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Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients.

ABSTRACT: Background:The concurrent use of sedating centrally acting drugs and opioids by chronic pain patients occurs routinely despite concerns of negative impacts on respiration during sleep. The effects of centrally acting drugs and opioids on sleep apnoea have not been well characterised. The objective of this study was to assess the effect of concomitant centrally acting drugs and opioids on the prevalence and severity of sleep apnoea in chronic pain patients. Methods:We conducted a prospective cohort study at five chronic pain clinics. Each participant underwent an in-laboratory polysomnography and daily morphine milligram equivalents were calculated. Participants were grouped into centrally acting drugs and opioid users versus sole opioid users. Results:Of the 332 consented participants, 204 underwent polysomnography and 120 (58.8%) had sleep apnoea (72% obstructive, 20% central, and 8% indeterminate sleep apnoea). Overall, 35% (71 of 204) were taking opioids alone, and 65% (133 of 204) were taking centrally acting drugs and opioids. There was a 69% decrease in the odds of having sleep apnoea (apnoea-hypopnoea index ?5?events·h-1) in participants taking benzodiazepine/opioids versus sole opioid users (OR 0.31, 95% CI:0.12-0.80, p=0.015). Additionally, concomitant benzodiazepine/opioids versus sole opioid use was associated with a decrease in respiratory arousal index scores (p=0.03). Mean overnight S pO2 was approximately 1% lower in the concomitant benzodiazepine/opioids group versus sole opioid users (93.1±2.5 versus 94.4±2.1%, p=0.01). Conclusion:In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.

SUBMITTER: Mir S

PROVIDER: S-EPMC7445118 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients.

Mir Soodaba S Wong Jean J Ryan Clodagh M CM Bellingham Geoff G Singh Mandeep M Waseem Rida R Eckert Danny J DJ Chung Frances F

ERJ open research 20200701 3

<h4>Background</h4>The concurrent use of sedating centrally acting drugs and opioids by chronic pain patients occurs routinely despite concerns of negative impacts on respiration during sleep. The effects of centrally acting drugs and opioids on sleep apnoea have not been well characterised. The objective of this study was to assess the effect of concomitant centrally acting drugs and opioids on the prevalence and severity of sleep apnoea in chronic pain patients.<h4>Methods</h4>We conducted a p ...[more]

PMID: 32864381

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Project description:IntroductionThe combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration.MethodsThis retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group.ResultsA total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group.ConclusionThere was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours.

Project description:ImportanceOpioid-prescribing policies and guidelines aimed at reducing inappropriate opioid prescribing may lead physicians to stop prescribing opioids. Patients may thus encounter difficulties finding primary care practitioners willing to care for them if they take opioids.ObjectivesTo assess practitioner willingness to accept and continue prescribing opioids to new patients with pain and whether this willingness differs across payer types.Design, setting, and participantsThis survey study used a simulated patient call audit method. A brief telephone survey was administered to all clinics followed by a call using a patient script simulating an adult patient with chronic pain who was taking long-term opioids. The patient had Medicaid or private insurance. Calls were made between June 22 and October 30, 2018, to 667 primary care clinics that served a general adult population in Michigan. Clinics that accepted both Medicaid and private insurance, took new patient appointments, and were successfully recontacted for the simulated call were eligible for the study.Main outcomes and measuresPrevalence of clinics' acceptance of new patients receiving prescription opioids overall and by clinic characteristics and insurance type.ResultsOf the 194 eligible clinics, 94 (48.4%) were randomized according to insurance type to receive calls from research assistants posing as children of patients with Medicaid and 100 (51.5%) to receive calls from those with private insurance. Overall, 79 (40.7%) stated that their practitioners would not prescribe opioids to the simulated patient. Thirty-three clinics (17.0%) requested more information before making a decision. Compared with single-practitioner clinics, clinics with more than 3 practitioners were more likely (odds ratio [OR], 2.99; 95% CI, 1.48-6.04) to accept new patients currently taking opioids. No difference was found in access based on insurance status (OR, 0.92; 95% CI, 0.52-1.64) or whether the clinic offered medications for opioid use disorders (OR, 1.10; 95% CI, 0.45-2.69).Conclusions and relevanceThe findings suggest that access to primary care may be reduced for patients taking prescription opioids, which could lead to unintended consequences, such as conversion to illicit substances or reduced management of other medical comorbidities.

