Association Between Complications after Vascular Surgery and Prolonged Postoperative Opioid Use.

BACKGROUND: Few studies have looked at the long-term risk of opioid use following major vascular surgery and no study has investigated the potential association between major complications and prolonged opioid use. We analyzed a population-based database linked to a prescription database to investigate factors associated with prolonged opioid use following major vascular surgery. METHODS: This population-based cohort study included all adults who underwent open lower extremity revascularization (LER) or nonruptured abdominal aortic aneurysm repair (open [AAA] and endovascular [EVAR]) in the province of Ontario, Canada, between 2013 and 2018. Prolonged opioid use was defined as 2 or more opioid prescriptions filled 6-12 months following surgery. Potential predictors of prolonged use were explored using modified Poisson regression with a generalized estimating equation approach to account for the clustering of patients within physicians and institutions. RESULTS: This study included a total of 11,104 patients with 5,652 patients undergoing open LER, 3,285 patients undergoing EVAR, and 2,167 patients undergoing AAA. The rates of prior opioid use were 35.4% for LER, 15.8% for AAA and 14.3% for EVAR. Major complication rates following each procedure were 59.5% for AAA, 35.1% for LER, and 21.0% for EVAR. Following surgery, prolonged opioid use was identified in 26.1% of LER, 13.2% of AAA, and 11.6% of EVAR patients. The strongest predictor of prolonged opioid use was prior use with an odds ratio (OR) of 13.27 (95% CI: 10.63-16.57) for AAA, 11.24 (95% CI: 9.18-13.75) for EVAR, and 4.69 (95% CI: 4.16-5.29) for LER. The occurrence of a major complication was only associated with prolonged opioid use for patients undergoing LER (OR 1.10; 95% CI: 1.03-1.19), while it had a protective effect on patients undergoing EVAR (OR 0.83; 95% CI: 0.69-0.99) and no association for patients undergoing open AAA repair (OR 1.11; 95% CI: 0.95-1.29). Older age was also protective with a reduced rate of prolonged opioid use for every 10 years of age increase: AAA (OR 0.87; 95% CI: 0.77-0.99); EVAR (OR 0.83; 95% CI: 0.76-0.91); and LER (OR 0.91; 95% CI: 0.87-0.94). CONCLUSIONS: Prolonged opioid use is common following major vascular surgery, occurring in over 10% of patients undergoing either open or endovascular aneurysm repair and over 25% of patients undergoing open LER. Prior opioid use is the strongest predictor for prolonged use, while the occurrence of postoperative complications is associated with a slight increased risk of prolonged use in patients undergoing LER. These patient populations should be targeted for multimodal methods of opioid reduction following their procedures.

Opioid use after outpatient elective general surgery: quantifying the burden of persistent use.

Purpose: Surgery is a major risk factor for chronic opioid use among patients who had not recently been prescribed opioids. This study identifies the rate of, and risk factors for, persistent opioid use following laparoscopic cholecystectomy and open inguinal hernia repair in patients not recently prescribed opioids. Methods: This retrospective population-based cohort study included all patients who had not been prescribed opioids in the 6 months prior to undergoing open inguinal hernia repair or laparoscopic cholecystectomy from January 2013 to July 2016 in Ontario. Opioid prescription was identified from the provincial Narcotics Monitoring System and data were obtained from the Institute for Clinical Evaluative Sciences. The primary outcome was persistent opioid use after surgery (3, 6, 9 and 12 months). Associated risk factors and prescribing patterns were also examined. Results: Among the 90,326 patients in the study cohort, 80% filled an opioid prescription after surgery, with 11%, 9%, 5% and 1% filling a prescription at 3, 6, 9 and 12 months, respectively. Significant variability was identified in the type of opioid prescribed (41% codeine, 31% oxycodone, 18% tramadol) and in regional prescribing patterns (mean prescription/region range, 135-225 oral morphine equivalents). Predictors of continued opioid use included age, female gender, lower income quintile and being operated on by less experienced surgeons. Conclusion: Most patients who undergo elective cholecystectomy and hernia repair will fill a prescription for an opioid after surgery, and many will continue to fill opioid prescriptions for considerably longer than clinically anticipated. There is important variability in opioid type, regional prescribing patterns and risk factors that identify strategic targets to reduce the opioid burden in this patient population.

