Hyperoxia on Ventilation During Recovery From General Anesthesia

The Effect of Hyperoxia on Ventilation During Recovery From General Anesthesia: A Crossover Preliminary Investigation

In this preliminary, crossover investigation the investigators will examine the effect of oxygen supplementation on the recovery of breathing in the immediate post-anesthesia period.

Study Overview

• Status: Completed
• Conditions: Ventilatory Depression; Postoperative Respiratory Failure
• Intervention / Treatment: Other: Oxygen gas

Detailed Description

In a pilot randomized-controlled trial (NCT04723433) the investigators found that, compared with standard O2 supplementation, hyperoxia enhanced ventilation, as estimated by the fraction of time at a transcutaneous PCO2 (TcPCO2) > 45 mmHg.

More specifically, patients treated with hyperoxia (O2 titrated to: SpO2 > 96%, N=10; Liberal O2) for 90 minutes post-anesthesia, spent 61.2% of the time at TcPCO2 > 45 mmHg, compared with 80.6% of the time in those receiving standard O2 supplementation (O2 titrated to: SpO2 between 90-94%, N=9; Conservative O2 - between-group difference of 19.4% (95% Confidence Intervals: -18.7% to 57.6%), ANCOVA adjusted P = 0.140]. Results were consistent across the 90-min monitoring period. With an observed effect size of 0.73, it was estimated that 30 participants per group are required, to demonstrate this difference with a power of 80% at a two-sided alpha of 5%.

In a follow-up RCT (IRB-63878, NCT05379673) in 18 patients the investigators found that over a 90-minute window, the average percentage of time spent at TcPCO2 > 45mmHg for patients in the Conservative O2 group (N=9) was 57.8% (52 ± 44 minutes), compared with a 45.6% (41 ± 46 minutes) for those in the Liberal O2 group (N=9), (P=0.6134; two-sided two sample t-test). In addition, during the same period, respiratory disturbance index (RDI; events per hour) was higher in the Conservative O2 [median (range): 23.9 (11.0-78.6)], compared with the Liberal O2 group [19.6 (2.8-40.4), Mann-Whitney test, P=0.1615].

Due to the high variability observed in the evaluated respiratory parameters (i.e., TcPCO2 and upper airway obstruction expressed by Respiratory Disturbance Index), the researchers believe that a crossover, rather than a randomized controlled trial, design would improve the power and efficiency of this investigation and also provide an opportunity to characterize better those patients who respond, and separate them from those who do not respond to hyperoxia treatment.

This preliminary investigation will assess how ventilation during recovery from general anesthesia is affected by conservative (Conservative O2: 90% ≤ SpO2 ≤ 94%), compared with liberal (Liberal O2: SpO2 > 96%) O2 supplementation. Using a crossover study design, the investigators aim to: a) assess the breathing pattern and estimate and compare the number of apnea/hypopnea episodes between the two interventions, and b) estimate and compare the cumulative segment of time during which the transcutaneous partial pressure of carbon dioxide (TcPCO2) will exceed 45 mmHg, between the two interventions.

Hypothesis: Conservative O2 will be associated with more unstable and obstructed breathing and less time spent with TcPCO2 > 45 mmHg, compared with Liberal O2 supplementation, during recovery from anesthesia.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physical status I-III
• Body mass index (BMI) less than 35 kg/m2
• Scheduled to undergo robotic-assisted radical laparoscopic nephrectomy.

Exclusion Criteria:

• Patients with a diagnosis of chronic obstructive pulmonary disorder (COPD), severe neurological, cardiopulmonary, psychiatric, or untreated thyroid disorder
• Chronic pain condition that is being treated with opioids
• Patients with a hematocrit lower than 30% at the end of surgery, or those with an excessive blood loss, requiring transfusion of blood products during surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: "Conservative O2"; During the first treatment session, which will last for 40 minutes, O2 supplementation will be titrated to an SpO2 between 90% and 94%.	Other: Oxygen gas; Administration of Oxygen by inhalation
Experimental: "Liberal O2"; During the second treatment session, which will last for 40 minutes, O2 supplementation will be titrated to an SpO2 > 96%.	Other: Oxygen gas; Administration of Oxygen by inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory disturbance index (RDI)	The number of apnea/hypopnea episodes detected using respiratory inductance plethysmography and nasal flow.	Forty minutes of monitoring for each treatment arm
Transcutaneous carbon dioxide pressure (TcPCO2)	The cumulative segment of time during which the transcutaneous partial pressure of carbon dioxide will exceed an upper limit of 45 mmHg (i.e., TcPCO2 > 45 mmHg)	Forty minutes of monitoring for each treatment arm

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Anthony Doufas, MD, PhD, Professor, Department of Anesthesiology, Stanford University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Actual): December 12, 2023
• Study Completion (Actual): December 12, 2023

Study Registration Dates

• First Submitted: June 18, 2023
• First Submitted That Met QC Criteria: June 18, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 9, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hyperoxia
• Other Study ID Numbers: IRB-70628

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No