Pharmacogenetic Predictors of Postoperative Opioid-Related Adverse Events: A Systematic Review.

Purpose. Opioid-related adverse drug events (ORADEs) increase patient length of stay (LOS) and health care costs. However, ORADE rates may be underreported. This study attempts to understand the degree to which ORADEs are underreported in Medicare patients undergoing cardiac surgery. Materials and Methods. The Center for Medicare and Medicaid Services administrative claims database was used to identify ORADEs in 110 158 Medicare beneficiaries who underwent cardiac valve (n = 50 525) or coronary bypass (n = 59 633) surgery between April 2016 and March 2017. The International Classification of Disease (ICD)-10 codes specifically linked to ORADEs were used to identify an actual ORADE rate, while additional ICD codes, clinically associated with butas not specific to adverse drug events were analyzed as potential ORADEs. Length of stay (LOS) and hospital daily revenue were analyzed among patients with or without a potential ORADE. Results. Among patients undergoing valve or bypass surgery, the documented ORADE rate was 0.7% (743/110 158). However, potential ORADEs may have occurred in up to 32.4% (35 658/110 158) of patients. In patients with a potential ORADE, mean LOS was longer (11.4 vs 8.2 days; P < .0001) and mean Medicare revenue/day was lower ($4016 vs $4412; P < .0001). The mean net difference in revenue/day between patients with and without an ORADE varied between $231 and $1145, depending on the Diagnosis-Related Group analyzed. Conclusions. ORADEs are likely underreported following cardiac surgery. ORADEs can be associated with increased LOS and decreased hospital revenue. Understanding the incidence and economic impact of ORADEs may expedite changes to postoperative pain management. Adopting multimodal pain management strategies that reduce exposure to opioids may improve outcomes by reducing complications, side effects, and health care costs.

Potential opioid-related adverse events following spine surgery in elderly patients

Preventing Iatrogenic Overdose: A Review of In–Emergency Department Opioid-Related Adverse Drug Events and Medication Errors

Opioids are commonly used for pain control during and after invasive procedures. However, opioid-related adverse drug events (ORADEs) are common and have been associated with worse patient outcomes. To examine the incidence of ORADEs in patients undergoing hospital-based surgical and endoscopic procedures and to evaluate the association of ORADEs with clinical and cost outcomes. In this retrospective study of clinical and administrative data, ORADEs were identified using International Classification of Diseases, Ninth Revision diagnosis codes for known adverse effects of opioids or by opioid antagonist use. Multivariable regression analysis was used to measure the association of ORADEs with outcomes after adjusting for potential confounding factors. The setting was 21 acute care hospitals in a large integrated health care delivery system. Participants were 135 379 patients (aged ≥18 years, admitted from January 1, 2013, to September 30, 2015) who underwent surgical and endoscopic procedures and were given opioids. Opioid use, reported as morphine milligram equivalent doses. Opioid-related adverse drug events and their association with inpatient mortality, discharge to another care facility, length of stay, cost of hospitalization, and 30-day readmission. Among 135 379 adult patients in this study (67.5% female), 14 386 (10.6%) experienced at least one ORADE. Patients with ORADEs were more likely to be older, of white race/ethnicity, and male and have more comorbidities. Patients with ORADEs received a higher total dose of opioids (median morphine milligram equivalent dose, 46.8 vs 30.0 mg; P < .001) and for a longer duration (median, 3.0 vs 2.0 days; P < .001). In adjusted analyses, ORADEs were associated with increased inpatient mortality (odds ratio [OR], 28.8; 95% CI, 24.0-34.5), greater likelihood of discharge to another care facility (OR, 2.9; 95% CI, 2.7-3.0), prolonged length of stay (OR, 3.1; 95% CI, 2.8-3.4), high cost of hospitalization (OR, 2.7; 95% CI, 2.4-3.0), and higher rate of 30-day readmission (OR, 1.3; 95% CI, 1.2-1.4). ORADEs were associated with a 2.9% increase in absolute mortality, an $8225 increase in cost for the index hospitalization, and a 1.6-day increase in length of stay for the index hospitalization. Opioid-related adverse drug events were common among patients undergoing hospital-based invasive procedures and were associated with significantly worse clinical and cost outcomes. Hospital-acquired harm from ORADEs in the surgical patient population is an important opportunity for health systems to improve patient safety and reduce cost.

