Intraoperative Hypocapnia in PROVHILO and PROBESE

Completed

• Conditions: Intraoperative Complications; Postoperative Complications; Mechanical Ventilation Complication; Pulmonary Complication; Surgery
• Interventions: Behavioral: intraoperative mechanical ventilation with hypocapnia (etCO2 < 35 mm Hg)

• Registration Number: NCT05550181
• Lead Sponsor: NMC Specialty Hospital

Brief Summary

To gain a better understanding of the epidemiology of intraoperative hypocapnia, in particular the associations of intraoperative hypocapnia with patient demographics, ventilator characteristics, and perioperative complications we will perform an individual patient-level meta-analysis of two recent randomized clinical trials of intraoperative ventilation, the 'PROtective Ventilation using High versus LOw PEEP trial' (PROVHILO), and the 'Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients trial' (PROBESE).

Detailed Description

Lung-protective intraoperative ventilation (LPV) has the potential to improve the outcome of surgery patients through a reduction in postoperative pulmonary complications. Use of intraoperative ventilation strategies that use a low tidal volume could result in intraoperative hypercapnia. However, hypocapnia remains surprisingly common during intraoperative ventilation, possibly meaning that anesthesiologists continue to use high, if not too high respiratory rates or tidal volumes.

Previous studies suggested associations between intraoperative derangement of end-tidal carbon dioxide (etCO2) and postoperative outcomes. Indeed, two studies in highly selected patient groups showed associations of intraoperative hypocapnia with prolonged length of hospital stay, in patients undergoing pancreaticoduodenectomy, and in patients undergoing hysterectomy.

To gain a better understanding of the epidemiology of intraoperative hypocapnia, in particular the associations of intraoperative hypocapnia with patient demographics, ventilator characteristics, and perioperative complications we will perform an individual patient-level meta-analysis of two recent randomized clinical trials of intraoperative ventilation; PROVHILO and PROBESE.

Study Timeline

• Study First Submitted: 2022-09-17
• Study First Submitted QC: 2022-09-21
• Study First Posted: 2022-09-22
• Study Start: 2022-11-29
• Primary Completion: 2023-01-10
• Study Completion: 2023-03-31
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-02
• Last Update Posted: 2023-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2793

Inclusion Criteria

• Planned for major (abdominal) surgery.
• At risk for postoperative pulmonary complications.

Exclusion Criteria

• Planned thoracic surgery or neurosurgery.
• Unscheduled surgery (i.e., urgent, or emergent surgeries) were excluded because these patients may have had metabolic abnormalities at the moment of surgery, i.e., metabolic acidosis, for which the anesthesiologist may have adjusted the intraoperative ventilator settings. This may have led to a 'compensatory' low etCO2.
• Patients with etCO2 recordings are missing from the study databases.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
with hypocapnia	intraoperative mechanical ventilation with hypocapnia (etCO2 < 35 mm Hg)	We will use the intraoperatively collected etCO2 levels to classify patients as either 'with hypocapnia' or 'without hypercapnia', using the cutoff of 35 mmHg. A patient is considered 'hypocapnic' if the etCO2 was \< 35 mm Hg at any point during surgery, from start of the study till end of the study

Primary Outcome Measures

Name	Time	Method
Incidence of postoperative pulmonary complications	Until day seven or hospital discharge, whichever comes first	Composite of predefined and collected postoperative pulmonary complications. Postoperative pulmonary complications included mild, moderate, and severe respiratory failure; acute respiratory distress syndrome; bronchospasm; new pulmonary infiltrate; pulmonary infection; aspiration pneumonitis; pleural effusions; atelectasis; cardiopulmonary edema; and pneumothorax.

Secondary Outcome Measures

Name	Time	Method
Incidence of intraoperative complications	Intraoperatively	Defined as intraoperative hypotension, arrhythmias; or need for rescue for desaturations; or need for vasoactive drugs.
Incidence of intensive care unit admission	Until hospital discharge, death or 100 days, whichever comes first	Incidence of intensive care unit admission during hospital stay
Incidence of extrapulmonary pulmonary complications	Until day seven or hospital discharge, whichever comes first
Incidence of 7-day mortality	Mortality during the first seven days of hospitalization	Until day seven or hospital discharge, whichever comes first
Incidence of in-hospital mortality	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 days
Incidence of major postoperative complications	Until day seven or hospital discharge, whichever comes first	Collapsed composite of complications developing within the first seven postoperative combining severe postoperative pulmonary complications, sepsis, septic shock and/or acute kidney injury

Trial Locations

Locations (4)

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, Brazil

University Hospital Carl Gustav Carus, Technische Universität Dresden; 🇩🇪 Dresden, Germany

IRCCS San Martino Policlinico Hospital; 🇮🇹 Genoa, Italy

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain