Association Between Opioid and Benzodiazepine Use and Clinical Deterioration in Ward Patients.
Ontology highlight
ABSTRACT:
SUBMITTER: Lyons PG
PROVIDER: S-EPMC5695213 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Association Between Opioid and Benzodiazepine Use and Clinical Deterioration in Ward Patients.
Lyons Patrick G PG Snyder Ashley A Sokol Sarah S Edelson Dana P DP Mokhlesi Babak B Churpek Matthew M MM
Journal of hospital medicine 20170601 6
<h4>Background</h4>Opioids and benzodiazepines are frequently used in hospitals, but little is known about outcomes among ward patients receiving these medications.<h4>Objective</h4>To determine the association between opioid and benzodiazepine administration and clinical deterioration.<h4>Design</h4>Observational cohort study.<h4>Setting</h4>500-bed academic urban tertiary-care hospital.<h4>Patients</h4>All adults hospitalized on the wards from November 2008 to January 2016 were included. Patie ...[more]
Similar Datasets
Project description:ImportanceThe association between preoperative benzodiazepine use and long-term postoperative outcomes is not well understood.ObjectiveTo characterize the association between preoperative benzodiazepine use and postoperative opioid use and health care costs.Design, setting, and participantsIn this cohort study, retrospective analysis of private health insurance claims data on 946 561 opioid-naive patients (no opioid prescriptions filled in the year before surgery) throughout the US was conducted. Patients underwent 1 of 11 common surgical procedures between January 1, 2004, and December 31, 2016; data analysis was performed January 9, 2020.ExposuresBenzodiazepine use, defined as long term (≥10 prescriptions filled or ≥120 days supplied in the year before surgery) or intermittent (any use not meeting the criteria for long term).Main outcomes and measuresThe primary outcome was opioid use 91 to 365 days after surgery. Secondary outcomes included opioid use 0 to 90 days after surgery and health care costs 0 to 30 days after surgery.ResultsIn this sample of 946 561 patients, the mean age was 59.8 years (range, 18-89 years); 615 065 were women (65.0%). Of these, 23 484 patients (2.5%) met the criteria for long-term preoperative benzodiazepine use and 47 669 patients (5.0%) met the criteria for intermittent use. After adjusting for confounders, long-term (odds ratio [OR], 1.59; 95% CI, 1.54-1.65; P < .001) and intermittent (OR, 1.47; 95% CI, 1.44-1.51; P < .001) benzodiazepine use were associated with an increased probability of any opioid use during postoperative days 91 to 365. For patients who used opioids in postoperative days 91 to 365, long-term benzodiazepine use was associated with a 44% increase in opioid dose (additional 0.6 mean daily morphine milligram equivalents [MMEs]; 95% CI, 0.3-0.8 MMEs; P < .001), although intermittent benzodiazepine use was not significantly different (0.0 average daily MMEs; 95% CI, -0.2 to 0.2 MMEs; P = .65). Preoperative benzodiazepine use was also associated with increased opioid use in postoperative days 0 to 90 for both long-term (32% increase, additional 1.9 average daily MMEs; 95% CI, 1.6-2.1 MMEs; P < .001) and intermittent (9% increase, additional 0.5 average daily MMEs; 95% CI, 0.4-0.6 MMEs; P < .001) users. Intermittent benzodiazepine use was associated with an increase in 30-day health care costs ($1155; 95% CI, $938-$1372; P < .001), while no significant difference was observed for long-term benzodiazepine use.Conclusions and relevanceThe findings of this study suggest that, among opioid-naive patients, preoperative benzodiazepine use may be associated with an increased risk of developing long-term opioid use and increased opioid dosages postoperatively, and also may be associated with increased health care costs.
