The Impact of Higher Positive End Expiratory Pressure on Patient-Ventilator Asynchrony

The Impact of Higher Positive End Expiratory Pressure on Patient-Ventilator Asynchrony in Patients With Acute Respiratory Distress Syndrome: a Cross-Over Randomized Trial

Patient-ventilator asynchrony is known to frequently occur during lung protective ventilation in patients with ARDS. Previous clinical studies showed that patient-ventilator asynchrony was associated with worse outcome in ICU. Therefore, strategies to reduce patient-ventilator asynchrony need to be established promptly. Several asynchronies, e.g., breath stacking are caused by vigorous spontaneous breathing effort. Recently, the investigators' group found that higher positive end expiratory pressure (PEEP) reduced the intensity of spontaneous breathing effort of in severe ARDS model (rabbits, pigs) and patients with ARDS. Thus, the investigators conjectured that higher PEEP may reduce the intensity of spontaneous breathing effort and thereby reduce patient-ventilator asynchrony during protective ventilation strategy, compared with lower PEEP in patients with ARDS.

Study Overview

• Status: Unknown
• Conditions: Critical Illness
• Intervention / Treatment: Other: Higher PEEP setting; Other: Lower PEEP setting

Detailed Description

The cross-over study will enroll 10 participants fulfilled with the criteria of Berlin definition of moderate-to-severe ARDS and under mechanical ventilation in intensive care unit (ICU) at Osaka University Hospital. Informed consent will be obtained by legal representatives. After obtaining informed consent, participants will be randomly assigned to one of two groups: "higher PEEP - lower PEEP" or "lower PEEP - higher PEEP". PEEP, either higher or lower, will be set according to higher or lower PEEP/FIO2 table. The depth of sedation will be monitored quantitively and maintained to be the same throughout the protocol. The intensity of spontaneous breathing activity will be assessed with esophageal balloon manometry and electrical activity of diaphragm. At each PEEP setting, asynchrony index will be calculated.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Suita, Osaka, Japan
      • Recruiting
      • Osaka University Hospital
      • Contact: Takeshi Yoshida, M.D., Ph.D.; Phone Number: +81668795820; Email: takeshiyoshida@hp-icu.med.osaka-u.ac.jp

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:

1. Patients ≧ 18 years old
2. Patients with moderate to severe ARDS under mechanical ventilation＊ ＊ Definition of moderate to severe ARDS is as per the Berlin definition (PaO2/FiO2 ≦ 200 mmHg with PEEP ≧ 5 cmH2O)

Exclusion Criteria:

1. Lack of informed consent
2. Continuous neuromuscular blockade at enrollment
3. DNR (do-not-resuscitate)
4. Moribund patient not expected to survive 24 hours
5. Massive hemoptysis
6. Increased intracranial pressure (> 18 mmHg)
7. Existence or high risk of pneumothorax
8. Known pregnancy
9. Actual body weight exceeding 1 kg/cm
10. Patient judged to be inappropriate for the trial by intensivist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: A group from higher PEEP to lower PEEP; Patient allocated for this arm are received from higher to lower PEEP setting.	Other: Higher PEEP setting; PEEP levels are determined according to the higher PEEP-FiO2 tables set plateau pressure less than 30 cmH2O. The duration of measurement at each PEEP levels is 1 hour.; Other: Lower PEEP setting; PEEP levels are determined according to the lower PEEP-FiO2 tables set plateau pressure less than 30 cmH2O. The duration of measurement at each PEEP levels is 1 hour.
Other: A group from lower PEEP to higher PEEP; Patient allocated for this arm are received from lower to higher PEEP setting.	Other: Higher PEEP setting; PEEP levels are determined according to the higher PEEP-FiO2 tables set plateau pressure less than 30 cmH2O. The duration of measurement at each PEEP levels is 1 hour.; Other: Lower PEEP setting; PEEP levels are determined according to the lower PEEP-FiO2 tables set plateau pressure less than 30 cmH2O. The duration of measurement at each PEEP levels is 1 hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Asynchrony index of all types of patient ventilator asynchrony at higher and lower PEEP.	Through study completion (up to 24 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
Asynchrony index of each types of patient ventilator asynchrony at higher and lower PEEP.	Through study completion (up to 24 hours)
The intensity of spontaneous breathing effort measured by esophageal manometry at higher and lower PEEP	Through study completion (up to 24 hours)
Minute volume at higher and lower PEEP	Through study completion (up to 24 hours)
The efficiency of diaphragmatic contraction measured by electrical activity of diaphragm at higher and lower PEEP.	Through study completion (up to 24 hours)

Collaborators and Investigators

• Sponsor: Osaka University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: November 1, 2020
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 11, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: positive end expiratory pressure; patient ventilator asynchrony
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: PEEPPVA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No