LACTATE, PROCALCITONIN, AND AMINO-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE VERSUS CYTOKINE MEASUREMENTS AND CLINICAL SEVERITY SCORES FOR PROGNOSTICATION IN SEPTIC SHOCK

The biomarkers lactate, procalcitonin, and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are often promoted as being useful for prognostication in septic shock. This study aimed to compare the prognostic utility of these biomarkers with each other and with cytokine measurements and clinical severity scores, and to assess how these biomarkers may be combined to improve their prognostic utility. Seventy-two patients with septic shock were studied. The biomarkers were measured on the first 3 days of stay in the intensive care unit together with serum IL-1&bgr;, IL-6, IL-10, and TNF-&agr; levels. Although elevated baseline lactate levels predicted 28-day mortality, elevated procalcitonin and NT-proBNP levels were only predictive from days 2 and 3, respectively. The prognostic utility of baseline lactate levels was poorer than that of baseline cytokine levels, the Acute Physiology and Chronic Health Evaluation II score, and the Sequential Organ Failure Assessment score. However, a rising trend in lactate and procalcitonin levels between days 1 and 2 had superior prognostic utility compared with absolute levels. Indeed, using multivariate analysis, the presence of a concurrent increase in both lactate and procalcitonin levels between days 1 and 2 superseded all cytokine measurements and clinical severity scores as the sole independent predictor of 28-day mortality. In conclusion, elevated baseline lactate levels offer superior prognostic accuracy to baseline procalcitonin levels, which in turn are superior to NT-proBNP levels. To improve their prognostic utility beyond those of cytokine measurements and clinical severity scores, serial lactate and procalcitonin measurements may be combined.ABBREVIATIONS - APACHE-Acute Physiology and Chronic Health Evaluation; CI-confidence interval; ICU-intensive care unit; NPV-negative predictive value; NS-not significant; NT-proBNP-amino-terminal pro-B-type natriuretic peptide; OR-odds ratio; PPV-positive predictive value; ROC-receiver operating characteristics; rs-Spearman &rgr;; SOFA-Sequential Organ Failure Assessment

[1]  D. Pittet,et al.  Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. , 2001, American journal of respiratory and critical care medicine.

[2]  S. Trzeciak,et al.  A novel biomarker panel with a Multimarker Index value for the diagnosis of sepsis in the Emergency Department , 2006, Critical Care.

[3]  J. Vincent,et al.  Blood lactate levels are better prognostic indicators than TNF and IL-6 levels in patients with septic shock , 1996, Intensive Care Medicine.

[4]  D. Annane,et al.  A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. , 2000, JAMA.

[5]  K. Werdan,et al.  Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction , 2003, Intensive Care Medicine.

[6]  G. Hillis,et al.  B‐Type natriuretic peptide and the prediction of outcome in patients admitted to intensive care , 2005, Anaesthesia.

[7]  R. Westendorp,et al.  Endotoxin, cytokines, and procalcitonin in febrile patients admitted to the hospital: identification of subjects at high risk of mortality. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  J. Jensen,et al.  Procalcitonin increase in early identification of critically ill patients at high risk of mortality* , 2006, Critical care medicine.

[9]  Mitchell M. Levy,et al.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference , 2003, Intensive Care Medicine.

[10]  J. Chiche,et al.  Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis , 2004, Critical care medicine.

[11]  T. Yamashita,et al.  Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. , 1999, Critical care medicine.

[12]  S. Bornstein,et al.  Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: Diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol , 2003, Critical care medicine.

[13]  P. Bollaert,et al.  Baseline Cortisol Levels, Cortisol Response to Corticotropin, and Prognosis in Late Septic Shock , 2003, Shock.

[14]  Patrick Nicolas,et al.  Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: A systematic review and meta-analysis , 2006, Critical care medicine.

[15]  T. Fehr,et al.  Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. , 2006, Chest.

[16]  J. Puyana,et al.  A membrane TNF-alpha/TNFR ratio correlates to MODS score and mortality. , 1996, Shock.

[17]  M. Meisner Biomarkers of sepsis: clinically useful? , 2005, Current opinion in critical care.

[18]  G. Jacobsen,et al.  Early lactate clearance is associated with improved outcome in severe sepsis and septic shock* , 2004, Critical care medicine.

[19]  H. K. Bourns Management of Sepsis , 1960, The Medical journal of the South-West.

[20]  M. Béné,et al.  Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis , 2005, Critical care medicine.

[21]  S. Tschoeke,et al.  PLASMA CYTOKINE MEASUREMENTS AUGMENT PROGNOSTIC SCORES AS INDICATORS OF OUTCOME IN PATIENTS WITH SEVERE SEPSIS , 2005, Shock.

[22]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .

[23]  K. Okuchi,et al.  PROGNOSTIC VALUE OF INCREASED PLASMA LEVELS OF BRAIN NATRIURETIC PEPTIDE IN PATIENTS WITH SEPTIC SHOCK , 2006, Shock.

[24]  A. Loundou,et al.  NH2 terminal pro–brain natriuretic peptide plasma level as an early marker of prognosis and cardiac dysfunction in septic shock patients* , 2005, Critical care medicine.

[25]  M. Borggrefe,et al.  Increased plasma levels of NT-proANP and NT-proBNP as markers of cardiac dysfunction in septic patients. , 2005, Clinical laboratory.

[26]  X Viviand,et al.  Effect of norepinephrine on the outcome of septic shock , 2000, Critical care medicine.

[27]  Djillali Annane,et al.  Current epidemiology of septic shock: the CUB-Réa Network. , 2003, American journal of respiratory and critical care medicine.

[28]  Hui-ying Zhao,et al.  [Prognostic values of B-type natriuretic peptide in severe sepsis and septic shock]. , 2009, Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue.

[29]  Djillali Annane,et al.  Cardiovascular response to dopamine and early prediction of outcome in septic shock: A prospective multiple-center study* , 2005, Critical care medicine.

[30]  K. Larsen,et al.  Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study , 2007, Critical care.

[31]  E. Ruokonen,et al.  Predictive value of N-terminal pro–brain natriuretic peptide in severe sepsis and septic shock* , 2007, Critical care medicine.

[32]  C. Clec’h,et al.  Diagnostic and prognostic value of procalcitonin in patients with septic shock , 2004, Critical care medicine.

[33]  M. Levy,et al.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference , 2003, Intensive care medicine.

[34]  V. Pettilä,et al.  Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis , 2002, Intensive Care Medicine.

[35]  T. Hornemann,et al.  Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure* , 2006, Critical care medicine.

[36]  G. Slotman Prospectively validated prediction of organ failure and hypotension in patients with septic shock: the Systemic Mediator Associated Response Test (SMART). , 2000, Shock.

[37]  F. Gorus,et al.  Plasma procalcitonin and C-reactive protein in acute septic shock: Clinical and biological correlates , 2002, Critical care medicine.