Project description:ImportanceRecent increases in US opioid-related deaths underscore the need to understand drivers of fatal overdose. The initial prescription of opioids represents a critical juncture because it increases the risk of future opioid use disorder and is preventable.ObjectiveTo examine new opioid prescribing patterns in US patients at increased risk of overdose from benzodiazepine use.Design, setting, and participantsThis study used publicly available data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from January 1, 2005, through December 31, 2015, to identify adults 20 years or older receiving new opioid prescriptions and concurrently using a benzodiazepine.Main outcomes and measuresPopulation-based rates of new opioid prescriptions stratified by use of benzodiazepines.ResultsThis study analyzed 13?146 visits, representing 214 million visits nationally, with a new opioid prescription. Rates of new opioid prescriptions among adults using a benzodiazepine increased from 189 to 351 per 1000 persons between 2005 and 2010 (rate difference, 162; 95% CI, 29-295; P?=?.02) and decreased to 172 per 1000 persons by 2015 (rate difference, -179; 95% CI, -310 to -48; P?=?.008). New opioid prescriptions in the general population not using benzodiazepines increased nonsignificantly from 78 to 93 per 1000 US persons between 2005 and 2010 (rate difference, 15; 95% CI, -3 to 33; P?=?.10) and decreased nonsignificantly to 79 per 1000 persons by 2015 (rate difference, -14; 95% CI, -38 to 11; P?=?.28). The likelihood of receiving a new opioid prescription during an ambulatory visit remained higher for patients concurrently using benzodiazepines compared with the general population after adjusting for demographic characteristics, comorbidities, and diagnoses associated with pain (adjusted relative risk, 1.83; 95% CI, 1.56-2.15; P?<?.001). Naloxone was coprescribed in less than 1% of visits when a patient concurrently used a benzodiazepine.Conclusions and relevanceIn 2010, new opioid prescriptions for US adults stopped increasing and began to decrease among higher-risk patients who used benzodiazepines. These patterns suggest that the recent increase in opioid-related deaths may be associated with factors other than physicians writing new opioid prescriptions. Nevertheless, prescribing among higher-risk patients still occurred at rates higher than rates in the general population, representing an important opportunity to improve quality of care for patients experiencing pain.

Project description:BackgroundCurrent guideline-recommended monitoring of patients prescribed long-term opioid therapy (LTOT) for chronic pain will likely result in increased identification of behaviors of concern for misuse and addiction, but there is a dearth of empiric evidence about how these behaviors should be managed.ObjectiveTo establish expert consensus about treatment approaches for common and challenging concerning behaviors that arise among patients on LTOT.DesignWe used a Delphi approach, which allows for generation of consensus.ParticipantsParticipants were clinical experts in chronic pain and opioid prescribing recruited from professional societies and other expert groups.Main measuresThe Delphi process was conducted online, and consisted of an initial brainstorming round to identify common and challenging behaviors, a second round to identify management strategies for each behavior, and two rounds to establish consensus and explore disagreement/uncertainty.Key resultsForty-two participants completed round 1, 22 completed round 2, 30 completed round 3, and 28 completed round 4. Half of round 1 participants were female (52%), and the majority were white (83%). Most (71%) were physicians, and most participants practiced in academic primary (40%) or specialty care (19%).The most frequently cited common and challenging behaviors were missing appointments, taking opioids for symptoms other than pain, using more opioid medication than prescribed, asking for an increase in opioid dose, aggressive behavior, and alcohol and other substance use. Across behaviors, participants agreed that patient education and information gathering were important approaches. Participants also agreed that stopping opioids is not important initially, but if initial approaches do not work, tapering opioids and stopping opioids immediately may become important approaches.ConclusionsThis study presents clinical expert consensus on how to manage concerning behaviors among patients on LTOT. Future research is needed to investigate how implementing these management strategies would impact patient outcomes, practice and policy.

