High-dose Opioids Research Articles

Opioid-related adverse drug events in surgical patients: risk factors and association with clinical outcomes

ABSTRACT Background Opioid analgesics are commonly used to treat acute post-operative pain. The primary objective of this study was to identify the risk factors for opioid-related adverse drug events (ORADEs) in surgical patients and the association between ORADEs and clinical outcomes. Research design and methods A retrospective cohort study was conducted using data from July 2016 to April 2020. ORADEs were defined using the International Classification of Diseases 10th Revision Australian Modification codes. Multivariate logistic regression was performed to identify ORADE risk factors. To investigate the association between ORADEs and clinical outcomes, propensity score matching was performed. Results Among 17,886 surgical patients who received opioid analgesics during hospital stay, 1,814 patients (10.2%) experienced ORADEs. Risk factors for general ORADEs included advanced age, comorbidities, concurrent use of benzodiazepines or gabapentinoids and a higher opioid daily dose. Patients who experienced ORADEs were associated with longer length of stay (Rate Ratio 3.00, 95% CI 2.97–3.04) but similar 28-day readmission rate (Odds Ratio 0.89, 95% CI 0.71–1.11). Conclusions Risk factors for general ORADEs were advanced age, specific comorbidities, use of benzodiazepines or gabapentinoids and higher opioid dose. Routine use of opioids with gabapentinoids should be avoided and only used after careful consideration.

Long-term opioid treatment and endocrine measures in patients with cancer-related pain: asystematic review.

Opioid analgesics are the main stay for cancer pain management; however, long-term opioid treatment (L-TOT) may suppress the endocrine system. This systemic review aimed at investigating effects of L-TOT on the endocrine system in patients with cancer-related pain. A search on MEDLINE, EMBASE and Web of Science databases was performed. Inclusion criteria were clinical studies investigating endocrine measures in adult patients with cancer-related pain in L-TOT (≥4weeks). Outcomes and quality of evidence were assessed. A total of 252 abstracts were identified; out of which 247 were excluded and five cross-sectional studies were included and analyzed. L-TOT was associated with lower serum concentration levels of total- and free testosterone in males, follicular stimulating hormone in females, and luteinizing hormone in both sexes. Moreover, higher morphine equivalent daily doses (MEDDs) were correlated with higher levels of cortisol and lower levels of LH in both sexes, and lower levels of total- and free testosterone in males. Sexual dysfunction was associated with low sex hormone levels. Level of evidence was low/very low. The studies identified demonstrated that patients with cancer-related pain in L-TOT may have gonadal hypofunction causing sexual dysfunction, which may be correlated with opioid dose level. In addition, high serum concentrations of cortisol were positively correlated with high opioid dose levels. However, the evidence was weak and further research is necessary. PROSPERO, ID-number: CRD42020213059.

Predictive factors of postoperative fentanyl consumption in patients with inflammatory bowel disease: a retrospective cohort study

BackgroundPatients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, might present difficulties in achieving postoperative analgesia. Prior studies have suggested that patients with IBD undergoing major abdominal surgery require higher doses of perioperative opioids than do patients without IBD. Considering patients with IBD potentially require high-dose opioids, identifying those requiring higher opioid doses will allow clinicians to optimize the perioperative opioid dose and avoid insufficient pain management or complications of opioid overdose. Therefore, we conducted this study to identify predictive factors that might influence postoperative opioid consumption in patients with IBD.MethodsThis single-center, historical cohort study reviewed the medical records of all patients admitted to the IBD center of our institution for surgery and who used intravenous fentanyl patient-controlled analgesia (PCA) after open abdominal surgery between June 2013 and April 2017. Ultimately, 179 patients were enrolled in the analysis. Variables expected to influence and/or represent pain, analgesia, inflammation, disease condition, and extent of surgery were selected as potential explanatory variables for predicting postoperative opioid consumption. Multivariable linear regression analysis was used to examine the effect of independent variables on postoperative fentanyl consumption.ResultsOf the nine predictive variables selected using the stepwise-selection method, eight were significant. Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect on postoperative fentanyl consumption, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect. Preoperative use of opioids was a non-significant variable. The adjusted coefficient of determination was 0.302.ConclusionsIntraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect on postoperative fentanyl consumption. These factors should be considered when adopting postoperative intravenous fentanyl PCA administration for patients with IBD.Trial registrationRegistry: UMIN Clinical Trials Registry.Clinical Trial Number: UMIN000031198.Date of registration: February 8, 2018.

