Mismatched Postsurgical Opioid Prescription to Liver Transplant Patients: A Retrospective Cohort Study From a Single High-volume Transplant Center.

BACKGROUND: Improper opioid prescription after surgery is a well-documented iatrogenic contributor to the current opioid epidemic in North America. In fact, opioids are known to be overprescribed to liver transplant patients, and liver transplant patients with high doses or prolonged postsurgical opioid use have higher risks of graft failure and death. METHODS: This is a retrospective cohort study of 552 opioid-naive patients undergoing liver transplant at an academic center between 2012 and 2019. The primary outcome was the discrepancy between the prescribed discharge opioid daily dose and each patient's own inpatient opioid consumption 24 h before discharge. Variables were analyzed with Wilcoxon and chi-square tests and logistic regression. RESULTS: Opioids were overprescribed in 65.9% of patients, and 54.3% of patients who required no opioids the day before discharge were discharged with opioid prescriptions. In contrast, opioids were underprescribed in 13.4% of patients, among whom 27.0% consumed inpatient opioids but received no discharge opioid prescription. The median prescribed opioid daily dose was 333.3% and 56.3% of the median inpatient opioid daily dose in opioid overprescribed and underprescribed patients, respectively. Importantly, opioid underprescribed patients had higher rates of opioid refill 1 to 30 and 31 to 90 d after discharge, and the rate of opioid underprescription more than doubled from 2016 to 2019. CONCLUSIONS: Opioids are both over- and underprescribed to liver transplant patients, and opioid underprescribed patients had higher rates of opioid refill. Therefore, we proposed to prescribe discharge opioid prescriptions based on liver transplant patients' inpatient opioid consumption to provide patient-centered opioid prescriptions.

Mismatched opioid prescription in patients discharged after neurological surgeries: a retrospective cohort study.

ABSTRACT: Although postsurgical overprescription has been well-studied, postsurgical opioid underprescription remains largely overlooked. This retrospective cohort study was to investigate the extent of discharge opioid overprescription and underprescription in patients after neurological surgeries. Six thousand nine hundred forty-nine adult opioid-naive patients who underwent inpatient neurosurgical procedures at the University of California San Francisco were included. The primary outcome was the discrepancy between individual patient's prescribed daily oral morphine milligram equivalent (MME) at discharge and patient's own inpatient daily MME consumed within 24 hours of discharge. Analyses include Wilcoxon, Mann-Whitney, Kruskal-Wallis, and χ 2 tests, and linear or multivariable logistic regression. 64.3% and 19.5% of patients were opioid overprescribed and underprescribed, respectively, with median prescribed daily MME 360% and 55.2% of median inpatient daily MME in opioid overprescribed and underprescribed patients, respectively. 54.6% of patients with no inpatient opioid the day before discharge were opioid overprescribed. Opioid underprescription dose-dependently increased the rate of opioid refill 1 to 30 days after discharge. From 2016 to 2019, the percentage of patients with opioid overprescription decreased by 24.8%, but the percentage of patients with opioid underprescription increased by 51.2%. Thus, the mismatched discharge opioid prescription in patients after neurological surgeries presented as both opioid overprescription and underprescription, with a dose-dependent increased rate of opioid refill 1 to 30 days after discharge in opioid underprescription. Although we are fighting against opioid overprescription to postsurgical patients, we should not ignore postsurgical opioid underprescription.

Racial Differences in Postoperative Opioid Prescribing Practices in Spine Surgical Patients.

