Opioid-related Adverse Drug Events Research Articles

Optimizing Pain Management in Cardiac Surgery: A Review of Analgesic Adjuvants.

Pain management following cardiac surgery is a critical component in optimizing both short- and long-term patient outcomes, with poor pain management associated with significant acute and chronic opioid use, opioid dependence and a significant rate of opioid related adverse drug events. The significant burden of both acute and chronic pain following cardiac surgery has given rise to the need for multimodel analgesic strategies, to optimize outcomes and minimize side effects. While significant research has focused recently on the additive value of peripheral nerve blocks, less emphasis has been given to the value of non-opioid based analgesics in preference to traditional opioid based anesthetic and analgesic strategies. In this review, we examine the evidence for several common analgesics, highlighting the evidence supporting efficacy following cardiac surgery, as well as the safety concerns with each agent. We demonstrate the value of a multimodal analgesic strategy to reduce pain scores and improve patient-centered outcomes, and highlight the need for further studies of combination analgesic strategies.

The OPI•AID Zone Tool as a composite outcome for postoperative pain management quality-A protocol for an observational pilot study.

Managing postoperative pain while minimizing opioid-related adverse drug events (ORADEs) remains a significant challenge. The OPI•AID Zone Tool is proposed as a novel clinical decision support tool that - both graphically and in a scoring-system -represents the relationship between pain management and the occurrence of ORADEs, aiming to enhance patient outcomes in postoperative care. The OPI•AID Zone Tool places pain scoreon the x-axis and an ORADE score on the y-axis, and stratifies patients into five zones to reflect the composite impact of pain severity and ORADEs on the quality of postoperative patient care. The study will have two key aims: (1) to explore whether the OPI•AID Zone Tool can function as a composite outcome measure for postoperative pain and ORADEs, and (2) to evaluate the use of the OPI•AID Zone Tool in visual presentations and for evaluation of patients' postoperative pain management quality. This prospective observational cohort study will include 200 adults undergoing various surgical procedures in general anesthesia with a subsequent stay in the post-anesthesia care unit (PACU) at Bispebjerg Hospital, Denmark. Substudy 1 primary outcome: To assess whether a zone score in the OPI•AID Zone Tool is associated with patient-perceived health (EQ VAS), quality of recovery (QoR-PACU), and time to discharge readiness in PACU, and if the zone score has a stronger association than pain and ORADE score in themselves. Substudy 2 primary outcome: To assess how the use of intraoperative non-opioid analgesics impact where patients are placed in the OPI•AID Zone Tool's XY scatterplot right after surgery. To assess if patients who receive more comprehensive non-opioid analgesic basic regimens, generally fall into lower zones. The OPI•AID Zone Tool could potentially be a valuable clinical decision-making tool for optimizing postoperative care by simultaneously addressing pain management and the risk of ORADEs. By computing a composite measure of these two critical outcomes, the tool could guide more nuanced and patient-centered analgesic regimens, potentially improving patient satisfaction and operational efficiency in postoperative settings. The tool's applicability will be explored in this observational pilot and followed up in a planned series of studies (opiaid.dk).

Tapentadol Versus Oxycodone for Opioid-Related Adverse Drug Events and Clinical Outcomes After Inpatient Surgery

