Información del artículo
Resumen
El descubrimiento de los esteroides marcó un hito médico, tanto fisiológico, al comprender el funcionamiento suprarrenal, como terapéutico, al encontrar una hormona antiinflamatoria e inmunosupresora que cambió la historia natural de las enfermedades autoinmunitarias.
La sepsis es la inflamación sistémica secundaria a una infección y, por ende, el uso de esteroides resulta plausible biológicamente. Sin embargo, la historia aporta datos negativos de su uso a dosis altas (inmunosupresión). Las dosis bajas activan mecanismos no genómicos con respuestas inmunomoduladoras y neuroendocrinas que restauran la sensibilidad adrenérgica y mejoran el contexto hemodinámico en pacientes con shock séptico y han abierto un camino hacia una indicación terapéutica razonable y sustentada.
El objetivo de esta revisión es recorrer el camino histórico de los esteroides desde su descubrimiento hasta su indicación actual en el shock séptico.
Palabras clave:
Esteroides
Shock séptico
Hidrocortisona
Fludrocortisona
Abstract
The discovery of steroids marked a medical milestone, both physiologically, by understanding adrenal function; and therapeutically, by finding an anti-inflammatory and immunosuppressive hormone that changed the natural history of autoimmune diseases.
Sepsis is systemic inflammation secondary to an infection, therefore, the use of steroids is biologically plausible. However, history provides negative data on their use at high doses (immunosuppression). Low doses activate non-genomic mechanisms with immunomodulatory and neuroendocrine responses that restore adrenergic sensitivity and improve the hemodynamic context in patients with septic shock and have opened a path towards a reasonable and supported therapeutic indication.
The objective of this review is to trace the historical path of steroids from their discovery to their current indication in septic shock.
Keywords:
Steroids
Septic Shock
Hydrocortisone
Fludrocortisone
Artículo
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Bibliografía
[1]
I. Francisco Pizarro.
Historia de los corticoides.
Rev Méd Clín Las Condes., 25 (2014), pp. 858-860
[2]
J.L. Velez, A. Martinez, F. Md.
Pulsos o megadosis de esteroides: ¿cuándo están indicados?.
Avances Biomed., 8 (2019), pp. 12-20
[3]
H. Martínez Cordero, P. Montenegro González, J.F. Restrepo, F. Rondón Herrera, G. Quintana, A. Iglesias Gamarra.
Historia de los glucocorticoides.
Rev Colomb Reumatol., 17 (2010), pp. 147-171
[4]
M.C. Bottino, C. Lanari.
[Extra nuclear localization of steroid receptors and non genomic activation mechanisms].
Medicina (B Aires)., 70 (2010), pp. 173-184
[5]
G.D. Nethathe, J. Lipman, R. Anderson, P.J. Fuller, C. Feldman.
Glucocorticoids with or without fludrocortisone in septic shock: a narrative review from a biochemical and molecular perspective.
Br J Anaesth., 132 (2024), pp. 53-65
[6]
M. Singer, C.S. Deutschman, C.W. Seymour, M. Shankar-Hari, D. Annane, M. Bauer, et al.
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA., 315 (2016), pp. 801-810
[7]
S. Weitzman, S. Berger.
Clinical Trial Design in Studies of Corticosteroids for Bacterial Infections.
Ann Intern Med., 81 (1974), pp. 36-42
[8]
W. Schumer.
Steroids in the Treatment of Clinical Septic Shock.
Ann Surg., 184 (1976), pp. 333-341
[9]
Veterans Administration Systemic Sepsis Cooperative Study Group.
Effect of High-Dose Glucocorticoid Therapy on Mortality in Patients with Clinical Signs of Systemic Sepsis.
N Engl J Med., 317 (1987), pp. 659-665
[10]
R.C. Bone, C.J. Fisher Jr., T.P. Clemmer, G.J. Slotman, C.A. Metz, R.A. Balk.
A Controlled Clinical Trial of High-Dose Methylprednisolone in the Treatment of Severe Sepsis and Septic Shock.
N Engl J Med., 317 (1987), pp. 653-658
[11]
L. Cronin, D.J. Cook, J. Carlet, D.K. Heyland, D.B.M. King, M.A.D. Lansang, et al.
Corticosteroid treatment for sepsis: A critical appraisal and meta-analysis of the literature.
Crit Care Med., 23 (1995), pp. 1430-1439
[12]
R. Lefering, E.A.M. Neugebauer.
Steroid controversy in sepsis and septic shock: A meta-analysis.
Crit Care Med., 23 (1995), pp. 1294-1303
[13]
P.E. Bollaert, C. Charpentier, B. Levy, M. Debouverie, G. Audibert, A. Larcan.
Reversal of late septic shock with supraphysiologic doses of hydrocortisone.
Crit Care Med., 26 (1998), pp. 645-650
[14]
D. Annane, E. Bellissant, V. Sebille, O. Lesieur, B. Mathieu, J.C. Raphael, et al.
Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve.
Br J Clin Pharmacol., 46 (1998), pp. 589-597
[15]
G.U. Meduri, A.S. Headley, E. Golden, S.J. Carson, R.A. Umberger, T. Kelso, et al.
Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome A Randomized Controlled Trial.
JAMA., 280 (1998), pp. 159-165
[16]
J. Briegel, H. Forst, M. Haller, G. Schelling, E. Kilger, G. Kuprat, et al.
Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.
Crit Care Med., 27 (1999), pp. 723-732
[17]
D. Annane, V. Sébille, G. Troché, J.-C. Raphaël, P. Gajdos, E. Bellissant.
A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin.
JAMA., 283 (2000), pp. 1038-1045
[18]
D. Annane, V. Sébille, C. Charpentier, P.-E. Bollaert, B. François, J.-M. Korach, et al.
Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock.