BACKGROUND: As the opioid epidemic accelerates in the United States, numerous sociodemographic factors have been implicated its development and are, furthermore, a driving factor of the disparities in postoperative pain management. Recent studies have suggested potential associations between the influence of race and ethnicity on pain perception but also the presence of unconscious biases in the treatment of pain in minority patients. OBJECTIVE: To characterize the perioperative opioid requirements across racial groups after spine surgery. METHODS: A retrospective, observational study of 1944 opioid-naive adult patients undergoing a neurosurgical spine procedure, from June 2012 to December 2019, was performed at a large, quaternary care institute. Postoperative inpatient and outpatient opioid usage was measured by oral morphine equivalents, across various racial groups. RESULTS: Case characteristics were similar between racial groups. In the postoperative period, White patients had shorter lengths of stay compared with Black and Asian patients ( P < .05). Asian patients used lower postoperative inpatient opioid doses in comparison with White patients ( P < .001). White patients were discharged with significantly higher doses of opioids compared with Black patients ( P < .01); however, they were less likely to be readmitted within 30 days of discharge ( P < .01). CONCLUSION: In a large cohort of opioid-naive postoperative neurosurgical patients, this study demonstrates higher inpatient and outpatient postoperative opioid usage among White patients. Increasing physician awareness to the effect of race on inpatient and outpatient pain management would allow for a modified opioid prescribing practice that ensures limited yet effective opioid dosages void of implicit biases.

Opioid prescribing practices at hospital discharge for surgical patients before and after the Centers for Disease Control and Prevention's 2016 opioid prescribing guideline.

BACKGROUND: The Centers for Disease Control and Prevention's (CDC) March 2016 opioid prescribing guideline did not include prescribing recommendations for surgical pain. Although opioid over-prescription for surgical patients has been well-documented, the potential effects of the CDC guideline on providers' opioid prescribing practices for surgical patients in the United States remains unclear. METHODS: We conducted an interrupted time series analysis (ITSA) of 37,009 opioid-naïve adult patients undergoing inpatient surgery from 2013-2019 at an academic medical center. We assessed quarterly changes in the discharge opioid prescription days' supply, daily and total doses in oral morphine milligram equivalents (OME), and the proportion of patients requiring opioid refills within 30 days of discharge. RESULTS: The discharge opioid prescription declined by -0.021 (95% CI, -0.045 to 0.003) days per quarter pre-guideline versus -0.201 (95% CI, -0.223 to -0.179) days per quarter post-guideline (p < 0.0001). Likewise, the mean daily and total doses of the discharge opioid prescription declined by -0.387 (95% CI, -0.661 to -0.112) and -7.124 (95% CI, -9.287 to -4.962) OME per quarter pre-guideline versus -2.307 (95% CI, -2.560 to -2.055) and -20.68 (95% CI, -22.66 to -18.69) OME per quarter post-guideline, respectively (p < 0.0001). Opioid refill prescription rates remained unchanged from baseline. CONCLUSIONS: The release of the CDC opioid guideline was associated with a significant reduction in discharge opioid prescriptions without a concomitant increase in the proportion of surgical patients requiring refills within 30 days. The mean prescription for opioid-naïve surgical patients decreased to less than 3 days' supply and less than 50 OME per day by 2019.

The association of multimodal analgesia and high-risk opioid discharge prescriptions in opioid-naive surgical patients.

BACKGROUND: Opioids and multimodal analgesia are widely administered to manage postoperative pain. However, little is known on how improvements in inpatient pain control are correlated with high-risk (> 90 daily OME) discharge opioid prescriptions for opioid naïve surgical patients. METHODS: We conducted a retrospective observational study of adult opioid-naïve patients undergoing surgery from June 2012 through December 2018 at a large academic medical center. We used multivariate logistic regression to assess whether multimodal analgesic drugs consumed in the 24 h prior to discharge was associated with a reduction in high-risk opioid discharge prescriptions. We identified other risk factors for receiving a high-risk discharge opioid prescription. RESULTS: Among the 32,511 patients, 83% of patients were discharged with an opioid prescription. In 2013, 34.1% of patients with a discharge opioid prescription received a high-risk prescription and this declined to 17.7% by 2018. Use of multimodal analgesic agents during the final 24 h of hospitalization increased each year, with over 80% receiving at least one multimodal analgesic agent by 2018. The median OME consumed in the 24 h prior to discharge peaked in 2013 at 31 and steadily decreased to 19.8 by 2018. There was a significant association between the use of acetaminophen in the 24 h prior to discharge and a high-risk prescription at discharge (p < 0.01). OMEs consumed in the 24 h prior to discharge was a significant predictor of receiving a high-risk discharge prescription, even at low doses. Other factors associated with receipt of a high-risk discharge opioid prescription included male gender, race, history of anxiety disorder, and discharge service. DISCUSSION: Use of multimodal analgesia regimens in hospitalized surgical patients in the 24 h prior to hospital discharge increased between 2012 and 2018. Simultaneously, opioid use prior to hospital discharge decreased. Despite these gains, approximately one in five discharge prescriptions was high-risk (> 90 daily OME). In addition, we found that prescribing of discharge opioids above inpatient opioid requirements remains common in opioid naive surgical patients. CONCLUSION: Providers should account for pre-discharge opioid consumption and use of multimodal analgesia when considering the total and daily OME's that may be appropriate for an individual surgical patient on the discharge opioid prescription.