Oxycodone is a commonly prescribed opioid for postoperative pain. However, there has been a marked increase in the use of tapentadol over the previous decade due to a perceived superior safety profile of tapentadol compared to oxycodone. There is limited real-world evidence on the safety of tapentadol compared to oxycodone after surgery. The primary objective was to examine the impact of tapentadol compared to oxycodone use on the incidence of opioid-related adverse drug events after surgery. Data for adult surgical patients receiving tapentadol or oxycodone during hospitalization between January 1, 2018, and December 31, 2021, were collected from electronic medical records of 3 tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events. Patients receiving tapentadol or oxycodone were matched using nearest-neighbour propensity score matching. In the matched cohorts (n = 1,530 vs n = 2,775; mean [standard deviation] age 62.3 [17.0] years vs 61.9 [standard deviation 17.9] years; 43% vs 45% male for the tapentadol vs oxycodone groups, respectively), patients given tapentadol experienced a similar incidence of adverse events overall (14.4%, 220/1,530 vs 12.6%, 349/2,775; P = .100; 95% CI −.35% to 3.95%). Secondary outcomes included an increased risk of delirium (2.7%, 41/1,530 vs 1.3%, 37/2,775), arrhythmias (3.4%, 52/1,530 vs 2.2%, 62/2,775), and length of hospital stay (5 [range 1–201] vs 4 [range 1–226] days) compared with oxycodone use. Further real-world studies are warranted to determine the impact of tapentadol use on a broad range of patient outcomes. PerspectiveThis study provides an early signal that tapentadol use may be associated with an increased risk of some adverse events and a longer length of stay. Further research is needed to examine the impact of tapentadol use on a broad range of patient outcomes in clinical practice settings.

Risk Factors for Opioid-Related Adverse Drug Events Among Older Adults After Hospitalization for Major Orthopedic Procedures.

Older adults undergoing orthopedic procedures are commonly discharged from the hospital on opioids, but risk factors for postdischarge opioid-related adverse drug events (ORADEs) have not been previously examined. We aimed to identify risk factors for ORADEs after hospital discharge following orthopedic procedures. This is a retrospective cohort study of a national sample of Medicare beneficiaries 65 years or older, who underwent major orthopedic surgery during hospitalization in 2016 and had an opioid fill within 2 days of discharge. We excluded beneficiaries with hospice claims and those admitted from or discharged to a facility. We used billing codes and medication claims to define potential ORADEs requiring a hospital revisit within 30 days of discharge. Among 30,514 hospitalizations with a major orthopedic procedure (89.7% arthroplasty, 5.6% treatment of fracture of dislocation, 4.7% other) and an opioid claim, a potential ORADE requiring hospital revisit occurred in 750 (2.5%). Independent risk factors included age of 80 years or older (hazard ratio [HR], 1.65; 95% confidence interval, 1.38-1.97), female sex (HR, 1.34 [1.16-1.56]), and clinical conditions, including heart failure (HR, 1.34 [1.10-1.62]), respiratory illness (HR, 1.23 [1.03-1.46]), kidney disease (HR, 1.23 [1.04-1.47]), dementia/delirium (HR, 1.63 [1.26-2.10]), anxiety disorder (HR, 1.42 [1.18-1.71]), and musculoskeletal/nervous system injuries (HR, 1.54 [1.24-1.90]). Prior opioid use, coprescribed sedating medications, and opioid prescription characteristics were not associated with ORADEs after adjustment for patient characteristics. Potential ORADEs occurred in 2.5% of older adults discharged with opioids after orthopedic surgery. These risk factors can inform clinician decision making, conversations with older adults, and targeting of harm reduction strategies.

Implementation of required sedation assessment in nursing workflow to address naloxone utilization.

Opioid-related adverse drug events continue to occur. This study aimed to characterize the patient population receiving naloxone to inform future intervention efforts. We describe a case series of patients who received naloxone in the hospital during a 16-week time frame in 2016. Data were collected on other administered medications, reason for admission to the hospital, pre-existing diagnoses, comorbidities, and demographics. Twelve hospitals within a large healthcare system. 46,952 patients were admitted during the study period. 31.01 percent (n = 14,558) of patients received opioids, of which 158 received naloxone. Administration of naloxone. Main outcome of interest: Sedation assessment via Pasero Opioid-Induced Sedation Scale (POSS), administration of sedating medications. POSS score was documented prior to opioid administration in 93 (58.9 percent) patients. Less than half of patients had a POSS documented prior to naloxone administration with 36.8 percent documented 4 hours prior. 58.2 percent of patients received multimodal pain therapy with other nonopioid medications. Most patients received more than one sedating medication concurrently (n = 142, 89.9 percent). Our findings highlight areas for intervention to prevent opioid oversedation. Investing in electronic clinical decision support mechanisms, such as sedation assessment, could detect patients at risk for oversedation and ultimately prevent the need for naloxone. Coordinated order sets for pain management can reduce the percentage of patients receiving multiple sedating medications and promote the use of multimodal pain management in efforts to reduce opioid reliance while optimizing pain control.