JAMA., 288 (2002), pp. 862-871
[19]
C.L. Sprung, D. Annane, D. Keh, R. Moreno, M. Singer, K. Freivogel, CORTICUS Study Group, et al.
Hydrocortisone Therapy for Patients with Septic Shock.
N Engl J Med., 358 (2008), pp. 111-124
[20]
D. Annane, E. Bellissant, P.E. Bollaert, J. Briegel, M. Confalonieri, R. De Gaudio, et al.
Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults: A Systematic Review.
JAMA., 301 (2009), pp. 2362-2375
[21]
D. Keh, E. Trips, G. Marx, S.P. Wirtz, E. Abduljawwad, S. Bercker, et al.
The HYPRESS Randomized Clinical Trial. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.
JAMA., 316 (2016), pp. 1775-1785
[22]
B. Venkatesh, S. Finfer, J. Cohen, D. Rajbhandari, Y. Arabi, R. Bellomo, ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group, et al.
Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.
N Engl J Med., 378 (2018), pp. 797-808
[23]
J. Briegel, P. Möhnle.
Surviving Sepsis Campaign. Internationale Leitlinien der Surviving Sepsis Campaign: Update 2012 [International guidelines of the Surviving Sepsis Campaign: update 2012].
Anaesthesist., 62 (2013), pp. 304-309
[24]
J. Briegel, P. Möhnle.
Internationale Leitlinien der Surviving Sepsis Campaign: Update 2016 [International guidelines from the Surviving Sepsis Campaign: 2016 update].
Anaesthesist., 66 (2017), pp. 530-538
[25]
M. Janssen, H. Endeman, L.D.J. Bos.
Targeted immunomodulation: a primer for intensivists.
Intensive Care Med., 49 (2023), pp. 462-464
[26]
J.L. Vélez-Paez.
New Frontiers in Immunological Therapeutics in the Critically Ill Patient: From Immunosuppression to Immunomodulation.
Microbes Infect Chemother., 3 (2023), pp. e1976
[27]
P.L.W. Horby, J.R. Emberson, M. Mafham, J.L. Bell, L. Linsell, N. Staplin, RECOVERY Collaborative Group, et al.
Dexamethasone in Hospitalized Patients with Covid-19.
N Engl J Med., 384 (2021), pp. 693-704
[28]
R. Knoll, E.T. Helbig, K. Dahm, O. Bolaji, F. Hamm, O. Dietrich, et al.
The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.
Cell., 187 (2024), pp. 4318-4335
[29]
T. Iba, C.L. Maier, J. Helms, R. Ferrer, J. Thachil, J.H. Levy.
Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines.
Ann Intensive Care., 14 (2024), pp. 64
[30]
J.L. Vélez, M. Montalvo, S. Aguayo, P.A. Vélez, G. Velarde, F.E. Jara González, et al.
Glicocálix endotelial: relevancia clínica y enfoque traslacional.
Horiz Med (Lima)., 19 (2019), pp. 84-92
[31]
D. Annane, L. Ouanes-Besbes, D. de Backer, B. Du, A.C. Gordon, G. Hernández, et al.
A global perspective on vasoactive agents in shock.
Intensive Care Med., 44 (2018), pp. 833-846
[32]
T. Pitre, K. Drover, D. Chaudhuri, D. Zeraaktkar, K. Menon, H. Gershengorn, et al.
Corticosteroids in sepsis and septic shock: A systematic review, pairwise, and dose-response meta-analysis.
Crit Care Explor., 6 (2024), pp. e1000
[33]
P.-F. Dequin, F. Meziani, J.-P. Quenot, T. Kamel, J.-D. Ricard, J. Badie, et al.
Hydrocortisone in Severe Community-Acquired Pneumonia.
N Engl J Med., 388 (2023), pp. 1931-1941
[34]
D. Chaudhuri, A.M. Nei, B. Rochwerg, R.A. Balk, K. Asehnoune, R. Cadena, et al.
2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia.
Crit Care Med., 52 (2024), pp. e219-e233
[35]
T. Pitre, D. Abdali, D. Chaudhuri, S.M. Pastores, A.M. Nei, D. Annane, et al.
Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis.
J Gen Intern Med., 38 (2023), pp. 2593-2606
[36]
G.U. Meduri, M.-C. Shih, L. Bridges, T.J. Martin, A. El-Solh, N. Seam, et al.
Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.
Intensive Care Me., 48 (2022), pp. 1009-1023
[37]
F. Fadel, G. André-Grégoire, B. Gravez, B. Bauvois, S. Bouchet, C. Sierra-Ramos, et al.
Aldosterone and Vascular Mineralocorticoid Receptors in Murine Endotoxic and Human Septic Shock.
Crit Care Med., 45 (2017), pp. e954-e962
[38]
B. Teja, M. Berube, T.V. Pereira, A.C. Law, C. Schanock, B. Pang, et al.
Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Am J Respir Crit Care Med., 209 (2024), pp. 1219-1228
[39]
N.A. Bosch, B. Teja, A.C. Law, B. Pang, S.R. Jafarzadeh, A.J. Walkey.
Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock.
JAMA Inter Med., 183 (2023), pp. 451-459
[40]
J. Walsham, N. Hammond, A. Blumenthal, J. Cohen, J. Myburgh, S. Finfer, et al.
Fludrocortisone dose–response relationship in septic shock: a randomised phase II trial.
Intensive Care Med., 50 (2024), pp. 2050-2060
[41]
L. Evans, A. Rhodes, W. Alhazzani, M. Antonelli, C.M. Coopersmith, C. French, et al.
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
Crit Care Med., 49 (2021), pp. e1063-e1143