A240 OPIOID-INDUCED HYPEREXCITABILITY IN DRG NEURONS IS MEDIATED BY DOR-DEPENDENT ENDOCYTOSIS

Abstract Background Opioids are effective for the treatment of abdominal pain but are also associated with tolerance, and increased dosing leads to severe side effects. We previously showed that prolonged exposure to high doses of opioids evoked paradoxical hyperexcitability of colonic afferent nerves that was mediated by δ-opioid receptor (DOR) signaling. Recent studies suggest that DOR-dependent analgesia is mediated not only by G proteins but also via receptor endocytosis and downstream signaling, but it is unclear what intracellular signaling mechanisms are underlying opioid-induced hyperexcitability. Aims To examine the mechanisms underlying DOR-mediated hyperexcitability of dorsal root ganglia (DRG) neurons. Methods We assessed the excitability of DRG neurons isolated from C57BL/6 mice by measuring the rheobase (minimal current to elicit an action potential, i.e. lower rheobase=increased excitability) using perforated patch-clamp recordings. Dissociated neurons were exposed to a high concentration (10 µM) of the μ-opioid receptor agonist DAMGO, the DOR agonist DADLE, or the weakly internalizing DOR agonist ARM390 overnight. To examine the role of receptor endocytosis and intracellular receptor activation underlying the excitatory effect by opioids, DRG neurons exposed to DAMGO or DADLE were preincubated with the membrane-permeable opioid receptor antagonist naloxone or the endocytosis inhibitor Pitstop2. To further understand the mechanisms involved in the hyperexcitability evoked by opioid re-exposure, following overnight incubation with high concentrations of DAMGO or DADLE, neurons were washed for 1 hr and treated either with the PKA inhibitor H89 or the PKC inhibitor GFX before re-exposure to DAMGO or DADLE at a low concentration (10 nM). Results Neurons exposed to 10 µM DAMGO or DADLE were hyperexcitable (rheobase decreased 25 % and 26 % compared to controls respectively; p≤0.05, 2-way ANOVA). Naloxone and Pitstop2 blocked the increased excitability of DRG neurons induced by overnight incubations with either DAMGO or DADLE. In contrast to the hyperexcitability induced by DAMGO and DADLE, overnight incubation with 10 µM ARM390 decreased excitability (rheobase increased 31%, p≤0.05, unpaired t-test). The hyperexcitability induced by DAMGO and DADLE was reversed after a 1 hr washout but acute reapplication of a low concentration of DAMGO or DADLE (10nM) now evoked hyperexcitability (rheobase decreased 34 and 35 % respectively, p≤0.05, 2-way ANOVA). This effect was prevented by inhibiting PKC but not PKA. Conclusions Our data suggest that the DOR-dependent hyperexcitability evoked by prolonged exposure to high concentrations of opioids is dependent on receptor endocytosis and downstream PKC signaling. Targeting these pathways could mitigate the hyperexcitability of pain signaling neurons caused by high doses of opioids. Funding Agencies CCC

The complications of opioid use during and post-intensive care admission: A narrative review.

Opioids are a commonly administered analgesic medication in the intensive care unit, primarily to facilitate invasive mechanical ventilation. Consensus guidelines advocate for an opioid-first strategy for the management of acute pain in ventilated patients. As a result, these patients are potentially exposed to high opioid doses for prolonged periods, increasing the risk of adverse effects. Adverse effects relevant to these critically ill patients include delirium, intensive care unit-acquired infections, acute opioid tolerance, iatrogenic withdrawal syndrome, opioid-induced hyperalgesia, persistent opioid use, and chronic post-intensive care unit pain. Consequently, there is a challenge of optimising analgesia while minimising these adverse effects. This narrative review will discuss the characteristics of opioid use in the intensive care unit, outline the potential short-term and long-term adverse effects of opioid therapy in critically ill patients, and outline a multifaceted strategy for opioid minimisation.