Incidence of and predictors for serious opioid-related adverse drug events.

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.

Multimodal Analgesia's Impact on Opioid Use and Adverse Drug Effects in a Multihospital Health System.

Purpose:In addition to opioid abuse and dependency, opioid use can lead to opioid related adverse drug events (ORADEs). ORADEs are associated with increased length of stay, cost of care, 30-day readmission rate, and inpatient mortality. The addition of scheduled non-opioid analgesic medications has shown to be effective in reducing opioid utilization in post-surgical and trauma populations, but evidence in entire hospital patient populations is limited. The objective of this study was to determine the effects of a multimodal analgesia order set on opioid utilization and adverse drug events in adult hospitalized patients. Methods: This retrospective pre/post implementation analysis was conducted at 3 community hospitals and a level II trauma center between January 2016 and December 2019. Patients included were 18 years of age or older, admitted for greater than 24 hours, and had at least one opioid ordered during hospital admission. The primary outcome of this analysis was the average oral morphine milligram equivalents (MME) used on days 1 through 5 of hospitalization. Secondary outcomes included the percentage of hospitalized patients with an opioid ordered for analgesia who received a scheduled non-opioid analgesic medication, the average number of ORADEs recorded in nursing assessments on hospitalization days 1 through 5, length of stay, and mortality. Multimodal analgesic medications included acetaminophen, gabapentinoids, non-steroidal anti-inflammatory drugs, muscle relaxants, and transdermal lidocaine. Results: The pre- and post-groups included 86 535 patients and 85 194 patients, respectively. The average oral MMEs used on days 1 through 5 were lower in the post-group (P < .0001). Utilization of multimodal analgesia as measured by the percentage of patients with 1 or more scheduled multimodal analgesia agent ordered increased from 33% to 49% at the end of the analysis. Conclusion: Utilization of a multimodal analgesia order set was associated with a decrease in opioid use and an increase in multimodal analgesia use in an entire hospital adult population.

Budget Impact and Cost-Effectiveness of Intravenous Meloxicam to Treat Moderate-Severe Postoperative Pain.

This study assesses the budget impact and cost-effectiveness of intravenous meloxicam (MIV) to treat moderate-severe acute postoperative pain in adults. A two-part Markov cohort model captured the pharmacoeconomic impact of MIV versus non-opioid intravenous analgesics (acetaminophen, ibuprofen, ketorolac) among a hypothetical adult cohort undergoing selected inpatient procedures and experiencing moderate-severe acute postoperative pain: Part1 (postoperative hour0 to discharge, cycled hourly), health states were defined by pain level. Pain transition rates, adverse event probabilities, and concomitant opioid utilization were derived from a network meta-analysis. Part2 (discharge to week52, cycled weekly), health states were defined by the presence/absence of pain-related readmission and opioid use disorder as determined by literature-based inputs relating to pain control outcomes. Healthcare utilization and direct medical costs were derived from an administrative claims database analysis. Primary outcomes were the incremental cost per member per month (PMPM) and cost per quality-adjusted life year (QALY) gained. Scenario, univariate, and probabilistic sensitivity analyses were conducted. The model assumed a private payer perspective in the USA (no discounting, 2019 US$). Modeled outcomes indicated MIV was associated with lower accumulated postoperative pain, fewer adverse events, and less opioid utilization for most procedures and comparators, with longer-term outcomes also generally favoring MIV. The budget impact of MIV was - $0.028PMPM. From a cost-effectiveness perspective, MIV had lower costs and better outcomes for all comparisons except against ketorolac in orthopedic procedures where the former was cost-effective but not cost saving ($95,925/QALY). Scenario and sensitivity analyses indicated that modeled outcomes were robust to alternative inputs and underlying input uncertainty. Differences in direct medical costs were driven by reduced costs attributable to length of stay and opioid-related adverse drug events. MIV was associated with modeled clinical and economic benefits compared to commonly used non-opioid intravenous analgesics.