| S-EPMC7592026 | biostudies-literature
Project description:ImportanceConcurrent benzodiazepine use is associated with an increased risk of opioid-related overdose; however, it remains unknown how the overdose risk varies with the days of exposure to both medications.ObjectiveTo evaluate the exposure-response association between the days with concurrent prescription opioid and benzodiazepine use and the risk of overdose.Design, setting, and participantsRetrospective cohort study of Medicare Part D claims data from January 1, 2013, to December 31, 2014. Analyses were conducted in fall 2017 and spring 2018. Participants were Medicare Part D beneficiaries who filled at least 1 prescription for an opioid in 2014.ExposuresPatients were divided into 2 groups based on whether they had opioid and benzodiazepine supplies on the day before overdose or censoring. The first group only had a supply of opioids (n?=?50?583) and the second group had supplies of opioids and benzodiazepines (n?=?20?665). The second group was further categorized into 4 subgroups based on the cumulative number of days with overlapping supplies of opioids and benzodiazepines: 1 to 90 days (n?=?3603), 91 to 180 days (n?=?2930), 181 to 270 days (n?=?4082), and 271 days or more (n?=?10?050).Main outcomes and measuresCox proportional hazard models were constructed to compare opioid-related overdose (including fatal and nonfatal overdoses) across time-dependent treatment groups, controlling for demographic characteristics, insurance factors, clinical characteristics, and number of unique opioid and benzodiazepine prescribers.ResultsOf 71?248 total participants, 25?600 (35.9%) were male and 59?532 (83.6%) were white. Mean (SD) age was 66.5 (14.8) years. On the day before overdose or censoring event, 20?665 of 71?248 patients with an opioid prescription (29.0%) were concurrently using benzodiazepines and 14?132 of 20?665 concurrent users (68.4%) had more than 180 days of overlapping supplies of both medications. The risk of overdose was highest on the first days of concurrent opioid and benzodiazepine use and decreased over time; compared with opioid use alone, the hazard ratio for overdose was 5.05 (95% CI, 3.68-6.93) during the first 90 days of concurrent opioid and benzodiazepine use and 1.87 (95% CI, 1.25-2.80) for days 91 to 180 among those who did not have an event before 90 days.Conclusions and relevanceDuring the first 90 days, concurrent benzodiazepine use is associated with a 5-fold increase in the risk of opioid-related overdose. The implementation of policies deterring concurrent opioid and benzodiazepine use is warranted. Patients using both medications should be closely monitored, particularly during the first days of concurrent use.
| S-EPMC6324417 | biostudies-literature
Project description:ImportanceAlthough overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death.ObjectiveTo evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants.Design, setting, and participantsThis retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from 1999 to 2015. Eight cycles of NHANES data were used, spanning 37 610 person-years of follow-up time among 5212 individuals. Statistical analysis was performed from August 24, 2019, through May 23, 2020.ExposuresThe primary exposure variable was benzodiazepine and opioid coprescriptions. Individuals taking selective serotonin reuptake inhibitors (SSRIs) served as an active comparator reference group.Main outcomes and measuresAll-cause mortality was obtained via linkage of NHANES to the National Death Index. Propensity scores were calculated from covariates associated with sociodemographic factors, comorbidities, and medication use for more than 1000 prescription types. Propensity score-weighted mortality hazards were calculated from Cox proportional hazards regression models.ResultsOf 5212 participants aged 20 years or older (1993 men [38.2%]; mean [SD] age, 54.8 [16.9] years) followed up for a median of 6.7 years (range, 0.2-16.8 years), 101 deaths (33.0 per 1000 person-years) occurred among those receiving cotreatment, 236 deaths (26.5 per 1000 person-years) occurred among those receiving only benzodiazepines, and 227 deaths (20.2 per 1000 person-years) occurred among SSRI recipients taking neither opioids nor benzodiazepines. After propensity score weighting, a significant increase in all-cause mortality was associated with benzodiazepine and opioid cotreatment (hazard ratio, 2.04 [95% CI, 1.65-2.52]) and benzodiazepines without opioids (hazard ratio, 1.60 [95% CI, 1.33-1.92]). Subgroup analyses revealed an increased risk of mortality for individuals receiving cotreatment who were 65 years or younger but not for those older than 65 years; similar findings were observed for those receiving benzodiazepines without opioids.Conclusions and relevanceThis study found a significant increase in all-cause mortality associated with benzodiazepine use with or without opioid use in comparison with SSRI use. Benzodiazepine and opioid cotreatment, in particular, was associated with a 2-fold increase in all-cause mortality even after taking into account medical comorbidities and polypharmacy burden.