Hypericum perforatum to Improve Postoperative Pain Outcome After Monosegmental Spinal Sequestrectomy (HYPOS): Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Patients undergoing lumbar spine surgery often suffer from severe radicular postoperative pain leading to the prescription of high-dose opioids. In Integrative Medicine, Hypericum perforatum is known as a remedy to relieve pain caused by nerve damage. Objectives: This trial investigated whether homeopathic Hypericum leads to a reduction in postoperative pain and a decrease in pain medication compared with placebo. Design: Randomized double blind, monocentric, placebo controlled clinical trial. Settings/Location: Department of Neurosurgery, Community Hospital Herdecke. Subjects: Inpatients undergoing lumbar sequestrectomy surgery. Interventions: Homeopathic treatment versus placebo in addition to usual pain management. Outcomes Measures: Primary endpoint was pain relief measured with a visual analog scale. Secondary endpoints were the reduction of inpatient postoperative analgesic medication and change in sensory and affective pain perception. Results: Baseline characteristics were comparable between the groups. Pain perception between baseline and day 3 did not significantly differ between the study arms. With respect to pain medication, total morphine equivalent doses did not differ significantly. However, a statistical trend and a moderate effect (d = 0.432) in the decrease of pain medication consumption in favor of the Hypericum group was observed. Conclusion: This is the first trial of homeopathy that evaluated the efficacy of Hypericum C200 after lumbar monosegmental spinal sequestrectomy. Although no significant differences between the groups could be shown, we found that patients who took potentiated Hypericum in addition to usual pain management showed lower consumption of analgesics. Further investigations, especially with regard to pain medication, should follow to better classify the described analgesic reduction. Clinical Trial Registration Number: German Clinical Trials Register No: DRKS00007913.

Ketamine reduces the dose of remifentanil required during prolonged head and neck surgery: a propensity-matched analysis.

ABSTRACTHigh-dose opioids induce hyperalgesia and tolerance, which negatively affects postoperative recovery. Prolonged surgery inevitably requires higher opioid doses. Ketamine reduces perioperative opioid consumption and prevents opioid-induced tolerance. However, its effects in cases of prolonged surgery remain unknown. This study aimed to evaluate the dose of intraoperative remifentanil, an ultrashort-acting µ-opioid agonist, administered after an intravenous ketamine bolus during prolonged head and neck surgery. This single-center, retrospective, observational study included 251 patients who underwent head and neck surgery (operation time ≥8 h) between January 2015 and December 2019. The participants were stratified into two groups: those who received an intravenous bolus of ketamine and those who did not (ketamine group and non-ketamine group, respectively). Propensity score-matching was used to match patients in a 1:1 ratio between the two groups, based on their covariates. The difference in intraoperative remifentanil dose administered between the two groups was assessed. After 1:1 propensity score-matching, 89 matched patients were selected from each group. The mean ± standard deviation dose of remifentanil administered was significantly lower in the ketamine group than in the non-ketamine group before (0.15±0.05 vs 0.17±0.05 µg/kg/min; P=0.01) and after matching (0.15±0.06 vs 0.17±0.05 µg/kg/min; P=0.03). In conclusion, intravenous ketamine administration may reduce the intraoperative dose of remifentanil required during prolonged head and neck surgery. However, further studies are required to evaluate the effect of this finding on enhanced recovery after surgery.

Impacts of an Opioid Safety Initiative onUS Veterans Undergoing Cancer Treatment.

