Effects Of Chronic Opioid Use Research Articles

Opioid use following cardio-thoracic intensive care: risk factors and outcomes: a cohort study

Opioid misuse has become a serious public health problem. Patients admitted to cardio-thoracic critical care are usually exposed to opioids, but the incidence and effects of chronic opioid use are not known. The primary objective was to describe opioid use after admission to a cardio-thoracic intensive care unit. Secondary objectives were to identify factors associated with chronic opioid usage and analyze risk of death. This cohort study included all cardio-thoracic ICU care episodes in Sweden between 2010 and 2018. Among the 34,200 patients included in the final study cohort, 4050 developed persistent opioid use after ICU care. Younger age, preadmission opioid use, female sex, presence of comorbidities and earlier year of ICU admission were all found to be associated with persistent opioid use. The adjusted hazard ratio for mortality between 6 and 18 months after admission among individuals with persistent opioid use was 2.2 (95% CI 1.8–2.6; P < 0.001). For opioid-naïve patients before ICU admission, new onset of chronic opioid usage was significant during the follow-up period of 24 months. Despite the absence of conclusive evidence supporting extended opioid treatment, the average opioid consumption remains notably elevated twelve months subsequent to cardio-thoracic ICU care.

Preoperative and Postoperative Hyperalgesia in Dental Patients on Chronic Opioid Therapy: A Pilot Study.

Opioid-induced hyperalgesia, a paradoxical increase in pain sensitivity associated with ongoing opioid use, may worsen the postoperative pain experience. This pilot study examined the effect of chronic opioid use on pain responses in patients undergoing a standardized dental surgery. Experimental and subjective pain responses were compared prior to and immediately following planned multiple tooth extractions between patients with chronic pain on opioid therapy (≥30 mg morphine equivalents/d) and opioid-naïve patients without chronic pain matched on sex, race, age, and degree of surgical trauma. Preoperatively, chronic opioid users rated experimental pain as more severe and appreciated less central modulation of that pain than did opioid-naïve participants. Postoperatively, chronic opioid-using patients rated their pain as more severe during the first 48 hours and used almost twice as many postoperative analgesic doses during the first 72 hours as the opioid-naïve controls. These data suggest that patients with chronic pain taking opioids approach surgical interventions with heightened pain sensitivity and have a more severe postoperative pain experience, providing evidence that their complaints of postoperative pain should be taken seriously and managed appropriately.

Pre-existing Opioid Use Worsens Outcomes in Patients With Diverticulitis.

Background and objective Diverticulitis occurs in 10-25% of patients with diverticulosis. Although opioids can decrease bowel motility, there is scarce data on the effect of chronic opioid use on the outcomes of diverticulitis. In this study, we aimed to explore the outcomes of diverticulitis in patients with pre-existing opioid use. Methods Data between 2008 and 2014 from the National Inpatient Sample (NIS) database was extracted using the International Classification of Diseases, 9th Revision (ICD-9) codes. Univariate and multivariate analyses were used to generate odds ratios (OR). Elixhauser Comorbidity Index (ECI) scores predicting mortality and readmission were calculated based on weighted scores from 29 different comorbidities. Scores were compared between the two groups using univariate analysis.Inclusion criteria included patients with a primary diagnosis of diverticulitis. Exclusion criteria included patients less than 18 years of age, and a diagnosis of opioid use disorder in remission. Studied outcomes included inpatient mortality, complications (including perforation, bleeding, sepsis event, ileus, abscess, obstruction, and fistula), length of hospital stay, and total costs. Results A total of 151,708 patients with diverticulitis and no active opioid use and 2,980 patients with diverticulitis and active opioid use were hospitalized in the United States from 2008 to 2014. Opioid users had a higher OR for bleeding, sepsis, obstruction, and fistula formation. Opioid users had a lower risk of developing abscesses. They had longer lengths of stay, higher total hospital charges, and higher Elixhauser readmission scores. Conclusion Hospitalized diverticulitis patients with comorbid opioid use are at an elevated risk of in-hospital mortality and sepsis. This could be attributed to complications from injection drug use predisposing opioid users to these risk factors. Outpatient providers caring for patients with diverticulosis should consider screening their patients for opioid use and try offering themmedication-assisted treatment to reduce their risk of poor outcomes.

