Substance Use Disorders: Basic Overview for the Anesthesiologist.

Substance use disorders (SUDs) represent a current major public health concern in the United States and around the world. Social and economic stressors secondary to the coronavirus disease 2019 (COVID-19) pandemic have likely led to an increase in SUDs around the world. This chronic, debilitating disease is a prevalent health problem, and yet many clinicians do not have adequate training or clinical experience diagnosing and treating SUDs. Anesthesiologists and other perioperative medical staff frequently encounter patients with co-occurring SUDs. By such, through increased awareness and education, physicians and other health care providers have a unique opportunity to positively impact the lives and improve the perioperative outcomes of patients with SUDs. Understanding commonly used terms, potentially effective perioperative screening tools, diagnostic criteria, basics of treatment, and the perioperative implications of SUDs is essential to providing adequate care to patients experiencing this illness.

Pain, Opioid Analgesics, and Cognition: A Conceptual Framework in Older Adults.

Chronic pain is highly prevalent in older adults and is associated with poor functional outcomes. Furthermore, opioid analgesics are commonly utilized for the treatment of pain in older adults despite well-described adverse effects. Importantly, both chronic pain and opioid analgesics have been linked with impairments in cognitive function, though data are limited. In this manuscript we summarize the evidence and critical knowledge gaps regarding the relationships between pain, opioid analgesics, and cognition in older adults. Furthermore, we provide a conceptual framework to guide future research in the development, implementation, and evaluation of strategies to optimize analgesic outcomes in older adults while minimizing deleterious effects on cognition.

Disparities in Hypoxemia Detection by Pulse Oximetry Across Self-Identified Racial Groups and Associations With Clinical Outcomes.

OBJECTIVES: To assess disparities in hypoxemia detection by pulse oximetry across self-identified racial groups and associations with clinical outcomes. DESIGN: Observational cohort study from May 5, 2018, to December 31, 2020. SETTING: Three academic medical centers in the United States. PATIENTS: Adults greater than or equal to 18 years who self-identified as White, Black, Asian, or American Indian admitted to the ICU or undergoing surgery during inpatient hospitalization with simultaneous measurements of pulse oximetry-estimated oxygen saturation and arterial blood gas-derived oxygen saturation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariable models were employed to assess the relationships between race, occult hypoxemia (i.e., arterial blood gas-derived oxygen saturation < 88% despite pulse oximetry-estimated oxygen saturation ≥ 92%), and clinical outcomes of hospital mortality and hospital-free days. One-hundred twenty-eight-thousand two-hundred eighty-five paired pulse oximetry-estimated oxygen saturation-arterial blood gas-derived oxygen saturation measurements were included from 26,603 patients. Pulse oximetry-estimated oxygen saturation on average overestimated arterial blood gas-derived oxygen saturation by 1.57% (1.54-1.61%). Black, Asian, and American Indian patients were more likely to experience occult hypoxemia during hospitalization (estimated probability 6.2% [5.1-7.6%], 6.6% [4.9-8.8%], and 6.6% [4.4-10.0%], respectively) compared with White patients (3.6% [3.4-3.8%]). Black patients had increased odds of occult hypoxemia compared with White patients after adjustment (odds ratio, 1.65; 1.28-2.14; p < 0.001). Differences in occult hypoxemia between Asian and American Indian patients compared with White patients were not significant after adjustment (odds ratio, 1.53; 0.95-2.47; p = 0.077 and odds ratio, 1.31; 0.80-2.16; p = 0.288, respectively). Occult hypoxemia was associated with increased odds of mortality in surgical (odds ratio, 2.96; 1.20-7.28; p = 0.019) and ICU patients (1.36; 1.03-1.80; p = 0.033). Occult hypoxemia was associated with fewer hospital-free days in surgical (-2.5 d [-3.9 to -1.2 d]; p < 0.001) but not ICU patients (0.4 d [-0.7 to 1.4 d]; p = 0.500). CONCLUSIONS: Occult hypoxemia is more common in Black patients compared with White patients and is associated with increased mortality, suggesting potentially important outcome implications for undetected hypoxemia. It is imperative to validate pulse oximetry with expanded racial inclusion.

Perioperative Opioid Consumption and Clinical Outcomes in Surgical Patients With a Pre-existing Opioid-Based Intrathecal Drug Delivery System.