There is limited research on how the opioid epidemic and consequent risk reduction policies have affected pain management among cancer patients. The purpose of this study was to analyze how the Opioid Safety Initiative (OSI) implemented at the Veterans Health Administration affected opioid prescribing patterns and opioid-related toxicity. We performed an interrupted time series analysis of 42 064 opioid-naïve patients treated at the Veterans Health Administration for prostate, lung, breast, and colorectal cancer from 2011 to 2016. Segmented regression was used to evaluate the impact of the OSI on the incidence of any new opioid prescriptions, high-risk prescriptions, persistent use, and pain-related emergency department (ED) visits. We compared the cumulative incidence of adverse opioid events including an opioid-related admission or diagnosis of misuse before and after the OSI. All statistical tests were 2-sided. The incidence of new opioid prescriptions was 26.7% (95% confidence interval [CI] = 25.0% to 28.4%) in 2011 and increased to 50.6% (95% CI = 48.3% to 53.0%) by 2013 before OSI implementation (monthly rate of change: +3.3%, 95% CI = 1.3% to 4.2%, P < .001). After the OSI, there was a decrease in the monthly rate of change for new prescriptions (-3.4%, 95% CI = -3.9 to -2.9%, P < .001). The implementation of the OSI was associated with a decrease in the monthly rate of change of concomitant benzodiazepines and opioid prescriptions (-2.5%, 95% CI = -3.2% to -1.8%, P < .001), no statistically significant change in high-dose opioids (-1.2%, 95% CI = -3.2% to 0.9%, P = .26), a decrease in persistent opioid use (-5.7%, 95% CI = -6.8% to -4.7%, P < .001), and an increase in pain-related ED visits (+3.0%, 95% CI = 1.0% to 5.0%, P = .003). The OSI was associated with a decreased incidence of opioid-related admissions (3-year cumulative incidence: 0.9% [95% CI = 0.7% to 1.0%] vs 0.5% [95% CI = 0.4% to 0.6%], P < .001) and no statistically significant change in the incidence of opioid misuse (3-year cumulative incidence: 1.2% [95% CI = 1.0% to 1.3%] vs 1.2% [95% CI = 1.1% to 1.4%], P = .77). The OSI was associated with a relative decline in the rate of new, persistent, and certain high-risk opioid prescribing as well as a slight increase in the rate of pain-related ED visits. Further research on patient-centered outcomes is required to optimize opioid prescribing policies for patients with cancer.

Opioids in COVID-19: Two Sides of a Coin.

Introduction: The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics–possibly in higher doses than usual–which was reported in the literature. The use of drugs that decrease mortality is necessary and opioids are important agents in procedures such as orotracheal intubation. However, these drugs seem to have been overestimated in the COVID-19 pandemic. We performed a review of the PubMed-Medline database to evaluate the use of opioids during this period. The following descriptors were used to enhance the search for papers: “Opioids”, “COVID-19,” “COVID-19 pandemic,” “SARS-CoV-2,” “Opioid use disorder,” “Opioid dependence” and the names of the drugs used. We also evaluated the distribution of COVID-19 patients in Brazil and the applicability of opioids in our country during the COVID-19 pandemic. Results: Several positive points were found in the use of opioids in the COVID-19 pandemic, for instance, they can be used for analgesia in orotracheal intubation, for chronic pain management, and as coadjutant in the management of acute intensification of pain. However, high doses of opioids might exacerbate the respiratory depression found in COVID-19 patients, their chronic use can trigger opioid tolerance and the higher doses used during the pandemic might result in greater adverse effects. Unfortunately, the pandemic also affected individuals with opioid use disorder, not only those individuals are at higher risk of mortality, hospitalization and need for ventilatory support, but measures taken to decrease the SARS-CoV-2 spread such as social isolation, might negatively affect the treatment for opioid use disorder. In Brazil, only morphine, remifentanil and fentanyl are available in the basic health care system for the treatment of COVID-19 patients. Out of the 5,273,598 opioid units used in this period all over the country, morphine, fentanyl, and remifentanil, accounted for, respectively, 559,270 (10.6%), 4,624,328 (87.6%), and 90,000 (1.8%) units. Many Brazilian regions with high number of confirmed cases of COVID-19 had few units of opioids available, as the Southeast region, with a 0.23 units of opioids per confirmed COVID-19 case, and the South region, with 0.05 units. In the COVID-19 pandemic scenario, positive points related to opioids were mainly the occurrence of analgesia, to facilitate intubation and their use as coadjutants in the management of acute intensification of pain, whereas the negative points were indiscriminate use, the presence of human immunosuppressor response and increased adverse effects due to higher doses of the drug. Conclusion: The importance of rational and individualized use of analgesic hypnotics and sedative anesthetics should be considered at all times, especially in situations of high demand such as the COVID-19 pandemic.