| S-EPMC7726637 | biostudies-literature
Project description:BackgroundThe association between long-term benzodiazepine use and risk of dementia remains controversial. Therefore, current study aimed to quantify this association, and to explore a potential dose-response pattern.MethodsWe searched PubMed, Embase and the Cochrane Library through August 17, 2014. We included nested case-control or prospective cohort studies that provided risk estimates on the association of benzodiazepine use with risk of dementia, and a clear definition of status of benzodiazepine use. Overall effect size was calculated using a random-effects model.FindingsSix studies were eligible for inclusion, involving 11,891 dementia cases and 45,391 participants. Compared with never users, pooled adjusted risk ratios (RRs) for dementia were 1.49 (95% confidence interval (CI) 1.30-1.72) for ever users, 1.55 (95% CI 1.31-1.83) for recent users, and 1.55 (95% CI 1.17-2.03) for past users. The risk of dementia increased by 22% for every additional 20 defined daily dose per year (RR, 1.22, 95%CI 1.18-1.25). When we restricted our meta-analyses to unadjusted RRs, all initial significant associations persisted.ConclusionsLong-term benzodiazepine users have an increased risk of dementia compared with never users. However, findings from our study should be treated with caution due to limited studies and potential reverse causation. Large prospective cohort studies with long follow-up duration are warranted to confirm these findings.
| S-EPMC4446315 | biostudies-literature
Project description:ImportanceIncreased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure and source of benzodiazepines among those who use them persistently.ObjectiveTo examine the frequency of use and persistent use of benzodiazepines among patients undergoing major and minor surgical procedures.Design, setting, and participantsThis cohort study included 2 509 599 adult patients who underwent 1 of 11 common surgical procedures in the United States from 2009 to 2017 and were recorded in the MarketScan database. The rates of perioperative and persistent benzodiazepine use were examined in benzodiazepine-naive patients. Data analysis was conducted from July to November 2020.Main outcomes and measuresReceipt of a perioperative benzodiazepine prescription and persistent use (ie, fill of a second prescription 90-180 days after surgery) among those who received a benzodiazepine perioperatively.ResultsAmong 2 509 599 included patients, the mean (SD) age was 54.4 (15.3) years, and 1 596 137 (63.6%) were women. Perioperative benzodiazepine use was noted in 63 931 patients (2.6%). The median (interquartile range) benzodiazepine supply was 10 (5-23) days. Among benzodiazepine-naive patients prescribed a perioperative benzodiazepine, the rate of persistent benzodiazepine use was 19.5% (95% CI, 19.2%-19.8%). During the 90 to 180-day period after surgery, 7013 of 12 468 patients (56.2%) received 1 prescription for benzodiazepines while 5455 (43.8%) received 2 or more prescriptions. Among patients prescribed a benzodiazepine, persistent use was more common in Medicaid recipients (vs patients with commercial insurance: adjusted rate ratio [aRR], 1.29; 95% CI, 1.03-1.62), patients 70 years or older (vs those aged 40-49 years: aRR, 1.14; 95% CI, 1.05-1.23), in women (vs men: aRR, 1.10; 95% CI, 1.06-1.15), in patients with more medical comorbidities (eg, Elixhauser comorbidity score ≥3 vs 0: aRR, 1.11; 95% CI, 1.04-1.19), and in those with diagnoses of anxiety, depression, insomnia or substance use disorder (eg, with vs without anxiety: aRR, 1.43; 95% CI, 1.37-1.50).Conclusions and relevanceIn this study, a relatively small percentage of surgical patients were prescribed benzodiazepines in the perioperative period; however, 1 in 5 of these patients went on to persistent benzodiazepine use.
| S-EPMC8176328 | biostudies-literature
Project description:Background:Opioid use is common in end-stage renal disease (ESRD) patients. However, safety of individual opioids and concomitant benzodiazepine use has not been studied. Objective:To study the epidemiology of opioid and concomitant benzodiazepine use in ESRD population. To study the clinical safety profile of individual opioids in patients on hemodialysis. Design:Retrospective analysis of the U.S. Renal Data System. A comprehensive review of the current literature was performed to update currently used opioid safety classification. Participants:ESRD patients ≥18 years on hemodialysis who were enrolled in Medicare A and B and Part D between 2006 and 2012, excluding those with malignancy. Main Measures:Hospital admission with diagnosis of prescription opioid overdose within 30, 60, and 90 days of prescription; death due to opioid overdose. Results:Annually, the percentage of patients prescribed any opioid was 52.2%. Overall trend has been increasing except for a small dip in 2011, despite which the admissions due to opioid overdose have been rising. 30% of those who got a prescription for opioids also got a benzodiazepine prescription. 56.5% of these patients received both prescriptions within a week of each other. Benzodiazepine use increased the odds of being on opioids by 3.27 (CI 3.21-3.32) and increased the odds of hospitalization by 50%. Opioids considered safe such as fentanyl and methadone were associated with 3 and 6 folds higher odds of hospitalization within 30 days of prescription. Hydrocodone had the lowest odds ratio (1.9, CI 1.8-2.0). Conclusions:Concurrent benzodiazepine use is common and associated with higher risk of hospitalization due to opioid overdose. Possible opioid-associated hospital admission rate is 4-5 times bigger in ESRD population than general population. Current safety classification of opioids in these patients is misleading, and even drugs considered safe based on pharmacokinetic data are associated with moderate to very high risk of hospitalization. We propose a risk-stratified classification of opioids and suggest starting to use them in all ESRD patients.
| S-EPMC6854236 | biostudies-literature
Project description:ImportanceThe number of patients prescribed long-term opioids and benzodiazepines and complications from their long-term use have increased. Information regarding the perioperative outcomes of patients prescribed these medications before surgery is limited.ObjectiveTo determine whether patients prescribed opioids and/or benzodiazepines within 6 months preoperatively would have greater short- and long-term mortality and increased opioid consumption postoperatively.Design, setting, and participantsThis retrospective, single-center, population-based cohort study included all patients 18 years or older, undergoing noncardiac surgical procedures at a national hospital in Iceland from December 12, 2005, to December 31, 2015, with follow-up through May 20, 2016. A propensity score-matched control cohort was generated using individuals from the group that received prescriptions for neither medication class within 6 months preoperatively. Data analysis was performed from April 10, 2018, to March 9, 2019.ExposuresPatients who filled prescriptions for opioids only, benzodiazepines only, both opioids and benzodiazepines, or neither medication within 6 months preoperatively.Main outcomes and measuresLong-term survival compared with propensity score-matched controls. Secondary outcomes were 30-day survival and persistent postoperative opioid consumption, defined as a prescription filled more than 3 months postoperatively.ResultsAmong 41 170 noncardiac surgical cases in 27 787 individuals (16 004 women [57.6%]; mean [SD] age, 56.3 [18.8] years), a preoperative prescription for opioids only was filled for 7460 cases (17.7%), benzodiazepines only for 3121 (7.4%), and both for 2633 (6.2%). Patients who filled preoperative prescriptions for either medication class had a greater comorbidity burden compared with patients receiving neither medication class (Elixhauser comorbidity index >0 for 16% of patients filling prescriptions for opioids only, 22% for benzodiazepines only, and 21% for both medications compared with 14% for patients filling neither). There was no difference in 30-day (opioids only: 1.3% vs 1.0%; P = .23; benzodiazepines only: 1.9% vs 1.5%; P = .32) or long-term (opioids only: hazard ratio [HR], 1.12 [95% CI, 1.01-1.24]; P = .03; benzodiazepines only: HR, 1.11 [95% CI, 0.98-1.26]; P = .11) survival among the patients receiving opioids or benzodiazepines only compared with controls. However, patients prescribed both opioids and benzodiazepines had greater 30-day mortality (3.2% vs 1.8%; P = .004) and a greater hazard of long-term mortality (HR, 1.41; 95% CI, 1.22-1.64; P < .001). The rate of persistent postoperative opioid consumption was higher for patients filling prescriptions for opioids only (43%), benzodiazepines only (23%), or both (66%) compared with patients filling neither (12%) (P < .001 for all).Conclusions and relevanceThe findings suggest that opioid and benzodiazepine prescription fills in the 6 months before surgery are associated with increased short-and long-term mortality and an increased rate of persistent postoperative opioid consumption. These patients should be considered for early referral to preoperative clinic and medication optimization to improve surgical outcomes.