BACKGROUND: Intrathecal drug delivery systems (IDDS) have been utilized for over 3 decades for management of chronic pain and spasticity. Patients with IDDS may present for surgical procedures unrelated to the IDDS device, although data are limited regarding perioperative outcomes. METHODS: This is a historical matched cohort study conducted between January 1, 2007 and December 31, 2016 of patients with an opioid-based IDDS versus matched control patients undergoing surgery excluding interventional pain procedures. Patients in the IDDS group were matched with up to 2 patients without an IDDS. Multivariable regression analyses were utilized to assess differences in the primary outcome of cumulative perioperative opioid consumption (ie, intraoperative and postanesthesia care unit [PACU] opioid consumption), and opioid consumption during the first 24 and 72 postoperative hours. Postoperative clinical outcomes were also assessed including escalating oxygen requirements, naloxone administration, pain-sedation mismatch, and perioperative pain service consultation. RESULTS: A total of 321 surgeries were included, 112 with IDDS and 209 controls, with median (interquartile range [IQR]) age of 57 (49-64) years. Compared to matched controls, patients with an IDDS had greater perioperative opioid consumption (median [IQR] oral morphine milligram equivalents [OME] of 110 [60-163] vs 93 [IQR, 53-142]; adjusted multiplicative increase 1.28 [95% confidence interval {CI}, 1.03-1.59]; P = .026). IDDS patients also had greater opioid consumption in the first 24 and 72 postoperative hours (multiplicative increases of 2.23 [95% CI, 1.36-3.63], P = .001, and 2.46 [95% CI, 1.41-4.32], P = .002, respectively). There were no significant differences in postoperative oxygen requirements, naloxone administration, or pain-sedation mismatch. Inpatient pain medicine consultation was more frequent in IDDS patients compared to controls (51.8% vs 6.2%; P < .001). CONCLUSIONS: Patients with opioid-based IDDS received more perioperative opioids and were more likely to receive postoperative pain service consultation compared to matched controls. There were no significant differences in clinical safety outcomes, suggesting tolerance for higher opioid doses. Further research is warranted to optimize perioperative outcomes in those with IDDS.

Abdominal Ice after Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To assess the impact of abdominal ice packs on opioid use and pain control after laparoscopic hysterectomy DESIGN: Randomized controlled trial. SETTING: Academic tertiary care medical center. PATIENTS: Total of 142 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy were randomized to control (n = 69) or intervention (n = 73). Exclusion criteria included preoperative opioid use, planned intensive care unit admission or same-day discharge, an incision ≥4 cm, and regional anesthesia use. INTERVENTIONS: Subjects in the intervention group had a large ice pack placed directly on the lower abdomen before leaving the operating room. The ice pack was maintained continuously for 12 hours postoperation, as desired thereafter until discharge, and continued use encouraged after discharge for up to 48 hours. MEASUREMENTS AND MAIN RESULTS: Total opioids administered postoperatively, while inpatient and after dismissal, were assessed in morphine milligram equivalents. Postoperative pain, as well as analgesia acceptability and side effects, were assessed using validated measures: Brief Pain Inventory and Overall Benefit of Analgesia Score. Median morphine milligram equivalent was lower in the intervention group than the controls from inpatient stay on the floor to completion of opioid use as an outpatient (22.5 vs 26.2) but was not statistically significant (p = .79). There was no significant difference between the groups in Brief Pain Inventory assessment of postoperative pain severity (p = .80) or pain interference (p = .36) or Overall Benefit of Analgesia Score total score (p = .88). Most patients in the intervention group were very satisfied with ice pack use (n = 51, 79.7%) and very likely to recommend it to friends or family (n = 54, 83.1%). There were no adverse events related to ice pack use. CONCLUSION: There was no significant difference in postoperative opioid use or pain assessment with ice pack use after laparoscopic hysterectomy. However, most of the subjects expressed high satisfaction specific to ice pack use and would recommend its use to others, suggesting potential desirability as adjunct therapy in postoperative pain control.

Impact of Perioperative Pain Control on Knee Range of Motion and Development of Arthrofibrosis Following Primary Total Knee Arthroplasty.