Buprenorphine Microdosing for the Pain and Palliative Care Clinician.

Buprenorphine (BUP) can be a safe and effective alternative to traditional opioids for many patients with chronic pain. For patients on higher doses of opioids, rotation to BUP is complicated by the requirement of an opioid-free interval or withdrawal during the transition. Microdosing inductions, in which BUP is gradually titrated, while full agonist opioids are continued, are a viable alternative to traditional inductions. The objective of this article is to review the current literature on BUP microdosing induction, with a focus on patients using opioids for pain. A literature review of the PubMed database was performed in the United States on articles published from inception to May 2021. A total of 34 publications were included. The most commonly utilized microdosing strategy involved administering divided doses of sublingual (SL) products marketed for opioid use disorder treatment, with 25 (73.5%) articles reporting use of partial SL tablets or films (ranging from 1/8 to 1/2 of a 2 mg product) at some point during the induction. Transdermal patches, low-dose SL BUP available in Europe, intravenous BUP, and buccal BUP have also been used. Beyond the products used, the speed of the microinduction, setting, final BUP dosing, and management of concomitant full agonists vary widely in the literature. Microdosing regimens should be individualized based on local guidelines and patient-specific factors. Further studies comparing the safety and efficacy of different protocols are warranted.

Pregabalin and intravenous lidocaine for management of postoperative pain and surgical stress response in elective laparotomies: A double blind randomised controlled trial

Introduction: Postoperative pain remains a significant problem in patients undergoing abdominal surgeries, and has a profound effect on patient recovery. High-dose opioids hamper bowel motility and increase nausea and vomiting. Intravenous lidocaine has been used as part of a multimodal analgesia protocol for providing effective pain relief and attenuating surgery-associated inflammatory response. Preoperative pregabalin also has a beneficial effect in reducing pain. This study was carried out to assess the efficacy of combining these drugs in reducing pain, paralytic ileus, and stress response. Method: Patients undergoing elective laparotomy were randomized into two groups. Group A patients received preoperative placebo and intraoperative lidocaine infusion. Group B patients received preoperative pregabalin and lidocaine. The pain was assessed using a visual analog scale at 2, 6, 18, and 24 hours postoperatively. Morphine consumption on a patient-controlled analgesia pump was also noted. Surgical stress response was assessed by measuring perioperative total leucocyte count, interleukin-6, and C-reactive protein. Result: Postoperative pain scores at 6, 18, and 24 hours were significantly lower in Group B patients who had received pregabalin. These patients also had lower morphine consumption and earlier bowel recovery as measured by the first passage of stools. Perioperative inflammatory markers were similar in both groups. Conclusion: Preoperative pregabalin when used with intravenous lidocaine has a synergistic effect on reducing postoperative pain and opioid consumption. This also has a beneficial effect on the return of bowel function.

Prescription opioid treatment for non-cancer pain and initiation of injection drug use: large retrospective cohort study

ObjectiveTo assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance...

