Comment to: Septic shock: current pathogenic concept from a clinical perspective Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J Med Sci Monit, 2005; 11(3): RA76-RA85 Future treatment prespictives in septic shock.

Author(s): Abhishek A, Anushree A, Ashutosh T, Ray S

Affiliation(s): Department of Neurosurgery, Sir Ganga Ram Hospital, New Delhi. C/O Dr. C. S. Agrawal, 2/22, First Floor, Shanti Niketan, Opp. Moti Bagh, New Delhi - 110021, India.

Publication date & source: 2005-11-24, Med Sci Monit., 11(12):LE22-23 [Epub ahead of print]

Publication type:

Dear Editor, We read with interest the well-written article by Tsiotou et al. [1], 'Septic shock: current pathogenic concept from a clinical perspective'. Septic shock indeed remains a major cause of morbidity and mortality among ICU patients worldwide [2]. Importantly, the presence of shock independently predicts mortality above that expected from sepsis alone [3] and rapid identification and effective, early intervention might influence the progression of shock and the mortality rate [4]. Current management of severe sepsis and septic shock consists of: a) early goal - directed resuscitation of the septic patient during the first 6 h after recognition; b) aggressive measures towards identification and containment of causative organisms & their source; c) supportive therapy for cardiovascular, respiratory & renal systems; d) general measures directed at maintaining euglycemia, sedation and analgesia as well as preventing deep-vein thrombosis, stress ulcers, ventilator-associated pneumonia, tissue hypoxemia and iatrogenic lung injury; e) therapy directed at modulating the host immune response to infection [5]. Various drugs developed for specific targets of the cytokine cascade have either failed to improve patient survival [6,7] or have not lived up to their potential to do so [1]. Corticosteroids were the first anti-inflammatory drugs tested in randomized trials. Annane et al. [8] showed that a 7-day replacement with low dose corticosteroids significantly reduced 28- day mortality & duration of vasopressor administration in all patients with septic shock. Another important & emerging mediator-inhibition therapy for severe sepsis is activated protein C [drotrecogin alfa (activated)]. Activated protein C inhibits factor Va and factor VIIIa and has effects on in vitro coagulation, fibrinolysis and immune system, based on a phase 3, randomized, placebo controlled trial [PROWESS] [9] which showed an absolute reduction in the relative risk of death at 28 days with somewhat increase in serious bleeding complications. The regulatory agencies in the United States & Europe, in 2001, approved activated protein C for the treatment of adult patients with severe sepsis & at high risk of death (as defined by an APACHE II score ?x25 in the United States & by the failure of at least two organs in Europe). However, a phase 4 placebo-controlled randomized trial of activated protein C (ADDRESS) [10] has confirmed the lack of its efficacy in reducing mortality in adults with severe sepsis but at low risk of death (APACHE II scores <25 or single organ failure). To conclude, newer therapies aimed at controlling the pathogenic processes of sepsis are emerging, slowly but surely. Their effective & efficient usage is likely to involve judicious patient selection & accurate knowledge of the stage of the disease process; but we still have a long way to go. Sincerelly, Dr. Agrawal Abhishek1, Dr. Agrawal Anushree2, Dr. Ashutosh3, Dr. Sumit Ray4, 1 Department of Neurosurgery, Sir Ganga Ram Hospital, New Delhi. C/O Dr. C. S. Agrawal, 2/22, First Floor, Shanti Niketan, Opp. Moti Bagh, New Delhi - 110021, India, e-mail: dr_abhi_agrawal@yahoo.co.in 2 Department of Radiology, Sir Ganga Ram Hospital, New Delhi, India 3 Department of Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi, India. 4 Department of Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi, India. References: 1.Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J. Septic shock: current pathogenic concept from a clinical perspective. Med Sci Monit, 2005; 11(3): RA76-RA85 2.Sands K, Batis D, Lanken P et al: Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA, 1997; 278: 234-40 3.Rello J, Ricart M, Mirelis B et al: Nosoceomial bacteremia in a medical-surgical intensive care unit: epidemiologic characteristics & factors influencing mortality in 111 episodes. Intensive Care Med, 1994; 20: 94-98 4.Balk RA: Outcome of septic shock: location, location, location. Crit Care Med, 1998; 26: 983-84 5.Dellinger RP, Carlet JM, Masur H et al: Surviving sepsis: campaign guidelines for management of severe sepsis and septic shock. Crit Care Med, 2004; 32: 858-73 6.Zeni F, Freeman B, Natanson C: Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med, 1997; 25: 1095-100 7.Wheeler AP, Bernard GR: Treating patients with severe sepsis. N Engl J Med, 1999; 340: 207-14 8.Annane D, Sebile V, Charpentier C et al: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA, 2002; 288: 862-71 9.Bernard GR, Vincent JL, Laterre PF et al: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med, 2001; 344: 699-709 10Abraham E, Laterre PF, Garg R et al: Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med, 2005; 353: 1332-41 Received: 2005.10.25.