BACKGROUND: Inadequate pain control following total knee arthroplasty (TKA) has been postulated to negatively impact knee range of motion (ROM). We sought to determine the association between perioperative pain levels and knee ROM at 3-month follow-up or need for manipulation under anesthesia (MUA). METHODS: We retrospectively reviewed 2243 primary TKAs performed from 2002 to 2019 at a single academic center using an institutional total joint registry. Mean age was 68, mean body mass index was 32.8, and 59% were female. Knee ROM was measured preoperatively and 3 months postoperatively. Change in knee ROM, rates of soft tissue contracture, and MUA were assessed in relation to in-hospital 10-point pain visual analog scale (VAS) measurements. RESULTS: Overall, 44% had improved ROM at 3-month follow-up, 29% had no change in ROM, and 27% had worsened ROM. There was no significant difference in mean VAS scores of patients with improved, unchanged, or worsened ROM postoperatively (3.0 vs 2.8 vs 3.0; P = .068). There was no significant difference in mean VAS scores of patients who developed a soft tissue contracture or required MUA vs those who did not develop these complications (2.7 vs 2.9; P = .24). Similarly, no significant relationship with these outcomes was identified when maximum and discharge VAS scores were analyzed. CONCLUSION: Comparable ROM and rates of MUA based on in-hospital pain levels were observed in this large series of primary TKA patients. While significant early pain may limit participation in ROM exercises initially, this does not appear to have a marked impact on ROM-related complications for most patients. LEVEL OF EVIDENCE: III, Therapeutic.

Peripheral Nerve Stimulation and Clinical Outcomes: A Retrospective Case Series.

PURPOSE: Peripheral nerve stimulation (PNS) is a rapidly expanding field within neuromodulation; however, there is limited data on therapeutic efficacy. This study describes the indications and clinical outcomes for patients undergoing PNS for chronic pain states. PATIENTS AND METHODS: This is a retrospective case series of adults undergoing PNS implantation from 2004 to 2017 at an academic medical center. The primary outcomes were changes in numeric rating scale (NRS) pain scores, opioid utilization in oral morphine milligram equivalent (MME), and self-reported patient functioning at 6 months postoperatively. Infectious and device-related complications were also assessed. RESULTS: A total of 72 patients underwent PNS implantation, including 59 patients that received a preceding PNS trial (59/78; 76% progression rate) and 13 that did not receive a PNS trial. The most common indication for stimulation was occipital neuralgia (47%) followed by lower-extremity neuropathies (17%). PNS implantation was associated with 6-month reductions in pain scores (7 [6, 8] baseline vs. 4 [2, 5] 6 months; P < 0.001) and opioid utilization (eg, median 60 [31, 104] vs. 18 [0, 52] MME among those with baseline opioid use; P < 0.001). Median functional improvement was 73% (50%, 88%). Seven patients (10%) suffered a postoperative surgical site infection at a median of 50 (30, 124) days, of which five devices were removed. CONCLUSION: Peripheral nerve stimulation was associated with reduced pain scores, lower opioid utilization, and improved patient function at 6 months. These data support PNS as a potentially effective nonopioid analgesic modality in chronic pain, though prospective multicenter evaluation is warranted to evaluate longer-term outcomes.

Peripheral Nerve Blockade with Combined Standard and Liposomal Bupivacaine in Major Lower-Extremity Amputation.

BACKGROUND AND OBJECTIVES: Optimizing perioperative analgesia for patients undergoing major lower-extremity amputation remains a considerable challenge. The utility of liposomal bupivacaine as a component of peripheral nerve blockade for lower-extremity amputation is unknown. METHODS: We conducted an observational study comparing three different perioperative analgesic techniques for adults undergoing major lower-extremity amputation under general anesthesia between 2012 and 2017 at an academic medical center: (1) no regional anesthesia, (2) peripheral nerve blockade with standard bupivacaine, and (3) peripheral nerve blockade with a mixture of standard and liposomal bupivacaine. The primary outcome of cumulative opioid oral morphine milligram equivalent utilization in the first 72 hours postoperatively was compared across groups utilizing multivariable linear regression. RESULTS: A total of 631 unique anesthetics were included for 578 unique patients, including 416 (66%) without regional anesthesia, 131 (21%) with peripheral nerve blockade with a mixture of standard and liposomal bupivacaine, and 84 (13%) with peripheral nerve blockade with standard bupivacaine alone. Cumulative morphine equivalents were lower in those receiving peripheral nerve blockade with combined standard and liposomal bupivacaine compared with those not receiving regional anesthesia (multiplicative increase 0.67; 95% CI 0.50 to 0.90; P = 0.007). There were no significant differences in opioid utilization between peripheral nerve blockade groups (P = 0.59). CONCLUSIONS: Peripheral nerve blockade is associated with reduced opioid requirements after lower-extremity amputation compared with general anesthesia alone. However, the incorporation of liposomal bupivacaine is not significantly different to blockade employing only standard bupivacaine.