Integrating Pharmacogenomic Results and Drug-Induced Phenoconversion Concepts while Conducting a Medication Safety Review Process

Opioid appropriateness is primarily focused on insufficient pain control; however, opioid-related adverse drug events (ADE) have also been associated with a negative impact on disability, mood, and quality of life.

Efficacy of ultrasound-guided parasternal block in adult cardiac surgery: a meta-analysis of randomized controlled trials.

Pain after cardiac surgery is a common and severe postoperative complication. As a new regional nerve block method, ultrasound-guided parasternal block (PSB) has been increasingly used to supplement the analgesic effects of opioids in order to eliminate opioid-related adverse drug events, but its efficacy still remains controversial. In the present meta-analysis, we aim to screen all eligible randomized controlled trials (RCTs) and give a comprehensive summary of the clinical value of PSB after adult cardiac surgery. We searched all RCTs about PSB after cardiac surgery in the database of PubMed, Embase, Cochrane, CNKI and Wanfang with no limitation of language from inception to September 2021. Two reviewers were independently involved in the process of data extraction. Meta-analysis was performed by using Review Manager software. The quality of included RCTs were assessed by using Cochrane's risk of bias assessment tool, and funnel plots were drawn to assess publication bias. A total of 12 RCTs with 366 patients in PSB group and 364 patients in control group were included in the present meta-analysis. Pooled analysis revealed that intraoperative and postoperative consumption of sufentanil were significantly decreased with the addition of PSB (P<0.05). Numerical rating scale (NRS) scores in PSB group were found to be significantly lower than that of control group at extubation, postoperative 4 h and 8 h (P<0.05) instead of postoperative 24 h or longer. PSB could reduce the incidence of postoperative nausea and vomiting (PONV) (P<0.05). In addition, we demonstrated that PSB was significantly related to decreased mechanical ventilation time, total length of ICU stay and hospital days (P<0.05). Through decreasing the consumption of opioids, ultrasound-guided PSB could relieve pain and limit opioid-related complications. Clinical outcomes, such as mechanical ventilation time, total length of ICU stay and hospital days, will also be improved. Our findings prove that ultrasound-guided PSB is an effective regional analgesic method after adult cardiac surgery.

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.

Patient risk factors for opioid-related adverse drug events in hospitalized patients: A systematic review.

Opioid utilization has increased fourfold over the past two decades among developed countries. Previous studies have found that opioid-related adverse drug events (ORADEs) are strongly associated with adverse clinical outcomes in hospitalized patients. The Society of Hospital Medicine in the United States recently published a Consensus Statement regarding opioid safety and suggested that extra caution is needed when using opioids in patients with risk factors for ORADEs. This systematic review aimed to summarize common patient risk factors for ORADEs in hospitalized patients. Five databases were searched including Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus. Search themes include opioids, adverse drug events, and acute care settings. Original full-text studies that were published and identified patient risk factors for ORADEs in hospitalized patients were included. A total of 16 observational studies were included, with only two studies considered as poor quality. Seven studies focused on severe ORADEs including over-sedation and respiratory depression. Common patient risk factors for severe ORADEs included comorbidities (eg, sleep apnea and renal diseases), concurrent use of sedatives, and prior opioid exposure. Nine studies focused on a combination of general ORADEs and common patient risk factors included advanced age, male gender, comorbidities (eg, chronic obstructive pulmonary disease and neurologic disorders), concurrent use of sedating medications, and prior opioid exposure. Successful identification of patient risk factors for ORADEs summarized by this systematic review could benefit clinicians when deciding on the appropriateness of opioid therapy in hospital patients. Future studies could focus on developing a validated risk assessment tool based on these risk factors.

