESULTS: Continuing buprenorphine was associated with a 1.3-point lower time-weighted average pain score than discontinuing (95% confidence interval, 0.39-2.21; P=0.005) but was not associated with a difference in opioid dose requirements (P=0.48). DISCUSSION: Continuing buprenorphine was associated with lower postoperative pain levels than discontinuing. Our results were primarily driven by patients on lower buprenorphine dose as only 22% of patients were on daily doses of 24 mg or above.

An Acute Pain Service experience initiating methadone for opioid use disorder in hospitalized patients with acute pain.

OBJECTIVE: Inform readers of the use of a clinical pathway that includes initiation of methadone in hospitalized patients with acute pain who have untreated opioid use disorder (OUD). DESIGN: A retrospective chart review with frequency distributions and descriptive statistics calculated to describe demo-graphic and clinical characteristics of the sample. SETTING: Urban academic hospital. PATIENTS: One hundred twenty consecutive patients with untreated OUD cared for by the Acute Pain Service (APS). INTERVENTIONS: APS leadership spearheaded development of a clinical pathway to standardize pain management and optimize outcomes. The authors outline pathway development and describe 120 patients managed using this pathway, initiated on methadone for OUD. RESULTS: The sample included patients, average age 40 years, predominantly non-Hispanic white (74.2 percent), male (61.7 percent), unemployed (88.2 percent), and on Medicaid (84.2 percent). 96.7 percent had a history of heroin use, and 52.1 percent had engaged in previous medication-assisted treatment (MAT). Methadone or other opioids were held for signs of intoxication/sedation in 10.9 percent or for prolonged corrected QT interval in 1.7 percent. The majority received at least one other analgesic agent. For those prescribed opioids upon discharge, the average maximum morphine equivalent dose was 68.2 mg/day for approximately 3 days. 68.3 percent agreed to schedule post-discharge MAT, and of these, 68 percent attended their intake appointment. A small percentage (4.7 percent) left the hospital against medical advice. CONCLUSION: This pathway provides an example of an effective and safe response to address the opioid epidemic and pro-vide quality care to patients with OUD and pain.

Extrapyramidal symptoms following administration of oral perphenazine 4 or 8 mg: an 11-year retrospective analysis.

BACKGROUND: Perphenazine is a treatment option in postoperative nausea and vomiting (PONV) prophylaxis. Chronic administration and high dose are known to cause extrapyramidal system (EPS) dysfunction at a frequency of 8%, but the incidence of acute EPS after a single 4 or 8 mg dose is unknown. OBJECTIVE: A retrospective analysis of patient medication billing data and departmental quality records was performed (January 2001 to 10 July 2012) to identify patients who experienced EPS dysfunction after oral perphenazine. DESIGN: A retrospective analysis. SETTING: Surgical outpatients presenting to any one of 10 hospitals in the area of Pittsburgh, Pennsylvania, USA. PATIENTS: Overall, 45 766 patients received 4 or 8 mg of perphenazine before same-day surgery. MAIN OUTCOME MEASURES: EPS dysfunction was defined as acute dystonia, akathisia or pseudoparkinsonism. Records were reviewed to determine the likely number of reactions to perphenazine, the nature of these reactions and impact on patient care. RESULTS: There were four 'likely' cases of EPS dysfunction, and two 'possible' cases. Five reported events were consistent with akathisia, with the sixth being a dystonic reaction. All six patients had resolution of symptoms, with five receiving intravenous diphenhydramine for treatment. The incidence of EPS dysfunction was 1.3 events per 10 000 patients (95% confidence interval (CI) 0.4 to 3.0, based on six events). All patients who experienced reactions pre-operatively were able to proceed to surgery without complications or delay. One patient required unplanned admission and 3-h observation owing to sedation from diphenhydramine. The incidence of EPS dysfunction after oral perphenazine is low. Reactions that did occur were mild and easily treated. CONCLUSION: Given the infrequent side effects, this single, low dose of perphenazine should be encouraged as a low-risk adjunct to any multimodal PONV prophylaxis regimen, based on the selection criteria described.

A multi-station dynamic-culture force monitor system to study cell mechanobiology.

To study mechanobiological responses of cells, a dynamic-culture force monitor (D-CFM) system has been developed. The D-CFM extends our previous work to measure contractile forces of a cell-populated collagen gel (CPCG) using a cantilever beam with semiconductor strain gauges. Linear actuators are used in the system and are computer controlled using a LabVIEW interface to independently apply precise motion waveforms to multiple CPCGs. The feasibility tests showed that the new system can detect the differences in force patterns resulting from different motion waveforms imparted to the CPCG. This new system will facilitate the study of the effects of dynamic mechanical loading on cells, remodeling of extracellular matrix, and cell-matrix interactions in vitro.

Cost cutting: substandard care.

Mr. Edwards is diagnosed with a heart arrhythmia and is treated with a successful regimen of medication. He joins an HMO and begins care under a new doctor who ponders whether he should switch Mr. Edwards' medical regimen. Changing the treatment would save the HMO money that could be allocated among other patients, but would expose Mr. Edwards to a small risk of fatal heart attack. I argue that the doctor should not change the medication without the patient's considerations for the following reasons: doctors ought to work solely for the welfare of the patient, the patient has no obligation to cut HMO costs; and allowing doctors' treatment decisions to be influenced by third a party would have negative social repercussions. Furthermore, an informative doctor-patient relationship would be preferred over other "relationship models" for determining Mr. Edwards' course of medication.