Opioid prescribing for acute postoperative pain after cutaneous surgery.

BACKGROUND: Little information is available to predict which patients require opioid analgesia following cutaneous surgery. When opioids are indicated, information regarding the optimal opioid agent selection and dosage is lacking. OBJECTIVE: To make recommendations for opioid prescription after cutaneous surgery. METHODS: A PubMed literature search was conducted to review the available literature. Recommendations are presented on the basis of available evidence and the opinion of the authors. RESULTS: Most patients undergoing cutaneous surgery do not require opioid analgesia. For those who do, the duration of pain warranting opioid analgesia is generally less than 36 hours. Opioid refill requests warrant a follow-up visit to ascertain the cause of ongoing pain after excisional procedures. LIMITATIONS: The recommendations are not based on prospective randomized trials. CONCLUSIONS: The presented recommendations for opioid prescription practice are derived from available evidence, recommendations, and expert opinion.

Cardiac Risk of Noncardiac Surgery After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents.

BACKGROUND: Noncardiac surgery (NCS) following percutaneous coronary intervention (PCI) with stenting is sometimes associated with major adverse cardiac events (MACEs). Second-generation drug-eluting stents (DES) were developed to decrease the incidence of MACE seen with bare metal and first-generation DES. METHODS: The medical records of all adult patients who underwent second-generation DES placement between July 29, 2008 and July 28, 2011 followed by NCS between September 22, 2008 and July 1, 2013 were reviewed. All episodes of MACE following surgery were recorded. RESULTS: A total of 282 patients (74.8% male) were identified who underwent NCS after PCI with second-generation DES. MACE occurred in 15 patients (5.3%), including 11 deaths. The incidence of MACE changed significantly with time from PCI to NCS: 17.1%, 10.0%, 0.0%, and 3.1% for patients undergoing NCS at 0-90, 91-180, 181-365, and ≥366 days, respectively. Compared with those having NCS ≥366 days after PCI, the odds ratio for MACE (95% confidence interval) was 6.4 (1.9 to 21.3) at 0-90 days and 3.4 (0.8 to 15.3) at 91-180 days. Seven days prior to NCS, 146 (52%) patients were on dual antiplatelet therapy (DAPT), 106 (38%) were on aspirin, and 30 (11%) did not receive antiplatelet therapy. Excessive surgical bleeding occurred in 19 cases (6.7%). While observed bleeding rates were lowest in those not receiving antiplatelet therapy, there were no statistically significant differences based on the presence or absence of antiplatelet therapy (3% [1/30] for no antiplatelet therapy compared to 6% [6/106] for aspirin monotherapy and 8% [12/146] for DAPT; Fisher exact test: P = .655). CONCLUSIONS: The incidence of MACE in patients with second-generation DES undergoing NCS was 5.3% and was highest in the first 180 days following DES implantation. The rate of excessive surgical bleeding was 6.7% with the highest observed rate in those on DAPT. However, differences by the presence or absence of antiplatelet therapy were not significant, and future large observational studies will be necessary to further define bleeding risk with continued DAPT.

Bleeding Complications in Patients Undergoing Intrathecal Drug Delivery System Implantation.

