scholarly journals Opioid toxicity due to CNS depressant polypharmacy: A case report

2021 ◽  
Vol 11 (2) ◽  
pp. 70-74
Author(s):  
Christine Lee ◽  
Annabelle Wanson ◽  
Sarah Frangou ◽  
David Chong ◽  
Katelyn Halpape

Abstract The interaction between methadone and central nervous system depressants can cause serious adverse effects, including profound sedation, respiratory depression, coma, and death. This poses a challenge in the treatment of patients with concurrent psychiatric and substance use disorders as the combined use is often unavoidable. We report a case of a patient with opioid use disorder, mood disorder unspecified, chronic pain, and chronic obstructive pulmonary disease who experienced 2 serious episodes of CNS and respiratory depression due to polypharmacy-induced opioid toxicity. Careful consideration of pharmacokinetics, pharmacodynamics, and patient-specific factors was imperative to identify the suspected contributing medications: methadone, lorazepam, divalproex, gabapentin, and cyclobenzaprine. Cognitive and system factors that contributed to these adverse events and strategies to mitigate risk of recurrence were also identified.

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 54-54
Author(s):  
Peter Treitler ◽  
Stephen Crystal ◽  
Richard Hermida ◽  
Jennifer Miles

Abstract High rates of opioid prescribing and comorbid medical conditions increase risk of overdose among older adults. As the US population ages and the rates of opioid use disorder (OUD) increase in the elderly population, there is a need to characterize trends and correlates of overdose in order to more effectively target policy and practice. Using a ~40% random sample of 2015-2017 Medicare beneficiaries ages 65 and older with Part D pharmacy coverage, this study examined medically treated opioid overdoses among US older adults. The sample included 13-14 million beneficiaries per year. The rate of medically treated opioid overdoses among elderly Medicare beneficiaries increased by 15% from 6 per 10,000 in 2015 to 6.9 per 10,000 in 2017. Those with overdose were disproportionately female (63%), non-Hispanic white (83%), with diagnoses of pain conditions (96%), with diagnoses of major depression (63%), and with high rates of conditions that decrease respiratory reserve such as chronic obstructive pulmonary disease. 13% had co-occurring diagnosed alcohol use disorder, 36% were diagnosed with opioid dependence or abuse, and 12% were diagnosed with hepatitis C. Older individuals with overdose represent a complex mix of risk factors; identifying those most at risk (as well as those who have very low risk, whose pain management may be compromised by overly-rigid interpretation of opioid use guidelines) is key in order to address multiple risks, balancing risk reduction with appropriate pain management.


2021 ◽  
Vol 11 (4) ◽  
pp. 225-230
Author(s):  
Payal H. Desai ◽  
Olesya Taylor ◽  
Kunal J. Shah ◽  
Kirk E. Evoy ◽  
Alyssa M. Peckham

Abstract Introduction Gabapentin and pregabalin (gabapentinoids) can be given with opioids for opioid-sparing and adjuvant analgesic effects. In the context of certain comorbidities and high dosages, coadministration of these agents can lead to respiratory depression or oversedation, necessitating naloxone administration. Methods A retrospective chart review from January 2015 to December 2017 was conducted to include patients who received naloxone and opioids with or without gabapentinoids. Exclusion criteria included pregnancy or having received naloxone in the emergency department, intensive care, or pediatrics units. The primary outcome was to characterize differences between groups regarding comorbidities, history of renal or hepatic dysfunction, history of SUD, opioid tolerance, initiation and dose appropriateness of gabapentinoids, and dose intensity of gabapentinoids and opioids. Secondary outcomes were concomitant CNS depressant use and naloxone episodes for documented respiratory depression. Results Of 126 patients who met inclusion criteria, 36 received opioids and gabapentinoids (gabapentinoid group) and 90 received opioids alone (nongabapentinoid group). There were 136 naloxone episodes between the 2 groups. More than 50% of the naloxone episodes in the gabapentinoid group involved opioids of at least 90 oral morphine mg equivalents. Respiratory depression accounted for 39% and 15.8% of the naloxone episodes in the gabapentinoid and nongabapentinoid groups, respectively. Discussion There may be increased naloxone episodes among patients receiving opioids and gabapentinoids. Future studies are needed to evaluate the incremental risk of respiratory depression and oversedation as it pertains to concomitant medication administration and patient-specific factors.