| S-EPMC6584895 | biostudies-literature
Project description:ImportanceThe receipt of overlapping opioid and benzodiazepine prescriptions is associated with increased overdose risk. It is unknown whether this increase in risk varies when overlapping prescriptions are written by multiple prescribers vs 1 prescriber.ObjectiveTo evaluate the association between receipt of overlapping opioid and benzodiazepine prescriptions from multiple prescribers and overdose risk.Design, setting, and participantsThis cohort study was conducted using 2017 to 2018 claims from the Optum deidentified Clinformatics Data Mart. Participants were patients with private insurance or Medicare Advantage aged 12 years or older with overlapping opioid and benzodiazepine prescriptions. Data were analyzed from March through November 2020.ExposuresFor each patient, person-days on which opioid and benzodiazepine prescriptions overlapped were identified. The exposure was whether these prescriptions were written by multiple prescribers vs 1 prescriber.Main outcomes and measuresThe outcome was a treated overdose, defined as the occurrence of 1 or more claims containing a diagnosis code for opioid or benzodiazepine poisoning on a person-day of opioid-benzodiazepine overlap. The association between exposure and outcome at the person-day level was estimated using logistic regression, controlling for opioid and benzodiazepine prescribing patterns, demographics, and comorbidities. The average marginal effect (AME) of the exposure, defined as the absolute difference in the probability of a treated overdose if all person-days of overlap involved prescriptions from multiple prescribers vs 1 prescriber, was calculated.ResultsAmong 529 053 patients, the mean (SD) age was 61.2 (15.6) years and 350 857 (66.3%) were female patients. Mean (SD) follow-up was 198.7 (249.8) days. During follow-up, overdose occurred on 1 or more person-days of opioid-benzodiazepine overlap for 2288 patients (0.4%, or 1 in 231 patients). There were 52 989 316 person-days of opioid-benzodiazepine overlap. Among 19 895 457 person-days (37.5%) involving prescriptions from multiple prescribers, there were 1390 overdoses (7.0 per 100 000 person-days), and among 33 093 859 person-days (62.5%) involving prescriptions from 1 prescriber, there were 1302 overdoses (3.9 per 100 000 person-days). Overdose risk was increased 1.8-fold (95% CI, 1.6-1.9) on person-days of overlap involving prescriptions from multiple prescribers vs 1 prescriber. The association between multiple prescribers and increased risk of overdose persisted in adjusted analyses (adjusted odds ratio, 1.20; 95% CI, 1.10-1.31; AME, 0.91 per 100 000 person-days of overlap; 95% CI, 0.46-1.37).Conclusions and relevanceThis study found that among patients already at increased risk of overdose owing to concurrent treatment with opioids and benzodiazepines, overdose risk was increased further when multiple prescribers were responsible for this treatment regimen compared with 1 prescriber. This increased risk was not fully accounted for by differences in prescribing patterns, demographics, or comorbidities. This finding suggests that other factors, such as poor care coordination, may be associated with the increase in risk.
