Intraoperative Hypocapnia in PROVHILO and PROBESE

NCT ID: NCT05550181

Last Updated: 2023-05-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

2793 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-11-29

Study Completion Date

2023-03-31

Brief Summary

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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

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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.

Conditions

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Mechanical Ventilation Complication Surgery Pulmonary Complication Intraoperative Complications Postoperative Complications

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

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

Intervention Type 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.

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.

No interventions assigned to this group

Interventions

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

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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

OTHER

Sponsor Role collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role collaborator

University Hospital Carl Gustav Carus

OTHER

Sponsor Role collaborator

Hospital Clínico Universitario de Valencia

OTHER

Sponsor Role collaborator

NMC Specialty Hospital

OTHER

Sponsor Role lead

Responsible Party

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Prashant Nasa

Head of the Department, Critical Care Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sabrine NT Hemmes, PhD

Role: STUDY_CHAIR

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

David MP van Meenen, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Frederique Paulus, PhD

Role: STUDY_CHAIR

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

Marcus J Schultz, PhD

Role: STUDY_DIRECTOR

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

Locations

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Hospital Israelita Albert Einstein

São Paulo, , Brazil

Site Status

University Hospital Carl Gustav Carus, Technische Universität Dresden

Dresden, , Germany

Site Status

IRCCS San Martino Policlinico Hospital

Genoa, , Italy

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Countries

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Brazil Germany Italy Spain

References

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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.

Reference Type BACKGROUND
PMID: 32007240 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25978326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24894577 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30430440 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28183549 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34357567 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33591427 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20613537 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31157366 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26947624 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25693014 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27620287 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33336298 (View on PubMed)

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 Sep 9:S0007-0912(25)00529-X. doi: 10.1016/j.bja.2025.07.076. Online ahead of print.

Reference Type DERIVED
PMID: 40930872 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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AUMC

Identifier Type: -

Identifier Source: org_study_id

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