INTRODUCTION: Intrathecal drug delivery systems (IDDSs) have dramatically improved analgesia and the functional status of cancer patients and those with chronic pain states. However, given the close proximity to the neuraxis and frequent concomitant use of antiplatelet or anticoagulant medications, this intervention is not without risk. The goal of this investigation was to determine the incidence of bleeding complications following IDDS placement. METHODS: This is a retrospective review from 2005 through 2014 of adult patients undergoing IDDS implantation or revision at a tertiary care center. The primary outcome was a bleeding-related neurological complication requiring emergency medicine, neurology, or neurosurgical evaluation within 31 days. RESULTS: A total of 247 procedures were performed on 216 unique patients. Patients received aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) within seven days of needle placement for 64 procedures (25.9%). A preprocedural platelet count or international normalized ratio (INR) was available within 30 days for 138 procedures (55.9%). Of these, two patients had a platelet count lower than 100 x 109/L and one patient had an INR of 1.5 or higher at the time of the procedure. One neurological complication was identified (0.4%) that was not related to procedural bleeding. Similarly, three patients (1.2%) received a periprocedural red blood cell transfusion, none of which were related to procedural bleeding. CONCLUSION: No cases of bleeding-related neurological complications were identified following IDDS placement or revision, including in those receiving aspirin or NSAIDs. Future investigations with larger numbers are needed to further explore the safety of antithrombotic therapy continuation or discontinuation periprocedurally.

Bleeding Complications in Patients Undergoing Percutaneous Spinal Cord Stimulator Trials and Implantations.

INTRODUCTION: Spinal cord stimulators (SCS) are indicated for the management of multiple pain states with strong evidence. Recent guidelines recommend discontinuing aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) for the described procedures. The goal of this investigation is to assess the rate of bleeding and neurologic sequelae in patients undergoing SCS trials and implantation. METHODS: This is a retrospective review from 2005 through 2014 of all patients 18 years or older undergoing the following procedures: Percutaneous SCS implantations, SCS revisions, and SCS trials. Baseline characteristics, antiplatelet and anticoagulation medications, coagulation parameters, and procedural details were extracted. The primary outcome was the presence of a bleeding complication within 31 days of the procedure requiring emergency medicine, neurology, or neurosurgical evaluation. The neurological complication was independently categorized for its potential relationship to procedural bleeding, and periprocedural red blood cell transfusion requirements were analyzed as a secondary outcome. RESULTS: A total of 642 percutaneous SCS procedures were performed on 421 unique patients, including 346 SCS trials, 255 SCS implantations, and 41 revision surgeries. Patients had received aspirin or NSAIDs within 7 days of needle placement for 101 procedures (15.7%). There were no bleeding or neurological complications identified in this cohort. CONCLUSION: Although the incidence of epidural hematoma is low, the development of bleeding complications following SCS lead placement can be devastating. In the present investigation, we identified no cases of epidural hematoma following percutaneous SCS lead placement, including more than 100 patients receiving aspirin or NSAIDs. Future investigations with larger numbers are needed to better define the relationships between periprocedural aspirin and NSAID utilization and bleeding complications.

Pain Management in Four-Limb Amputation: A Case Report.

Acute pain following amputation can be challenging to treat due to multiple underlying mechanisms and variable clinical responses to treatment. Furthermore, poorly controlled preoperative pain is a risk factor for developing chronic pain. Evidence suggests that epidural analgesia and peripheral nerve blockade may decrease the severity of residual limb pain and the prevalence of phantom pain after lower extremity amputation. We present the perioperative analgesic management of a patient with gangrene of the bilateral upper and lower extremities as a result of septic shock and prolonged vasopressor administration who underwent four-limb amputation in a single procedure. A multimodal analgesic regimen was utilized, including titration of preoperative opioid and neuropathic pain agents, perioperative intravenous, epidural and peripheral nerve catheter infusions, and postoperative oral medication titration. More than 8 months postoperatively, the patient has satisfactory pain control with no evidence for phantom limb pain. To our knowledge, there have been no publications to date concerning analgesic regimens in four-limb amputation.

Low dose lofexidine for medically directed outpatient opioid tapering in adults with chronic pain: a prospective case series.

