Intraoperative Hypocapnia in PROVHILO and PROBESE

Study Overview
=================
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.

Official Title
-----------------
Associations of Intraoperative Hypocapnia With Patient Demographics, Ventilation Characteristics and Outcomes--Statistical Analysis Plan for an Individual Patient Data Analysis of PROVHILO and PROBESE

Conditions
-----------------
Mechanical Ventilation Complication, Surgery, Pulmonary Complication, Intraoperative Complications, Postoperative Complications

Intervention / Treatment
-----------------
* Behavioral: intraoperative mechanical ventilation with hypocapnia (etCO2 < 35 mm Hg)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

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

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| with hypocapnia<br>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 | Behavioral: intraoperative mechanical ventilation with hypocapnia (etCO2 < 35 mm Hg)<br>* 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 and classified as 'without hypocapnia' otherwise. In case of a missing value immediately before extubation, we will use the values as reported in the last hour of surgery.<br>|
| without hypocapnia<br>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, and classified as 'without hypocapnia' otherwise. In case of a missing value immediately before extubation, we will use the values as reported in the last hour of surgery. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative pulmonary complications | 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. | Until day seven or hospital discharge, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of intraoperative complications | Defined as intraoperative hypotension, arrhythmias; or need for rescue for desaturations; or need for vasoactive drugs. | Intraoperatively | 
| Incidence of intensive care unit admission | Incidence of intensive care unit admission during hospital stay | Until hospital discharge, death or 100 days, whichever comes first | 
| Incidence of extrapulmonary pulmonary complications |  | Until day seven or hospital discharge, whichever comes first | 
| Incidence of 7-day mortality | Until day seven or hospital discharge, whichever comes first | Mortality during the first seven days of hospitalization | 
| 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 | Collapsed composite of complications developing within the first seven postoperative combining severe postoperative pulmonary complications, sepsis, septic shock and/or acute kidney injury | Until day seven or hospital discharge, whichever comes first | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Postoperative Complications, Intraoperative Complications, Hypocapnia, Mechanical Ventilation