Chronic Opioid Use Independently Increases Complications and Resource Utilization After Primary Total Joint Arthroplasty

BackgroundCurrent literature suggests a link between the chronic use of opioids and musculoskeletal surgical complications. Given the current opioid epidemic, the need to elucidate the effects of chronic opioid use (OD) on patient outcomes and cost has become important. The purpose of this study was to determine if OD is an independent risk factor for inpatient postoperative complications and resource utilization after primary total joint arthroplasty. MethodsA total of 3,545,565 patients undergoing elective, unilateral, primary total hip (THA) and knee (TKA) arthroplasty for osteoarthritis from January 2016 to December 2019 were identified using a large national database. In-hospital postoperative complications, length of stay, and total costs adjusted for inflation in opioid + patients were compared with patients without chronic opioid use (OD). Logistic regression analyses were used to control for cofounding factors. ResultsOD patients undergoing either THA or TKA had a higher risk of postoperative complications including respiratory (odds ratio (OR): 1.4 and OR: 1.3), gastrointestinal (OR: 1.8 and OR: 1.8), urinary tract infection (OR: 1.1 and OR: 1.2), blood transfusion (OR: 1.5 and OR: 1.4), and deep vein thrombosis (OR: 1.7 and OR: 1.6), respectively. Total cost ($16,619 ± $9,251 versus $15,603 ± $9,181, P < .001), lengths of stay (2.15 ± 1.37 versus 2.03 ± 1.23, P < .001), and the likelihood for discharge to a rehabilitation facility (17.8 versus 15.7%, P < .001) were higher in patients with OD. ConclusionOD was associated with higher risk for in-hospital postoperative complications and cost after primary THA and TKA. Further studies to find strategies to mitigate the impact of opioid use on complications are required.

Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward.

Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.

Chronic Opioid Use Is Highly Prevalent and Associated with Inferior Survival in Myeloma Patients in Remission after Autologous Transplant

