Mechanical Ventilation-induced Acute Kidney Injury [AKI]

Summary

Positive end-expiratory pressure (PEEP) is a fundamental tool in the management of patients with acute respiratory distress syndrome (ARDS). However, there is currently no common criterion for deciding which level of PEEP to use. In simple terms, there are two primary strategies for setting PEEP: low PEEP and high PEEP scales. Several clinical protocols have compared them, yet no significant differences in relevant clinical outcomes have been observed. The utilization of high levels of PEEP can provide multiple benefits to the respiratory system, such as improved compliance, reduced alveolar collapse, homogenization of lung parenchyma, and notably enhanced oxygenation. Preclinical studies have shown substantial reduction in ventilator-induced lung injury when high PEEP levels were compared to low PEEP levels. Given all these relevant physiological advantages of high PEEP, the question arises: why haven´t they translated into a survival benefit in randomized controlled trials? The most rational explanation is that high PEEP simultaneously induces significant adverse effects which may counteract the potential benefits.

Some adverse effects are well known, such as the risk of overdistension and hemodynamic impairment; however, these effects are easily detected at the bedside. Negative randomized trials comparing high and low PEEP have shown no evidence of a relevant role in outcomes. In this study, abdominal venous congestion will be explored as a new potential adverse effect of high PEEP, which has not yet been studied and may play a role in counteracting the benefits of high PEEP strategies. To address this question, a randomized crossover clinical study is proposed in patients with ARDS, utilizing two previously validated and globally accepted scales of PEEP. In the following sections, the concept of ventilator-induced lung injury (VILI) will first be introduced, followed by a discussion on the beneficial effects of high PEEP on lung function and VILI prevention, in contrast to the risks of overdistension and worsening of VILI. Second, the hemodynamic effects of higher PEEP levels will be analyzed. Third, the available evidence regarding the effects of PEEP on intra-abdominal blood flow will be reviewed, and its potential relationship with the concept of abdominal venous congestion, which is well-studied in chronic heart failure, will be discussed. Finally, the role of Doppler ultrasound and elastography in studying bedside abdominal venous congestion will be addressed.

Conditions

• ARDS
• Acute Kidney Injury

Interventions

OTHER

Sequence A involves administering Low PEEP for 12 hours, followed by High PEEP for 12 hours.

Patients will first receive the Low PEEP protocol for 12 hours, followed by the High PEEP protocol for 12 hours. This sequence is randomized and part of a crossover trial design to assess the effects of both PEEP strategies. Description: Patients will first receive the High or LOW PEEP protocol for 12 hours, followed by the Low or HIGH PEEP protocol for 12 hours. This sequence is randomized and part of a crossover trial design to assess the effects of both PEEP strategies.

OTHER

Sequence B involves setting High PEEP for 12 hours, followed by Low PEEP for 12 hours.

Sequence B involves setting High PEEP for 12 hours, followed by Low PEEP for 12 hours.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-11-01

Primary Completion

2026-06-01

Completion

2026-06-01

Countries

• Chile

Study Locations