Improving the Quality of Data for Inpatient Claims-Based Measures Used in Public Reporting and Pay-for-Performance Programs

Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM. We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.) of more than 216 million patients, yielding data ranging from 2009 to 2024. We included patients aged ≥18 years with sciatica, excluding those post-spine surgery, prior anesthesia, serious pathology, high risk of ORADEs, and an ORADE ≤ 1-year prior. Patients were divided into two cohorts: (1) CSM and (2) usual medical care. We used propensity score matching to control for confounding variables associated with ORADEs. Comparative outcomes were analyzed by calculating risk ratios (RRs) and 95% confidence intervals (CIs) for the incidence of ORADEs and oral opioid prescription between cohorts. 372,471 patients per cohort remained after matching. The incidence of ORADEs over 1-year follow-up was less in the CSM cohort compared to the usual medical care cohort (CSM: 0.09%; usual medical care: 0.30%), yielding an RR of 0.29 (95% CI: 0.25-0.32; P < .00001). CSM patients had a lower risk of receiving an oral opioid prescription (RR of 0.68 [95% CI: 0.68-0.69; P < .00001]). This study found that adults with sciatica who initially received CSM had a lower risk of an ORADE compared to matched controls not initially receiving CSM, likely explained by a lower probability of opioid prescription. These findings corroborate existing practice guidelines which recommend adding CSM to the management of sciatica when appropriately indicated.

To determine the prevalence of postsurgical opioid use in the inpatient setting, to ascertain the frequency of and risk factors for opioid-related adverse drug events (ORADEs) among patients who received opioids, and to evaluate the impact of ORADEs on clinical and economic outcomes. Retrospective cohort study using administrative data. Hospital system encompassing 26 hospitals in the southeastern United States. A total of 37,031 patients aged 18years or older who underwent a common surgical procedure between January 1, 2009, and December 31, 2010. Patients were evaluated for receipt of postsurgical opioids. Outcomes among opioid users included ORADE rates, hospital length of stay, total hospitalization costs, 30-day readmission rates, outlier status, and inpatient mortality. Factors associated with ORADEs were evaluated; length of stay, costs, readmissions, and mortality were compared between patients experiencing and not experiencing ORADEs by using propensity score matching on age, race-ethnicity, sex, presurgery opioid use, and comorbidities. Length of stay and cost rate ratios were generated by using negative binomial regression and generalized linear models. Odds ratios for 30-day readmissions and inpatient mortality were generated by using logistic regression. Among all surgical patients, 36,529 (98.6%) of patients received opioids, of whom 4955 (13.6%) experienced an ORADE. Increased risk of ORADEs was associated with age 65years or older, male sex, obesity, presurgery opioid use, and higher score on Charlson Comorbidity Index. Patients with an ORADE had a 55% longer length of stay, 47% higher costs of care, 36% increased risk of 30-day readmission, and 3.4 times higher risk of inpatient mortality than did patients who did not experience an ORADE. Opioid use was ubiquitous among hospitalized patients who underwent common surgical procedures. The observed negative outcomes of ORADEs and their impact on patients and the health care system should be considered when evaluating the balance between effectively managing postsurgical pain while minimizing the risk of ORADEs.

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.

We examined the prevalence of, and factors associated with, serious opioid-related adverse drug events (ORADEs) that led to an emergency department (ED) visit or hospitalization among patients with chronic gastrointestinal (GI) symptoms and disorders dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D. In this retrospective cohort study, we used linked national patient-level data (April 1, 2011, to October 31, 2014) from the VA and Centers for Medicare and Medicaid Services to identify serious ORADEs among dually enrolled veterans with a chronic GI symptom or disorder. Outcome measures included serious ORADEs, defined as an ED visit attributed to an ORADE or a hospitalization where the principal or secondary reason for admission involved an opioid. We used multiple logistic regression models to determine factors independently associated with a serious ORADE. We identified 3,430 veterans who had a chronic GI symptom or disorder; were dually enrolled in the VA and Medicare Part D; and had a serious ORADE that led to an ED visit, hospitalization, or both. The period prevalence of having a serious ORADE was 2.4% overall and 4.4% among veterans with chronic opioid use (≥90 consecutive days). Veterans with serious ORADEs were more likely to be less than 40 years old, male, white, and to have chronic abdominal pain, functional GI disorders, chronic pancreatitis, or Crohn's disease. They were also more likely to have used opioids chronically and at higher daily doses. There may be a considerable burden of serious ORADEs among patients with chronic GI symptoms and disorders. Future quality improvement efforts should target this vulnerable population.