Overuse of opioid analgesics has been associated with a significant public health crisis, but at the same time, these medications are critical as an adjunctive treatment for bone pain in multiple myeloma (MM). Despite this, opioid use patterns in MM have not been well studied. Given the prolonged survival after autologous stem cell transplant (ASCT) and maintenance therapy, the effect of chronic opioid use (COU) on outcomes in these patients has become an important area to address. We aimed to describe COU in our ASCT cohort and its impact on long-term outcomes. Adult patients ≥ 18 years (n=174) with MM who received ASCT between 2012 and 2019 at an urban medical center were included. COU was defined as having an active prescription for 3 consecutive months. Daily opioid doses were converted to morphine milligram milliequivalents (MME) using standard conversion factors (MME ≥ 20 mg/day has been correlated with risk for overdose events). A Poisson regression analysis including factors such as education level, alcohol, and illicit drug, use of non-opioid analgesics, and employment status, was performed to identify predictors of COU at baseline and 6 months after ASCT. Landmark OS and PFS analysis were performed at 6 months after ASCT to assess the impact of ongoing COU. A multivariate Cox proportional hazards ratio model adjusted for known prognostic factors was performed to identify predictors of OS. The median age was 59 (29-78) years, 90 (51.7%) were male, 105 (60%) were Black, 24 (13.8%) were Hispanic, and 23 (13.2%) were White. At diagnosis, 111 (63.8%) patents were found to have IMWG-defined bone disease and 45 (25.9%) patients experienced a myeloma-related fracture. At baseline (time of ASCT), COU was observed in 92 (52.9%) patients, 27 (29.3%) of whom did not have prior history of bone disease. The baseline average MME/day in the entire cohort was 65.3 mg (±70.0). Both COU rates (52.4% vs. 54%, p=0.98) and average MME/day (69.5 versus 55.2 mg; p=0.37) were similar in those with and without bone disease. In Poisson regression analysis, previous illicit drug use was associated with a higher baseline COU (RR 4.07, 95% CI 1.53-10.82; p=0.005). The use of non-opioid analgesic drugs (RR .024, 95% CI 0.09-0.63, p=0.004), being retired (RR 0.49, 95% CI 0.29-0.83; p=0.008), or employed (RR 0.37, 95% CI 0.15-0.91; p=0.031) were associated with lower baseline COU. Presence of bony disease was not associated with baseline COU (RR 1.11, 95% CI 0.78-1.58; p=0.569). In the entire cohort, 142 (81.6%) patients received opioids during ASCT admission, while 105 (60.3%) were discharged on opioids and 72 (41.4%) had COU at 6 months after ASCT. Documented reasons for being discharged on opioids were presence of musculoskeletal (n=38, 45.8%), generalized (n=16, 19.3%), neuropathic (n=12), residual mucositis-related (n=11, 14.5%), and headache-related (n=6, 7.2%) pain. In baseline non-opioid users, 30 (36.6%) patients became new opioid users on discharge, and of these 13 (15.9%) remained on opioids at 6 months. Opioid use at hospital discharge was associated with higher COU at 6 months (RR 4.21, 95% CI 1.46-12.11; p=0.008). Indicators of disease burden, including bony lesions, were not associated with 6 month COU. 6-month MME/day was found to be relatively high at an average of 47.51 (±75.96) mg. Although PFS was not different, OS was significantly worse in patients with COU at 6 months (48 months versus undefined, p=0.004; Figure 1) and in a multivariate model, we found that COU at 6 months strongly predicted for worse overall survival (HR 6.71, 95% CI 1.73-26.09; p=0.006). Here we describe patterns of COU among MM patients undergoing ASCT, and in particular in long term survivors. We demonstrate high rates of baseline COU not related to the presence of bone disease. We highlight a high rate of opiate use on discharge including a number of new users after ASCT, which result in ongoing COU at 6 months. We show the negative impact of COU at 6 months on OS but not PFS suggesting that opioid-related morbidity may play a role. Finally, we demonstrate that MME/day throughout disease course is relatively high. These data highlight the need to improve understanding and management of pain in MM. Non-opioid analgesic use correlated with lower risk of COU and may be appropriate in managing pain effectively and safely. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retinal nerve fiber layer decrease and choroidal layer increase after four weeks of buprenorphine/naloxone maintenance treatment in opioid use disorder

Background and ObjectivesSpectral-domain optical coherence tomography (SD-OCT) findings in substance use disorders have been investigated in recent years. In this study, we compared the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), and the choroid thickness (CT) of OUD and control groups before and after buprenorphine/naloxone maintenance treatment (BN-MT). MethodsThe OUD group consisted of 46 male subjects and the control group consisted of 49 male subjects. Patients with chronic opioid use and opioid positivity in their urine during the initial SD-OCT application were included in the study. At the end of the fourth week of BN-MT, SD-OCT was repeated and BN positivity was detected in the urine of the patients at this time. ResultsThere was a significant difference between OUD and control groups in terms of nasal superior and CT values of both eyes (p<0.05) before BN use. The values of RNFL sectors and CT of both eyes before and after BN-MT differed significantly (p<0.05); CT increased and RNFL sectors decreased. After BN-MT, psychometric scales differed significantly in favor of the patients (p<0.05). The SD-OCT values of the OUD group after BN-MT were compared with the control group: the right IPL (p=0.003), the left IPL (p=0.023), the right N (p=0.001) and the left N (p<0.001) values were significantly lower in the OUD group. ConclusionThis is the first study to show the SD-OCT findings of patients with OUD before and after BN-MT. The findings of this study may indicate possible effects of chronic opioid use in patients and/or possible effects of exogenous opioid or BN present in the body during SD-OCT applications. However, based on our findings, it is not possible to distinguish between the two possible outcomes. The fact that the use of BN acting through opioid receptors has different effects from exogenous opioids may be due to different receptor profiles.

