Opioid induced respiratory depression

OBJECTIVES: This study aims to assess whether a simulation-based training programme focusing on palliative care emergencies conducted in a hospice setting could improve the self-reported confidence and competence of nursing staff. METHODS: A training programme was developed to enable nursing professionals to practice clinical skills necessary for recognising and managing palliative care emergencies including opioid induced respiratory depression, catastrophic haemorrhage, anaphylaxis, seizure and acute airway obstruction...

INTRODUCTION: Intermediate efficacy mu opioid receptor (MOR) agonists have potential to retain analgesic effectiveness while improving safety, but the optimal MOR efficacy for effective and safe opioid analgesia is unknown. Preclinical assays of pain-depressed behavior can assess effects of opioids and other candidate analgesics on pain-related behavioral depression, which is a common manifestation of clinically relevant pain and target of pain treatment. Accordingly, the present study goal was to validate a novel assay of pain-depressed locomotor behavior in mice and evaluate the role of MOR efficacy as a determinant of opioid analgesic effects and related safety measures...

Synthetic opioids like fentanyl have improved the standard of care for many patients in the clinical setting, but their abuse leads to tens of thousands of overdose deaths annually. The current opioid epidemic underscores a critical need for insights into the physiological effects of fentanyl on vital functions. High doses of opioids in small mammals cause opioid-induced respiratory depression (OIRD) leading to hypoventilation, hypoxemia, and hypercapnia. In addition, opioids can also increase the alveolar to arterial oxygen (A-a) gradient and airway dysfunction...

A third of all patients are at risk for a serious adverse event, including death, in the first month after undergoing a major surgery. Most of these events will occur within 24 hours of the operation but are unlikely to occur in the operating room or postanesthesia care unit. Most opioid-induced respiratory depression events in the postoperative period resulted in death (55%) or anoxic brain injury (22%). A future state of mature artificial intelligence and machine learning will improve situational awareness of acute clinical deterioration, minimize alert fatigue, and facilitate early intervention to minimize poor outcomes...

OBJECTIVES: Surgical abortion is common, with most completed in the first trimester. Gold standard pain control is intravenous (IV) fentanyl and midazolam, requiring continuous cardio-respiratory monitoring, a potential challenge where this monitoring is unavailable. Ketamine is a sedative and analgesic without the cardio-respiratory depression risk associated with IV opioids, representing a potential alternative. Investigating non-opiate pain control methods is imperative given the context of the opioid crisis...

INTRODUCTION: Drug-induced respiratory depression is potentially fatal and can be caused by various drugs such as synthetic opioids and tranquilizers. The only class of respiratory depressants that has a specific reversal agent are opioids, such as naloxone. These reversal agents have limited utility in situations of polysubstance ingestion with agents from multiple respiratory depressant classes. Hence, there is an unmet need for drugs that stimulate breathing irrespective of the underlying cause of respiratory depression, i...

Introduction: Despite their inclination to induce tolerance, addictive states, and respiratory depression, synthetic opioids are among the most effective clinically administered drugs to treat severe acute/chronic pain and induce surgical anesthesia. Current medical interventions for opioid-induced respiratory depression (OIRD), wooden chest syndrome, and opioid use disorder (OUD) show limited efficacy and are marked by low success in the face of highly potent synthetic opioids such as fentanyl. D-Cysteine ethylester (D-CYSee) prevents OIRD and post-treatment withdrawal in male/female rats and mice with minimal effect on analgesic status...

BACKGROUND: Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units. METHODS: This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units...

This study provides an in-depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid-induced respiratory depression (OIRD). We explored the physiological implications of both drugs on ventilation and airway patency in anaesthetized mice. Our results revealed a similar reduction in respiratory frequency with equivalent scaled dosages of fentanyl and morphine, though the onset of suppression was more rapid with fentanyl. Additionally, fentanyl resulted in transient airflow obstructions during the inspiratory cycle, which were absent following morphine administration...