Outcomes Following Implementation of a Hospital-Wide, Multicomponent Delirium Care Pathway.

BACKGROUND: Delirium is associated with poor clinical outcomes that could be improved with targeted interventions. OBJECTIVE: To determine whether a multicomponent delirium care pathway implemented across seven specialty nonintensive care units is associated with reduced hospital length of stay (LOS). Secondary objectives were reductions in total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. METHODS: This retrospective cohort study included 22,708 hospitalized patients (11,018 preintervention) aged ≥50 years encompassing seven nonintensive care units: neurosciences, medicine, cardiology, general and specialty surgery, hematology-oncology, and transplant. The multicomponent delirium care pathway included a nurse-administered delirium risk assessment at admission, nurse-administered delirium screening scale every shift, and a multicomponent delirium intervention. The primary study outcome was LOS for all units combined and the medicine unit separately. Secondary outcomes included total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. RESULTS: Adjusted mean LOS for all units combined decreased by 2% post intervention (proportional change, 0.98; 95% CI, 0.96-0.99; P = .0087). Medicine unit adjusted LOS decreased by 9% (proportional change, 0.91; 95% CI, 0.83-0.99; P = .028). For all units combined, adjusted odds of 30-day readmission decreased by 14% (odds ratio [OR], 0.86; 95% CI, 0.80-0.93; P = .0002). Medicine unit adjusted cost decreased by 7% (proportional change, 0.93; 95% CI, 0.89-0.96; P = .0002). CONCLUSION: This multicomponent hospital-wide delirium care pathway intervention is associated with reduced hospital LOS, especially for patients on the medicine unit. Odds of 30-day readmission decreased throughout the entire cohort.

Opioid use prior to liver transplant is associated with increased risk of death after transplant.

BACKGROUND: Opioids are generally discouraged and used sparingly in liver transplant (LT) candidates prior to LT. This study examined the relationship between opioid use at the time of LT and graft and patient survival following transplantation. METHODS: A retrospective single center cohort study of LT recipients from June 2012 to December 2019 was performed. Primary outcomes were graft and patient survival, analyzed with the Kaplan-Meier method and Cox proportional hazards models; primary predictor was active opioid prescription at LT. RESULTS: 751 LT recipients were included; 16% had an opioid prescription at LT. Post-transplant death was significantly greater in opioid users (pvalue<0.001). In a multivariable Cox model examining predictors of death, opioid use remained associated with a significant increase in the risk of death (HR 2.4 CI 1.5-4.0, p < 0.001) even after controlling for other factors. CONCLUSION: Opioid use at LT is associated with a markedly increased risk of death following transplant.

Effects of a Clonidine Taper on Dexmedetomidine Use and Withdrawal in Adult Critically Ill Patients-A Pilot Study.

OBJECTIVES: Prolonged use of dexmedetomidine has become increasingly common due to its favorable sedative and anxiolytic properties. Hypersympathetic withdrawal symptoms have been reported with abrupt discontinuation of prolonged dexmedetomidine infusions. Clonidine has been used to transition patients off dexmedetomidine infusions for ICU sedation. The objective of this study was to compare the occurrence of dexmedetomidine withdrawal symptoms in ICU patients transitioning to a clonidine taper versus those weaned off dexmedetomidine alone after prolonged dexmedetomidine infusion. DESIGN: This was a single-center, prospective, double cohort observational study conducted from November 2017 to December 2018. SETTING: Medical-surgical, cardiothoracic, and neurosurgical ICUs in a tertiary care hospital. PATIENTS: We included adult ICU patients being weaned off dexmedetomidine after receiving continuous infusions for at least 3 days. INTERVENTIONS: Patients were either weaned off dexmedetomidine alone or with a clonidine taper at the discretion of the providers. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of at least two dexmedetomidine withdrawal symptoms during a single assessment within 24 hours of dexmedetomidine discontinuation. Time on dexmedetomidine after wean initiation and difference in medication cost were also evaluated. Forty-two patients were included in this study: 15 received clonidine (Group C) and 27 weaned off dexmedetomidine alone (Group D). There was no significant difference in the incidence of two or more withdrawal symptoms between groups (73% in Group C vs 59% in Group D; p = 0.51). Patients in Group C spent less time on dexmedetomidine after wean initiation compared with patients in Group D (19 vs 42 hr; p = 0.02). An average cost savings of $1,553.47 per patient who received clonidine was observed. No adverse effects were noted. CONCLUSIONS: Our study demonstrated that patients receiving clonidine were able to wean off dexmedetomidine more rapidly, with a considerable cost savings and no difference in dexmedetomidine withdrawal symptoms, compared with patients weaned off dexmedetomidine alone. Clonidine may be a safe, effective, and practical option to transition patients off prolonged dexmedetomidine infusions.

Perioperative Prescribing Practices of Extended-Release Opioids in Noncancer Surgical Patients, 2015-2018.

BACKGROUND: Extended-release (ER) opioids are indicated for the management of persistent moderate to severe pain in patients requiring around-the-clock opioid analgesics for an extended period of time. Concerns have been raised regarding safety of ER opioids due to its potential for abuse and dependence. However, little is known about perioperative prescribing practices of ER opioids. This study assessed perioperative prescribing practices of ER opioids in noncancer surgical patients stratified by type of opioid exposure prior to admission and examined predictors of postoperative opioid administration in oral morphine equivalents (OME). METHODS: This was a retrospective cohort study using the University of California San Francisco Medical Center electronic health record data. This study included 25,396 adult noncancer patients undergoing elective surgery under general anesthesia in the period 2015-2018. The primary study outcome was predictors of postoperative administration of opioids in hospitalized surgical patients. Secondary outcomes included patients discontinued and initiated on ER opioids during their hospital stay. RESULTS: substance use disorder diagnosis and use of opioids, surgery type, and postoperative administration of nonopioid analgesics were associated with postoperative administration of opioids (P < .0001). The estimated adjusted mean (95% confidence interval [CI]) of postoperative administration of OME prior to admission in ER opioid users (170.08 mg; 147.08-196.67) was twice the amount for opioid-naïve patients (81.36 mg; 70.7-93.63; P < .0001). One in 5 prior to admission ER opioid users were weaned off ER opioids while hospitalized without adversely affecting their postoperative pain or hospital length of stay (LOS). Four of 5 patients who used ER opioids prior to admission also received ER opioids after surgery, whereas, 1 in 100 opioid-naïve patients received ER opioids during their hospital stay. CONCLUSIONS: We found significant variability in the perioperative prescribing practices of ER opioids in hospitalized noncancer surgical patients by use of opioids prior to admission and surgery type. Pain medicine practitioners and surgeons may play a significant role tackling the surgery-related risk of exposure to ER opioids and decreasing opioid-related complications.

Residents as Key Effectors of Change in Improving Opioid Prescribing Behavior.