Morphine Accumulates in the Retina Following Chronic Systemic Administration.

Opioid transport into the central nervous system is crucial for the analgesic efficacy of opioid drugs. Thus, the pharmacokinetics of opioid analgesics such as morphine have been extensively studied in systemic circulation and the brain. While opioid metabolites are routinely detected in the vitreous fluid of the eye during postmortem toxicological analyses, the pharmacokinetics of morphine within the retina of the eye remains largely unexplored. In this study, we measured morphine in mouse retina following systemic exposure. We showed that morphine deposits and persists in the retina long after levels have dropped in the serum. Moreover, we found that morphine concentrations (ng/mg tissue) in the retina exceeded brain morphine concentrations at all time points tested. Perhaps most intriguingly, these data indicate that following chronic systemic exposure, morphine accumulates in the retina, but not in the brain or serum. These results suggest that morphine can accumulate in the retina following chronic use, which could contribute to the deleterious effects of chronic opioid use on both image-forming and non-image-forming visual functions.

Celiac Plexus Cryoneurolysis.

Intractable, chronic abdominal pain from upper abdominal malignant and benign diseases is a significant challenge for healthcare providers and burden on the healthcare system. While opioid analgesics are commonly used to provide pain relief, the adverse effects of chronic opioid use cannot be overlooked. Celiac plexus neurolysis via chemical or thermal means represents an alternative minimally invasive approach to provide palliative pain relief and increase patients' quality of life. Through the use of computed tomography guidance, celiac plexus neurolysis can be performed by accurately targeting the celiac plexus, while minimizing risks to adjacent structures. Historically, celiac plexus neurolysis was performed via instillation of ethanol or phenol; however, within the past decade cryoablation has gained increasing use with potentially fewer side effects.

Effect of chronic opioid use on the hematological and inflammatory markers: A retrospective study from North India.

BackgroundChronic opioid use affects biological functioning implicating the hematopoietic and immune system. It may alter various hematological parameters and inflammatory markers. This study aimed to assess the association of opioid dependence with the hematological parameters and inflammatory markers in the Indian population.MethodsA retrospective chart review was done among opioid dependent (ODS) males and healthy controls (HC) who visited the center’s laboratory between Jan 2017 and Dec 2018 for hematological investigations. Clinical records reviewed for opioid use details like type, duration, and route of administration. The hematological profile presented as Mean or median. Mann–Whitney U test was used to compare the hematological parameters between the cases and controls.ResultsThe study included 191 ODS patients and 123 controls. Among ODS patients, a significant decrease in the levels of hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin and an increase in RBC count and lymphocytes was observed when compared to controls. The inflammatory markers, Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio, were significantly lower among ODS. Longer duration of opioid use leads to increased NLR among ODS patients. Opioid use by injection did not alter any of the hematological parameters compared to non-injection drug use.ConclusionChronic opioid use has a significant effect on the hematopoietic cells. Opioid use for longer durations increases the inflammatory markers suggesting underlying infections.

Effect of Preoperative Chronic Opioid Use on Mortality and Morbidity in Vascular Surgical Patients

