Ventilation
The objectives of MV, either invasive or noninvasive, are to improve oxygenation, to reduce work of breathing, to move alveolar and interstitial fluids into capillaries, to reverse respiratory acidosis and hypercapnia, and finally to improve tissue perfusion.
The decision to initiate MV must be anticipated and should be based on clinical judgment, considering the overall clinical picture, but should not be delayed until the patient is in extremis or has an altered level of consciousness.
Even if invasive MV is a life-saving therapy in the care of critically ill patients, it use must be balanced with the potential deleterious cardiac effects.73 In a PO patient with hypertension, a decrease in preload may be beneficial. However, in a hypotensive patient a decrease in preload may lead to a decrease in CO and SBP. Other potential complications need to be considered, such as barotrauma, and systemic infections.74 Although the use of invasive MV was predictive of ACM (see Table 2), the prognosis of PO patients treated with MV may depend more on the severity of the hemodynamic perturbation rather than the degree of respiratory failure.73
NIMV may be considered as adjunctive therapy in patients with PO who have severe respiratory distress or whose condition does not improve with pharmacologic therapy.34 In a randomized study75 early NIMV therapy for PO patients decreased the need for invasive MV and its attendant complications and appeared to augment the response to therapies. PO patients with early NIMV exhibited significantly less respiratory fatigue and translated in lower rate of tracheal intubation. The treatment delay relative to time of hospital presentation may have substantial consequences on patient outcomes such as mortality, need for subsequent tracheal intubation, or subsequent cardiovascular deterioration requiring further medical care. When NIMV fails to improve oxygenation and respiratory acidosis, or encephalopathy worsens, intubation should be considered without delay.
Therapies Targeting Alveolar Ion and Fluid Transport Pathways
Although these agents were studied only in experimental studies, their knowledge may be clinically relevant as some of IV therapies and particular HF background therapies, such as digoxin, mineralocorticoid receptor antagonists, and diuretics may interfere with function of these channels.
Clinical studies show that impaired alveolar ionic and fluid transport mechanisms contribute to the development, severity, and outcome of PO in humans.
β2-adrenergic receptor signalling is required for upregulation of alveolar epithelial active sodium transport in the setting of excess alveolar oedema. The positive, protective effects of β2-adrenergic receptor signalling on alveolar active sodium transport provide substantial support for the use of β2-adrenergic agonists to accelerate alveolar fluid clearance in patients with PO, and some evidence suggests that pharmacologic treatment with β2-adrenergic agonists facilitate recovery from experimental PO.25,26
Active sodium transport across the alveolar epithelium is controlled by basolateral Na-K-ATPase.19,22,25,76 Na-K-ATPase is positively regulated by GCs, aldosterone, catecholamines (β2 and dopaminergic), and growth hormones, and inhibited by oabain-like compounds and mechanical signalling induced by increased left atrial pressure.19,22,24,25,77 In some experimental studies,78 aldosterone increased the Na-KATPase function and accelerated the clearance of hydrostatic PO, suggesting that aldosterone may be used as a strategy to increase lung oedema clearance.
Transient receptor potential vanilloid receptor 4 (TRPV4) is as one of the most potent agents that inhibit pressure-induced alveolar permeability and it was identified as a promising therapeutic strategy for the treatment of PO.79,80–82 TRPV4 was linked to elevated pulmonary vascular pressure-mediated Ca2+ uptake by lung endothelium and subsequent acute lung injury.80,83 TRPV4 is involved in multiple pathways81,82 including a role in lung vasomotor control, the inflammatory response, and its specific role in resolving PO should be carefully judged.