Opioid use after adult liver transplantation: Incidence, high-risk use, and adverse events in a large US cohort

Abstract

Background: Opioid use contributes to significant morbidity, posing specific risks to liver transplant recipients (LTRs). This study aimed to characterize outpatient opioid use before and after liver transplantation (LT) and identify risk factors for high-risk, incident, and chronic use and related complications.

Methods: Adult LTRs were identified from 2006 to 2021 in IQVIA PharMetrics Plus for Academics, a claims database representative of the commercially insured US population. Opioid use was evaluated 30-365 days after LT; high-risk use was defined as >50 morphine milligram equivalents (MMEs) per day or concurrent opioid-benzodiazepine use. Factors associated with use, including high-risk use, were identified using multivariable logistic regression analysis. Landmark analyses assessed the association between outpatient opioid use 30-120 days post-LT and incident adverse events (eg, psychiatric, substance use, chronic pain, fractures/falls, digestive).

Results: Among 1338 LTRs, 899 (67.2%) received outpatient opioid prescriptions >30 days post-LT, of whom 553 (41%) had incident use; 122 (13.6%) had high-risk opioid use. Factors significantly associated with high-risk use were female sex, pre-LT opioid use, and psychiatric disorder. Opioid use was significantly associated with increased adverse events 120-365 days post-LT; 59% of LTRs with opioid use within 1 year of LT developed complications compared to 39% of non-opioid users during this window (p<0.001). In adjusted landmark analyses, low/moderate opioid use within 30-120 days post-LT was associated with 1.87 times the hazard of complications compared to no opioid use at 120 days post-LT (95% CI: 1.14-3.07) and high-risk opioid use was associated with 2.87 (95% CI: 1.05-7.85) times the hazard.

Conclusions: Post-LT opioid use is associated with increased risk of adverse events. Caution is needed in opioid prescribing beyond the perioperative period, particularly for those with preexisting psychiatric conditions.

Keywords: liver transplant; opioid use; pain management; substance use.

Graphical abstract

FIGURE 1

Schematic representation of study design. Patients aged 18–64 enrolled in the IVQIA Pharmetrics with continuous medical and pharmacy coverage 6 months pre-LT and >12 months post-LT were included. The primary outcome was any opioid use >30 days post-LT, and the secondary outcome was high-risk opioid use evaluated at 30–120 days post-LT. Abbreviation: LT, liver transplant.

FIGURE 2

Temporal trends in opioid prescriptions in LTRs. The percentage of LTRs with any opioid use, high-risk use, and no high-risk use was compared between the years 2006–2010 and 2011–021. Overall, prescriptions have increased over time, although this difference was not significant across opioid use categories and time periods. Abbreviations: BZD, benzodiazepine; LT, liver transplantation; LTRs, liver transplant recipients; MME, morphine milligram equivalent.

FIGURE 3

Temporal trends in opioid prescriptions and other pain management strategies (2006–2021). The frequency of prescription claims for different pain modalities was compared between 2 time periods, 2006–2010 and 2011–2021, among liver transplant recipients. There was a significant increase in the prescription claims for NSAIDs and gabapentin/pregabalin, and a non-significant increase in opioid use over time. Abbreviation: LTRs, liver transplant recipients.

FIGURE 4

Proposed patient-centered approach to multimodal pain management post-LT. An alternative strategy for managing pain in LTRs prioritizes patient-centered care with the aim of minimizing opioid usage during the post-transplant phase. This personalized approach involves utilizing less-explored pain management methods, including lifestyle adjustments, physical therapy, and psychological interventions, to decrease reliance on opioids and mitigate associated complications. Abbreviations: LT, liver transplantation; OT, occupational therapy; PT, physical therapy.