Development, Validation, and Assessment of Clinical Impact of Real-time Alerts to Detect Inpatient As-Needed Opioid Orders With Duplicate Indications: Prospective Study.

BackgroundAs-needed (PRN) opioid orders with duplicate indications can lead to medication errors and opioid-related adverse drug events.ObjectiveThe objective of our study was to build and validate real-time alerts that detect duplicate PRN opioid orders and assist clinicians in optimizing the safety of opioid orders.MethodsThis single-center, prospective study used an iterative, 3-step process to refine alert performance by advancing from small sample evaluations of positive predictive values (PPVs) (step 1) through intensive evaluations of accuracy (step 2) to evaluations of clinical impact (step 3). Validation cohorts were randomly sampled from eligible patients for each step.ResultsDuring step 1, the PPV was 100% (one-sided, 97.5% CI 70%-100%) for moderate and severe pain alerts. During step 2, duplication of 1 or more PRN opioid orders was identified for 17% (34/201; 95% CI, 12%-23%) of patients during chart review. This bundle of alerts showed 94% sensitivity (95% CI 80%-99%) and 96% specificity (95% CI 92%-98%) for identifying patients who had duplicate PRN opioid orders. During step 3, at least 1 intervention was made to the medication profile for 77% (46/60; 95% CI 64%-87%) of patients, and at least 1 inappropriate duplicate PRN opioid order was discontinued for 53% (32/60; 95% CI 40%-66%) of patients.ConclusionsThe bundle of alerts developed in this study was validated against chart review by a pharmacist and identified patients who benefited from medication safety interventions to optimize PRN opioid orders.

Risk factors for opioid-related adverse drug events among older adults after hospital discharge.

Although opioids are initiated on hospital discharge in millions of older adults each year, there are no studies examining patient- and prescribing-related risk factors for opioid-related adverse drug events (ADEs) after hospital discharge among medical patients. A retrospective cohort study of a national sample of Medicare beneficiaries aged 65 years and older, hospitalized for a medical reason, with at least one claim for an opioid within 2 days of hospital discharge. We excluded patients receiving hospice care and patients admitted from or discharged to a facility. We used administrative billing codes and medication claims to define potential opioid-related ADEs within 30 days of hospital discharge, and competing risks regression to identify risk factors for these events. Among 22,879 medical hospitalizations (median age 74, 36.9% female) with an opioid claim within 2 days of hospital discharge, a potential opioid-related ADE occurred in 1604 (7.0%). Independent risk factors included age of 80 years and older (HR 1.18, 95% CI 1.05-1.33); clinical conditions, including kidney disease (HR 1.22, 95% CI 1.08-1.37), dementia/delirium (HR 1.38, 95% CI 1.22-1.56), anxiety disorder (HR 1.20, 95% CI 1.06-1.36), opioid use disorder (HR 1.20, 95% CI 1.03-1.39), intestinal disorders (HR 1.31, 95% CI 1.15-1.49), pancreaticobiliary disorders (HR 1.32, 95% CI 1.09-1.61), and musculoskeletal and nervous system injuries (HR 1.35, 95% CI 1.17-1.54); red flags for opioid misuse (HR 1.37, 95% CI 1.04-1.80); opioid use in the 30 days before hospitalization (HR 1.20, 95% CI 1.08-1.34); and prescription of long-acting opioids (HR 1.34, 95% CI 1.06-1.70). Potential opioid-related ADEs occurred within 30 days of hospital discharge in 7.0% of older adults discharged from a medical hospitalization with an opioid prescription. Identified risk factors can be used to inform physician decision-making, conversations with older adults about risk, and development and targeting of harm reduction strategies.

Opioid-related emergency department visits and hospitalizations among patients with chronic gastrointestinal symptoms and disorders dually enrolled in the Department of Veterans Affairs and Medicare Part D.

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.