IntroductionOpioid derivates are an essential part of everyday clinical pain management practice. They have excellent analgesic, sedative, and sympatholytic effects and are widely used in various conditions. Beyond advantageous aspects, there are numerous problems with the chronic use of these agents. Dependency and life-threatening complications are the biggest problems with both illegal and prescribed opioid derivates. In our current study, effects of chronic opioid use were observed on mortality and life quality in the case of vascular surgery.MethodsThis prospective, observational study was conducted between 2014 and 2017. After obtaining informed consent, all participants were asked to fill a questionnaire containing different psychological tests. Perioperative data, chronic medical therapy, and anthropometric data were also collected. Opioid user and non-user patients’ psychological results were compared with non-parametrical tests. The effect of chronic opioid administration was investigated with logistic regression method with bootstrapping.ResultsFinally, the data of 164 patients were analyzed. 64.0% of participants were male, the mean age was 67.05 years, and the standard deviation was 9.48 years. The median follow-up time was 1312 days [interquartile range (IQR): 930-1582 days]. During the follow-up time, 42 patients died (25.6%). In the examined patient cohort, the frequency of opioid derivate use was 3.7% (only six patients). In the non-survived group, opioid use was significantly higher (1.6% vs. 9.5%, p=0.019). Significant differences were found in the aspect of cognitive performance measured by Mini-Mental State Examination (MMSE), opioid users have had lower points [25.5 (IQR: 24.5-26.0) vs. 28.0 (IQR: 27.0-29.0) p=0.008]. Opioid users have showed higher score on Beck Depression Inventory (BDI) [15.5 (IQR: 10.0-18.0) vs. 6.0 (IQR: 3.0-11.0), p=0.030). In a multivariate Cox regression model built up from registered preoperative medical treatment, opioids were found as a risk factor for all-cause mortality [adjusted hazard ratio (AHR): 4.31, 95% CI: 1.77-10.55, p=0.001].ConclusionOur current findings suggest that chronic, preoperative use of opioids could associate with increased mortality. Furthermore, both decrease in cognitive performance and increased depression symptoms were found in the opioid user cohorts which emphasize the importance of further risk stratification of these patients.

Modulatory Potential of Cannabidiol on the Opioid-Induced Inflammatory Response.

Opioids are effective analgesics; however, there are many negative consequences of chronic use. One important side effect of chronic opioid use is the continuous engagement of the immune response that can exacerbate chronic pain. The opioid, morphine, initiates a Toll-like receptor 4 (TLR4) signaling cascade that drives the activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome proteins, resulting in cytokine production and effectively creating a positive feedback loop for continuous TLR4 activation. In addition to driving cytokine production, morphine drives changes in proinflammatory lipid signaling. The alteration of both cytokine and lipid signaling systems by morphine suggests that its chronic use leads to a pathological immune response that would benefit from targeted therapy. Engaging the endogenous cannabinoid system has shown therapeutic benefit, particularly regarding its anti-inflammatory and immunosuppressive effects. Promising preclinical and clinical investigations suggest that cannabidiol (CBD) is an effective adjuvant for treatment of symptoms of opioid use disorders; however, the mechanism through which CBD drives this outcome is unclear. One potential source of insight into this mechanism is in how CBD regulates immune regulators such as cytokines and lipid signaling systems, including endocannabinoids and related immune-responsive lipids. In this review, we outline the immune response to chronic opioid use as well as CBD in the context of a lipopolysaccharide-induced immune response and speculate on the mechanism of CBD as a modulator of chronic opioid-induced immune system dysregulation.

134 Acute effects of methadone, buprenorphine or naltrexone on sleep-like parameters evaluated with actigraphy in male rhesus monkeys

Abstract Introduction Opioid use disorder (OUD) is a significant public health problem, and it has been associated with the emergence of sleep disturbances. Effective treatment options for OUD exist, including medication-assisted therapy with methadone or buprenorphine. However, emerging evidence suggests that these treatments also may be associated with significant sleep impairment. The extent to which these effects are a result of the medication or an effect of chronic opioid use remains unknown. In the present study, we investigated the acute effects of methadone, buprenorphine or naltrexone in male rhesus monkeys in order to understand whether pharmacological treatment with these drugs per se would have deleterious effects on sleep. Methods Adult naïve male rhesus macaques (Macaca mulatta, n=5) maintained on a 12h/12h light/dark cycle were fitted with primate collars to which actigraphy monitors were attached. Actigraphy recording was conducted during baseline conditions and following acute injections of vehicle, methadone (0.03 – 1.0 mg/kg, i.m.), buprenorphine (0.01 – 1.0 mg/kg, i.m.) or naltrexone (0.03 – 1.0 mg/kg, i.m.) in the morning (10h, 4h after “lights on”) or in the evening (16:30h, 1.5h before “lights off”). Results Morning treatment with methadone or buprenorphine dose-dependently impaired sleep in rhesus monkeys, with at least one dose significantly increasing sleep latency and decreasing sleep efficiency. Evening treatment with methadone or buprenorphine also impaired sleep, with lower doses significantly inducing sleep alterations compared to morning treatments. The effects of buprenorphine on sleep was a biphasic function, with the highest doses not disrupting sleep. Treatment with naltrexone significantly improved sleep-like measures in rhesus monkeys, with evening treatments improving measures of both sleep latency and sleep efficiency. Conclusion Acute administration of methadone and buprenorphine induced marked sleep impairment in rhesus monkeys, even when the drugs were administered in the morning. Unexpectedly, acute administration of the opioid antagonist naltrexone significantly improved sleep-like measures. Our findings show that the currently available pharmacotherapies for OUD significantly affect sleep in naïve monkeys, and that opioid mechanisms yet to be determined may play a significant role in sleep-wake regulation. Support (if any) Supported by NIH grants DA049886 to L.F.B.; DA048586 to C.A.Z.; DA039167 to K.B.F.; DA011792, DA043204 and DA046778 to J.K.R..