An Opioid Prescription for Men Undergoing Minor Urologic Surgery Is Associated with an Increased Risk of New Persistent Opioid Use.

BACKGROUND: The opioid abuse epidemic has highlighted the risks associated with these medications. OBJECTIVE: To determine whether filling a postoperative opioid prescription after low acuity urologic surgery is associated with new persistent opioid use. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using linked administrative data from Ontario, Canada. Participants were adults who underwent their first vasectomy, transurethral prostatectomy, urethrotomy, circumcision, spermatocelectomy, or hydrocelectomy between 2013 and 2016. We excluded men with prior opioid use, confounding concurrent procedures, prolonged hospitalization, or cancer. INTERVENTION: Whether the patient filled a prescription for an opioid within 5 d of their surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was evidence of at least two opioid prescriptions filled 9-15 mo after urologic surgery. The secondary outcome was admission for opioid overdose. Primary analysis was adjusted logistic regression analysis. RESULTS AND LIMITATIONS: We identified 91 083 men, most of whom underwent vasectomy (78%). A total of 32 174 (35%) men filled a prescription for an opioid after their procedure. The most common opioid prescribed was codeine (70%), and urologists were the primary prescribers (81%). Men who filled a postprocedure opioid prescription did not differ, for most of the 57 medical comorbidities or markers of healthcare utilization that we measured, from those who did not fill an opioid prescription. There was long-term opioid use in 1447 (1.6%); men who had filled a postoperative opioid prescription had a significantly higher risk of long-term opioid use (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.3-1.6) and opioid overdose (OR 3.0, 95% CI 1.5-5.9). A limitation is that we could not determine the indication for long-term opioid prescriptions. CONCLUSIONS: Prescription of opioids after low acuity urology procedures is significantly associated with increased opioid use at 1yr after surgery; efforts should be made to reduce postoperative opioids, especially for urologic procedures that do not typically require opioids. PATIENT SUMMARY: Filling an opioid prescription after minor urologic surgeries is associated with an increased risk of persistent long-term use of opioid medications and a higher risk of serious long-term complications such as hospital visits for an opioid overdose.'

The Standardization of Outpatient Procedure (STOP) Narcotics: A Prospective Health Systems Intervention to Reduce Opioid Use in Ambulatory Breast Surgery.

BACKGROUND: During the past 15 years, opioid-related overdose death rates for women have increased 471%. Many surgeons provide opioid prescriptions well in excess of what patients actually use. This study assessed a health systems intervention to control pain adequately while reducing opioid prescriptions in ambulatory breast surgery. METHODS: This prospective non-inferiority study included women 18-75 years of age undergoing elective ambulatory general surgical breast procedures. Pre- and postintervention groups were compared, separated by implementation of a multi-pronged, opioid-sparing strategy consisting of patient education, health care provider education and perioperative multimodal analgesic strategies. The primary outcome was average pain during the first 7 postoperative days on a numeric rating scale of 0-10. The secondary outcomes included medication use and prescription renewals. RESULTS: The average pain during the first 7 postoperative days was non-inferior in the postintervention group despite a significant decrease in median oral morphine equivalents (OMEs) prescribed (2.0/10 [100 OMEs] pre-intervention vs 2.1/10 [50 OMEs] post-intervention; p = 0.40 [p < 0.001]). Only 39 (44%) of the 88 patients in the post-intervention group filled their rescue opioid prescription, and 8 (9%) of the 88 patients reported needing an opioid for additional pain not controlled with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) postoperatively. Prescription renewals did not change. CONCLUSION: A standardized pain care bundle was effective in minimizing and even eliminating opioid use after elective ambulatory breast surgery while adequately controlling postoperative pain. The Standardization of Outpatient Procedure Narcotics (STOP Narcotics) initiative decreases unnecessary and unused opioid medication and may decrease risk of persistent opioid use. This initiative provides a framework for future analgesia guidelines in ambulatory breast surgery.

