Beruflich Dokumente
Kultur Dokumente
Mervyn Mer Department of Medicine & ICU Johannesburg Hospital University of the Witwatersrand
Introduction
Much controversy and debate regarding the use of corticosteroids (CS) in clinical medicine CS use in CAP controversial and unclear
Introduction
Definition of Pneumonia
Introduction
Community-acquired pneumonia common Leading infectious cause of death Consistently among top 5 causes of death in both developed and under-developed countries At least 20% cases CAP will require hospitalisation - 25% of these will require ICU admission Mortality of up to 50%
Almirall J, et al. Eur Resp J 2000; 15: 757-763 Alvarez-Lemma F, Torres A. Curr Opin Crit Care 2004; 10: 369-74
Introduction
Mortality rates CAP relatively unchanged past half century
Evans GM, Gainsford WF. Lancet 1938; 2: 14-19
Landmark study: Austrian and Gold 1964 - deaths occurring within 1st 5 days of rx not due to failure to eradicate micro-organism - suggested due to specific inflammatory response of host
Austrian R, Gold J. Ann Intern Med 1964; 60 :759-770
Introduction
...inflammatory response of the host may be more important than the specific microorganism causing the infection or the type of antibiotic administered
Rano A, Torres A, et al. Curr Opin Infect Dis 2006; 19: 179-84
Mechanism of Action
CS modulate the inflammatory response
Inhibit the production of key substances in the inflammatory pathway which contribute to vascular permeability, oedema, leucocyte migration and fibrin deposition
Mechanism of Action
CS modulate the inflammatory response
- halt activation of various transcription
factors including NF- KB - occurs via an inhibitory action on histone acetylation and stimulation of histone deacetylation
Barnes PJ. Allergy 2001; 56: 928-36
CS stimulate
Histone deacetylation
AP-1
CS/GR
CBP / p300
HAT
NF-KB
STATs
CS inhibit
Histone acetylation
Severe CAP
CURB-65 score
History
Initial description 1956 Effects of hydrocortisone upon course pneumococcal pneumonia treated with penicillin
Wagner HNJ, et al. Bull John Hopkins Hosp 1956; 98: 197-215
Severe CAP
Randomized multicentre study in patients with severe CAP in ICU who received low-dose CS (HC) associated with - significant reduction length of hospital stay - significant reduction in mortality
Confalonieri M, et al. AJRCCM 2005; 171: 242-248
Recent Reviews
Severe CAP : approach to therapy - CS promising adjunct
Pineda L, et al. Expert Opin Pharmacother 2007; 8: 593-606
CS infusion in patients with severe CAP - powerful immunomodulatory effects - seems to be associated with significant reduction in morbidity, mortality, hospitalisation
Confalonieri M, Trevisan R. Recenti Prog Med 2006; 97: 32-36
Recent Reviews
Associated inflammatory response in pneumonia: role of adjunctive corticosteroids - adjunctive treatment with CS probably indicated in severe CAP
Rano A, Torres A, et al. Curr Opin Infect Dis 2006; 19: 179-184
An update on the diagnosis of adrenal insufficiency & the use of corticotherapy in critical illness - possible role for CS in severe CAP
Thomas Z, et al. Ann Pharmacother 2007; 41: 1456-65
Role of CS in Paediatrics
Severe Mycoplasma Pneumoniae Pneumonia MP responsible for 10-40% cases paediatric CAP Occasionally progression to severe pneumonia despite appropriate antibiotic therapy Retrospective evaluation effect prednisolone Dose : 1mg/kg x 3-7 days, tapered over 7 days
Lee KY, et al. Pediatr Pulmonol 2006; 41: 263-8
Role of CS in Paediatrics
Severe Mycoplasma Pneumoniae Pneumonia Results - recipients afebrile within 24 hours - improvement in clinical status and radiographically Conclusion - CS rx temporally associated with clinical & radiographic improvement - may be helpful for reducing morbidity
Lee KY, et al. Pediatr Pulmonol 2006; 41: 263-8
Critical Determinants
Timing Dose Duration
Timing of Initiation
Dosage
Duration of Treatment
New Data
Corticosteroids not effective in CAP RDBP trial, 213 hospitalised patients 7 days of adjunctive prednisolone (40mg dly) - did not improve outcome - increased late failure in nonsevere CAP
Snijders D, et al. Am J Respir Crit Care Med 2010; 181: 975-82
New Data
Limitations
73% patients CURB-65 2 Abrupt cessation of CS (rebound) Benefit in more severely ill patients cannot be excluded Underpowered No assessment of adrenal function Editorial: CS if admitted ICU with severe CAP with either shock or ALI
Snijders D, et al. Am J Respir Crit Care Med 2010; 181: 975-82 Meduri GU, Confalonieri M. Am J Respir Crit Care Med 2010; 181: 880-82
Recent Meta-analyses
Corticosteroid treatment Patients with severe sepsis (n = 1228) Acute lung injury-acute respiratory distress syndrome (n = 648) Conclusions - CS of benefit
Annane D, et al. JAMA 2009; 301: 2362-2375 Tang B, et al. Crit Care Med 2009; 37: 1594-1603
Consensus Guidelines
Patients admitted to ICU with severe CAP with either shock or acute lung injury - CS indicated
Future
ESCAPe Trial Extended Steroid (in) CAP(e) Patients admitted to ICU with severe CAP Randomised trial; 1400 patients Prolonged use low dose MP
Conclusion
Encouraging data regarding use of CS in severe CAP They should be used in this setting Dose Avoid in non-severe CAP Timing, dose, duration are critical variables