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Background

Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the µ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions.

Methods

Adult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures.

Results

A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients.

Conclusion

Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied.

Clinicaltrialsgov identifier

NCT02656875.

The number of children and adolescents seen in emergency departments (EDs) and primary care settings for mental health problems has skyrocketed in recent years, with up to 23% of patients in both settings having diagnosable mental health conditions. 1 -4 Even when a mental health problem is not the focus of an ED or primary care visit, mental health conditions, both known and occult, may challenge the treating clinician and complicate the patient's care.4 Although the American Academy of Pediatrics (AAP) has published a policy statement on mental health competencies and a Mental Health Toolkit for pediatric primary care providers, no such guidelines or resources exist for clinicians who care for pediatric mental health emergencies. 5, 6 Many ED and primary care physicians report paucity of training and lack of confidence in caring for pediatric psychiatry patients. The 2 clinical reports support the 2006 joint policy statement of the AAP and the American College of Emergency Physicians on pediatric mental health emergencies, 7 with the goal of addressing the knowledge gaps in this area. Although written primarily from the perspective of ED clinicians, it is intended for all clinicians who care for children and adolescents with acute mental health and behavioral problems. They are organized around the common clinical challenges pediatric caregivers face, both when a child or adolescent presents with a psychiatric chief complaint or emergency (part I) and when a mental health condition may be an unclear or complicating factor in a non-mental health ED presentation (part II). Part I of the clinical reports includes discussions of Medical Clearance of Pediatric Psychiatric Patients, Suicide and Suicidal Ideation, Restraint of the Agitated Patient Including Verbal, Chemical, and Physical Restraint, and Coordination of Care With the Medical Home, and it can be accessed online at www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1570. This executive summary is an overview of part II of the clinical reports. Full text of the following topics can be accessed online at www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1573.

The number of children and adolescents seen in emergency departments (EDs) and primary care settings for mental health problems has skyrocketed in recent years, with up to 23% of patients in both settings having diagnosable mental health conditions. 1 -4 Even when a mental health problem is not the focus of an ED or primary care visit, mental health conditions, both known and occult, may challenge the treating clinician and complicate the patient's care.4 Although the American Academy of Pediatrics has published a policy statement on mental health competencies and a Mental Health Toolkit for pediatric primary care providers, no such guidelines or resources exist for clinicians who care for pediatric mental health emergencies. 5, 6 Many ED and primary care physicians report a paucity of training and lack of confidence in caring for pediatric psychiatry patients. The 2 clinical reports (www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1570 and www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1573) support the 2006 joint policy statement of the American Academy of Pediatrics and the American College of Emergency Physicians on pediatric mental health emergencies, 7 with the goal of addressing the knowledge gaps in this area. Although written primarily from the perspective of ED clinicians, they are intended for all clinicians who care for children and adolescents with acute mental health and behavioral problems. The clinical reports are organized around the common clinical challenges pediatric caregivers face, both when a child or adolescent presents with a psychiatric chief complaint or emergency (part I) and also when a mental health condition may be an unclear or complicating factor in a non-mental health clinical presentation (part II). Part II of the clinical reports (www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1573) includes discussions of somatic symptom and related disorders, adverse effects of psychiatric medications including neuroleptic malignant syndrome and serotonin syndrome, caring for children with special needs such as autism and developmental disorders, and mental health screening. This executive summary is an overview of part I of the clinical reports. The full text of the below topics can be accessed online at (www.pediatrics.org/cgi/doi/10.1542/peds. 2016-1570). Key considerations are shown in the following sections.