Adjunctive drug treatment in severe hypoxic respiratory failure

This article reviews the pharmacological treatment of severely hypoxaemic critically ill patients, notably those with acute respiratory distress syndrome (ARDS), acute lung injury or the sepsis syndrome. Haemodynamic support in hypotensive patients often initially requires aggressive fluid resuscitation with crystalloids or colloids, combined with vasopressors to maintain adequate end-organ perfusion. The catecholamine of choice in severe hypotension with low systemic resistance is norepinephrine (noradrenaline); dopamine is often used in mild hypotension. Once haemodynamic stabilisation is achieved, loop diuretics such as furosemide (frusemide) are used to obtain the lowest volaemia that guarantees adequate perfusion. If the fraction of inspired oxygen necessary to achieve the satisfactory haemoglobin oxygen saturation of 90% approaches 1, a trial of nitric oxide with or without almitrine is justified. Oxygen consumption can be lowered by treating fever with paracetamol (acetaminophen) and physical cooling. Occasionally, deep sedation using a combination of an opioid (most often morphine or fentanyl) and a benzodiazepine (lorazepam or midazolam) is necessary; in the presence of renal or hepatic insufficiency, propofol is a valid, although expensive, alternative. Paralysis with pancuronium or vecuronium has been associated with critical illness polyneuropathy and is used only as a last resort. Corticosteroids may be indicated in the subacute (fibroproliferative) phase of ARDS. Other anti-inflammatory treatments (such as cytokine antagonists, cyclo-oxygenase inhibitors, antioxidants or monoclonal anti-endotoxin antibodies), as well as surfactant supplementation, have failed to improve prognosis in randomised trials.