Editorial [Steroids in ARDS and Sepsis: Is it Time for a Comeback?]

In their original description Ashbaugh and coworkers, in 1967, described a syndrome characterized by refractory hypoxemia, diffuse lung infiltrates on chest radiograph, and decreased lung compliance in a group of 12 patients suffering from severe respiratory failure [1]. This syndrome would be later known as the adult or acute respiratory distress syndrome (ARDS). The mainstay therapy of ARDS for the past 5 decades has remained the management of the underlying disorder causing it, when feasible. To date, there are no specific pharmacological interventions of proven value for the treatment of ARDS. Although corticosteroids and other agents have been widely used clinically, large multi-center trials in the past have failed to show any benefit in outcome, lung compliance, pulmonary shunts, chest radiograph, severity score or survival [2- 4]. For years, the role of corticosteroids in ARDS has been controversial at best. These agents may have, however, a role in situations when ARDS has been precipitated by a corticosteroid-responsive process, such as acute eosinophilic pneumonia. Sepsis is by far the most common cause ARDS [5,6]. The mortality rate for patients with sepsis complicated by ARDS has been reported to be as high as 60% [5,6]. In this clinical entity, the role of corticosteroids has been redefined in recent years. In this issue of Current Respiratory Medicine Reviews, Han and Hizy extensively review the role of corticosteroids in the critically ill patient with sepsis and ARDS [7]. These authors review the importance of the hypothalamic-pituitaryadrenal (HPA) axis in critical illness. Over the past two decades, evidence-based medicine has found that the activation of the HPA axis with the production of adrenocorticotrophin (ACTH) and cortisol is a fundamental part of the host response to stress such as ARDS or sepsis. Glucocorticoids in this context, appear to have two vital and disparate effects that allow the host to deal with acute stress. One is the permissive effect of steroids to prepare the host for a “fight and flight” response by providing a ready source of fuel (glucose) and adequate hemodynamic reserve. The second function is to suppress activated defense mechanisms, preventing them from overshooting and damaging the host. The HPA axis and the immune response are linked in a negative feedback loop, in which activated immune cells produce cytokines that signal increased immune activity to the brain, thereby stimulating the HPA axis, which through glucocorticoids suppress the immune reaction [8]. Cytokines, which are produced both in patients with sepsis and ARDS, however, also suppress the HPA-axis and glucocorticoid receptor function. For example, tumor necrosis factor (TNF) - alpha impairs ACTH release, and a number of clinical studies have reported inappropriately low ACTH levels in patients with severe sepsis and the systemic inflammatory response syndrome (SIRS) [9-10]. As noted by Han and Hizy, acute adrenal insufficiency should always be suspected in critically ill patients who fail to respond to catecholamines. An ACTH infusion test and a trial of stress doses of glucocorticoids pending the results is suggested when this disorder is suspected. Whether or not corticosteroids will be used routinely in patients with sepsis complicated with ARDS in the absence of adrenal dysfunction is a matter of constant debate and likely to continue for years to come. REFERENCES [1] Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967; 2: 319-323. [2] Luce JM, Montgomery AB, Marks JD, Turner J, Metz CA, Murray JF. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 1988; 138: 62-68. [3] Bernard GR, Luce J, Sprung C, et al. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 1987; 317: 1565-1570. [4] Melot C, Leujeune P, Leemam M, Moraine JJ, Neaije R. Prostaglandin E1 in the adult respiratory distress syndrome. Am Rev Respir Dis 1989; 139: 106-110. [5] Marik P, Varon J. Sepsis: State-of-the-art. Dis Month 2001; 42: 462-532. [6] Lechin AE, Varon J. Adult respiratory distress syndrome (ARDS): The basics. J Emerg Med, 1994; 12(1): 63-8. [7] Han MK, Hyzy RC: The role of corticosteroids in sepsis and acute respiratory distress syndrome. Curr Respir Med Rev 2007; 3: 141- 146......