Dataset Information

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

ABSTRACT:

Background

Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described.

Methods

We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung transplant (2006-2017), with risk-adjusted posttransplant survival (adjusted hazard ratio, _LCLaHR_UCL).

Results

Among 11,568 recipients, 33.7% filled an opioid prescription, and 25.8% filled a benzodiazepine prescription before transplant. Compared to patients without prescriptions, those who filled both short- and long-acting benzodiazepine prescriptions before transplant had 2-fold higher mortality in the first year posttransplant (aHR, _1.392.12_3.21), after adjustment for baseline factors and opioid fills, while pretransplant opioid fills were not associated with posttransplant mortality after adjustment for benzodiazepine fills. Pretransplant opioid and benzodiazepine use strongly predicted more use after transplant. Fills of both short- and long-acting benzodiazepines in the first year posttransplant were associated with 77% increased mortality >1-to-2 years posttransplant (aHR, _1.061.77_2.96). Compared with no posttransplant opioid fills, there was a dose-dependent association between first-year opioid fills and subsequent adjusted mortality risk (level 2: aHR, _1.171.50_1.92 to level 4: aHR, _1.562.01_2.59). These effects were independent, and interactions were not detected.

Conclusions

Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.

SUBMITTER: Lentine KL

PROVIDER: S-EPMC8169588 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

Lentine Krista L KL Salvalaggio Paolo R PR Caliskan Yasar Y Lam Ngan N NN McAdams-DeMarco Mara M Axelrod David D Segev Dorry L DL Myaskovsky Larissa L Dew Mary Amanda MA Bruschwein Heather H Levine Deborah J DJ Sweet Stuart S Hess Gregory P GP Kasiske Bertram L BL Schnitzler Mark A MA

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20210217 6

<h4>Background</h4>Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described.<h4>Methods</h4>We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung ...[more]

PMID: 33846078

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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.

Project description:BackgroundOpioid agonist treatment (OAT) is the preferred treatment for opioid dependence due to benefits such as treatment retention, reduced opioid use and mortality. Benzodiazepine co-dependence is common in OAT patients and has been linked to increased mortality. Prescribing benzodiazepines during OAT has been tried to reduce the harms of extra-medical benzodiazepine use. This systematic review examines association between benzodiazepine co-prescription during OAT and mortality.MethodsWe searched MEDLINE, Embase, Psych INFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Epistemonikos for reports published from database inception to June 2021. The searches were updated in February 2024. We included studies comparing mortality rates in OAT patients with and without benzodiazepine co-prescription. Two reviewers independently screened, extracted data, and assessed risk of bias from eligible studies with the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. We combined the effect estimates in meta-analyses where possible. The certainty of the pooled effect estimates was assessed using the GRADE approach.ResultsWe included six observational studies (N = 84,452) conducted in Sweden, Scotland, Canada, England, and the USA. Moderate-certainty evidence linked benzodiazepine prescription to higher all-cause mortality on OAT (HR 1.83; 95% CI 1.59 to 2.11). Moderate-certainty evidence associated benzodiazepine prescription with higher non-drug-induced mortality during OAT and the whole observation period (HR 1.73; 95% CI 1.33 to 2.25) and HR 2.02; 95% CI 1.29 to 3.18). Low-certainty evidence suggested an association with higher drug-induced mortality on OAT (HR 2.36; 95% CI 1.38 to 4.0). Very low-certainty evidence linked benzodiazepine prescription to higher all-cause and drug-induced mortality throughout the observation period (HR 1.49; 95% CI 1.02 to 2.18 and HR 2.19; 95% CI 0.80 to 6.0).ConclusionsThere is probably an association between prescribed benzodiazepine use and higher risk of all-cause mortality (on OAT) and mortality due to non-drug-induced causes (on OAT and on and off OAT). Benzodiazepine prescription may also be associated with higher all-cause mortality (on and off OAT) and drug-induced mortality (on OAT and on and off-OAT), but this is highly uncertain due to methodological issues and possible confounding.

Dataset Information

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

Background

Methods

Results

Conclusions

Publications

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

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