Lactate clearance as a simple bedside instrument to predict short-term mortality of severe septic patients

Hambali, W 1 Chen, K 1 2 Widodo, D 1 2 Dewiasty, E 1 Pohan, HT 1 2 Suwarto, S 1 2

[1 ] Internal Medicine Department, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia

[2 ] The Indonesian Society for the Study of Tropical Medicine and Infectious Diseases, Jakarta, Indonesia


Severe sepsis is major health problem with a high mortality rate, and still its incidence continues to rise [ 1- 5]. Lactate clearance, measurement of the lactate level at two consecutive times, is an inexpensive and simple clinical parameter that can be obtained by a minimally invasive means [ 6- 8]. This parameter represents kinetic alteration of the anaerobic metabolism that makes it a potential parameter to evaluate disease severity and intervention adequacy. Lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with improved outcome [ 7- 9]. Nevertheless, the relationship between lactate clearance and short-term mortality in severe septic patients is still poorly understood. Understanding the presence of confounder factors is also important to strengthen the role of lactate clearance in the treatment of severe septic patients.


To evaluate the clinical course between lactate clearance groups, and determine the role of confounder variables that influence its relationship.


This is a prospective cohort study conducted in Ciptomangun-kusumo Hospital, from March to May 2011. Patients were categorized into the high lactate clearance group if there were differences in 6-hour lactate levels ≥10%, and conversely were categorized into the low lactate clearance group [ 7, 8]. Deaths were observed within the first 10 days. After data collection, the statistical methods were analyzed using survival analysis. Analysis of confounder variables was performed by multivariate Cox regression test.


During the research period there were 60 patients recruited, consisting of 30 patients grouped into high lactate clearance and the remainder grouped into low lactate clearance. The survival rates in high and low lactate clearance groups were 60.0% versus 26.7% (see Figure 1). In the low lactate clearance group the median survival was 3 days, while the mortality rate did not reach 50% in the high lactate clearance group. The first interquartile was 1 day and 4 days. The hazard ratio between groups was 2.87 (95% CI = 1.41 to 5.83). Steps taken to analyze the role of variables that potentially act as confounder factors were by using bivariate analysis, in which variables that influenced the occurrence of deaths (indicated by P < 0.25) underwent multivariate analysis subsequently. On multivariate analysis the presence of septic shock, degree of organ dysfunction, vasoactive drug usage, blood transfusion, and fluid resuscitation change the hazard ratio by no more than 10% (Table 1). For that reason, these parameters were not considered as confounders.

Figure 1

Kaplan-Meier curves between lactate clearance groups.

Kaplan-Meier curves between lactate clearance groups.
Table 1

Variables that potentially act as confounder factors

Variable Nonsurvivors Survivors P value Adjusted HR (95% CI) HR change (%)
Septic shock within 6 hours
 With septic shock 11 4 0.081 3.083 (1.505 to 6.317) 7.4
 Without septic shock 23 22
Initial SOFA score
 >9 11 3 0.038 2.919 (1.388 to 6.138) 1.7
 ≤9 19 21
Vasoactive drugs within 6 hours
 Without vasoactive drugs 22 23 0.013 2.988 (1.462 to 6.106) 4.1
 With vasoactive drugs 12 3
Invasive ventilation within 6 hours a
 Without mechanical ventilation 31 23 0.777 - -
 With mechanical ventilation 3 3
PRC transfusion within 6 hours
 Without transfusion 29 25 0.069 3.077 (1.493 to 6.340) 7.2
 With transfusion 5 1
Fluid resuscitation within 6 hours
 <1,000 cm 3 15 18 0.166 2.942 (1.444 to 5.994) 2.5
 ≥1,000 cm 3 19 8

HR, hazard ratio; SOFA, Sequential Organ Failure Assessment; PRC, packed red cells. aInvasive ventilation parameter not included in multivariate analysis, because P < 0.25.


Severe septic patients with high lactate clearance have a better survival rate compared with the low lactate clearance group, and its relationship is not influenced by the presence of confounder variables.


The authors thank the nurses and administrative staff in the Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, Faculty Medicine, University of Indonesia for their assistance in this study.


Moss MEpidemiology of sepsis: race, sex, and chronic alcohol abuseClin Infect Dis(2005) 41: Suppl 7S490S497 Pubmed ID: 16237652


Guidet B, Aegerter P, Gauzit R, Meshaka P, Dreyfuss DIncidence and impact of organ dysfunctions associated with sepsisChest(2005) 127: 942951 10.1378/chest.127.3.942 Pubmed ID: 15764780


O'brien JMJr, Ali NA, Abraham EYear in review in critical care, 2004: sepsis and multi-organ failureCrit Care(2005) 9: 409413 10.1186/cc3728 Pubmed ID: 16137392


Ely EW, Kleinpell RM, Goyette REAdvances in the understanding of clinical manifestations and therapy of severe sepsis: an update for critical care nursesAm J Crit Care(2003) 12: 120133 Pubmed ID: 12625170


Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MREpidemiology of severe sepsis in the united states: analysis of incidence, outcome, and associated costs of careCrit Care Med(2001) 29: 13031310 10.1097/00003246-200107000-00002 Pubmed ID: 11445675


Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, Suarez A, Parekh H, Jaehne A, Rivers EPEarly lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shockJ Inflamm(2010) 7: 617 10.1186/1476-9255-7-6


Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MCEarly lactate clearance is associated with improved outcome in severe sepsis & septic shockCrit Care Med(2004) 32: 16371642 10.1097/01.CCM.0000132904.35713.A7 Pubmed ID: 15286537


Arnold RC, Shapiro NI, Jones AE, Schorr C, Pope J, Casner E, Parrillo JE, Dellinger P, Trzeciak SMulticenter study of early lactate clearance as a determinant of survival in patients with presumed sepsisShock(2009) 32: 3539 10.1097/SHK.0b013e3181971d47 Pubmed ID: 19533847


Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JALactate clearance vs central venous oxygen saturation as goals of early sepsis therapyJAMA(2010) 303: 739746 10.1001/jama.2010.158 Pubmed ID: 20179283