The Kidney During Mechanical Ventilation

Mechanical Ventilation Versus Spontaneous Breathing

During spontaneous breathing, respiratory muscles establish negative intrathoracic and intrapulmonary pressures and, by downward movement of the diaphragm, a positive intra-abdominal pressure. The resulting intrathoracic pressure–to–ambient pressure gradient allows air to flow into the lungs. The physiologic mechanism of spontaneous breathing facilitates venous return, thereby supporting hemodynamics. In contrast with spontaneous breathing, mechanical ventilation uses positive pressure to inflate the lungs.

In most patients with ARDS, either volume-controlled or pressure-controlled ventilation is used. In the volume control mode, a volume is preset on the ventilator, resulting in a variable airway pressure, whereas in the pressure control mode, the inspiratory pressure is preset, resulting in a certain tidal volume. Thus the airway pressure results from the applied tidal volume or preset inspiratory pressure and on the preset basic end-expiratory volume and depends on lung compliance, airway resistance, and air flow.

During mechanical ventilation, pressure gradients are altered considerably compared with pressure gradients in spontaneously breathing subjects. Intrathoracic, intrapulmonary, and intra-abdominal pressures increase during inspiration and remain positive during the breathing cycle. Only at the end of expiration do they equalize with ambient pressure, when no positive end-expiratory pressure (PEEP) is applied. PEEP usually is applied to prevent the alveoli from collapsing at end expiration. Consequently, mechanical ventilation exerts systemic hemodynamic effects through a complex interaction among intrathoracic pressure, intravascular volume, and cardiac performance. Mechanical ventilation decreases cardiac output by decreasing preload, affecting left ventricular geometry and pulmonary vascular volume and resistance, and, in addition, increasing right ventricular afterload. Evidence for these proposed mechanisms has been known for decades, based on studies in animal models and human subjects during spontaneous ventilation or controlled mandatory ventilation in combination with PEEP.

Indications for Mechanical Ventilation

The most common and obvious indication for mechanical ventilation in patients under ICU care is ARDS. This condition can be defined qualitatively as any respiratory pathologic process associated with failure of arterial oxygenation and inadequate alveolar ventilation, with a subsequent decrease in PaO ₂ or rise in PaCO ₂ , or both. Although in most mechanically ventilated patients, normal gas exchange is targeted, in many patients with ARDS managed in the ICU, the maintenance of normal gas exchange is impossible. In such cases, to avoid ventilator-associated lung injury (VALI), a low PaO ₂ or a high PaCO ₂ is accepted. The former occurs despite measures to improve oxygenation and despite avoidance of high, potentially toxic inspired oxygen concentrations. The latter may be associated with a strategy of small tidal volume ventilation with adequate mean airway pressure to achieve satisfactory oxygenation, thereby avoiding toxic inspired oxygen concentrations and allowing PaCO ₂ to increase if necessary. These strategies are called permissive hypoxemia and permissive hypercapnia , respectively. In this regard, it is important to recognize that patients in the ICU may be subjected to acute changes in PaO ₂ and PaCO ₂ , or to mild chronic hypoxemia or hypercapnia, as a result of the applied ventilatory strategy or their underlying condition.

Ventilator-Induced Lung Injury

Besides the adverse effects mechanical ventilation has on systemic hemodynamics, it also can cause direct damage to the lungs, which is termed ventilator-induced lung injury (VILI). VALI is used when a causal relationship between mechanical ventilation and lung injury cannot be established, which is usually a clinical setting. Initial experimental research on the induction and course of VILI focused primarily on the contribution of mechanical factors such as pressure and volume. Based on these studies, innovative and lung-protective strategies have been proposed to avoid VILI by limiting tidal volume and plateau pressure and by maintaining recruitment of alveolar regions with sufficient PEEP. Clinical trials subsequently made clear that ventilator management can alter mortality in patients with ARDS. In 2000 the ARDS Network clinical trial revealed that mortality rate was significantly lower in the group managed with lower tidal volumes than for managed with traditional high tidal volumes (31.0% vs. 39.8%).

Mechanical stresses caused by mechanical ventilation can affect cellular and molecular processes in the lung, a mechanism that has been called biotrauma . Two independent pathways of the biotrauma hypothesis have been distinguished: (1) Ventilation may cause release of mediators, and (2) these mediators have biologic activity. Ventilation strategies using “large” tidal volumes and zero PEEP in already-injured lungs can promote the release of inflammatory mediators in the lungs. This potentiation of the inflammatory response is supported by evidence from experimental models ranging from mechanically stressed cell systems to isolated lungs and intact animals and humans. The possible pivotal role for biotrauma in the development of multisystem organ failure was based on the suggestion that this inflammatory reaction may not be limited to the lungs but, by way of spillover of mediators in the circulation, also may initiate and propagate a systemic inflammatory response. Indirect evidence from experimental models ranging from an isolated perfused and ventilated mouse lung, intact animals with preinjured lungs, and humans with ARDS supports this hypothesis. However, conflicting evidence exists. In addition, other mechanisms by which mechanical ventilation may affect distant organs include suppression of peripheral immune response and translocation of bacteria and endotoxin from lung and intestine to the systemic circulation.