Project description:ImportanceLong-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes.ObjectiveTo compare all-cause mortality for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain.Design, setting, and participantsRetrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care.ExposuresPropensity score-matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications).Main outcomes and measuresTotal and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication.ResultsThere were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean [SD] age, 48 [11] years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10,000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10,000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10,000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10,000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10,000 person-years.Conclusions and relevancePrescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.

Project description:BackgroundOpioid use for chronic non-cancer pain (CNCP) is complex. In the absence of pan-European guidance on this issue, a position paper was commissioned by the European Pain Federation (EFIC).MethodsThe clinical practice recommendations were developed by eight scientific societies and one patient self-help organization under the coordination of EFIC. A systematic literature search in MEDLINE (up until January 2020) was performed. Two categories of guidance are given: Evidence-based recommendations (supported by evidence from systematic reviews of randomized controlled trials or of observational studies) and Good Clinical Practice (GCP) statements (supported either by indirect evidence or by case-series, case-control studies and clinical experience). The GRADE system was applied to move from evidence to recommendations. The recommendations and GCP statements were developed by a multiprofessional task force (including nursing, service users, physicians, physiotherapy and psychology) and formal multistep procedures to reach a set of consensus recommendations. The clinical practice recommendations were reviewed by five external reviewers from North America and Europe and were also posted for public comment.ResultsThe key clinical practice recommendations suggest: (a) first optimizing established non-pharmacological treatments and non-opioid analgesics and (b) considering opioid treatment if established non-pharmacological treatments or non-opioid analgesics are not effective and/or not tolerated and/or contraindicated. Evidence- and clinical consensus-based potential indications and contraindications for opioid treatment are presented. Eighteen GCP recommendations give guidance regarding clinical evaluation, as well as opioid treatment assessment, monitoring, continuation and discontinuation.ConclusionsOpioids remain a treatment option for some selected patients with CNCP under careful surveillance.SignificanceIn chronic pain, opioids are neither a universal cure nor a universally dangerous weapon. They should only be used for some selected chronic noncancer pain syndromes if established non-pharmacological and pharmacological treatment options have failed in supervised pain patients as part of a comprehensive, multi-modal, multi-disciplinary approach to treatment. In this context alone, opioid therapy can be a useful tool in achieving and maintaining an optimal level of pain control in some patients.

Project description:Background:Opioid use is common in end-stage renal disease (ESRD) patients. However, safety of individual opioids and concomitant benzodiazepine use has not been studied. Objective:To study the epidemiology of opioid and concomitant benzodiazepine use in ESRD population. To study the clinical safety profile of individual opioids in patients on hemodialysis. Design:Retrospective analysis of the U.S. Renal Data System. A comprehensive review of the current literature was performed to update currently used opioid safety classification. Participants:ESRD patients ≥18 years on hemodialysis who were enrolled in Medicare A and B and Part D between 2006 and 2012, excluding those with malignancy. Main Measures:Hospital admission with diagnosis of prescription opioid overdose within 30, 60, and 90 days of prescription; death due to opioid overdose. Results:Annually, the percentage of patients prescribed any opioid was 52.2%. Overall trend has been increasing except for a small dip in 2011, despite which the admissions due to opioid overdose have been rising. 30% of those who got a prescription for opioids also got a benzodiazepine prescription. 56.5% of these patients received both prescriptions within a week of each other. Benzodiazepine use increased the odds of being on opioids by 3.27 (CI 3.21-3.32) and increased the odds of hospitalization by 50%. Opioids considered safe such as fentanyl and methadone were associated with 3 and 6 folds higher odds of hospitalization within 30 days of prescription. Hydrocodone had the lowest odds ratio (1.9, CI 1.8-2.0). Conclusions:Concurrent benzodiazepine use is common and associated with higher risk of hospitalization due to opioid overdose. Possible opioid-associated hospital admission rate is 4-5 times bigger in ESRD population than general population. Current safety classification of opioids in these patients is misleading, and even drugs considered safe based on pharmacokinetic data are associated with moderate to very high risk of hospitalization. We propose a risk-stratified classification of opioids and suggest starting to use them in all ESRD patients.

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Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients.

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Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients.

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