2021 ◽  
Vol 11 (9) ◽  
pp. 919
Author(s):  
Asima Karim ◽  
Tahir Muhammad ◽  
Rizwan Qaisar

Patients with chronic obstructive pulmonary disease (COPD) present with an advanced form of age-related muscle loss or sarcopenia. Among multiple pathomechanisms of sarcopenia, neuromuscular junction (NMJ) degradation may be of primary relevance. We evaluated the circulating biomarkers of NMJ degradation, including c-terminal agrin fragment -22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of sarcopenia in COPD during pulmonary rehabilitation (PR). Male, 61–77-year-old healthy controls and patients of COPD (n = 77–84/group) were recruited for measurements of circulating CAF22, BDNF, and GDNF levels. Functional assessment and measurements of plasma biomarkers were performed at diagnosis and following six months of PR. CAF22 levels were elevated while BDNF and GDNF levels were reduced in COPD patients at diagnosis, which were incompletely restored to normal levels following PR. These biomarkers showed varying degrees of associations with indexes of sarcopenia and functional recovery during PR. Logistic regression revealed that the combined use of three biomarkers enhanced the diagnostic accuracy of sarcopenia better than single biomarkers. Altogether, measurements of plasma CAF22, BDNF, and GDNF may be helpful for the accurate diagnosis of sarcopenia and functional capacity in COPD during PR.


Author(s):  
Yohsuke Imai ◽  
Takahito Miki ◽  
Masanori Nakamura ◽  
Takuji Ishikawa ◽  
Shigeo Wada ◽  
...  

Chronic Obstructive Pulmonary Disease (COPD) refers to a group of diseases that are characterized by airflow obstruction. Currently, COPD is the fourth leading cause of death worldwide, but fluid dynamics in airways of COPD patients has not been well understood. Multi-slice Computer Tomography (CT) images provide three-dimensional realistic geometry of patient airways. Computational Fluid Dynamics (CFD) analysis using the patient-specific geometry will greatly help the understanding of the mechanism of COPD. However, few studies have performed such a patient-specific pulmonary airflow simulation. Our aim is to develop a patient-specific CFD method applicable to multi-scale airways, involving trachea, bronchi, bronchioles, and alveoli. We propose a CFD method using multi-level voxel modeling of airway geometry, in which voxel size in a local domain is adaptively refined or coarsened to the local flow scale.


2020 ◽  
Vol 7 (1) ◽  
pp. e000483 ◽  
Author(s):  
Tham Thi Le ◽  
Siyeon Park ◽  
Michelle Choi ◽  
Marniker Wijesinha ◽  
Bilal Khokhar ◽  
...  

BackgroundOpioids and sedatives are commonly prescribed in chronic obstructive pulmonary disease (COPD) patients for symptoms of dyspnoea, pain, insomnia, depression and anxiety. Older adults are advised to avoid these medications due to increased adverse events, including respiratory events. This study examines respiratory event risks associated with concomitant opioid and sedative use compared with opioid use alone in older adults with COPD.MethodsA 5% nationally representative sample of Medicare beneficiaries with COPD and opioid use between 2009 and 2013 was used for this retrospective cohort study. Current and past concomitant use were identified using drug dispensed within 7 days from the censored date: at respiratory event, at death, or at 12 months post index. Concomitant opioid and sedative use were categorised into no overlap (opioid only), 1 to 10, 11 to 30, 31 to 60 and >60 days of total overlap. The primary outcome was hospitalisation or emergency department (ED) visits for respiratory events (COPD exacerbations or respiratory depression). Propensity score matching was implemented and semi-competing risk models were used to address competing risk by death.ResultsAmong 48 120 eligible beneficiaries, 1810 (16.7%) concomitant users were matched with 9050 (83.3%) opioid only users. Current concomitant use of 1 to 10, 11 to 30 and 31 to 60 days was associated with increased respiratory events (HRs (95% CI): 2.8 (1.2 to 7.3), 9.3 (4.9 to 18.2) and 5.7 (2.5 to 12.5), respectively), compared with opioid only use. Current concomitant use of >60 days or past concomitant use of ≤60 days was not significantly associated with respiratory events. Consistent findings were found in sensitivity analyses, including in subgroup analysis of non-benzodiazepine sedatives. Additionally, current concomitant use significantly increased risk of death.ConclusionShort-term and medium-term current concomitant opioid and sedative use significantly increased risk of respiratory events and death in older COPD Medicare beneficiaries. Long-term past concomitant users, however, demonstrated lower risks of these outcomes, possibly reflecting a healthy user effect or developed tolerance to the effects of these agents.


2020 ◽  
Vol 8 (7_suppl6) ◽  
pp. 2325967120S0046
Author(s):  
Jacqueline Baron ◽  
Alan Shamrock ◽  
Trevor Gulbrandsen ◽  
Brian Wolf ◽  
Kyle Duchman ◽  
...  