Standardization of Outpatient Procedure (STOP) Narcotics: A Prospective Non-Inferiority Study to Reduce Opioid Use in Outpatient General Surgical Procedures.

BACKGROUND: There has been a dramatic rise in opioid abuse, and diversion of excess, unused prescriptions is a major contributor. We assess the impact of implementing a new standardized pain care bundle to reduce postoperative opioids in outpatient general surgical procedures. STUDY DESIGN: This study was designed to demonstrate non-inferiority for the primary end point: patient-reported average pain in the first 7 postoperative days. We prospectively evaluated 224 patients who underwent laparoscopic cholecystectomy or open hernia repair (inguinal, umbilical) pre-intervention to 192 patients post-intervention. We implemented a multimodal intra- and postoperative analgesic bundle, including promoting co-analgesia, opioid-reduced prescriptions, and patient education designed to clarify patient expectations. Patients completed a brief pain inventory at their first postoperative visit. Groups were compared using chi-square test, Mann-Whitney U test, and independent samples t-test, where appropriate. RESULTS: No difference was seen in average postoperative pain scores in the pre- vs post-intervention groups (2.3 vs 2.1 of 10; p = 0.12). The reported quality of pain control improved post-intervention (good/very good pain control in 69% vs 85%; p < 0.001). The median total morphine equivalents for prescriptions filled in the post-intervention group were significantly less (100; interquartile range 75 to 116 pre-intervention vs 50; interquartile range 50 to 50 post-intervention; p < 0.001). Only 78 of 172 (45%) patients filled their opioid prescription in the post-intervention group (p < 0.001), with no significant difference in prescription renewals (3.5% pre-intervention vs 2.6% post-intervention; p = 0.62). CONCLUSIONS: For outpatient open hernia repair and cholecystectomy, a standardized pain care bundle decreased opioid prescribing significantly and frequently eliminated opioid use, and adequately treating postoperative pain and improving patient satisfaction.

Structural and Functional Brain Changes at Early and Late Stages of Complex Regional Pain Syndrome.

Brain plasticity is demonstrated in complex regional pain syndrome (CRPS), although it is unclear how it modulates at different stages of CRPS. The observation that symptoms can progress over time suggests that the pattern of brain changes might also evolve. We measured structural and functional changes as well as sensorimotor integration at the early stage (ES) and late stage (LS) of CRPS. Twelve ES patients, 16 LS patients, and 16 age- and sex-matched controls were recruited. Gray matter (GM) volume was estimated using voxel-based morphometry. Cerebral perfusion was measured using arterial spin labeling, because it provides a measure of resting neural activity. Connectivity to sensorimotor regions was evaluated using blood-oxygen level-dependent images. The ES group showed reduced GM volume and perfusion in areas associated with spatial body perception, somatosensory cortex, and the limbic system, whereas the LS group exhibited increased perfusion in the motor cortex but no changes in GM volume. However, in the LS group, GM volume in areas associated with pain processing was negatively correlated with average pain levels, likely reflecting a response to ongoing pain. Furthermore, connectivity to sensorimotor cortex showed disruptions in regions associated with motor control and planning, implying impairment of higher-order motor control. PERSPECTIVE: This article presents brain changes at ES and LS of CRPS. We found different patterns of brain changes between these 2 stages. Understanding modulation of brain plasticity at different stages of CRPS could help understand the diversity in outcomes and treatment response and hopefully improve treatment planning.

Neuraxial drug delivery for the management of cancer pain: cost, updates, and society guidelines.