The macrocyclic tetrapeptide CJ-15,208 ( cyclo [Phe-D-Pro-Phe-Trp]) and its D-Trp isomer exhibit kappa opioid receptor (KOR) antagonism which prevents stress-induced reinstatement of extinguished cocaine-conditioned place preference. Here, we evaluated the effects of substitution of Trp and D-Trp on the peptides' opioid activity, antinociceptive tolerance, and the ability to prevent relapse to extinguished drug-CPP. Six analogs were synthesized using a combination of solid-phase peptide synthesis and cyclization in solution...

Toxic leukoencephalopathy (TLE) is a rare pathology caused by various substances including opioids (notably heroin), immunosuppressants, chemotherapy agents, cocaine, alcohol and carbon monoxide. However, although heroin is metabolised by the body into morphine, there is a striking paucity in cases of primary oral morphine-induced TLE, especially in the adult population. We present the case of a man in his 40s admitted to hospital in respiratory depression with a Glasgow Coma Scale (GCS) score of 6 after taking an overdose of oral morphine sulphate...

INTRODUCTION: Canada is in the midst of an overdose crisis. The use of prescription opioids in Canada has increased steadily over the past two decades, with stark increases in opioid-induced respiratory depression and related deaths. Opioids are the mainstay of treatment for cancer-related pain. Patients with cancer are not immune to the risks associated with opioid use but are underrepresented in available literature outlining risk mitigation strategies. Pharmacists are ideally placed to employ opioid risk mitigation practices to support safe and effective opioid use for patients with cancer-related pain...

Both L- and D-isomers of S-nitrosocysteine (CSNO) can bind to the intracellular domain of voltage-gated potassium channels in vitro. CSNO binding inhibits these channels in the carotid body, leading to increased minute ventilation in vivo. However, only the l-isomer is active in vivo because it requires the l-amino acid transporter (LAT) for transmembrane transport. In rodents and dogs, the esterified D-CSNO precursor-d-cystine dimethyl ester (ATLX-0199)-overcomes opioid- and benzodiazepine-induced respiratory depression while maintaining analgesia...

No abstract text is available yet for this article.

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects...

Opioid overdose is the leading cause of drug overdose lethality, posing an urgent need for investigation. The key brain region for inspiratory rhythm regulation and opioid-induced respiratory depression (OIRD) is the preBötzinger Complex (preBötC) and current knowledge has mainly been obtained from animal systems. This study aims to establish a protocol to generate human preBötC neurons from induced pluripotent cells (iPSCs) and develop an opioid overdose and recovery model utilizing these iPSC-preBötC neurons...

Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We sought to test the effects of the clinically-relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated utility of serotonin 5-HT1A agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing outcomes following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague Dawley rats anesthetized with sodium pentobarbital...

RATIONALE: Novel synthetic opioids (NSOs) are emerging in recreational drug markets worldwide. In particular, 2-benzylbenzimidazole 'nitazene' compounds are problematic NSOs associated with serious clinical consequences, including fatal respiratory depression. Evidence from in vitro studies shows that alkoxy chain length can influence the potency of nitazenes at the mu-opioid receptor (MOR). However, structure-activity relationships (SARs) of nitazenes for inducing opioid-like effects in animal models are not well understood compared to relevant opioids contributing to the ongoing opioid crisis (e...

BACKGROUND: Experts recommend using the lowest effective dose of naloxone to balance the reversal of opioid-induced respiratory depression and avoid precipitated opioid withdrawal, however, there is no established dosing standards within the emergency department (ED). OBJECTIVES: The aim of this review was to determine current naloxone dosing practice in the ED and their association with adverse events. METHODS: We conducted a systematic review by searching PubMed, Cochrane, Embase, and EBSCO from 2000-2021...

Opiates produce analgesia via G-protein signaling, and adverse effects, such as respiratory depression and decreased bowel motility, by β-arrestin pathway. Oliceridine, a G protein-biased MOR agonist, only presents modest safety advantages as compared to other opiates in clinical trials, possibly due to its limited bias. Our previous study shown that LPM3480392, a full MOR biased agonist, is selective for the Gi pathway over the β-arrestin-2. In the present article, we evaluated the subacute toxicity of LPM3480392 in rats...