Objectives: The current opioid epidemic in the United States is a significant cause of increasing morbidity and mortality. The purpose of this study was to determine rate of opioid use before and after arthroscopic meniscal surgery, and assess patient factors associated with prolonged opioid use following primary arthroscopic meniscal surgery. Methods: Patients undergoing primary arthroscopic meniscal surgery procedures from 2007-2016 were retrospectively accessed from the Humana Inc. administrative claims database. Patients were categorized as patients who filled opioid prescriptions within 3 months (OU), within 1 month (A-OU), between 1 to 3 months (C-OU), and never filled opioid prescriptions (N-OU) before surgery. Rates of opioid use were evaluated preoperatively and longitudinally tracked for OU and N-OU cohorts. Prolonged opioid use was defined as continued opioid prescription filling at ≥3 months after surgery. Multiple logistic regression analysis was used to control for various patient characteristics and identify factors associated with opioid use at 12 months after surgery, with significance defined as P<0.05 Results: There were 107,717 patients (54% female) that underwent arthroscopic meniscal surgery during the study period, of which 46.1% (n=49,630) were N-OU. One year after surgery, opioid fill rate was significantly higher in the OU group compared to the N-OU group with a relative risk of 6.98 (21.1% vs 3.02%; 95% CI: 6.61-7.36; p<0.0001). Multiple logistic regression model identified C-OU (OR:10.23, 95% CI: 9.74-10.76, p<0.0001) as the strongest predictor of opioid use at 12 months postoperatively. Furthermore, patients with acute preoperative opioid use (p<0.0001), preoperative diagnosis of diabetes mellitus (p<0.0001), hypertension (p<0.0001), chronic obstructive pulmonary disease (p<0.0001), anxiety or depression (p<0.0001), alcohol abuse (p= 0.0019), and tobacco use (p=0.0345) had a significantly increased odds of opioid use at 12 months postoperatively. However, males (p<0.0001) and patients <40 years (p<0.0001) had a significantly decreased odds of opioid use 12 months postoperatively. Conclusion: Preoperative opioid use is a significant risk factor for opioid use at 12 months following surgery. Diabetes mellitus, hypertension, chronic obstructive pulmonary disease, smoking status, and psychiatric diagnosis were independent risk factors for opioid use 1-year following surgery.


2013 ◽  
Vol 3 (2) ◽  
pp. 20120057 ◽  
Author(s):  
K. S. Burrowes ◽  
J. De Backer ◽  
R. Smallwood ◽  
P. J. Sterk ◽  
I. Gut ◽  
...  

The respiratory system comprises several scales of biological complexity: the genes, cells and tissues that work in concert to generate resultant function. Malfunctions of the structure or function of components at any spatial scale can result in diseases, to the detriment of gas exchange, right heart function and patient quality of life. Vast amounts of data emerge from studies across each of the biological scales; however, the question remains: how can we integrate and interpret these data in a meaningful way? Respiratory disease presents a huge health and economic burden, with the diseases asthma and chronic obstructive pulmonary disease (COPD) affecting over 500 million people worldwide. Current therapies are inadequate owing to our incomplete understanding of the disease pathophysiology and our lack of recognition of the enormous disease heterogeneity: we need to characterize this heterogeneity on a patient-specific basis to advance healthcare. In an effort to achieve this goal, the AirPROM consortium ( Air way disease Pr edicting O utcomes through patient-specific computational M odelling) brings together a multi-disciplinary team and a wealth of clinical data. Together we are developing an integrated multi-scale model of the airways in order to unravel the complex pathophysiological mechanisms occurring in the diseases asthma and COPD.


2021 ◽  
Vol 2 (4) ◽  
pp. 365-378
Author(s):  
Amber N. Edinoff ◽  
Catherine A. Nix ◽  
Tanner D. Reed ◽  
Elizabeth M. Bozner ◽  
Mark R. Alvarez ◽  
...  

Opioid use disorder is a well-established and growing problem in the United States. It is responsible for both psychosocial and physical damage to the affected individuals with a significant mortality rate. Given both the medical and non-medical consequences of this epidemic, it is important to understand the current treatments and approaches to opioid use disorder and acute opioid overdose. Naloxone is a competitive mu-opioid receptor antagonist that is used for the reversal of opioid intoxication. When given intravenously, naloxone has an onset of action of approximately 2 min with a duration of action of 60–90 min. Related to its empirical dosing and short duration of action, frequent monitoring of the patient is required so that the effects of opioid toxicity, namely respiratory depression, do not return to wreak havoc. Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose. Nalmefene is also known as 6-methylene naltrexone. Its main features of interest are its prolonged duration of action that surpasses most opioids and its ability to serve as an antidote for acute opioid overdose. This can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.


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