Workers' compensation prescription medication patterns and associated outcomes

Opioid use in the treatment of musculoskeletal injuries is a complex decision where benefits must be balanced with risk. Previous research has shown an association between higher opioid doses and adverse health effects. The study's objective was to investigate whether opioid prescriptions are associated with increased costs and deaths through an injury mechanism or as a direct result of the opioid prescription. Data for 144,553 deidentified Ohio Bureau of Workers' Compensation claims from 2010 to 2014 with shoulder, knee, and low back injuries were obtained and followed until 2016. Each claim had associated prescription information. Injury claims were further classified using the allowed diagnoses by single or multiple body areas affected and injury severity ("simple" or "complex"). The outcome variables were medical and indemnity costs, lost days, MaxMED (maximum claim-prescribed daily morphine equivalent dose), and death status. Association between maximum opioid dose with deaths was determined by logistic regression analysis. Several outcome variables, including claim medical and indemnity costs, and the likelihood of claimant death, showed significant associations with the MaxMED. In the analysis of claim deaths, these associations held for all claim types (except complex), even after adjusting for age, gender, surgery, and lost time. The association between increasing opioid doses and deaths for low-severity diagnoses was disturbing given the lack of demonstrated efficacy of opioids for treatment of minor injuries. A focus on provider education, increased utilization of non-opioids, and early intervention for minor soft-tissue injuries could reduce claims costs, disability, and future deaths.

70-Year-Old Man With Chronic Nausea and Vomiting

70-Year-Old Man With Chronic Nausea and Vomiting

A Comprehensive, Multimodal, Interdisciplinary Approach to Chronic Non-Cancer Pain Management in a Family Medicine Clinic: A Retrospective Cohort Review.

The complexity of chronic non-cancer pain in the setting of regulatory efforts to curb opioid usage presents a novel challenge for the medical community. Much of this burden falls on primary care clinics. We retrospectively quantified the reduction of opioid usage by patients in a multimodal, interdisciplinary, primary care clinic for chronic pain. A multimodal, interdisciplinary, chronic pain clinic embedded in a large academic military family medicine clinic operated one-half day weekly to address referrals from within the clinic at large. Appointment times were longer than typical primary care appointments. The clinic was equipped with support staff, ancillary specialty providers, and non-pharmacologic complementary treatment resources. A retrospective cohort review was conducted on 78 patients referred to this clinic from March 1, 2015 (the inception date of the clinic) through December 31, 2015. Fifty-four of 78 patients met inclusion criteria. Overall mean morphine equivalent daily dosing (MEDD) dropped from 31.5 MEDD to 20.5 MEDD (p = 0.0005) 12 months post-intervention and from 31.5 MEDD to 9.5 MEDD (p < 0.0001) 36 months post-intervention. Four patients with a high mean baseline opioid dose of 185.2 MEDD dropped to 29.9 MEDD 36 months post-intervention. The mean 0-10 pain score decreased from 5.3 ± 2.2 to 4.0 ± 2.5 (p = 0.001). A multimodal, interdisciplinary, primary care-based, chronic pain clinic equipped with extended appointment times, non-pharmacologic treatment resources, and specialty access can curb opioid usage. Leadership support for protracted appointment duration, complementary treatment resources, and interdisciplinary personnel is crucial to success.

Opioids and obstructive sleep apnea.

Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647-652.

Has Declining Opioid Dispensing to Cancer Patients Been Tailored to Risk of Opioid Harms?

ContextOpioid prescribing to cancer patients is declining, but it is unknown whether reductions have been tailored to those at highest risk of opioid-related harms. ObjectivesExamine whether declines in opioid dispensing to patients receiving active cancer treatment are sharper in patients with substance use disorder (SUD) or mental health diagnoses. MethodsWe used 2008–2018 national, commercial healthcare claims data to examine adjusted and unadjusted trends in opioid dispensing (receipt of ≥1 fill; average daily dosage; receipt of high-dose opioids; receipt of concurrent opioids and benzodiazepines) to patients ages ≥18 receiving treatment for one of four cancer types (breast; colorectal; head and neck; sarcoma; N = 324,789 patients). To compare declines across subgroups with varying risk of opioid-related harms, we stratified by SUD and mental health diagnosis. To address potential confounding, we estimated subgroup-specific trends using generalized estimating equations, adjusting for covariates. ResultsAcross groups, rate of ≥1 opioid fill per quarter fell 32.5% (95% CI: 31.8%–33.2%) from 2008 to 2018; daily dose among those receiving opioids fell 37.6% (95% CI: 36.7%–38.6%). In most cases, these declines were not sharper in subgroups at greater risk of opioid-related harms. For example, patients with opioid use disorder experienced the smallest declines in dispensing frequency, and there was no evidence that declines were sharper in patients with mental health diagnoses. ConclusionSharp declines in opioid prescribing during the drug overdose crisis have affected a wide range of patients undergoing cancer treatment and may not have been sufficiently tailored to patient characteristics. Research on implications for opioid-related harms and pain management is needed.