Opioid-related adverse drug events (ORADEs) are common causes of hospitalization and increased health care costs. To (a) estimate rates of specific adverse drug events (ADEs) among gastrointestinal (GI) surgery patients receiving postoperative opioids; (b) examine the utility of a risk-scoring model in categorizing patients at high risk of experiencing ORADEs; and (c) quantify potential clinical/economic benefits of targeting high-risk GI surgical patients for opioid-sparing regimens in terms of hospitalization cost, length of stay (LOS), and 30-day readmission rates. Using a retrospective design based on an administrative database, patients with an inpatient surgical procedure between January 1, 2010, and December 31, 2010, were included. GI surgical patients aged greater than 18 years followed from admission through 30 days postdischarge were characterized as high or low risk using clinical/demographic characteristics and were evaluated for several outcomes. Using multivariate logistic regression, the ORADE incidence, total hospitalization cost, LOS, and 30-day readmissions were compared for high-risk and low-risk patients. In 87.8% (n = 3,235) of the surgical population, there was a strong concordance between risk assignment and ORADE incidence. Among the remaining 12.2% (n = 449) of patients, 5.5% (n = 202) were low risk with an ORADE, and 6.7% (n = 247) were high risk without an ORADE. Overall, 20.6% (n = 344) of high-risk patients experienced ≥1 ORADE (mean cost: $31,988; LOS: 12.1 days) compared with only 5.3% (n = 107) of low-risk patients (mean cost: $25,216; LOS: 8.0 days). High-risk patients had higher hospitalization costs and longer LOS than low-risk patients, respectively (mean cost: $19,234 vs. $13,036; mean LOS: 6.8 days vs. 3.3 days). These differences correspond to 47.0% higher costs for high-risk patients and an LOS approximately twice as long compared with low-risk patients. Patient clinical/demographic characteristics influence the risk of developing ORADEs. Risk assessment tools can effectively identify high-risk patients, thereby enabling interventions that can reduce ORADEs, decrease hospital costs, and improve postsurgical experiences for patients.

To determine the incidence of and predictors for serious opioid-related adverse drug events (ORADEs) in postoperative inpatients. A retrospective cohort study design of serious ORADEs in surgical inpatients between 2015 and 2017, who were abstracted from the electronic health record, in an 800-bed academic medical health center. A total of 27,942 surgery patients met the inclusion criteria. Of those, 25,208 patients (90%) were exposed to opioids after surgery. A total of 25,133 (99.7%) patients exposed to opioids did not experience a serious ORADE while 75 (0.3%) patients did experience a serious ORADE and required naloxone. The predictors for ORADEs include age (OR = 1.040, P-value < .0001); gender (OR = 0.394, P-value = .0006); psychiatric disorder (OR = 4.440, CI: 2.435, 8.095); morphine level with respect to hydrocodone-acetaminophen (OR = 5.841, P-value = .0384); and were almost six times more likely to experience a serious ORADE when morphine is prescribed and 4.44 times more likely in patients with a psychiatric disorder (P-value < .0001). Once a baseline incidence is known, predictors for serious ORADEs in surgical inpatients are useful in guiding medical-surgical nurses' opioid safety practices, with more frequent focused respiratory assessments before opioid dosing and closer monitoring when opioids are prescribed postoperatively, especially in higher-risk surgical inpatients.

Results of a study of postsurgical opioid-related adverse drug events (ORADEs) within a large health system are reported. In a retrospective cohort study, data from the information database of an 11-hospital Texas health system were analyzed to (1) describe postsurgical opioid use among adult patients undergoing elective or emergency surgery over a one-year period, (2) identify ORADE risk factors and associated costs, and (3) compare clinical and economic outcomes in patients who experienced ORADEs and those who did not. Multivariate logistic regression was used to identify ORADE risk factors. Propensity score-matched comparisons of outcomes in patients with and without ORADEs were conducted. Among 6,285 patients in the study population, 6,274 (99.8%) received postsurgical opioids; 11.5% of those patients experienced an ORADE. ORADE risk factors included age (≥65 years), male sex, prior opioid use, chronic obstructive pulmonary disease, cardiac dysrhythmias, regional enteritis, diverticulitis, and ulcerative colitis. Patients with multiple risk factors had higher mean hospitalization costs ($21,073) relative to patients with one risk factor ($14,110) or no risk factor ($11,433) and accounted for a disproportionately large share of overall costs; patients who experienced ORADEs were more likely to be cost and length of stay (LOS) outliers. Analysis of information from a large database demonstrated that opioid-treated postsurgical inpatients who had multiple risk factors for ORADEs were more likely to have higher mean costs, greater readmission rates, and longer LOS than patients with fewer risk factors.

