Very Low Tidal Volume vs Conventional Ventilatory Strategy for One-lung Ventilation in Thoracic Anesthesia

Multicenter Randomized Trial on Protective Ventilation Versus Conventional Ventilation During OLV in Patients Undergoing Thoracic Surgery

The purpose of this study is to determine if a protective ventilatory strategy during one-lung ventilation (OLV) based on low tidal volume, PEEP and alveolar recruitment maneuver can reduce Acute Respiratory Distress Syndrome (ARDS) and Postoperative pulmonary complications (PPCs) after major pulmonary resection.

Primary endpoint: Evaluation of postoperative ARDS incidence

Secondary endpoint: Evaluation od PPC incidence and postoperative outcomes (other complications, unplanned Intensive Care Admission, hospital and ICU length of stay, in-hospital mortality)

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Procedure: Protective one lung ventilation

Detailed Description

Pulmonary postoperative complications (PPCs) are the most frequent adverse events after thoracic surgery. Acute respiratory distress syndrome (ARDS) is the most severe among PPCs. Injurious mechanical ventilation is a recognized risk factor associated with ARDS and PPCs after major thoracic surgery.

International literature reports a wide use of tidal volume around 5-6 ml/kg predicted body weight (PBW) during one lung ventilation (OLV) but variable use of PEEP and alveolar recruitment maneuver (ARM).

The aim of this multicenter, randomized, single blind study is to determine if a protective ventilatory strategy during OLV based on low tidal volume, PEEP and alveolar recruitment maneuver compared to conventional strategy can reduce ARDS and PPCs after major pulmonary resection.

Primary outcome is the incidence of in-hospital ARDS.

Secondary outcomes are in-hospital incidence of postoperative pulmonary complications (PPCs), major cardiovascular events, unplanned Intensive Care Unit admission, in-hospital length of stay and mortality

RANDOMIZATION

Patients are randomly assigned to receive protective or conventional OLV according to a computer-generated randomization list (1:1 ratio) before anesthesia induction.

Patients are blinded to the treatment. Anesthesiologists and surgeons are unblinded to the treatment during the surgical procedure and the postoperative outcome assessment.

MEASUREMENTS

Intraoperative collection of ventilatory settings, airway pressures, arterial blood gases analysis at the following time points:

T1: two lung ventilation in supine position before placing the patient in lateral decubitus; T2: 30 minutes after OLV start; T3: 60 minutes after OLV start; T4: 20 minutes after lobectomy/pneumonectomy (during OLV); T5: 15 minutes after ARM in supine position and during two lung ventilation.

Postoperative data collection 1, 12, 24, 36, 48 hours after surgery and at discharge. Arterial blood gas analysis will be performed 1 hour after extubation and 24 and 72 hours after surgery (or in case of respiratory insufficiency).

• Study Type: Interventional
• Enrollment (Actual): 984
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy
    • Asst Papa Giovanni XXIII
  • Bologna, Italy
    • IRCCS Policlinico Sant'Orsola-Malpighi
  • Bolzano, Italy
    • Ospedale Centrale
  • Cagliari, Italy
    • Azienda Ospedaliera Brotzu - Ospedale Oncologico Businco
  • Genova, Italy
    • IRCCS Ospedale Policlinico San Martino
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale Tumori
  • Milan, Italy
    • Irccs Ospedale San Raffaele
  • Modena, Italy
    • Azienda Ospedaliera-Universitaria
  • Napoli, Italy
    • Istituto Nazionale Tumori Fondazione Pascale
  • Padova, Italy
    • Azienda Ospedaliero-Universitaria
  • Rionero In Vulture, Italy
    • IRCCS Centro Di Riferimento Oncologico Della Basilicata
  • Rome, Italy
    • Istituto Nazionale Tumori Regina Elena
  • Siena, Italy
    • Azienda Ospedaliera Universitaria Senese
  • Trieste, Italy
    • Ospedale di Cattinara
  • Udine, Italy, 33100
    • Department of Anesthesia and Intensive Care Unit
  • Varese, Italy
    • Ospedale di Circolo e Fondazione Macchi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥ 18 years
• ASA IV
• Elective thoracotomies or thoracoscopic major lung resection surgery (lobectomy, bilobectomy, pneumonectomy)

Exclusion Criteria:

• Emergency surgery
• Wedge resection or atypical resection
• Non-resective lung surgery requiring OLV
• Patients < 18 years
• BMI < 20 and BMI > 29
• Heart disease with ejection fraction <50% and/or severe valvulopathy
• Pulmonary hypertension
• Renal failure requiring dialytic treatment
• Drug addiction
• Mental retardation, depression and psychiatric disease
• Motor or sensory deficit
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protective; Two-lung ventilation (TLV): tidal volume = 8 mL / kg PBW, peak airway pressure ≤ 25 cm H2O, I: E = 1:2; after lung re-expansion to the closure of the chest will set a PEEP of 5 cmH2O OLV (OLV): 4 mL / kg PBW, peak airway pressure ≤ 35 cmH2O, respiratory rate <30, I:E = 1:2 / 1:3. During OLV in case of desaturation (before increasing the FiO2) and every 60 minutes alveolar recruitment maneuvers followed by the setting of PEEP to 5 cmH2O	Procedure: Protective one lung ventilation; Low tidal volume, PEEP and alveolar recruitment maneuver
No Intervention: Conventional; Two-lung ventilation (TLV): tidal volume = 8 mL / kg PBW, peak airway pressure ≤ 25 cmH2O; I: E = 1:2; after lung re-expansion to the closure of the chest PEEP set to 5 cmH2O OLV (OLV): 6 mL / kg PBW, peak airway pressure ≤ 35 cmH2O; I: E = 1:2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Respiratory Distress Syndrome (ARDS) incidence	incidence of ARDS (%)	Hospital stay (7 days average expected)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pulmonary complications (PPCs)	Incidence of PPCs (%)	Hospital stay (7 days average expected)
In-hospital mortality	To determine mortality (%)	Hospital stay (7 days average aspected)
Postoperative complications	To determine how many patients (%) would have any postoperative complications	Hospital stay (7 days average expected)
Unplanned Intensive Care Unit (ICU) admission	To determine how many patients would require an ICU admission (%)	Hospital stay (7 days average aspected)
Intensive Care Unit (ICU) Length of stay	Length of stay in ICU (days)	Hospital stay (7 days average aspected)
Length of hospital stay	Duration of hospital length of stay	Hospital stay (7 days average expected)

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera S. Maria della Misericordia
• Investigators: Principal Investigator: Giorgio Della Rocca, MD, Prof, Azienda Ospedaliero-Universitaria S. Maria della Misericordia - Udine. Italy

Publications and helpful links

General Publications

• Yang M, Ahn HJ, Kim K, Kim JA, Yi CA, Kim MJ, Kim HJ. Does a protective ventilation strategy reduce the risk of pulmonary complications after lung cancer surgery?: a randomized controlled trial. Chest. 2011 Mar;139(3):530-537. doi: 10.1378/chest.09-2293. Epub 2010 Sep 9.
• Licker M, Diaper J, Villiger Y, Spiliopoulos A, Licker V, Robert J, Tschopp JM. Impact of intraoperative lung-protective interventions in patients undergoing lung cancer surgery. Crit Care. 2009;13(2):R41. doi: 10.1186/cc7762. Epub 2009 Mar 24.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: December 30, 2011
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: ARDS; thoracic surgery; PEEP; One lung ventilation; lobectomy and pneumonectomy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: ALI01