Mechanical ventilation increases the risk of acute kidney injury (AKI) in critically ill patients, with studies indicating a three-fold higher risk compared to non-ventilated patients. The lung-kidney cross-talk during mechanical ventilation occurs through three primary mechanisms: (1) gas exchange abnormalities (hypoxaemia and hypercapnia) impair renal blood flow, (2) inflammatory mediators released from the lungs cause renal tubular damage, and (3) haemodynamic changes reduce venous return and cardiac output, leading to renal impairment.
Positive end-expiratory pressure (PEEP) is particularly linked to AKI due to its impact on venous congestion and renal blood flow reduction. Additional factors, including increased intrarenal pressure, hormonal dysregulation, and impaired renal oxygenation, further contribute to kidney dysfunction.
A new review explores the role of high PEEP in AKI development, the transfer of hydrostatic pressure from the lungs to the renal venous system, and potential future research directions.
PEEP is a key component of mechanical ventilation, particularly in acute respiratory distress syndrome (ARDS), where it prevents alveolar collapse and enhances oxygenation. By improving lung compliance and redistributing pulmonary oedema, PEEP supports respiratory function. However, improper adjustment can lead to alveolar overdistension, systemic inflammation, and haemodynamic alterations.
Finding the optimal PEEP level remains challenging. While high PEEP improves oxygenation, it does not consistently enhance survival or ventilator-free days. Its effects vary depending on lung recruitment potential, with high PEEP in non-recruitable lungs increasing mortality. PEEP influences systemic physiology by altering lung expansion, compressing the vena cava, and affecting pulmonary vascular resistance, potentially leading to venous congestion and right heart strain.
Overdistension from excessive PEEP can contribute to ventilator-induced lung injury (VILI) and systemic inflammation, impacting distant organs like the kidneys. Since renal function depends on cardiac output and vascular integrity, PEEP-induced haemodynamic changes may impair renal blood flow and contribute to AKI. Thus, individualised PEEP settings are essential to balance its benefits while minimising adverse effects.
PEEP significantly affects haemodynamics by influencing both venous return and cardiac output, ultimately impacting systemic oxygen transport. Increased intrathoracic pressure raises right atrial pressure, reducing the pressure gradient for venous return and compromising right ventricular preload, which can impair systemic organ perfusion. In lungs with low recruitability, excessive PEEP increases pulmonary vascular resistance, worsening right ventricular function and causing systemic venous congestion. In highly recruitable lungs, PEEP-induced lung expansion and diaphragm descent may compress the inferior vena cava, further restricting venous return.
Mechanical ventilation with PEEP can compromise both arterial and venous circulation in ARDS patients, leading to reduced renal perfusion pressure and impaired glomerular filtration rate. Fluid balance plays a critical role in these haemodynamic effects—hypovolaemia worsens PEEP-induced reductions in mean arterial pressure (MAP), cardiac output, and renal blood flow, while volume overload increases the risk of AKI by exacerbating congestion in abdominal organs.
These haemodynamic disturbances parallel the mechanisms of cardiorenal syndrome in heart failure, where venous congestion and fluid overload create a vicious cycle of decreased cardiac output, increased filling pressures, and worsening organ dysfunction. In severe cases, chronic congestion can lead to cirrhosis, terminal renal failure, and increased intestinal permeability, highlighting the need for careful fluid and PEEP management to protect renal and systemic function.
Recent studies have highlighted the harmful effects of high PEEP levels on renal function, firmly establishing a connection between increased PEEP and AKI. In preclinical studies using pigs under mechanical ventilation, higher PEEP levels were linked to increased AKI severity, elevated central venous pressure (CVP), and reduced mean perfusion pressure (MPP), contributing to fluid retention and organ edema. Specifically, higher PEEP levels (18 cmH₂O) were associated with increased renal oedema, as measured by the wet/dry ratio. However, the direct causality between PEEP and AKI could not be definitively established.
Clinical studies, including a meta-analysis of seven studies, found no significant correlation between high PEEP and AKI risk, though variations in study design and AKI measurement criteria limited the ability to draw clear conclusions. Despite these limitations, observational studies continue to support the theory that high airway pressure from increased PEEP contributes to venous congestion and kidney dysfunction. These findings underline the potential mechanisms by which high PEEP may induce AKI, primarily through venous congestion and reduced renal perfusion.
The kidneys have a lower oxygen demand compared to organs like the heart or brain, using about 7% of the body's total oxygen consumption (7-8 mL/min), primarily for filtration and reabsorption. Despite receiving a significant renal blood flow, oxygen extraction increases when blood flow decreases or metabolism rises. In cases of renal congestion, impaired blood flow increases the demand for oxygen due to 0edema and tissue damage, causing an oxygen supply-demand mismatch. The kidneys are particularly vulnerable to hypoxia during renal hypoperfusion, leading to cellular damage, reduced glomerular filtration rate, and potential ischaemic acute renal failure.
Understanding the physiological mechanisms behind how high PEEP levels in ARDS patients can lead to AKI is crucial for clinical practice. This underscores the need to consider the interconnectedness of organs and systems in critically ill patients. Future studies should tailor PEEP adjustments not only based on respiratory effects but also from a lung-heart-kidney perspective, recognizing the variability of ARDS in individual patients. A personalised approach is essential, with a focus on monitoring the splanchnic venous system during PEEP adjustments.
Inadequate PEEP settings in compliant lungs can lead to lung distension, contributing to renal congestion via vena cava compression. The retrograde pressure transmission from the right atrium to abdominal veins, along with impaired renal blood flow, may also play a role in AKI. These findings highlight the importance of further research to validate these mechanisms and develop strategies that optimise PEEP settings, balancing respiratory benefits while minimising negative renal effects.
Source: Critical Care
Image Credit: iStock