Bilateral continuous erector spinae plane block using a programmed intermittent bolus regimen versus intrathecal morphine for postoperative analgesia in living donor laparoscopic hepatectomy: A randomized controlled trial

Study objectiveTo determine if continuous bilateral erector spinae plane (ESP) blocks would improve the postoperative analgesia in the first 48 h after laparoscopic donor hepatectomy, compared to intrathecal morphine (ITM). DesignProspective, randomized controlled trial. SettingA single tertiary care center from October 2019 and September 2020. PatientsA total of 60 donors scheduled to undergo elective laparoscopic right hepatectomy. InterventionsSixty donors were randomized to receive either bilateral continuous T8 ESP blocks with a programmed intermittent bolus regimen of 10 mL 0.2% ropivacaine every 3 h for 48 h (n = 30) or 400 μg ITM (n = 30), in addition to IV fentanyl PCA and multimodal analgesia. MeasurementsThe primary outcome was cumulative opioid consumption over the first 48 h, expressed as IV morphine equivalents. Secondary outcomes included pain scores, Quality of Recovery-15 scores, ambulation within 24 h, time to first flatus, and opioid-related adverse drug events over 72 h. Main resultsFifty-nine donors were analyzed. Cumulative 48-h opioid consumption was similar between the ITM and ESP groups (29.8 ± 18.2 vs. 35.1 ± 21.9 mg, mean difference (ESP-ITM) (95% CI), 5.3 (−11.5 to 22) mg; p > 0.99). Resting pain scores at 48 and 72 h postoperatively were significantly lower in the ESP group (0 [0–2] vs. 3 [1.5–3], and 0 [0–2] vs. 3 [1–3] respectively, both p<0.001) (Goldaracena and Barbas, 2019; Ko et al., 2009; Choi et al., 2007 [1–3]) respectively, both p < 0.001). The ESP group had significantly lower incidences of postoperative nausea, vomiting, and pruritus at all timepoints. There were no differences in recovery outcomes. ConclusionsContinuous ESP blocks did not reduce cumulative 48-h opioid consumption compared to 400 μg ITM after laparoscopic donor hepatectomy, but it was associated with a significantly reduced risk of postoperative nausea, vomiting and pruritus. Clinical trial number and registry URLClinical Trial Registry of Korea; https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0004313; date of registration: October 15, 2019; principal investigator's name: Justin Sangwook Ko.

Transcutaneous Electrical Acupoint Stimulation Reduces Postoperative Analgesic Requirement in Patients Undergoing Inguinal Hernia Repair: A Randomized, Placebo-Controlled Study.

Given the rising rate of opioid-related adverse drug events during postsurgical pain management, a nonpharmacologic therapy that could decrease analgesic medication requirements would be of immense value. We designed a prospective, placebo-and-randomized controlled trial to assess the clinical effect of transcutaneous acupoint electrical stimulation (TEAS) on the postoperative patient-controlled analgesia (PCA) requirement for morphine, as well as side effects and recovery profile after inguinal hernia repair. Seventy-one subjects undergoing inguinal hernia repair with a standardized anesthetic technique were randomly assigned to one of three analgesic treatment regimens: PCA + TEAS (n = 24); PCA + sham-TEAS (no electrical stimulation) (n = 24), and PCA only (n = 23). The postoperative PCA requirement, pain scores, opioid-related side effects, and blood cortisol levels were recorded. TEAS treatment resulted in a twofold decrease in the analgesic requirement and decreased pain level reported by the patients. In addition, a significant reduction of cortisol level was reported in the TEAS group at 24 h postoperatively compared to the sham and control groups. We conclude that TEAS is a safe and effective option for reducing analgesic consumption and postoperative pain following inguinal hernia repair.

