Top

Published in:

01-12-2012 | Experimental

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

Authors: Caitlin W. Hicks, Daniel A. Sweeney, Robert L. Danner, Peter Q. Eichacker, Anthony F. Suffredini, Jing Feng, Junfeng Sun, Brad Moriyama, Robert Wesley, Ellen N. Behrend, Steven B. Solomon, Charles Natanson

Published in: Intensive Care Medicine | Issue 12/2012

Abstract

Purpose

The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock.

Methods

Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80–90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose.

Results

Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p ≤ 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05–9.11; p = 0.04).

Conclusions

Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.

Available only for authorised users

Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y (2004) Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. Br Med J 329:480CrossRef

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J, CORTICUS Study Group (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124PubMedCrossRef

Minneci PC, Deans KJ, Eichacker PQ, Natanson C (2009) The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis. Clin Microbiol Infect 15:308–318PubMedCrossRef

Kalil AC, Sun J (2008) Why are clinicians not embracing the results from pivotal clinical trials in severe sepsis? A bayesian analysis. PLoS ONE 3:e2291PubMedCrossRef

Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, Gerstenberger EP, Fitz Y, Danner RL, Natanson C (2002) Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 166:1197–1205PubMedCrossRef

Skornik WA, Dressler DP (1974) The effects of short-term steroid therapy on lung bacterial clearance and survival in rats. Ann Surg 179:415–421PubMedCrossRef

Heller AR, Heller SC, Borkenstein A, Stehr SN, Koch T (2003) Modulation of host defense by hydrocortisone in stress doses during endotoxemia. Intensive Care Med 29:1456–1463PubMedCrossRef

Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ Jr (1995) Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23:1430–1439PubMedCrossRef

Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C (2004) Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141:47–56PubMed

10.

Hicks CW, Sweeney DA, Danner RL, Eichacker PQ, Suffredini AF, Feng J, Sun J, Behrend EN, Solomon SB, Natanson C (2012) Efficacy of selective mineralocorticoid and glucocorticoid agonists in canine septic shock. Crit Care Med 40(1):199–207

11.

Minneci PC, Deans KJ, Hansen B, Parent C, Romines C, Gonzales DA, Ying SX, Munson P, Suffredini AF, Feng J, Solomon MA, Banks SM, Kern SJ, Danner RL, Eichacker PQ, Natanson C, Solomon SB (2007) A canine model of septic shock: balancing animal welfare and scientific relevance. Am J Physiol Heart Circ Physiol 293:H2487–H2500PubMedCrossRef

12.

Becker KL (2001) Principles and practice of endocrinology and metabolism. Lippincott Williams & Wilkins, Philadelphia, pp 2108–2121

13.

Plumb DC (2005) Plumb’s veterinary drug handbook, 5th edn. PhrmaVet, Stockholm, Iowa, pp 578–80

14.

Knaus WA, Harrell FE Jr, LaBrecque JF, Wagner DP, Pribble JP, Draper EA, Fisher CJ Jr, Soll L (1996) Use of predicted risk of mortality to evaluate the efficacy of anticytokine therapy in sepsis. The rhIL-1ra Phase III Sepsis Syndrome Study Group. Crit Care Med 24:46–56PubMedCrossRef

15.

Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Volk HD, Doecke WD, Falke KJ, Gerlach H (2003) 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 167:512–520PubMedCrossRef

16.

Oppert M, Schindler R, Husung C, Offermann K, Graf KJ, Boenisch O, Barckow D, Frei U, Eckardt KU (2005) Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock. Crit Care Med 33:2457–2464PubMedCrossRef

17.

Briegel J, Jochum M, Gippner-Steppert C, Thiel M (2001) Immunomodulation in septic shock: hydrocortisone differentially regulates cytokine responses. J Am Soc Nephrol 12[Suppl 17]:S70–S74PubMed

18.

Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E (1993) Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 103:565–575PubMedCrossRef

19.

Novotny AR, Reim D, Assfalg V, Altmayr F, Friess HM, Emmanuel K, Holzmann B (2011) Mixed antagonist response and sepsis severity-dependent dysbalance of pro- and anti-inflammatory responses at the onset of postoperative sepsis. Immunobiology 31(1):201–213

20.

Osuchowski MF, Connett J, Welch K, Granger J, Remick DG (2009) Stratification is the key: inflammatory biomarkers accurately direct immunomodulatory therapy in experimental sepsis. Crit Care Med 37:1567–1573PubMedCrossRef

21.

van der Goes A, Hoekstra K, van den Berg TK, Dijkstra CD (2000) Dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro. J Leukoc Biol 67:801–807PubMed

22.

Meduri GU, Kanangat S, Bronze M, Patterson DR, Meduri CU, Pak C, Tolley EA, Schaberg DR (2001) Effects of methylprednisolone on intracellular bacterial growth. Clin Diagn Lab Immunol 8:1156–1163PubMed

23.

