Mechanical Ventilation-induced Acute Kidney Injury [AKI]

NCT06638255 | Not Yet Recruiting DMC

• 1 other identifier: 230607001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

ARDS; Acute Kidney Injury; Mechanical ventilation; venous congestion

Outcome Measures

Primary Outcomes (1)

• Elevation of plasma and urinary biomarkers of acute kidney injury (NGAL - KIM-1)

  Elevation of plasma and urinary biomarkers of acute kidney injury associated with high PEEP strategy.

  12 hours

Study Arms (2)

Sequence A: First Low PEEP for 12 hours, then High PEEP for 12 hours

EXPERIMENTAL

Arm Information Experimental Arm Title: Sequential PEEP Protocol - Low and High PEEP Strategies Arm Description: Participants in this clinical trial will be randomized into one of two pre-specified sequences to receive both high and low PEEP ventilation strategies over two sequential 12-hour periods. Intervention for Arm 1: Participants will receive the Low PEEP protocol for the first 12-hour period, followed by the High PEEP protocol for the next 12-hour period. Intervention for Arm 2 (Sequence B): Patients will receive High PEEP for the first 12 hours, then Low PEEP for the next 12 hours.

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

Sequence B: First High PEEP for 12 hours, then low PEEP for 12 hours

EXPERIMENTAL

Sequence B: First High PEEP for 12 hours, then low PEEP for 12 hours

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

Interventions

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

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.

Also known as: Secuence A: Low PEEP vs High PEEP, Secuence B: High PEEP vs Low PEEP

Sequence A: First Low PEEP for 12 hours, then High PEEP for 12 hours

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

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

Also known as: Only PEEP setting

Sequence B: First High PEEP for 12 hours, then low PEEP for 12 hours

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Moderate and severe ARDS, as defined by the Berlin Definition
• Connection to mechanical ventilation for less than seven days

You may not qualify if:

• Acute respiratory failure due to exacerbation of chronic respiratory disease or cardiogenic pulmonary edema
• Acute or chronic hepatic failure
• Chronic renal failure
• Acute renal failure (KDIGO Stage 3)
• Patients with a decision not to resuscitate
• Critically ill patients who are unable to tolerate ventilatory changes
• Patients in the prone position

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 8330033, Chile

Location

Related Publications (6)

• Gattarello S, Lombardo F, Romitti F, D'Albo R, Velati M, Fratti I, Pozzi T, Nicolardi R, Fioccola A, Busana M, Collino F, Herrmann P, Camporota L, Quintel M, Moerer O, Saager L, Meissner K, Gattinoni L. Determinants of acute kidney injury during high-power mechanical ventilation: secondary analysis from experimental data. Intensive Care Med Exp. 2024 Mar 21;12(1):31. doi: 10.1186/s40635-024-00610-1.

  PMID: 38512544 BACKGROUND

• Beurton A, Haudebourg L, Simon-Tillaux N, Demoule A, Dres M. Limiting positive end-expiratory pressure to protect renal function in SARS-CoV-2 critically ill patients. J Crit Care. 2020 Oct;59:191-193. doi: 10.1016/j.jcrc.2020.07.008. Epub 2020 Jul 10. No abstract available.

  PMID: 32683213 BACKGROUND

• Fogagnolo A, Grasso S, Dres M, Gesualdo L, Murgolo F, Morelli E, Ottaviani I, Marangoni E, Volta CA, Spadaro S. Focus on renal blood flow in mechanically ventilated patients with SARS-CoV-2: a prospective pilot study. J Clin Monit Comput. 2022 Feb;36(1):161-167. doi: 10.1007/s10877-020-00633-5. Epub 2021 Jan 1.

  PMID: 33385260 BACKGROUND

• Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.

  PMID: 15269312 BACKGROUND

• Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):637-45. doi: 10.1001/jama.299.6.637.

  PMID: 18270352 BACKGROUND

• Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

  PMID: 10793162 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury; Hyperemia

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Jaime Retamal A Jaime A Retamal, PhD in Medical Science

CONTACT

+56942611087; jaimeretamal@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Invsetigator

Model Details: To test the hypothesis, a crossover clinical-experimental protocol has been designed. Clinical and physiological data will be collected from patients with ARDS undergoing protective mechanical ventilation. Patients will be randomly allocated to two clinical protocols validated for setting PEEP levels: ARDSNet (low PEEP) and LOV (high PEEP), each for a duration of 12 hours. Clinical and physiological data, advanced ultrasound assessments, organ dysfunction markers, and a complete respiratory and hemodynamic assessment will be collected. Both PEEP strategies (Low vs High PEEP) will be applied to each patient included in the study. The PEEP setting will be selected through a computerized randomization system at the beginning of the study.

Study Record Dates

• First Submitted: October 9, 2024
• First Posted: October 15, 2024
• Study Start: November 1, 2024
• Primary Completion: June 1, 2026
• Study Completion: June 1, 2026
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

CL (1)