Intraoperative Hypocapnia in PROVHILO and PROBESE

NCT05550181 | Completed

• 1 other identifier: AUMC
• Study Type: observational
• Target: 2,793
• Locations: 4 countries
• Sites: 4

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).

Conditions

Mechanical Ventilation Complication; Surgery; Pulmonary Complication; Intraoperative Complications; Postoperative Complications

Keywords

Postoperative Complications; Intraoperative Complications; Hypocapnia; Mechanical Ventilation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Incidence of intraoperative complications

  Intraoperatively

• Incidence of intensive care unit admission

  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

  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

Study Arms (2)

with hypocapnia

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)

without hypocapnia

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.

Interventions

intraoperative mechanical ventilation with hypocapnia (etCO2 < 35 mm Hg) BEHAVIORAL

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.

with hypocapnia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing mechanical ventilation for general anesthesia for surgery.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NMC Specialty Hospital: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Hospital Israelita Albert Einstein: collaborator
• University Hospital Carl Gustav Carus: collaborator
• Hospital Clínico Universitario de Valencia: collaborator

Study Sites (4)

Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

University Hospital Carl Gustav Carus, Technische Universität Dresden

Dresden, Germany

Location

IRCCS San Martino Policlinico Hospital

Genoa, Italy

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Related Publications (14)

• Deng QW, Tan WC, Zhao BC, Wen SH, Shen JT, Xu M. Intraoperative ventilation strategies to prevent postoperative pulmonary complications: a network meta-analysis of randomised controlled trials. Br J Anaesth. 2020 Mar;124(3):324-335. doi: 10.1016/j.bja.2019.10.024. Epub 2020 Jan 30.

  PMID: 32007240 BACKGROUND

• Serpa Neto A, Hemmes SN, Barbas CS, Beiderlinden M, Biehl M, Binnekade JM, Canet J, Fernandez-Bustamante A, Futier E, Gajic O, Hedenstierna G, Hollmann MW, Jaber S, Kozian A, Licker M, Lin WQ, Maslow AD, Memtsoudis SG, Reis Miranda D, Moine P, Ng T, Paparella D, Putensen C, Ranieri M, Scavonetto F, Schilling T, Schmid W, Selmo G, Severgnini P, Sprung J, Sundar S, Talmor D, Treschan T, Unzueta C, Weingarten TN, Wolthuis EK, Wrigge H, Gama de Abreu M, Pelosi P, Schultz MJ; PROVE Network Investigators. Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis. Anesthesiology. 2015 Jul;123(1):66-78. doi: 10.1097/ALN.0000000000000706.

  PMID: 25978326 BACKGROUND

• PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology; Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014 Aug 9;384(9942):495-503. doi: 10.1016/S0140-6736(14)60416-5. Epub 2014 Jun 2.

  PMID: 24894577 BACKGROUND

• Akkermans A, van Waes JAR, Thompson A, Shanks A, Peelen LM, Aziz MF, Biggs DA, Paganelli WC, Wanderer JP, Helsten DL, Kheterpal S, van Klei WA, Saager L. An observational study of end-tidal carbon dioxide trends in general anesthesia. Can J Anaesth. 2019 Feb;66(2):149-160. doi: 10.1007/s12630-018-1249-1. Epub 2018 Nov 14.

  PMID: 30430440 BACKGROUND

• Dony P, Dramaix M, Boogaerts JG. Hypocapnia measured by end-tidal carbon dioxide tension during anesthesia is associated with increased 30-day mortality rate. J Clin Anesth. 2017 Feb;36:123-126. doi: 10.1016/j.jclinane.2016.10.028. Epub 2016 Dec 2.

  PMID: 28183549 BACKGROUND

• Dong L, Takeda C, Yamazaki H, Kamitani T, Kimachi M, Hamada M, Fukuhara S, Mizota T, Yamamoto Y. Intraoperative end-tidal carbon dioxide and postoperative mortality in major abdominal surgery: a historical cohort study. Can J Anaesth. 2021 Nov;68(11):1601-1610. doi: 10.1007/s12630-021-02086-z. Epub 2021 Aug 6.