Safety of opioid prescribing among older cancer survivors.

Cancer survivors receive more long-term opioid therapy (LTOT) than people without cancer, but the safety of LTOT prescribing is unknown. Opioid-naive adults aged ≥66 years who had been diagnosed in 2008-2015 with breast, lung, head and neck, or colorectal cancer were identified with data from Surveillance, Epidemiology, and End Results cancer registries linked with Medicare claims. Survivors with 1 or more LTOT episodes (≥90 consecutive days) occurring ≥1 year after their cancer diagnosis and before censoring at hospice entry, another cancer diagnosis, 6 months before death, or December 2016 were included. The safety of prescribing during the first 90 days of the first LTOT episode was measured during follow-up. As a positive safety indicator, the proportion of survivors with concurrent nonopioid pain management was measured. Indicators of less safe prescribing were the proportion of survivors with a high average daily opioid dose (≥90 morphine milligram equivalents) and the proportion of survivors with concurrent benzodiazepine dispensing. Multivariable logistic regression analyses were conducted to identify clinical predictors of each safety outcome. In all, 3628 cancer survivors received LTOT during follow-up (median duration, 4.9 months; interquartile range, 3.5-8.0 months). Seventy-two percent of the survivors received multimodal pain management concurrently with LTOT. Eight percent of the survivors had high-dose opioid prescriptions; 25% of the survivors received benzodiazepines during LTOT. Multivariable analyses identified variations in safety measures by multiple clinical factors, although none were consistently significant across outcomes. To improve safe LTOT prescribing for survivors, efforts should focus on increasing multimodal pain management and reducing inappropriate benzodiazepine prescribing. Different clinical predictors of each outcome suggest different drivers of safe prescribing.

Demographic and clinical factors associated with variations in opioid administration using conscious sedation during HDR brachytherapy for cervical cancer

PURPOSE/OBJECTIVES To examine patient characteristics that predispose to higher opioid administration during tandem and ovoid (T&O) high-dose rate (HDR) brachytherapy. METHODS A single-institution retrospective review was performed on patients who underwent brachytherapy for cervical cancer. Patients were included if they received at least one fraction of HDR T&O brachytherapy with analgesia administration recorded in the Medication Administration Record. Fentanyl dose was dichotomized as "low" (mean <125 μg per fraction), or "high" (mean ≥ 125 μg per fraction). Descriptive statistics and multiple logistic regression analysis were performed comparing mean opioid dose per fraction with demographic and clinical information. RESULTS From July 2014 through May 2020, 113 patients underwent 531 T&O HDR brachytherapy fractions with oral benzodiazepine and intravenous opioid fentanyl for conscious sedation. The median opioid dose per fraction was 100 μg fentanyl (range 0-250 μg). Using multiple logistic regression analysis, younger age (OR 1.071, p = 0.002) and higher BMI (OR 1.091, p = 0.019) were associated with increased opioid administration during brachytherapy. Black women received less opioid during brachytherapy when compared to White women (OR 0.296, p = 0.047). FIGO stage, ECOG score, smoking status, prior narcotic use, prior illicit drug use, parity, prior cervical procedure, Smit sleeve placement, and distance to treatment center were not associated with high opioid dose. CONCLUSION Cervical cancer patients who are younger or have higher BMI receive more narcotic analgesia during HDR brachytherapy whereas Black women received less narcotic analgesia, irrespective of age and BMI. This underscores the immediate need to address how pain is assessed and managed during brachytherapy.