Characterization of the clinical and economic impact of opioid-related adverse drug events (ORADEs) after total knee arthroplasty (TKA) may guide provider and hospital system approach to managing postoperative pain after TKA. Our analysis quantifies the rate of potential ORADEs after TKA, the impact of potential ORADEs on length of stay (LOS) and hospital revenue, as well as their association with specific patient risk factors and comorbid clinical conditions. We conducted a retrospective study using the Centers for Medicare and Medicaid Services administrative database to analyze Medicare discharges involving two knee replacement surgery diagnosis-related groups (DRGs) in order to identify potential ORADEs. The impact of potential ORADEs on mean hospital LOS and hospital revenue was analyzed. The potential ORADE rate in patients who underwent TKA was 25,523 out of 316,858 records analyzed (8.0%). The mean LOS for patients who experienced a potential ORADE was 1.04days longer than those without an ORADE. The mean hospital revenue per day with a potential ORADE was $1334 (USD) less than without an ORADE. Potential ORADEs were significantly associated with poor patient outcomes such as pneumonia, septicemia, and shock. Potential ORADEs in TKA are associated with longer hospitalizations, decreased hospital revenue, and poor patient outcomes. Certain risk factors may predispose patients to experiencing an ORADE, and thus perioperative pain management strategies that reduce the frequency of ORADEs particularly in at-risk patients can improve patient satisfaction and increase hospital revenue following TKAs.

Opioid-related adverse drug events (ORADEs) include a range of complications, from respiratory arrest to ileus and urinary retention. ORADEs correlate to morbidity, mortality, and increased costs. The Centers for Medicare & Medicaid Services database, which represents approximately 35% of hospital discharges. The authors searched for previously published ICD-9 codes that defined ORADEs. A group of surgical diagnosis-related groups (DRGs) were selected. Recurring queries were programmed using these ICD codes and DRGs and used to update an online dashboard. The dashboard presents an estimate of the burden of ORADEs to frontline clinicians and hospital leadership and allows users to compare local data on ORADEs rates to other hospitals. Users are able to refine their search by surgery type or ORADE type. An interface was created, using national administrative claims data, to allow hospitals to access their ORADEs and benchmark local data against national trends.

Opioid analgesics are a mainstay for acute pain management, but postoperative opioid administration has risks. We examined the prevalence, risk factors, and consequences of opioid-related adverse drug events (ORADEs) in a previously opioid-free surgical population. A retrospective, observational, cohort study using administrative, billing, clinical, and medication administration data from two hospitals. Data were collected for all adult patients who were opioid-free at admission, underwent surgery between October 1, 2015, and September 30, 2016, and received postoperative opioids. Potential ORADEs were determined based on inpatient billing codes or postoperative administration of naloxone. We determined independent predictors of ORADE development using multivariable logistic regression. We measured adjusted inpatient mortality, hospital costs, length of hospital stay, discharge destination, and readmission within 30 days for patients with and without ORADEs. Among 13,389 hospitalizations where opioid-free patients had a single qualifying surgery, 12,218 (91%) received postoperative opioids and comprised the study cohort. Of these, we identified 1111 (9.1%) with a potential ORADE. Independent predictors of ORADEs included older age, several markers of disease severity, longer surgeries, and concurrent benzodiazepine use. Opioid-related adverse drug events were strongly associated with the route and duration of opioids administered postoperatively: 18% increased odds per day on intravenous opioids. In analyses adjusted for several covariates, presence of an ORADE was associated with 32% higher costs of hospitalization, 45% longer postoperative length of stay, 36% lower odds of discharge home, and 2.2 times the odds of death. We demonstrate a high rate and severe consequences of potential ORADEs in previously opioid-free patients receiving postoperative opioids. Knowledge of risk factors and predictors of ORADEs can help develop targeted interventions to minimize the development of these potentially dangerous and costly events.