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer

National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population. To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment. This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020. Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims. Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics. Among 38 310 women included in the study (mean [SD] age, 74.3 [6.3] years), there were 0.010 (95% CI, 0.008-0.011) adverse drug events related to substance misuse per 1000 person-days, 0.237 (95% CI, 0.229-0.245) other adverse drug events associated with opioid use per 1000 person-days, and 0.675 (95% CI, 0.662-0.689) all-cause hospitalizations per 1000 person-days. Opioid use was associated with increased risk of adverse drug events related to substance misuse (aRR, 14.62; 95% CI, 9.69-22.05; P < .001), other adverse drug events related to opioid use (aRR, 2.50; 95% CI, 2.11-2.96; P < .001), and all-cause hospitalization (aRR, 2.77; 95% CI, 2.55-3.02; P < .001). In a dose-response effect, individuals with high daily opioid doses had consistently higher risks of all study outcomes compared with individuals who had low opioid doses. Compared with days with no opioid exposure, the risk of any adverse drug event related to substance misuse was 3.4-fold higher for individuals with a current opioid supply ≥50 mg morphine equivalent dose per day (aRR, 3.40; 95% CI, 2.47-4.68; P < .001), while the risk was 2.3-fold higher for individuals with 1 to 49 mg morphine equivalent dose per day (aRR, 2.29; 95% CI, 1.89-2.77; P < .001). These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy.

Nature of adverse events with opioids in hospitalised patients: a post-hoc analysis of three patient record review studies.

ObjectiveOpioids are increasingly prescribed and frequently involved in adverse drug events (ADEs). The underlying nature of opioid-related ADEs (ORADEs) is however understudied. This hampers our understanding of risks related to opioid use during hospitalisation and when designing interventions. Therefore, we provided a description of the nature of ORADEs.DesignA post-hoc analysis of data collected during three retrospective patient record review studies (in 2008, 2011/2012 and 2015/2016).SettingThe three record review studies were conducted in 32 Dutch hospitals.ParticipantsA total of 10 917 patient records were assessed by trained nurses and physicians.Outcome measuresPer identified ORADE, we described preventability, type of medication error, attributable factors and type of opioids involved. Moreover, the characteristics of preventable and non-preventable ORADEs were compared to identify risk factors.ResultsOut of 10 917 patient records, 357 ADEs were identified, of which 28 (8%) involved opioids. Eleven ORADEs were assessed as preventable. Of these, 10 were caused by dosing errors and 4 probably contributed to patients’ death. Attributable factors identified were mainly on patient and organisational levels. Morphine and oxycodone were the most frequently involved opioids. The risk for ORADEs was higher in elderly patients.ConclusionsOnly 8% of ADEs identified in our sample were related to opioids. Although the frequency is low, the risk of serious consequences is high. We recommend to use our findings to increase awareness among physicians and nurses. Future interventions should focus on safe dosing of opioids when prescribing and administering, especially in elderly patients.

Predictors of Serious Opioid-Related Adverse Drug Events in Hospitalized Patients.

Opioids are high-risk medications in the inpatient setting because of their potential for significant patient harm. The primary objective was to identify risk factors that predispose inpatients to develop opioid-related adverse drug events (ORADE) requiring the use of naloxone. In a retrospective case-control study, patients were included according to the following criteria: 18 years or older, 1 administered opioid doses or more, and admitted for 24 hours or more. Patients were excluded if they had a prehospital drug overdose, other indications for naloxone use, or were admitted to an intensive care unit, psychiatric medical unit, or in the emergency department. Patients were classified as cases if naloxone was administered and a selection of controls were frequency matched 2:1 based on medical or surgical status. A logistic regression model was used to evaluate for risk factors for ORADE. A total of 275 cases and 592 control patients were included into the final analysis. Variables that were associated with greater odds of naloxone administration included age of 65 years or older, female, length of stay, pulmonary diagnoses, use of gabapentinoids, and patient-controlled analgesia use. Antihistamines, continuous infusion, and intermittent nurse administered intravenous bolus routes had a negative association with naloxone use. Several risk factors were found to be associated with ORADE supporting many of the previously described risk factors, and the discovery of potential new ones, such as gabapentinoid use. Health care providers should consider the risk factors for hospitalized patients receiving opioids who may warrant lower doses, additional monitoring, or alternative agents.