Phenotypes of remodeling in respiratory physiology due to chronic opioid use

Deaths related to synthetic opioids have increased six-fold over the past 20 years. In comparison to the expansive foundation of literature investigating circuit and cellular level mechanisms involved with acute opioid induced respiratory depression (OIRD), very little is known about how chronic opioid use remodels respiration. Similarly, the understanding of tolerance to the euphoric and analgesic effects of opioids has been well studied, yet tolerance to the respiratory side effects of chronic opioid use has been largely ignored. One reason that this gap in knowledge may exist is that the rates of tolerance to the analgesic and euphoric effects of opioids appear to emerge faster than respiratory tolerance to opioids. The goal of this ongoing work is to investigate the mechanisms by which chronic fentanyl use influences the control of breathing and the development of tolerance to its depressive respiratory effects. Here, we introduce an adult mouse model of chronic opioid use. In this model, the synthetic opioid, fentanyl (0.7 mg/kg) was administered for up to ten days. Breathing was assessed prior to, during and after OIRD using unrestrained whole body plethysmography. Our preliminary findings indicate that after five days of fentanyl administration, the magnitude of OIRD is approximately 50% less (n=5) as compared to ORID during the first day of fentanyl. Moreover, assessing the hypoxic chemoreflex after five days of chronic fentanyl treatment reveals that the hypoxic ventilatory response (outside of the window of OIRD). In 2 of 5 subjects, pronounced periodic breathing emerged during baseline conditions after the fifth day of fentanyl administration. These results are consistent with phenotypes observed in individuals who chronically use opioids and/or receive treatment for chronic opioid use and suggest that chronic fentanyl use perturbs respiratory control outside of the immediate window of OIRD. Thus, our model can be used to examine the mechanisms that that drive pharmacodynamic changes to opioids and promote respiratory-related morbidities associated with chronic fentanyl use.

Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity

ABSTRACT Over the past three decades the United States has experienced a devastating opioid epidemic. One of the many debilitating side effects of chronic opioid use is opioid-induced bowel dysfunction. We investigated the impact of methadone maintenance treatment (MMT) on the gut microbiome, the gut bacterial metabolite profile, and intestinal barrier integrity. An imbalance in key bacterial communities required for production of short-chain fatty acids (SCFAs), mucus degradation, and maintenance of barrier integrity was identified. Consistent with dysbiosis, levels of fecal SCFAs were reduced in MMT. We demonstrated that metabolites synthesized by Akkermansia muciniphila modulate intestinal barrier integrity in vitro by strengthening the pore pathway and regulating tight junction protein expression. This study provides essential information about the therapeutic potential of A. muciniphila and warrants development of new clinical strategies that aim to normalize the gut microbiome in individuals affected by chronic opioid use.

