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Open Access 01-12-2022 | Acute Respiratory Distress-Syndrome | Study protocol

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

Authors: Domenico Luca Grieco, Salvatore Maurizio Maggiore, Giacomo Bellani, Savino Spadaro, Elena Spinelli, Tommaso Tonetti, Luca S. Menga, Marco Pozzi, Denise Battaglini, Rosa Di Mussi, Andrea Bruni, Andrea De Gaetano, Carmine Giovanni Iovino, Matteo Brioni, Francesco Mojoli, Giuseppe Foti, Carlo Aberto Volta, Paolo Pelosi, Paolo Navalesi, Salvatore Grasso, V. Marco Ranieri, Massimo Antonelli, the IPERPEEP study group

Published in: Trials | Issue 1/2022

Abstract

Background

In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients’ individual response is warranted.

End-expiratory lung volume (EELV) assessment by nitrogen washin-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient’s individual recruitability.

We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).

Methods

IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO₂/FiO₂ ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH₂O.

To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH₂O for 30 min (EXPRESS PEEP).

Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH₂O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28–30 cmH₂O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized.

The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.

Discussion

The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.

Trial registration

ClinicalTrials.govNCT04012073. Registered 9 July 2019.

Available only for authorised users

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Title: Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial
Authors: Domenico Luca Grieco
Salvatore Maurizio Maggiore
Giacomo Bellani
Savino Spadaro
Elena Spinelli
Tommaso Tonetti
Luca S. Menga
Marco Pozzi
Denise Battaglini
Rosa Di Mussi
Andrea Bruni
Andrea De Gaetano
Carmine Giovanni Iovino
Matteo Brioni
Francesco Mojoli
Giuseppe Foti
Carlo Aberto Volta
Paolo Pelosi
Paolo Navalesi
Salvatore Grasso
V. Marco Ranieri
Massimo Antonelli
the IPERPEEP study group
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Acute Respiratory Distress-Syndrome
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-021-05993-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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