Intraoperative PEEP Optimization: Effects on Postoperative Pulmonary Complications and Inflammatory Response

Intraoperative PEEP Optimization: Effects on Postoperative Pulmonary Complications and Inflammatory Response. A Double-center, Prospective, Randomized Controlled Trial

The purpose of this prospective randomized controlled trial is to determine the effects of intraoperative lung protective mechanical ventilation using an individual optimal PEEP value on postoperative pulmonary complications and inflammatory response. A total number of 40 patients undergoing open radical cystectomy and urinary diversion will be enrolled and randomized into two groups. Standard lung protective ventilation using a PEEP of 6 cmH2O will be performed in control group and an optimal PEEP value determined during a static pulmonary compliance (Cstat) directed PEEP titration procedure will be applyed in study group. Low tidal volumes (6mL/Kg IBW) and a fraction of inspired oxygen (FiO2) of 0.5 will be applyed in both groups. Procalcitonin kinetics will be monitored during and after surgery until the third postoperative day as well as postoperative pulmonary complications. Clinical condition and extrapulmonary complications will be evaluated by the Sequential Organ Failure Assessment (SOFA) Score and in-hospital stay, 28-days and in-hospital mortality will also be followed.

Study Overview

• Status: Completed
• Conditions: Inflammatory Response; Pulmonary Complications
• Intervention / Treatment: Procedure: Optimal PEEP; Procedure: Standard PEEP

Detailed Description

Patients undergoing general anesthesia and mechanical ventilation during major abdominal surgery commonly develop pulmonary atelectasis or even hyperdistension of the lungs can occur leading to adverse consequences either intraoperatively or postoperatively. Lung protective ventilation (LPV, PEEP = 6 cmH2O, TV = 6 mL/Kg IBW and regular recruitments) during the intraoperative period can reduce the risk of ventilator induced lung injury (VILI) and prevent the formation of pulmonary atelectasis.

In our investigator-initiated, double-center, single-blinded, prospective, randomized, controlled clinical trial a total number of 40 patients with bladder cancer undergoing open radical cystectomy and urinary diversion (ileal conduit or orthotopic bladder substitute) will be enrolled and randomized into two groups. Standard lung protective mechanical ventilation with the use of 6 cmH2O of PEEP and low tidal volumes (6mL/Kg IBW), a fraction of inspired oxygen (FiO2) of 0.5 and a respiratory rate to maintain an end tidal carbon dioxide (ETCO2) between 35-40 mmHg will be performed in control group, and a strategy of lung protective mechanical ventilation applying an optimal, individual PEEP determined by static pulmonary compliance (Cstat) directed PEEP titration procedure will be performed in study group.

During preoperative assessment, respiratory failure risk index (RFRI) will be recorded and informed consent will be obtained. Regarding to the protocol, a central vein catheter will be placed on the day before surgery, serum procalcitonin (PCT) level will be measured and a chest X-ray examination will be performed.

Before induction of anesthesia, an epidural catheter and an arterial canula for invasive blood pressure monitoring will be inserted. Immediately after induction of anesthesia and orotracheal intubation, all patients will be submitted to an alveolar recruitment maneuver (ARM) using the sustained airway pressure by the CPAP method, applying 30 cmH2O PEEP for 30 seconds. After ARM PEEP will be set to 6 cmH2O in the control group ("standard PEEP") and LPV will be performed. In the study group ("optimal PEEP") PEEP will be set to 14 cmH2O and a Cstat directed decremental PEEP titration procedure will be performed (every 4 minutes PEEP will be decreased by 2 cmH2O, until a final PEEP of 6 cmH2O) to determine the best individual PEEP. During surgery ARM will be repeated and arterial and central vein blood gas samples (ABGs, CVBGs) will be evaluated every 60 minutes. PCT levels will be measured 2, 6, 12, 24, 48 and 72 hours after surgical incision.

After extubation, patients will be addmitted to the Department of Anesthesiology and Intensive Care. ABGs and CVBGs will be collected and evaluated, PaO2/FiO2 and dCO2 will be calculated every 6 hours until 72 hours after surgery. On the first postoperative day chest X-ray will be performed and repeated on the following days if developing of pulmonary complications were suspected. Continuous epidural analgesia will be introduced, and evaluated effective if numeric pain rating scale point would be lower than 3 points.

During postoperative care continuous intraabdominal pressure (IAP) monitoring via a direct intraperitoneal catheter placed before closure of the abdominal wall will be performed to eliminate bias caused by the elevation of intraabdominal pressure.

Patients' clinical progress and secondary endpoints will be monitored by daily SOFA Scores, laboratory and physical examinations.

