Intravenous Oliceridine and Opioid-related Complications

Study Overview
=================
Brief Summary
-----------------
The investigator will evaluate the side effects of oliceridine.

Detailed Description
-----------------
The investigator will evaluate the side effects of oliceridine. Limited information suggests that oliceridine may cause fewer side effects than the standard opioids given post surgery. Oliceridine is effective for treating acute pain, and is approved by the FDA. Patients will wear a device that continuously monitors breathing. Data from this monitor will be blinded to the clinical staff. Primary Aims include: The investigators will evaluate the proportion of patients having an adjudicated meaningful respiratory compromise with a specified precision of 0.15 using a 95% confidence interval at 24 hours post first study dose.

Official Title
-----------------
Intravenous Oliceridine and Opioid-related Complications: VOLITION: A Multicenter Pilot Cohort Study

Conditions
-----------------
Major Surgery

Intervention / Treatment
-----------------
* Drug: Oliceridine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years old American Society of Anesthesiologists physical status 1-4 Scheduled for major noncardiac surgery expected to last at least 2 hours Expected to remain hospitalized at least two postoperative nights Scheduled for general endotracheal, spinal anesthesia, or the combination Expected to require substantial opioid analgesia, defined as ≥20 mg morphine equivalents Expected to have patient-controlled intravenous analgesia. Exclusion Criteria: Are demented or otherwise cannot provide valid consent Have contraindications to oliceridine Used legal or illegal opioids chronically, defined as >15 mg morphine equivalents for >15 days during the month before consenting by history Have language, vision, or hearing impairments that may compromise continuous ventilation monitoring Have planned epidural anesthesia/analgesia Planned spinal morphine administration Are designated Do Not Resuscitate, hospice, or receiving end of life therapy Are expected to require postoperative mechanical ventilation or ICU admission Are expected to receive intrathecal opioids Are expected to receive gabapentin, pregabalin or other analgesic adjuvants Use oxygen at home Are unwilling or unable to comply fully with study procedures (including not tolerating the capnography cannula) Are known to be pregnant or breastfeeding Use CPAP at home Have previously participated in the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oliceridine<br>Patients receive Oliceridine for pain control. | Drug: Oliceridine<br>* Near the end of surgery, patients will be given ≤1.5 mg of oliceridine as a bolus. Postoperatively, patient-controlled analgesia (PCA) will be started with no background infusion, demand doses of 0.35 mg, with a 6 minute lock-out. Additional boluses (≤1 mg) of oliceridine will be given as deemed necessary (based on NRS score and clinical assessment of the patient) as soon as 15 minutes after the initial 1.5 mg loading dose. In addition to supplemental 1 mg bolus doses, the PCA demand dose can be increased to a maximum of 0.5 mg oliceridine.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who have respiratory compromise. | Respiratory compromise will be defined by a collapsed (one or more) composite of 1) end-tidal carbon dioxide <15mmHg for ≥3 minutes; 2) respiratory rate ≤5 breaths/minute for ≥3 minutes; 3) SpO2 ≤ 85% for ≥3 minutes; 4) Apnea episode lasting >30 seconds; 5)any serious respiratory event. | 24 hours post first study dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative duration of oxygen saturation < 90% | The sum of minutes with SpO2<90% from monitoring data | 48 hours post first study dose. | 
| Cumulative duration of respiratory rate < 8 breaths/ minute | The sum of minutes with respiratory rate < 8 from monitoring data | 48 hours post first study dose. |