Low Incidence of Opioid-Induced Respiratory Depression Observed with Oliceridine Regardless of Age or Body Mass Index: Exploratory Analysis from a Phase 3 Open-Label Trial in Postsurgical Pain

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

Advanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65 years) and/or obese (BMI ≥ 30 kg/m ²) patients and analyzed risk factors of OIRD.

Methods

Patients aged ≥ 18 years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48 h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate < 10 breaths per minute and/or oxygen saturation < 90%.

Results

A total of 724 surgical patients with a mean age of 54.5 ± 15.9 years and a mean NRS score of 6.2 ± 2.1 were included in this analysis; 33.3% (241/724) were ≥ 65 years of age and 46.3% (335/724) had BMI (body mass index) ≥ 30 kg/m ². The overall OIRD incidence was 13.7% with no patients requiring naloxone. The OIRD incidence was similar in the elderly and younger adults’ cohorts [10.8 vs. 15.1%, OR 0.68 (0.42, 1.1), p = 0.11], and in obese and non-obese groups [14.0 vs. 13.4%, OR 1.06 (0.69, 1.62), p = 0.80]. In patients that were both elderly and obese ( n = 120), the incidence was 10.8%. The multivariate analysis identified baseline NRS ≥ 6 [OR 1.6 (1.0, 2.4), p = 0.0499], PCA administration [OR 1.9 (1.2, 3.1), p = 0.005], and concomitant use of benzodiazepines and/or gabapentinoids [OR 1.6 (1.0, 2.6), p = 0.045], as being associated with OIRD.

Conclusions

Postoperative oliceridine use in patients with advanced age and/or increased BMI was not associated with increased risk of OIRD.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40122-020-00232-x.

Related collections

Most cited references 47

Record: found
Abstract: found
Article: not found

Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council.

Roger Chou, Debra B Gordon, Oscar A de Leon-Casasola … (2016)

Most patients who undergo surgical procedures experience acute postoperative pain, but evidence suggests that less than half report adequate postoperative pain relief. Many preoperative, intraoperative, and postoperative interventions and management strategies are available for reducing and managing postoperative pain. The American Pain Society, with input from the American Society of Anesthesiologists, commissioned an interdisciplinary expert panel to develop a clinical practice guideline to promote evidence-based, effective, and safer postoperative pain management in children and adults. The guideline was subsequently approved by the American Society for Regional Anesthesia. As part of the guideline development process, a systematic review was commissioned on various aspects related to various interventions and management strategies for postoperative pain. After a review of the evidence, the expert panel formulated recommendations that addressed various aspects of postoperative pain management, including preoperative education, perioperative pain management planning, use of different pharmacological and nonpharmacological modalities, organizational policies, and transition to outpatient care. The recommendations are based on the underlying premise that optimal management begins in the preoperative period with an assessment of the patient and development of a plan of care tailored to the individual and the surgical procedure involved. The panel found that evidence supports the use of multimodal regimens in many situations, although the exact components of effective multimodal care will vary depending on the patient, setting, and surgical procedure. Although these guidelines are based on a systematic review of the evidence on management of postoperative pain, the panel identified numerous research gaps. Of 32 recommendations, 4 were assessed as being supported by high-quality evidence, and 11 (in the areas of patient education and perioperative planning, patient assessment, organizational structures and policies, and transitioning to outpatient care) were made on the basis of low-quality evidence.

