Abstract

Dear Editor, I really enjoyed the article of Dr A. Tsiotou et al. entitled"Septic shock; current pathogenetic concepts from a clinical perspective" [1]. I found it very interestingbecause it is well known that the yearly incidence of sepsis is 50-95 cases per 100.000, and has beenincreasing by 9% each year [2]. Furthermore, 3% of patients with severe sepsis experience septic shockwhich accounts for 10% of admissions to intensive care units [3,4]. The pathophysiologic process of septicshock is an extremely complex cascade of events that includes proinflammatory, anti-inflammatory, humoral,cellular, and circulatory involvement [5]. These factors are extensively and analytically reviewed inthis article. Excessive production of Nitric Oxide(NO) has been implicated in the pathogenesis of septicshock for a long time. As it is noticed in the article, the inhibition of NO in the context of septicshock in experimental models has demonstrated a survival advantage. But it has to be noticed that inthe pivotal clinical trial for the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride(546C88)the mortality was higher in the treatment arm [6]. Furthermore, another clinical trial showed that theintravenous administration of the nitric oxide synthase inhibitor 546C88 had as a result more rapid shockresolution although with reduced cardiac output and no survival difference [7,8]. Critical illness polyneuropathyand polymyopathy is a syndrome that has to be always mentioned when facing patients with sepsis because,as it is noticed in this review, the incidence is often more than 50% in ICU patients. Finally it iswell pointed out in this review that sometimes organ dysfunction may be due to a therapeutic intervention.The use of packed erythrocyte transfusions, for example, is associated with the transmission of potentialviral and bacterial infections, immune modulation, graft-versus-host disease, volume overload, and transfusion-relatedacute lung injury [9,10]. Administration of packed erythrocytes has also been suspected of triggeringa proinflammatory response that may serve as a "second hit" which could trigger the development of multipleorgan dysfunction syndrome [11]. Thus the patient with sepsis is subject to the various complicationsthat are frequently encountered in the critically ill patient, many of which are preventable with theuse of prophylactic strategies. Sincerelly, Konstantinos G. Tsalis, Associate Professor of Surgery, SurgicalDepartment, Aristotle University of Thessaloniki, Thessaloniki, Greece, e-mail: ctsalis@med.auth.gr References:1. Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J: Septic shock; current pathogenetic conceptsfrom a clinical perspective. Med Sci Monit, 2005; 11(3): RA76-85 2. American College of Chest Physicians/Societyof Critical Care Medicine. Consensus Conference: definitions for sepsis and organ failure and guidelinesfor the use of innovative therapies in sepsis. Crit Care Med, 1992; 20: 864-74 3. Rangel-Frausto MS,Pittet D, Hwang T et al: The dynamics of disease progression in sepsis: Markov modeling describing thenatural history and the likely impact of effective antisepsis agents. Clin Infec Dis, 1998; 27: 185-904. Annane D, Aegerter P, Jars-Guinsestre MC, Guidet B: Current epidemiology of septic shock: the CUB-ReaNetwork. Am J Respir Crit Care Med, 2003; 1687: 165-72 5. Hotchkiss RS, Karl IE: The pathophysiologyand treatment of sepsis. N Engl J Med, 2003; 342: 138-50 6. Lopez A, Lorente JA, Steingrub J et al: Multiple-center,randomized, placebo-controlled, double-blind study of nitric oxide synthase inhibitor 546C88: effecton survival in patients with septic shock. Crit Care Med, 2004; 32: 21-30 7. Watson D, Grover R, AnzuetoA, et al. Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride(546C88)in patients with septic shock: results of a randomised, double-blind, placebo-controlled multicenterstudy(study no. 144-002). Crit Care Med, 2004; 32: 13-20 8. Bakker J, Griver R, McLuckie A et al: Administrationof nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride(546C88) by intravenous infusionfor up to 72 hours can promote the resolution of shock in patients with severe sepsis; results of a randomised,double-blind, placebo-controlled multicenter study(study no.144-002). Crit Care Med, 2004; 32-1-12 9.Kopko PM, Marshall CS, Mackenzie MR: Transfusion-related acute lung injury. JAMA, 2002; 287: 1968-7110. Tsalis K, Ganidou M, Blouchos K et al: Transfusion related acute lung injury: a life threateningtransfusion reaction. Med Sci Monit, 2005; 11(5): CS19-22 11. Aiboshi J, Moore EE, Ciesla DJ et al: Bloodtransfusion and the two-insult model of post-injury multiple organ failure. Shock, 2001; 12: 302-6.

Keywords: Nitric Oxide - metabolism, Shock, Septic - pathology