Hydrocortisone infusion for severe community-acquired pneumonia: Immunomodulation or just treatment of adrenal insufficiency?
Jorge Salluh, Hospital Barra D
27 December 2005
In a recent number of the AJRCCM, Confalonieri et al. (1) reported the effects of hydrocortisone infusion in patients with severe community acquired pneumonia (CAP). They observed a significant improvement in survival, oxygenation and levels of C- reactive protein in patients receiving steroids, when compared to controls. The use of steroids as an adjunct therapy for pneumonia is not a novel measure, since it was proposed more than 60 years ago (2). However, their benefits were never so apparent. The authors justify the clinical improvement based on possible immunomodulatory effects of the steroid infusion, thus hastening the resolution of acute lung injury and organ failures. Unfortunately, their study did not evaluate other markers of systemic or lung inflammation such as IL-6 or IL-8. Moreover, adrenal function tests were not performed. Recent studies have shown improvements of survival (3), severity of organ failures (3,4) and circulating inflammatory mediators (5) in patients with severe sepsis and adrenal insufficiency treated with hydrocortisone. In these studies, 35%-50% of the patients presented with pneumonia. In addition, Confalonieri et al. report a reduced frequency of “delayed septic shock” in patients treated with hydrocortisone. Currently, the differentiation between severe sepsis and septic shock is made on the basis of the vasopressor-dependency in the latter group. The results of clinical trials on the use of steroids in septic patients are variable regarding immunomodulation, reversal of organ failures and impact on the survival rates. In contrast, the effect of hydrocortisone in reducing the need for vasopressors is indisputable (6).
Recently, we assessed the adrenal function of 40 patients with severe CAP (7). Cortisol levels were measured in all patients within the first 72 hours of admission. Twenty-six patients (65%) had corisol levels < 20g/dl. When other frequently used cut-off levels of cortisol were evaluated,30 patients (75%) had cortisol levels below 25g/dl and 19 (47.5%) had cortisol levels below 15g/dl. When patients with septic shock (n=19) were studied, 12 (63%) had cortisol levels <20g/dl, a frequency that was similar to the total population regardless of the hemodynamic status (p=0.99). Accordingly, Annane et al recently evaluated patients with septic shock (most of them pneumonia-related; 60%) showed that low doses of corticosteroids were associated with better outcomes in septic shock-associated ARDS nonresponders to a corticotropin test, but not in responders.
With these results in mind, we suggest that part of the benefits of the use of hydrocortisone for severe CAP reported in the study of Confalonieri et al. might have been achieved by simply treating the adrenal insufficiency associated with severe sepsis of pulmonary etiology.
Jorge Ibrain Figueira Salluh,MD, MSC
Hospital Barra D’or, Rio de Janeiro, Brazil
Instituto Nacional de Câncer, Rio de Janeiro, Brazil
Marcio Soares, MD, PhD
Instituto Nacional de Câncer, Rio de Janeiro, Brazil
References
1- Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G, Della Porta R, Giorgio C, Blasi F, Umberger R, Meduri GU. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 2005;171:242-248.
2- Perla D, Marmorston J. Suprarenal cortical hormone and salt in the treatment of pneumonia and other severe infections. Endocrinology 1940;27:367–374.
3- Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
4- Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 1999;27:723-732.
5- Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Volk HD, Doecke WD, Falke KJ, Gerlach H. Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 2003;167:512-520.
6- Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, and Kupfer Y.Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 2004;329: 480.
7- Salluh JIF, Verdeal JC, Mello GW, Araújo LV, Martins GAR, Santino MS, Soares M. Cortisol Levels in Patients with Severe Community-Acquired Pneumonia. Intensive Care Medicine In press 2006
8- Annane D, Sebille V, Bellissant E; for the Ger-Inf-05 Study Group. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med. 2006 ;34(1):22-30.
Critical Care
Hydrocortisone infusion for severe community-acquired pneumonia: Immunomodulation or just treatment of adrenal insufficiency?
27 December 2005
In a recent number of the AJRCCM, Confalonieri et al. (1) reported the effects of hydrocortisone infusion in patients with severe community acquired pneumonia (CAP). They observed a significant improvement in survival, oxygenation and levels of C- reactive protein in patients receiving steroids, when compared to controls. The use of steroids as an adjunct therapy for pneumonia is not a novel measure, since it was proposed more than 60 years ago (2). However, their benefits were never so apparent. The authors justify the clinical improvement based on possible immunomodulatory effects of the steroid infusion, thus hastening the resolution of acute lung injury and organ failures. Unfortunately, their study did not evaluate other markers of systemic or lung inflammation such as IL-6 or IL-8. Moreover, adrenal function tests were not performed. Recent studies have shown improvements of survival (3), severity of organ failures (3,4) and circulating inflammatory mediators (5) in patients with severe sepsis and adrenal insufficiency treated with hydrocortisone. In these studies, 35%-50% of the patients presented with pneumonia. In addition, Confalonieri et al. report a reduced frequency of “delayed septic shock” in patients treated with hydrocortisone. Currently, the differentiation between severe sepsis and septic shock is made on the basis of the vasopressor-dependency in the latter group. The results of clinical trials on the use of steroids in septic patients are variable regarding immunomodulation, reversal of organ failures and impact on the survival rates. In contrast, the effect of hydrocortisone in reducing the need for vasopressors is indisputable (6).
Recently, we assessed the adrenal function of 40 patients with severe CAP (7). Cortisol levels were measured in all patients within the first 72 hours of admission. Twenty-six patients (65%) had corisol levels < 20g/dl. When other frequently used cut-off levels of cortisol were evaluated,30 patients (75%) had cortisol levels below 25g/dl and 19 (47.5%) had cortisol levels below 15g/dl. When patients with septic shock (n=19) were studied, 12 (63%) had cortisol levels <20g/dl, a frequency that was similar to the total population regardless of the hemodynamic status (p=0.99). Accordingly, Annane et al recently evaluated patients with septic shock (most of them pneumonia-related; 60%) showed that low doses of corticosteroids were associated with better outcomes in septic shock-associated ARDS nonresponders to a corticotropin test, but not in responders.
With these results in mind, we suggest that part of the benefits of the use of hydrocortisone for severe CAP reported in the study of Confalonieri et al. might have been achieved by simply treating the adrenal insufficiency associated with severe sepsis of pulmonary etiology.
Jorge Ibrain Figueira Salluh,MD, MSC
Hospital Barra D’or, Rio de Janeiro, Brazil
Instituto Nacional de Câncer, Rio de Janeiro, Brazil
Marcio Soares, MD, PhD
Instituto Nacional de Câncer, Rio de Janeiro, Brazil
References
1- Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G, Della Porta R, Giorgio C, Blasi F, Umberger R, Meduri GU. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 2005;171:242-248.
2- Perla D, Marmorston J. Suprarenal cortical hormone and salt in the treatment of pneumonia and other severe infections. Endocrinology 1940;27:367–374.
3- Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
4- Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 1999;27:723-732.
5- Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Volk HD, Doecke WD, Falke KJ, Gerlach H. Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 2003;167:512-520.
6- Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, and Kupfer Y.Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 2004;329: 480.
7- Salluh JIF, Verdeal JC, Mello GW, Araújo LV, Martins GAR, Santino MS, Soares M. Cortisol Levels in Patients with Severe Community-Acquired Pneumonia. Intensive Care Medicine In press 2006
8- Annane D, Sebille V, Bellissant E; for the Ger-Inf-05 Study Group. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med. 2006 ;34(1):22-30.
Competing interests
none