S1005 The Implications of Chronic Opioid Use on Post-Transplant Clinical Outcomes: A Systematic Review and Meta-Analysis

INTRODUCTION: Based on current literature, pre-transplant chronic opioid use (COU) for analgesia is highly prevalent among patients awaiting solid-organ transplant. However, there are very few large-scale studies on the effect of COU on post-transplant outcomes. We conducted a systematic review and meta-analysis to evaluate the impact of pre-transplant COU on solid-organ transplantation clinical outcomes. METHODS: A comprehensive literature review was conducted by searching the PubMed, Ovid Medline, Embase, Web of Science, and Cochrane databases from inception to April 2020 to identify all studies that evaluated the impact of pre-transplant COU on post-transplant clinical outcomes. COU was defined as >3 months of consecutive opioid use entering transplant listing. The search included studies regarding heart, lung, kidney, and liver transplantation (Figure 1). Our primary outcome was all-cause mortality, and secondary outcomes were graft failure and the one-year readmission rate. A random-effect model was used to estimate the pooled hazard ratios (HR) or odds ratios (OR) of our outcomes. RESULTS: Nine retrospective studies involving 166,765 patients were included in the primary meta-analysis. The all-cause mortality rate was significantly higher in patients who were on chronic opioids preceding transplant compared to those who were not (HR 1.42; 95% CI 1.34-1.50). The included studies demonstrated low heterogeneity (Figure 2). Additionally, COU patients had an increased risk of graft failure compared to non-COU patients (HR 1.26; 95% CI (1.13–1.40) (Figure 3). With regards to the one-year readmission rates, only three studies were included. There was no statistically significant difference in the readmission rate between the two groups (HR 1.78; 95% CI (0.87–3.63). The three studies had high heterogeneity. CONCLUSION: This study demonstrates that pre-transplant COU in solid-organ transplant patients is associated with an increased risk of all-cause mortality and graft failure. Pre-transplant COU may be a surrogate for comorbidities causing chronic pain or psychosocial traits that can contribute to non-compliance post-transplant. These potential risk factors may explain the increased risk of poor outcomes post-transplant. Therefore, a careful evaluation of opioid use patterns and consideration of alternative analgesic strategies is warranted in this population to lessen the reliance on opioid use and associated adverse outcomes.Figure 1.: Literature review process.Figure 2.: Forest plot of mortality.Figure 3.: Forest plot of graft loss.

Chronic Opioid Therapy and Sleep: An American Academy of Sleep Medicine Position Statement.

There is a complex relationship among opioids, sleep and daytime function. Patients and medical providers should be aware that chronic opioid therapy can alter sleep architecture and sleep quality as well as contribute to daytime sleepiness. It is also important for medical providers to be cognizant of other adverse effects of chronic opioid use including the impact on respiratory function during sleep. Opioids are associated with several types of sleep-disordered breathing, including sleep-related hypoventilation, central sleep apnea (CSA), and obstructive sleep apnea (OSA). Appropriate screening, diagnostic testing, and treatment of opioid-associated sleep-disordered breathing can improve patients' health and quality of life. Collaboration among medical providers is encouraged to provide high quality, patient-centered care for people who are treated with chronic opioid therapy.

SUN-489 Opioid Epidemic and Related Endocrine Effects: A Systematic Review and Meta-analysis.

