Ventilation-induced acute kidney injury in acute respiratory failure: Do PEEP levels matter?

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a leading cause of morbidity and mortality among critically ill patients, and mechanical ventilation (MV) plays a critical role in its management. One of the key parameters of MV is the level of positive end-expiratory pressure (PEEP), which helps to maintain an adequate lung functional volume. However, the optimal level of PEEP remains controversial. The classical approach in clinical trials for identifying the optimal PEEP has been to compare "high" and "low" levels in a dichotomous manner. High PEEP can improve lung compliance and significantly enhance oxygenation but has been inconclusive in hard clinical outcomes such as mortality and duration of MV. This discrepancy could be related to the fact that inappropriately high or low PEEP levels may adversely affect other organs, such as the heart, brain, and kidneys, which could counteract its potential beneficial effects on the lung. Patients with ARDS often develop acute kidney injury, which is an independent marker of mortality. Three primary mechanisms have been proposed to explain lung-kidney crosstalk during MV: gas exchange abnormalities, such as hypoxemia and hypercapnia; remote biotrauma; and hemodynamic changes, including reduced venous return and cardiac output. As PEEP levels increase, lung volume expands to a variable extent depending on mechanical response. This dynamic underlies two potential mechanisms that could impair venous return, potentially leading to splanchnic and renal congestion. First, increasing PEEP may enhance lung aeration, particularly in highly recruitable lungs, where previously collapsed alveoli reopen, increasing lung volume and pleural pressure, leading to vena cava compression, which can contribute to systemic venous congestion and abdominal organ impairment function. Second, in lungs with low recruitability, PEEP elevation may induce minimal changes in lung volume while increasing airway pressure, resulting in alveolar overdistension, vascular compression, and increased pulmonary vascular resistance. Therefore, we propose that high PEEP settings can contribute to renal congestion, potentially impairing renal function. This review underscores the need for further rigorous research to validate these perspectives and explore strategies for optimizing PEEP settings while minimizing adverse renal effects.

Keywords: Acute kidney injury; Acute respiratory failure; Positive end-expiratory pressure; Venous congestion.

Fig. 1

Three mechanisms proposed to explain lung-kidney cross-talk during mechanical ventilation. Abnormalities in gas exchange disrupt renal blood flow. Mechanical ventilation (MV) induces inflammation and damages renal cells. Hemodynamic changes from MV impair venous return and cardiac output, worsening the tubular injury. PEEP-induced venous stasis compromise is linked to acute kidney injury (AKI)

Fig. 2

High PEEP levels exacerbate abdominal organ congestion. Proposed systemic effects generated by PEEP levels in patients with acute respiratory failure. Low PEEP levels do not contribute to abdominal venous stasis. High PEEP levels increase the lung volume and may induce extrathoracic venous congestion. Liver, gastrointestinal tract, and kidney congestion are depicted by the prominence of veins (blue color) under high PEEP conditions

Fig. 3

Proposal on how inadequately high PEEP levels affect renal perfusion, lead to venous congestion and impact renal function