Nurse Practitioner Opioid Prescribing and Safety Measure Utilization Patterns in Ontario: An Explanatory Sequential Mixed Methods Study

Background: Across Canada, opioid-related hospitalizations, emergency department visits, and mortality have increased. A literature gap exists related to opioid prescribing and safety measure utilization patterns among nurse practitioners (NPs). Purpose: The objectives of this study were to (a) identify opioids prescribed by NPs in Ontario for pain, (b) examine safety measure utilization when prescribing opioids, (c) explore factors associated with safety measure utilization, and (d) survey NPs’ opioid prescribing confidence. Methods: An explanatory sequential mixed method approach was used to measure quantitative and qualitative results in a sequential approach that achieves methodological triangulation. A survey was distributed to 2,094 NPs practicing in Ontario between May and August 2020. After quantitative analysis of 158 completed surveys, a qualitative phase was conducted that involved one-on-one semi-structured interviews with 14 NPs who completed the survey and agreed to follow up. Results: The top three opioids prescribed for acute and chronic pain reported by 158 NPs were hydromorphone followed by acetaminophen with codeine and oxycocet. The top three acute opioid-treated conditions were (1) fracture, (2) postoperative pain, and (3) joint or muscle strain/sprain. The top three chronic pain conditions were (1) cancer/palliative care, (2) chronic low back pain, and (3) osteoarthritis. Results from interviews demonstrated that inpatient NPs used safety measures less often than community NPs because of institutional policies that aid safe prescribing. NP preference for hydromorphone was rooted in its appealing side effect profile and ability to prescribe smaller doses. Limiting medication supply was considered the most effective opioid prescribing safety measure. NPs were more confident prescribing opioids with established diagnoses and less confident with unclear diagnoses, history of addiction, and chronic pain patients taking high dosages of opioids. Conclusion: Findings from this research can inform curricula changes to incorporate education related to opioid prescribing in the populations in which NPs expressed less confidence and opioid tapering for patients on high doses of opioids. Background: Across Canada, opioid-related hospitalizations, emergency department visits, and mortality have increased. A literature gap exists related to opioid prescribing and safety measure utilization patterns among nurse practitioners (NPs). Purpose: The objectives of this study were to (a) identify opioids prescribed by NPs in Ontario for pain, (b) examine safety measure utilization when prescribing opioids, (c) explore factors associated with safety measure utilization, and (d) survey NPs’ opioid prescribing confidence. Methods: An explanatory sequential mixed method approach was used to measure quantitative and qualitative results in a sequential approach that achieves methodological triangulation. A survey was distributed to 2,094 NPs practicing in Ontario between May and August 2020. After quantitative analysis of 158 completed surveys, a qualitative phase was conducted that involved one-on-one semi-structured interviews with 14 NPs who completed the survey and agreed to follow up. Results: The top three opioids prescribed for acute and chronic pain reported by 158 NPs were hydromorphone followed by acetaminophen with codeine and oxycocet. The top three acute opioid-treated conditions were (1) fracture, (2) postoperative pain, and (3) joint or muscle strain/sprain. The top three chronic pain conditions were (1) cancer/palliative care, (2) chronic low back pain, and (3) osteoarthritis. Results from interviews demonstrated that inpatient NPs used safety measures less often than community NPs because of institutional policies that aid safe prescribing. NP preference for hydromorphone was rooted in its appealing side effect profile and ability to prescribe smaller doses. Limiting medication supply was considered the most effective opioid prescribing safety measure. NPs were more confident prescribing opioids with established diagnoses and less confident with unclear diagnoses, history of addiction, and chronic pain patients taking high dosages of opioids. Conclusion: Findings from this research can inform curricula changes to incorporate education related to opioid prescribing in the populations in which NPs expressed less confidence and opioid tapering for patients on high doses of opioids. Gina Pittman, MN, NP, PhD, is an Assistant Professor, Faculty of Nursing, University of Windsor, Ontario, Canada. Jody Ralph, RN, BSc, BScN, MSc, PhD, is an Associate Professor, Faculty of Nursing, University of Windsor. Michelle Freeman, RN, BScN, BA, MScN, PhD, CPPS, is a Professor Emeritus, Faculty of Nursing, University of Windsor. Laurie Freeman, RN, BScN, MSN, PhD, is an Associate Professor, Faculty of Nursing, University of Windsor. Sylwia Borawski, is a third-year undergraduate nursing student, University of Windsor.