OBJECTIVE: There is a national imperative to curb the flow of opioids into our communities. In academic medical centers, the majority of discharge opioid prescriptions are written by residents who receive predominantly ad hoc, peer-to-peer education on perioperative analgesia. We aimed to reduce opioid overprescribing after common general surgical operations through a resident led quality improvement project that involved formal educational interventions and feedback on prescribing habits. DESIGN: A transdisciplinary team was formed to identify how current prescribing habits differed from best practices, and to identify the educational needs to bridge this gap. We then focused on multiple educational interventions, including department-wide grand rounds, case-based conferences with residents, and dedicated didactic sessions on opioid prescribing. Feedback reports of opioid prescribing habits of the residents were developed. Residents' attitudes toward opioid prescribing were assessed using an anonymous survey before and after our interventions. Actual opioid prescribing data were abstracted from the electronic health record. SETTING: A single academic medical center. PARTICIPANTS: A surgical resident led a transdisciplinary team consisting of faculty, anesthesiologists, pharmacists, advanced practice providers, and health informaticians within the Department of Surgery. RESULTS: After our educational intervention, residents' impression of the appropriate number of opioid pills necessary after common general surgical operations decreased significantly, as measured by surveys pre- and postintervention. Electronic health record data regarding actual opioid prescribing behavior show significant discrepancy from the survey responses, but does show a significant decrease in the quantity of opioids prescribed for most evaluated operations following the educational intervention. CONCLUSIONS: Opioid prescribing is an ideal target for resident led education and quality improvement. Residents' attitudes toward appropriate opioid prescribing tend to differ from actual prescribing habits. Our results demonstrate that a well-scoped, resident-driven quality improvement program can lead to change in both attitudes and practice surrounding opioid prescribing.

A Practical First Step Using Needs Assessment and a Survey Approach to Implementing a Clinical Pharmacogenomics Consult Service.

INTRODUCTION: Genetic-guided selection of non-oncologic medications is not commonly practiced in general, and at University of California, San Francisco (UCSF) Health, specifically. Understanding the unique position of clinicians with respect to clinical pharmacogenetics (PG) at a specific institution or practice is fundamental for implementing a successful PG consult service. OBJECTIVES: To assess clinicians' current practices, needs, and interests with respect to clinical PG at UCSF Health, a large tertiary academic medical center. METHODS: A list of 42 target medications with clinical PG recommendations was complied. Clinical specialties that routinely used the target medications were identified. A 12-question survey focused on practice of PG for target medications was developed. Pharmacists and physicians were surveyed anonymously in several clinical specialties. Survey results were analyzed using descriptive statistics. RESULTS: Of the 396 clinicians surveyed, 76 physicians and 59 pharmacists participated, resulting in 27% and 50% average response rates, respectively. The current use of PG in clinical practice for physicians and pharmacists was 29% and 32%, respectively, however this number varied across clinical specialties from 0% to 80%. Of clinicians whom reported they do not currently apply PG, 63% of physicians and 54% of pharmacists expressed interest in integrating PG. However, the level of interest varied from 20% to 100% across specialties. Of the respondents, 64% of physicians and 56% of pharmacists elected to provide contact information to investigators to further discuss their interest related to clinical PG. CONCLUSIONS: While PG is not uniformly practiced at UCSF Health, there is considerable interest in utilizing PG by the respondents. Our approach was successful at identifying clinicians and services interested in PG for specific drug-gene pairs. This work has set a foundation for next steps to advance PG integration at UCSF Health. Clinicians can adopt our approach as preliminary work to build a clinical PG program at their institutions.

Incidence of Dexmedetomidine Withdrawal in Adult Critically Ill Patients: A Pilot Study.

To determine the incidence of dexmedetomidine withdrawal in adult critically ill patients. DESIGN: This was a prospective, observational study of patients from November 2017 to December 2018. SETTING: Medical-surgical, cardiothoracic, and neurosurgical ICUs in a tertiary care hospital. PATIENTS: Adult critically ill patients on dexmedetomidine infusions for at least 3 days. INTERVENTIONS: Indicators of withdrawal were assessed at baseline and at least daily during the dexmedetomidine wean period. Delirium was assessed using the Confusion Assessment Method for the ICU. Sedation was assessed using the Richmond Agitation-Sedation Scale. The Withdrawal Assessment Tool-1 was performed and vital signs were recorded during each assessment. Patients were considered positive for dexmedetomidine withdrawal if they had two or more of the following symptoms: positive Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale greater than +1, positive Withdrawal Assessment Tool-1 assessment, tachycardia (heart rate > 90 beats/min), and hypertension (systolic blood pressure > 140 mm Hg or mean arterial pressure > 90). MEASUREMENTS AND MAIN RESULTS: Forty-two patients were included in the study, with 64% of patients experiencing signs of dexmedetomidine withdrawal. The median time on dexmedetomidine for all patients was 9.6 days (5.8-12.7 d), and the median dose of dexmedetomidine received was 0.8 µg/kg/hr (0.5-1 µg/kg/hr). Of the patients who were positive for withdrawal, the most prevalent withdrawal symptoms observed included delirium, hypertension, and agitation (93%, 48%, and 33%, respectively). We found no correlation between chronic opioid tolerance and incidence of withdrawal symptoms. Peak dexmedetomidine doses greater than 0.8 µg/kg/hr and cumulative daily doses of dexmedetomidine greater than 12.9 µg/kg/d were associated with a higher incidence of withdrawal. CONCLUSIONS: The majority of patients in our study demonstrated signs that may be indicative of dexmedetomidine withdrawal. Peak and cumulative daily dexmedetomidine dose, rather than duration of therapy, may be associated with a higher incidence of withdrawal signs. Regular screening of patients on prolonged dexmedetomidine infusions is recommended to ensure safe and effective use in critically ill patients.