| S-EPMC8356065 | biostudies-literature
Project description:Given the severity of the ongoing opioid epidemic, it is essential to understand the mechanisms of risk for development and maintenance of opioid use disorder (OUD). The aim of the current large-scale psychophysiological investigation was to test whether patients with OUD had lower resting-state high-frequency heart rate variability (HF-HRV) than those without OUD, controlling for sociodemographic and clinical confounds. Additionally, we tested whether HF-HRV was associated with opioid craving in this population. Participants in this cross-sectional study were 490 chronic pain patients (50.4% female) treated with long-term opioid therapy. OUD diagnosis was determined by psychiatric interview. HF-HRV was measured at resting baseline. We computed the association between OUD and resting-state HF-HRV, controlling for age, gender, race, pain severity, emotional distress and opioid dose. Opioid craving was measured with visual analogue scales to assess whether HF-HRV was associated with craving. Results showed that resting HF-HRV was significantly lower for patients with OUD than for those without OUD (p < 0.001, d = 0.36), indicating deficits in autonomic flexibility. OUD diagnosis (p = 0.002) and OUD severity (p = 0.03) were associated with lower HF-HRV in regression models accounting for a range of confounders. Additionally, lower HF-HRV was significantly (but weakly) correlated with heightened opioid craving (r = -0.166, p < 0.001). Overall, findings suggest that resting-state HF-HRV may serve as a valid biomarker of addiction among people on long-term opioid therapy.
| S-EPMC10234179 | biostudies-literature
Project description:BackgroundThe morbidity and mortality associated with opioid and benzodiazepine co-prescription is a pressing national concern. Little is known about patterns of opioid and benzodiazepine use in patients with acute low back pain or lower extremity pain.ObjectiveTo characterize patterns of opioid and benzodiazepine prescribing among opioid-naïve, newly diagnosed low back pain (LBP) or lower extremity pain (LEP) patients and to investigate the relationship between benzodiazepine prescribing and long-term opioid use.Design/settingWe performed a retrospective analysis of a commercial database containing claims for more than 75 million enrollees in the USA.ParticipantsParticipants were adult patients newly diagnosed with LBP or LEP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6 months prior to diagnosis, and had 12 months of continuous enrollment after diagnosis.Main outcomes and measuresAmong patients receiving at least one opioid prescription within 12 months of diagnosis, we defined discrete patterns of benzodiazepine prescribing-continued use, new use, stopped use, and never use. We tested the association of these prescription patterns with long-term opioid use, defined as six or more fills within 12 months.ResultsWe identified 2,497,653 opioid-naïve patients with newly diagnosed LBP or LEP. Between 2008 and 2015, 31.9% and 11.5% of these patients received opioid and benzodiazepine prescriptions, respectively, within 12 months of diagnosis. Rates of opioid prescription decreased from 34.8% in 2008 to 27.0% in 2015 (P?<?0.001); however, prescribing of benzodiazepines only decreased from 11.6% in 2008 to 10.8% in 2015. Patients with continued or new benzodiazepine use consistently used more opioids than patients who never used or stopped using benzodiazepines during the study period (one-way ANOVA, P?<?0.001). For patients with continued and new benzodiazepine use, the odds ratio of long-term opioid use compared with those never prescribed a benzodiazepine was 2.99 (95% CI, 2.89-3.08) and 2.68 (95% CI, 2.62-2.75), respectively.LimitationsThis study used administrative claims analyses, which rely on accuracy and completeness of diagnostic, procedural, and prescription codes.ConclusionOverall opioid prescribing for low back pain or lower extremity pain decreased substantially during the study period, indicating a shift in management within the medical community. Rates of benzodiazepine prescribing, however, remained at approximately 11%. Concurrent prescriptions of benzodiazepines and opioids after LBP or LEP diagnosis were associated with increased risk of long-term opioid use.
| S-EPMC6957597 | biostudies-literature