0 comments Cited 411 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Poorly controlled postoperative pain: prevalence, consequences, and prevention

Tong Gan (2017)

This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs. In addition, the presence and intensity of acute pain during or after surgery is predictive of the development of chronic pain. More effective analgesic/anesthetic measures in the perioperative period are needed to prevent the progression to persistent pain. Although clinical findings are inconsistent, some studies of local anesthetics and nonopioid analgesics have suggested potential benefits as preventive interventions. Conventional opioids remain the standard of care for the management of acute postoperative pain; however, the risk of opioid-related adverse events can limit optimal dosing for analgesia, leading to poorly controlled acute postoperative pain. Several new opioids have been developed that modulate μ-receptor activity by selectively engaging intracellular pathways associated with analgesia and not those associated with adverse events, creating a wider therapeutic window than unselective conventional opioids. In clinical studies, oliceridine (TRV130), a novel μ-receptor G-protein pathway-selective modulator, produced rapid postoperative analgesia with reduced prevalence of adverse events versus morphine.

0 comments Cited 254 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Benzodiazepine pharmacology and central nervous system-mediated effects.

Charles Griffin, Adam Kaye, Franklin Rivera Bueno … (2013)

Owing to the low therapeutic index of barbiturates, benzodiazepines (BZDs) became popular in this country and worldwide many decades ago for a wide range of conditions. Because of an increased understanding of pharmacology and physiology, the mechanisms of action of many BZDs are now largely understood, and BZDs of varying potency and duration of action have been developed and marketed. Although BZDs have many therapeutic roles and BZD-mediated effects are typically well tolerated in the general population, side effects and toxicity can result in morbidity and mortality for some patients. The elderly; certain subpopulations of patients with lung, liver, or kidney dysfunction; and patients on other classes of medication are especially prone to toxicity.

0 comments Cited 174 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Marek Brzezinski: marek.brzezinski@ucsf.edu

Journal

Journal ID (nlm-ta): Pain Ther

Journal ID (iso-abbrev): Pain Ther

Title: Pain and Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 2193-8237

ISSN (Electronic): 2193-651X

Publication date (Electronic): 21 January 2021

Publication date PMC-release: 21 January 2021

Publication date (Print): June 2021

Volume: 10

Issue: 1

Pages: 457-473

Affiliations

[1 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, VA Medical Center, , University of California San Francisco, ; San Francisco, CA USA

[2 ]GRID grid.168010.e, ISNI 0000000419368956, Stanford University School of Medicine, ; Stanford, CA USA

[3 ]GRID grid.430197.8, ISNI 0000 0004 0598 6008, Department of Anesthesiology, , University of Miami/Jackson Health System, ; Miami, FL USA

[4 ]GRID grid.36425.36, ISNI 0000 0001 2216 9681, School of Medicine, , Stony Brook University, ; Stony Brook, NY USA

[5 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Wake Forest School of Medicine, ; Winston-Salem, NC USA

[6 ]GRID grid.416871.d, ISNI 0000 0004 0446 9287, Salt Lake Orthopaedic Clinic, , St. Marks Hospital, ; Utah, USA

[7 ]Trevena, Inc., Chesterbrook, PA USA

[8 ]GRID grid.189509.c, ISNI 0000000100241216, Duke University Medical Center, ; Durham, NC USA

Article

Publisher ID: 232

DOI: 10.1007/s40122-020-00232-x

PMC ID: 8119589

PubMed ID: 33502739

SO-VID: 5764334e-3685-4c70-abe5-bc78209252bc

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 4 November 2020

Date accepted : 22 December 2020

Custom metadata

Keywords: analgesia,biased opioid,oliceridine,postoperative pain,respiratory depression

Data availability:

Keywords: analgesia, biased opioid, oliceridine, postoperative pain, respiratory depression

Low Incidence of Opioid-Induced Respiratory Depression Observed with Oliceridine Regardless of Age or Body Mass Index: Exploratory Analysis from a Phase 3 Open-Label Trial in Postsurgical Pain

Read this article at

Abstract

Introduction

Methods

Results

Conclusions

Supplementary Information

Related collections

IODP Expedition 378: South Pacific Paleogene Climate

Most cited references 47

Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council.

Poorly controlled postoperative pain: prevalence, consequences, and prevention

Benzodiazepine pharmacology and central nervous system-mediated effects.

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 124

Cited by 8

Most referenced authors 405