The interaction of depression and prior opioid use on pain and opioid requirements after total joint arthroplasty.

BACKGROUND: Preoperative opioid use causes increased pain and opioid requirements after total joint arthroplasty (TJA), but the effect of depression on this relationship is not well defined. METHODS: We conducted a retrospective review of primary TJA patients using an institutional database. Demographic variables, inpatient opioid requirements, and discharge prescription quantities were collected and compared between patients with and without a prior diagnosis of depression in both the prior opioid-using and nonusing cohorts. RESULTS: Four hundred and three patients were analyzed between August 1, 2016, and July 31, 2017. Among prior opioid users, patients with depression experienced higher inpatient pain levels (4 vs 3; P = .001), required more inpatient opioids (117 oral morphine equivalents [OMEs] vs 70 OMEs; P = .022), were prescribed more opioids at discharge (1163 OMEs vs 750 OMEs; P = .02), and required more long-term opioid refills (57.7% vs 15.4%; P < .001) than patients without depression. However, depression was not associated with increased pain, opioid requirements, prescription quantities, or refill rates among opioid-naive patients. CONCLUSIONS: Depression is not associated with increased pain or opioid requirements among opioid-naive patients after TJA but is associated with significantly higher pain and opioid requirements among patients who use opioids preoperatively. The interaction of these variables may highlight a target for preoperative counseling and risk modification in the arthroplasty population.

The influence of preoperative opioid use on inpatient opioid requirements and discharge prescriptions after primary shoulder arthroplasty.

BACKGROUND: Active opioid users experience more pain and require more opioids after primary shoulder arthroplasty than non-opioid users. However, it is unknown whether discharge prescription regimens are tailored to these different postoperative opioid requirements. METHODS: We performed a retrospective analysis of a prospectively collected cohort of patients who underwent primary shoulder replacement over a 15-month period. Demographic and operative variables were collected and compared between prior opioid users and non-opioid users. Inpatient opioid requirements, daily discharge prescription regimens, total prescription quantities, and rates of persistent opioid use 6 weeks after surgery were also compared between these cohorts. RESULTS: A total of 119 patients were analyzed (mean age, 68 years; 53% men; 39.5% prior opioid users). Prior opioid users required considerably more opioids on the first (60 oral morphine equivalents [OMEs] vs 45 OMEs, P = .01) and last (42 OMEs vs 15 OMEs, P < .001) hospitalization days but were discharged with similar daily opioid regimens (90 OMEs vs 90 OMEs, P = .3), total opioid quantities (600 OMEs vs 600 OMEs, P = .24), and total pills (80 vs 60, P = .27) compared with non-opioid users. Persistent opioid use 6 weeks after surgery was 7-fold higher for prior opioid users than nonusers (71.0% vs 9.1%, P < .001). CONCLUSIONS: Daily and total opioid regimens prescribed after primary shoulder arthroplasty were similar between prior opioid users and nonusers despite large differences in their inpatient opioid requirements. Tailoring discharge opioid prescription regimens to inpatient use appears feasible and warrants further study.