Kaufmann I, Briegel J, Schliephake F, Hoelzl A, Chouker A, Hummel T, Schelling G, Thiel M (2008) Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions. Intensive Care Med 34:344–349PubMedCrossRef

24.

Shurin MR, Kusnecov A, Hamill E, Kaplan S, Rabin BS (1994) Stress-induced alteration of polymorphonuclear leukocyte function in rats. Brain Behav Immun 8:163–169PubMedCrossRef

25.

Rojas IG, Padgett DA, Sheridan JF, Marucha PT (2002) Stress-induced susceptibility to bacterial infection during cutaneous wound healing. Brain Behav Immun 16:74–84PubMedCrossRef

26.

Cetinkaya RA, Gorenek L, Coskun O, Eyigun CP, Senses Z, Ide T, Kilic S (2009) The effect of methylprednisolone on treatment in rats with induced sepsis. Clin Exp Med 9:45–50PubMedCrossRef

27.

Sibila O, Luna CM, Agusti C, Baquero S, Gando S, Patron JR, Morato JG, Absi R, Bassi N, Torres A (2008) Effects of glucocorticoids in ventilated piglets with severe pneumonia. Eur Respir J 32:1037–1046PubMedCrossRef

28.

Tagliabue C, Salvatore CM, Techasaensiri C, Mejias A, Torres JP, Katz K, Gomez AM, Esposito S, Principi N, Hardy RD (2008) The impact of steroids given with macrolide therapy on experimental Mycoplasma pneumoniae respiratory infection. J Infect Dis 198:1180–1188PubMedCrossRef

29.

Flynn PM, Shenep JL, Stokes DC, Hildner WK, Mackert PW, Snellgrove RL, Rehg JE (1986) Effect of methylprednisolone on bacterial clearance and endotoxin liberation during experimental sepsis induced by gram-negative bacteria. Infect Immun 52:26–30PubMed

30.

Fadel MV, Repka JC, Cunha CL, Leao MT (2008) Inadequate timing between corticosteroid and antibiotics applications increases mortality due to sepsis. Braz J Infect Dis 12:416–422PubMedCrossRef

31.

Assfalg V, Huser N, Reim D, Kaiser-Moore S, Rossmann-Bloeck T, Weighardt H, Novotny AR, Stangl MJ, Holzmann B, Emmanuel KL (2010) Combined immunosuppressive and antibiotic therapy improves bacterial clearance and survival of polymicrobial septic peritonitis. Shock 33:155–161PubMedCrossRef

32.

Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A (1998) Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 26:645–650PubMedCrossRef

33.

Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K (1999) Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 27:723–732PubMedCrossRef

34.

Chawla K, Kupfer Y, Goldman I (1999) Hydrocortisone reverses refractory septic shock. Crit Care Med 27:A33CrossRef

35.

Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871PubMedCrossRef

36.

Mussack T, Briegel J, Schelling G, Biberthaler P, Jochum M (2005) Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and polymorphonuclear elastase levels in human septic shock. Clin Chem Lab Med 43:259–268PubMedCrossRef

37.

Tandan SM, Guleria R, Gupta N (2005) Low dose steroids and adrenocortical insufficiency in septic shock: a double-blind randomized controlled trial from India. Am J Respir Crit Care Med 171:A43

38.

Li Y, Cui X, Li X, Solomon SB, Danner RL, Banks SM, Fitz Y, Annane D, Natanson C, Eichacker PQ (2008) Risk of death does not alter the efficacy of hydrocortisone therapy in a mouse E. coli pneumonia model: risk and corticosteroids in sepsis. Intensive Care Med 34:568–577PubMedCrossRef

39.

COIITSS Study Investigators, Annane D, Cariou A, Maxime V, Azoulay E, D’honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santre C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec’h C, Mayaud J, Lejeune J, Chevret S (2010) Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA 303:341–348PubMedCrossRef

40.

Scott WA, Pongiglione G, Bromberg BI, Schaffer MS, Deal BJ, Fish FA, Dick M (1995) Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope. Am J Cardiol 76:400–402PubMedCrossRef

Title: Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia
Authors: Caitlin W. Hicks
Daniel A. Sweeney
Robert L. Danner
Peter Q. Eichacker
Anthony F. Suffredini
Jing Feng
Junfeng Sun
Brad Moriyama
Robert Wesley
Ellen N. Behrend
Steven B. Solomon
Charles Natanson
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 12/2012
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-012-2735-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2012

The relationship between blood lactate concentration, the Paediatric Index of Mortality 2 (PIM2) and mortality in paediatric intensive care

Diaphragm electromyographic activity as a predictor of weaning failure

Hypertriglyceridemia: a potential side effect of propofol sedation in critical illness

The repeatability of Stewart’s parameters and anion gap in a cohort of critically ill adult patients

Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study

Electrical impedance tomography: the holy grail of ventilation and perfusion monitoring?