During follow-up period in-hospital stay, 28-days and in-hospital mortality will also be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hungary
  • Csongrád
    • Szeged, Csongrád, Hungary, 6722
      • University of Szeged, Faculty of Medicine, Department of Anaesthesiology and Intensive Therapy
  • Pest
    • Budapest, Pest, Hungary, 1076
      • Péterfy Sándor Hospital

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 with bladder cancer undergoing radical cystectomy and urinary diversion (ileal conduit or orthotopic bladder substitute)

Exclusion Criteria:

• Age < 18 years
• ASA grade IV
• History of severe chronic obstructive pulmonary disease (COPD, GOLD grade III or IV)
• History of severe or uncontrolled bronchial asthma
• History of severe restrictive pulmonary disease
• Pulmonary metastases
• History of any thoracic surgery
• Need for thoracic drainage before surgery
• Renal replacement therapy prior to surgery
• Congestive heart failure (NYHA grade III or IV)
• Extreme obesity (BMI > 35 Kg/m2)
• Lack of patient's consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Optimal PEEP; Patients submitted to general anesthesia and open radical cystectomy and urinary diversion (20 subjects) will be submitted an alveolar recruitment maneuver using the sustained airway pressure by the CPAP method, applying 30 cmH2O PEEP for 30 seconds followed by a decremental PEEP titration procedure directed by static pulmonary compliance (Cstat). During PEEP titration procedure PEEP will be decreased from 14 cmH2O by 2 cmH2O every 4 minutes, until a final PEEP of 6 cmH2O. Optimal PEEP is considered as a PEEP value resulting the highest possible Cstat measured by ventilator. After PEEP titration procedure a lung protective mechanical ventilation will be performed using optimal PEEP and low tidal volumes (6 mL/Kg IBW).	Procedure: Optimal PEEP; Optimal PEEP determined by Cstat during PEEP titration procedure.
Active Comparator: Standard PEEP; Patients submitted to general anesthesia and open radical cystectomy and urinary diversion (20 subjects) will be submitted an alveolar recruitment maneuver using the sustained airway pressure by the CPAP method, applying 30 cmH2O PEEP for 30 seconds followed by a standard lung protective mechanical ventilation using a PEEP value of 6 cmH2O and low tidal volumes (6 mL/Kg).	Procedure: Standard PEEP; Lung protective mechanical ventilation applying a PEEP value of 6 cmH2O

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pulmonary Complications	New infiltrates or atelectasis on chest X-ray, abnormal breathing sounds on auscultation, excessive bronchial secretions, unexplained fever, respiratory failure defined as PaO2/FiO2 < 300 or need for non-invasive or invasive ventilatory support.	72 hours
Procalcitonin Kinetics	Serum procalcitonin levels during and after surgery.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Circulatory Failure	Severe hypotension, arrhytmias, decreased cardiac output, severe metabolic acidosis, congestive heart failure, acute coronary syndrome, pulmonary embolism and cardiac arrest.	28 days
Incidence of Gastrointestinal Dysfunctions	Constipation or ileus, anastomotic leakage and need for urgent reoperation, disorders of liver function.	28 days
Incidence of Renal Dysfunction	RIFLE Criteria	28 days
Incidence of Hematologic and Coagulation Disorders	Severe bleeding and/or coagulopathy	72 hours
Infection	Any infections except from pneumonia.	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU days	Defined as a period from the first postoperative day until emission from the ICU.	28 days
In-hospital Stay	From the day of surgery until emission from hospital.	28 days
Mortality	In-hospital and 28 days mortality.	28 days

Collaborators and Investigators

• Sponsor: Péterfy Sándor Hospital
• Collaborators: Szeged University
• Investigators: Study Director: Zsolt Molnár, Prof, MD, PhD, DEAA, University of Szeged, Faculty of Medicine, Department of Anaesthesiology and Intensive Therapy; Principal Investigator: Zoltán Ruszkai, MD, Péterfy Sándor Hospital, Department of Anaesthesiology and Intensive Care

Publications and helpful links

General Publications

• Ruszkai Z, Kiss E, Laszlo I, Bokretas GP, Vizseralek D, Vamossy I, Surany E, Buzogany I, Bajory Z, Molnar Z. Effects of intraoperative positive end-expiratory pressure optimization on respiratory mechanics and the inflammatory response: a randomized controlled trial. J Clin Monit Comput. 2021 May;35(3):469-482. doi: 10.1007/s10877-020-00519-6. Epub 2020 May 9.
• Ruszkai Z, Kiss E, Laszlo I, Gyura F, Surany E, Bartha PT, Bokretas GP, Racz E, Buzogany I, Bajory Z, Hajdu E, Molnar Z. Effects of intraoperative PEEP optimization on postoperative pulmonary complications and the inflammatory response: study protocol for a randomized controlled trial. Trials. 2017 Aug 11;18(1):375. doi: 10.1186/s13063-017-2116-z.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: October 5, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimate): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): April 2, 2019
• Last Update Submitted That Met QC Criteria: April 1, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Postoperative pulmonary complications; Procalcitonin; Positive end-expiratory pressure; Static pulmonary compliance; Lung Protective Ventilation; Radical cystectomy and urinary diversion
• Other Study ID Numbers: 21586-4/2016/EKU; CO-338-045 (Péterfy Sándor Hospital Scientific Research Ethics Committe); 149/2016-SZTE (Other Identifier: University of Szeged Human Investigation Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD are not relevant in terms of results.