BACKGROUND: In adults with chronic pain, mild-to-moderate withdrawal symptoms during medically directed opioid tapering in the outpatient setting may not be accompanied by hypertension or tachycardia. This clinical scenario could limit the use of lofexidine at dosages reported in clinical trials of opioid withdrawal precipitated by abrupt opioid discontinuation. Thus, the primary aim of this prospective case series is to describe the use of low dose lofexidine for opioid withdrawal in patients with chronic pain undergoing medically directed opioid tapering in an outpatient setting. METHODS: Six patients (white 5, Latino 1) admitted to an outpatient interdisciplinary pain rehabilitation program met inclusion and exclusion criteria. Patients self-selected to undergo medically directed opioid tapering, and the medication the patients were prescribed upon admission was used in the taper schedule. Upon initiation of the opioid taper, patients received 0.18 mg of lofexidine every 6 hours. RESULTS: Five of the six patients were women, and the median morphine milligram equivalents at baseline were 36.9. The median taper duration was 15 days, and the median duration of lofexidine administration was 14 days. Withdrawal scores were mild throughout the taper in four patients, and two patients with fibromyalgia experienced single episodes of moderately severe withdrawal symptoms at the median morphine milligram equivalent midpoint of the taper. No hypotension or sustained bradycardia were observed, and no adverse effects related to lofexidine were reported. CONCLUSION: The observations from this prospective case series suggest that low-dose lofexidine may be a feasible adjunct medication to attenuate withdrawal symptoms in adults with chronic pain undergoing outpatient opioid tapering.

Prescription Opioids and Brain Structure in Community-Dwelling Older Adults.

OBJECTIVE: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging. METHODS: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures. White matter outcomes included fractional anisotropy in 40 tracts and global white matter hyperintensity volumes. The primary exposure was prescription opioid availability expressed as the per-year rate of opioid days preceding magnetic resonance imaging, with a secondary exposure of per-year total morphine milligram equivalents (MME). Multivariable models assessed associations between opioid exposures and brain structures. RESULTS: The study included 2185 participants; median (interquartile range) age was 80 (75 to 85) years, 47% were women, and 1246 (57%) received opioids. No significant associations were found between opioids and gray matter. Increased opioid days and MME were associated with decreased white matter fractional anisotropy in 15 (38%) and 16 (40%) regions, respectively, including the corpus callosum, posterior thalamic radiation, and anterior limb of the internal capsule, among others. Opioid days and MME were also associated with greater white matter hyperintensity volume (1.02 [95% CI, 1.002 to 1.036; P=.029] and 1.01 [1.001 to 1.024; P=.032] increase in the geometric mean, respectively). CONCLUSION: The duration and dose of prescription opioids were associated with decreased white matter integrity but not with gray matter structure. Future studies with longitudinal imaging and clinical correlation are warranted to further evaluate these relationships.

Prescription opioids and longitudinal changes in cognitive function in older adults: A population-based observational study.

BACKGROUND: Opioids are frequently prescribed to alleviate pain in older adults, yet the relationships between prescription opioids and long-term cognitive function are unclear. METHODS: In this analysis of the Mayo Clinic Study of Aging, a longitudinal population-based cohort study of older adults with formal neuropsychological testing and cognitive evaluations performed every 15 months, the associations between prescription opioids, global and domain-specific cognitive function, and mild cognitive impairment were evaluated through time-dependent linear mixed effects and Cox proportional hazards models. RESULTS: Four thousand two hundred eighteen participants (51% male) were included with enrollment between 11/1/2004 and 4/1/2019 and median age of 76 (interquartile range 72, 82) years. Two thousand nine hundred seventy-seven subjects (71%) received at least 1 opioid prescription during a median follow-up of 7.5 (5.0, 10.7) years. Overall, there was an estimated 0.096 reduction in the global cognitive Z-score per year, including decreases of 0.050 in memory, 0.080 in language, 0.044 in visual-spatial cognition, and 0.112 in attention. In multivariable analyses, each receipt of an opioid prescription resulted in an additional -0.007 (95% CI -0.009, -0.005) change in global cognitive Z-score (p < 0.001), with significant effects seen in the domains of memory (-0.005, 95% CI -0.007, -0.003; p < 0.001), language (-0.002, 95% CI -0.003, 0.000; p = 0.024) and attention (-0.004, 95% CI -0.006, -0.002; p < 0.001) but not visual-spatial function (0.000, 95% CI -0.001, 0.001; p = 0.897). Opioid prescriptions were associated with incident mild cognitive impairment (MCI) in adjusted analysis (hazard ratio 1.21, 95% CI 1.04, 1.42; p = 0.014). CONCLUSION: Prescription opioids are associated with small but statistically significant declines in long-term cognitive function in older adults, which may represent effects of opioids or other related factors.