OBJECTIVE The increased use of opioids has resulted in an unprecedented opioid epidemic, with non-negligible numbers of opioid-induced deaths. It is well-known that chronic opioid use affects the activity of the gonadal axis, but the frequency of this and other potential pituitary hormone deficiencies remains unclear. The aim of this systematic review and meta-analysis was to systematically review the effect of exogenous opioids on endocrine function METHODS Following the PRISMA statement, eight electronic databases were searched in May 2018 for randomized, and observational studies assessing endocrine function in patients using exogenous opioids. A random effects model meta-analysis was performed to obtain weighted proportions of hypogonadism and hypocortisolism with a 95% confidence interval. Due to the heterogeneity in studies, meta-analysis for the effects on other axes, and for subgroups could not be performed, and is systematically reviewed. RESULTS 52 articles were included with 18.428 patients in total. The patient population consisted mainly of pain patients (n=21 studies), patients on maintenance treatment for opioid addiction (n=9) and healthy volunteers (n=4) with similar opioid effects between these groups. Morphine (n=17) was mostly used, followed by methadone (n=15) and opioid dose defined as morphine equivalent daily dose (MEDD) (n=14) with no difference in effects between groups. Based on 15 studies containing 3.250 patients (% male: 99.5) on chronic opioids, the prevalence of hypogonadism was 65% (95% CI: 57% to 73%, I2=91.16%). Based on 5 studies with a total of 207 patients (% male: 57.5), the prevalence of hypocortisolism, based on non-dynamic testing, was 19% (95% CI: 10%, 29%, I2=74.21). Results of the systematic review showed an increasing trend for serum prolactin concentrations, and no clear effects on the somatotropic (n=5) and thyrotropic axes (n=7). Six studies reported that testosterone replacement in opioid induced hypogonadism increased testosterone levels, but clinical effects were not reported. CONCLUSION While the evidence on other endocrine axes remains insufficient, hypogonadism occurs in more than half of the male chronic opioid users, and hypocortisolism in approximately a fifth of all patients. Periodical evaluation of endocrine function, especially of the activity of the gonadal and adrenal axes, is mandatory in these patients. More studies are needed on the effects of chronic opioid use on the female gonadal axis and the other endocrine axes, also focusing on experienced symptoms and symptom management.

Effects of Chronic Opioid Use on Sleep and Wake.

Chronic use of opioids negatively affects sleep on 2 levels: sleep architecture and breathing. Patients suffer from a variety of daytime sequelae. There may be a bidirectional relationship between poor sleep quality, sleep-disordered breathing, and daytime function. Opioids are a potential cause of incident depression. The best therapeutic option is withdrawal of opioids, which proves difficult. Positive airway pressure devices are considered first-line treatment for sleep-related breathing disorders. New generation positive pressure servo ventilators are increasingly popular as a treatment option for opioid-induced sleep-disordered breathing. Treatments to improve sleep quality, sleep-related breathing disorders, and quality of life in patients who use opioids chronically are discussed.

Successful use of buprenorphine/naloxone to treat opioid addiction after cancer therapy.

126 Background: Cancer pain prevalence is 55-70% and it is treated with opioids. Tapering opioids after completion of cancer treatment may be complicated by addiction, one of the known side effects of chronic opioid use. To improve access to addiction treatment Suboxone has become widely available to patients with addiction and non-malignant pain. We present a case series of successful use of Suboxone in cancer survivors and patients. Methods: Our comprehensive cancer center (CCC) Pain Registry contains patient characteristics, treatments, and outcomes for a prospective cohort of 2320 chronic pain cancer patients seen in 2011-2016 in outpatient palliative and pain service clinics. We respectively reviewed the database and EMR to evaluate prevalence of addiction and use of Suboxone in cancer pain patients. Results: Of 134 (6%) patients with ICD-9/10 diagnosis of opioid dependence 11 (8%) patients received Suboxone. Eight were male and average age was 55. Eight patients were cancer survivors, one with stable metastatic prostate cancer and two developed end-stage bladder and breast cancer. Eight cancer survivors and one patient with stable metastatic prostate remained on Suboxone and received no other opioids. The two patients with advanced cancers were ultimately taken off Suboxone and discharged to hospice on TD fentanyl and hydromorphone. Suboxone was prescribed by outside prescribers for eight patients and by a CCC certified Suboxone prescriber for three patients: 75-y-o female dependent on morphine for over 10 years was successfully tapered off morphine and ultimately off Suboxone, 51-y-o lymphoma survivor remains in stable remission for addiction, and a 67-y-o man with stable metastatic prostate cancer and stable remission for addiction has been refusing opioids other than Suboxone for 2 years. Conclusions: Although cancer patients are appropriately exempt from CDC opioid guidelines cancer patients with comorbid addiction may benefit from stopping opioids when pain resolves. In addition to screening for opioid use disorder, use of Suboxone may further improve care for the patients with cancer pain and addiction and increase safety for the caregivers and community.