  PMID: 34357567 BACKGROUND

• Park JH, Lee HM, Kang CM, Kim KS, Jang CH, Hwang HK, Lee JR. Correlation of Intraoperative End-Tidal Carbon Dioxide Concentration on Postoperative Hospital Stay in Patients Undergoing Pylorus-Preserving Pancreaticoduodenectomy. World J Surg. 2021 Jun;45(6):1860-1867. doi: 10.1007/s00268-021-05984-x. Epub 2021 Feb 16.

  PMID: 33591427 BACKGROUND

• Wax DB, Lin HM, Hossain S, Porter SB. Intraoperative carbon dioxide management and outcomes. Eur J Anaesthesiol. 2010 Sep;27(9):819-23. doi: 10.1097/EJA.0b013e32833cca07.

  PMID: 20613537 BACKGROUND

• Writing Committee for the PROBESE Collaborative Group of the PROtective VEntilation Network (PROVEnet) for the Clinical Trial Network of the European Society of Anaesthesiology; Bluth T, Serpa Neto A, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE Collaborative Group; Bluth T, Bobek I, Canet JC, Cinnella G, de Baerdemaeker L, Gama de Abreu M, Gregoretti C, Hedenstierna G, Hemmes SNT, Hiesmayr M, Hollmann MW, Jaber S, Laffey J, Licker MJ, Markstaller K, Matot I, Mills GH, Mulier JP, Pelosi P, Putensen C, Rossaint R, Schmitt J, Schultz MJ, Senturk M, Serpa Neto A, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H. Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial. JAMA. 2019 Jun 18;321(23):2292-2305. doi: 10.1001/jama.2019.7505.

  PMID: 31157366 BACKGROUND

• Neto AS, Hemmes SN, Barbas CS, Beiderlinden M, Fernandez-Bustamante A, Futier E, Gajic O, El-Tahan MR, Ghamdi AA, Gunay E, Jaber S, Kokulu S, Kozian A, Licker M, Lin WQ, Maslow AD, Memtsoudis SG, Reis Miranda D, Moine P, Ng T, Paparella D, Ranieri VM, Scavonetto F, Schilling T, Selmo G, Severgnini P, Sprung J, Sundar S, Talmor D, Treschan T, Unzueta C, Weingarten TN, Wolthuis EK, Wrigge H, Amato MB, Costa EL, de Abreu MG, Pelosi P, Schultz MJ; PROVE Network Investigators. Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data. Lancet Respir Med. 2016 Apr;4(4):272-80. doi: 10.1016/S2213-2600(16)00057-6. Epub 2016 Mar 4.

  PMID: 26947624 BACKGROUND

• Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.

  PMID: 25693014 BACKGROUND

• Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.

  PMID: 27620287 BACKGROUND

• van Meenen DMP, Serpa Neto A, Paulus F, Merkies C, Schouten LR, Bos LD, Horn J, Juffermans NP, Cremer OL, van der Poll T, Schultz MJ; MARS Consortium. The predictive validity for mortality of the driving pressure and the mechanical power of ventilation. Intensive Care Med Exp. 2020 Dec 18;8(Suppl 1):60. doi: 10.1186/s40635-020-00346-8.

  PMID: 33336298 BACKGROUND

• Nasa P, van Meenen DMP, Paulus F, Ferrando C, Bluth T, Gama de Abreu M, Ball L, Bossers SM, Schober P, Schultz MJ, Serpa Neto A, Hemmes SNT; REPEAT; PROVHILO; PROBESE; investigators of the PROVE network; ESAIC CTN. Association of intraoperative end-tidal CO2 levels with postoperative outcomes: a patient-level analysis of two randomised clinical trials. Br J Anaesth. 2025 Dec;135(6):1761-1769. doi: 10.1016/j.bja.2025.07.076. Epub 2025 Sep 10.

  PMID: 40930872 DERIVED

MeSH Terms

Conditions

Intraoperative Complications; Postoperative Complications; Hypocapnia

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Officials

• Sabrine NT Hemmes, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY CHAIR

• David MP van Meenen, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• Frederique Paulus, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY CHAIR

• Marcus J Schultz, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Department, Critical Care Medicine

Study Record Dates

• First Submitted: September 17, 2022
• First Posted: September 22, 2022
• Study Start: November 29, 2022
• Primary Completion: January 10, 2023
• Study Completion: March 31, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: After the publication of the main results

Locations

DE (1); IT (1); BR (1); ES (1)