PURPOSE OF REVIEW: The present study discusses the utilization of neuraxial drug delivery (NDD) for the management of cancer pain, based on recent trials, reviews, and guidelines with a focus on cost analysis. RECENT FINDINGS: Almost all recent publications suggest that more stringent research is needed to improve evidence on NDD, particularly as conflicting reports exist regarding cost effectiveness of drug delivery systems. The combination of local anesthetics and opioids, with or without clonidine, continues to be reported as beneficial with the utilization of patient controlled systems providing an advantage over continuous ones. Interestingly, the use of opioids as an adjunct to local anesthetics may not enhance analgesia but the addition of dexamethasone is useful for incident cancer-related bone pain. Ziconitide remains supported as first-line therapy in districts where it is available - United States and Europe. Although new targeted drugs are being designed for cancer pain management, none have seen human clinical trials in the last year. SUMMARY: The ability to demonstrate cost effectiveness of NDD is variable from region to region. Less expensive externalized systems may pose a viable alternative. With the exception of dexamethasone, no new drugs have been shown to provide any benefit to conventional medications.

Residual limb pain is not a diagnosis: a proposed algorithm to classify postamputation pain.

BACKGROUND: Although postamputation pain (PAP) syndromes have been described since the 16th century, taxonomy of these conditions remains ill-defined. The term "Residual Limb Pain" fails to distinguish between distinct diagnostic entities such as neuroma, complex regional pain syndrome, and somatic pathology. Even phantom limb pain (PLP), although easily distinguished from residual limb pain (RLP), has not been consistently delineated from other PAP syndromes. METHODS: A systematic review of the literature was conducted to identify the degree of delineation of various post amputation pain states and what diagnostic criteria were utilized if any. Furthermore, papers that involved treatment modalities were reviewed to determine efficacy of treatment. RESULTS: Of the 151 papers reviewed, none further categorized RLP into more specific diagnostic criteria. Furthermore, the literature contains numerous case reports, case series, letters to the editors, and grossly underpowered studies demonstrating significant positive results, yet few high-quality randomized controlled trials. CONCLUSIONS: Describing and defining the distinct clinical entities, intuitively, is a prerequisite to developing optimal treatments. The reported variation in the incidence of PAP phenomena may well represent inconsistency in assessment tools and diagnostic categories rather than variation in prevalence of these conditions. In this paper, we review the historical evolution of the current understanding of these syndromes and propose an algorithm for uniform classification.

Functional imaging for interpretation of pain pathways: current clinical application/relevance and future initiatives.

Functional imaging of the central nervous system has been utilized since the 1970s focusing on the concept that neural functioning is coupled to regional cerebral blood flow. This has allowed for extensive mapping of the neural pathways associated with pain, the "pain-matrix." The study of the functional anatomy utilizes positron electron tomography and 2 magnetic resonance imaging techniques known as arterial spin labeling and blood oxygen dependent imaging. This area of study has greatly improved in recent years in being able to assist in the diagnosis of conditions and support in the creation of targeted therapies. The goal of this review is to educate the reader on the evolution of functional imaging and its application to the study of pain and furthermore to highlight the advances in this field that may allow for further clinical applications of this modality.

Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management.

There has been a growing interest in opioid-induced hyperalgesia (OIH), which is an increased sensitivity to pain caused by opioid exposure. Multiple underlying pathways may contribute to the development of OIH, and the mechanism may vary with the duration of opioid exposure, dose, type and route of administration. In addition, the distinction between OIH, tolerance and withdrawal should be made in both the basic and clinical science literature so as to help translate findings to the clinical phenomenon and to help determine the best strategies to prevent or treat OIH.

Measuring the neural response to continuous intramuscular infusion of hypertonic saline by perfusion MRI.

PURPOSE: To determine the extent to which arterial spin labeling (ASL), a functional magnetic resonance imaging technique that directly measures cerebral blood flow (CBF), is able to measure the neural activation associated with prolonged experimental muscle pain. MATERIALS AND METHODS: Hypertonic saline (HS) (5% NaCl) was infused into the brachioradialis muscle of 19 healthy volunteers for 15 min. The imaging volume extended from the dorsal side of the pons to the primary somatosensory cortices, covering most of the cortical and subcortical regions associated with pain perception. RESULTS: Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9 ± 0.5 (mean ± SE). Group activation maps showed that the slow infusion of HS evoked CBF increases primarily in bilateral insula, with additional activation in right frontal regions. In the activated areas, CBF gradually increased at the onset of HS infusion and was maintained at relatively constant levels throughout the remainder of the infusion period. However, the level and extent of activation were smaller than observed in previous studies involving acute muscle pain. CONCLUSION: This study demonstrates the ability of ASL to measure changes in CBF over extended periods of time and that the neural activation caused by muscle pain is paradigm specific.

Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review.

Despite being a recognized clinical entity for over 140 years, complex regional pain syndrome (CRPS) remains a difficult-to-treat condition. While there have been multiple therapies explored in the treatment of CRPS, NMDA antagonists such as ketamine continue to hold significant interest because of their potential ability to alter the central sensitization noted in chronic pain states. The objective of this review is to identify published literature for evidence of the efficacy and safety of ketamine in the treatment of CRPS. PubMed and the Cochrane Controlled Trials Register were searched (final search 26 May 2011) using the MeSH terms 'ketamine', 'complex regional pain syndrome', 'analgesia' and 'pain' in the English literature. The manuscript bibliographies were then reviewed to identify additional relevant papers. Observational trials were evaluated using the Agency for Healthcare Research and Quality criteria; randomized trials were evaluated using the methodological assessment of randomized clinical trials. The search methodology yielded three randomized, placebo-controlled trials, seven observational studies and nine case studies/reports. In aggregate, the data available reveal ketamine as a promising treatment for CRPS. The optimum dose, route and timing of administration remain to be determined. Randomized controlled trials are needed to establish the efficacy and safety of ketamine and to determine its long-term benefit in CRPS.

Damaged insulation mimicked symptoms of occipital stimulator lead migration.

INTRODUCTION: The use of occipital nerve stimulators for the treatment of migraines has recently been suggested. However, there have been reports of complications, including lead migration causing local muscle stimulation and spasm with local burning sensation and loss of successful neuromodulation. CASE: We report a case of a patient who had successful permanent implantation and then presented with suspicion of lead migration. Upon examination of the lead at time of repositioning it was found that the insulation had eroded and the conducting wires exposed at the anchor site. DISCUSSION: Disruption of occipital nerve stimulator lead insulation may mimic lead migration with failure of neuromodulation, spasm, and local burning sensations. Prior to reimplanting, a lead should be thoroughly inspected to ensure there is no mechanical failure. Anchoring should be performed with gentle direct suturing or the use of a protective anchoring device.

Virtual reality imaging with real-time ultrasound guidance for facet joint injection: a proof of concept.

Facet interventions continue to be used in pain management. Computed tomographic (CT) images can be registered into a virtual world that includes images generated by an ultrasound (US) probe tracked in real time, permitting guidance of tracked needles. We acquired CT-generated 3-dimensional (3D) images of 2 models and a cadaver. Three-dimensional representations of a US probe and needle were generated. A magnetic system tracked the needle and US probe. Using the US, 3D CT images were registered to the model/cadaver. Images were fused on a single interface. Facet injections were performed in the models and cadaver with radio-opaque markers. A postprocedure CT image determined appropriate placement. The virtual reality system described demonstrates technical innovations that may lead to future advancements in the area of percutaneous interventions in the management of pain.

Using perfusion MRI to measure the dynamic changes in neural activation associated with tonic muscular pain.

Knowledge regarding neural pain processing is primarily the result of studies involving models of brief cutaneous pain; however, clinical pain generally originates in deep tissue and is prolonged. This study measured the dynamic neural activation associated with a muscular pain model incorporating both acute and tonic states. Hypertonic saline (5% NaCl) was infused into the brachioradialis muscle of eleven healthy volunteers for 15min after an initial bolus of 0.5mL. Ten controls followed the same protocol with normal saline (0.9% NaCl). Magnetic resonance images of cerebral blood flow (CBF) were acquired using an arterial spin labelling method. The imaging volume extended from the thalamus to the primary somatosensory cortices, but did not include the brainstem and cerebellum. Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9+/-0.6 and remained near 5 for the remainder of the trial. Controls experienced minimal pain, reporting a peak value of 1.8+/-0.4. Significant CBF increases in rostral and caudal anterior insula bilaterally, anterior mid-cingulate cortex (aMCC), bilateral thalamus, and contralateral posterior insula were observed. The time courses of CBF revealed significant differences in the activation pattern during tonic pain. In particular, a more rapid return to baseline in aMCC versus insula was interpreted as a preferential decrease in the affective component of pain. This conclusion was supported by the strong correlation between pain intensity ratings and CBF in the contralateral insula (R(2)=0.911, p<0.01), which is a region believed to be responsible for pain intensity processing.

Emergency department discharge instructions comprehension and compliance study.

OBJECTIVES: To assess patient comprehension of emergency department discharge instructions and to describe other predictors of patient compliance with discharge instructions. METHODS: Patients departing from the emergency department of an inner-city teaching hospital were invited to undergo a structured interview and reading test, and to participate in a follow-up telephone interview 2 weeks later. Two physicians, blinded to the other's data, scored patient comprehension of discharge information and compliance with discharge instructions. Inter-rater reliability was assessed using a kappa-weighted statistic, and correlations were assessed using Spearman's rank correlation coefficient and Fisher's exact test. RESULTS: Of 106 patients approached, 88 (83%) were enrolled. The inter-rater reliability of physician rating scores was high (kappa = 0.66). Approximately 60% of subjects demonstrated reading ability at or below a Grade 7 level. Comprehension was positively associated with reading ability (r = 0.29, p = 0.01) and English as first language (r = 0.27, p = 0.01). Reading ability was positively associated with years of education (r = 0.43, p < 0.0001) and first language (r = 0.24, p = 0.03), and inversely associated with age (r = -0.21, p = 0.05). Non-English first language and need for translator were associated with poorer comprehension of discharge instructions but not related to compliance. Compliance with discharge instructions was correlated with comprehension (r = 0.31, p = 0.01) but not associated with age, language, education, years in anglophone country, reading ability, format of discharge instructions, follow-up modality or association with a family physician. CONCLUSIONS: Emergency department patients demonstrated poor reading skills. Comprehension was the only factor significantly related to compliance; therefore, future interventions to improve compliance with emergency department instructions will be most effective if they focus on improving comprehension.

Patients who leave the emergency department without being seen by a physician: a control-matched study.

OBJECTIVE: To describe the socio-demographic characteristics and clinical outcomes of patients who leave the emergency department (ED) without being seen by a physician. METHODS: This 3-month prospective study was conducted at a downtown Toronto teaching hospital. Patients who left the ED without being seen (LWBS) were matched with controls based on registration time and triage level. Subjects and controls were interviewed by telephone within 1 week after leaving the ED. RESULTS: During the study period, 386 (3.57%) of 10,808 ED patients left without being seen. One-third of these had no fixed address or no telephone, and only 92 (23.8%) consented to a telephone interview. They cited excessive wait time as the most common reason for leaving the ED (in 36.7% of cases). Despite leaving the ED without being seen, they were no more likely than those in the control group to seek follow-up medical attention (70 % in both groups). Among those from both groups who did seek follow-up, the LWBS patients were more likely to do so the same day or the day after leaving the ED. The LWBS patients often lacked a regular physician (39.1% v. 21.7%; p = 0.01) and were more likely to attend an ED or urgent care clinic (34.8% v. 12.0%; p < 0.001). Controls were more likely to follow up with a family physician (37.0% v. 23.9%; p = 0.06). The LWBS and control groups did not differ in subjective health status at 48 hours after leaving the ED, nor in subsequent re-investigation in hospital. CONCLUSIONS: Patients who leave the ED without being seen have different socio-demographic features, methods of accessing the health care system, affiliations and expectations than the general ED population. They are often socially disenfranchised, with limited access to traditional primary care. These patients are generally low acuity, but they are at risk of important and avoidable adverse outcomes.