Intensive Care Med (2015) 41:1862–1863

DOI 10.1007/s00134-015-3955-2 LETTER

Wan-Jie Gu the potential to be such a promising event proportion obtained from the
Zhongheng Zhang goal for quantitative resuscitation. results of the meta-analysis, and a
Jan Bakker We performed a meta-analysis of relative risk reduction of 20 % in
randomized controlled trials (RCTs) all-causes mortality, using standard
to evaluate the effect of early lactate software TSA version 0.9 Beta
clearance-guided therapy on mortality (http://www.ctu.dk/tsa).
Early lactate clearance-guided and other outcomes in patients with Four RCTs enrolling 547 patients
sepsis. were included in the meta-analysis
therapy in patients with sepsis: We searched PubMed, Embase, [2–5]. The main characteristics of the
a meta-analysis with trial and Cochrane Central Register of four included RCTs are presented in
sequential analysis Controlled Trials to identify RCTs Table 1 in the Electronic Supple-
of randomized controlled trials that evaluated the effect of early mentary Material (ESM). Assessment
lactate clearance-guided therapy on of the risk of bias is summarized in
Accepted: 8 June 2015 clinical outcomes in adults with Table 2 (ESM). Overall, two RCTs
Published online: 8 July 2015 sepsis. The search terms used were were categorized as at lower risk of
Ó Springer-Verlag Berlin Heidelberg and ‘‘lactate clearance’’, and ‘‘sepsis’’, or bias [2, 3], and two as at unclear risk
ESICM 2015 ‘‘severe sepsis’’ or ‘‘septic shock’’. of bias [4, 5]. Data on primary out-
W.-J. Gu and Z. Zhang contribute equally to We used the Cochrane collaboration come were provided in all four trials
the work. tool to assess risk of bias, and the (547 patients) [2–5]. Early lactate
GRADE (Grades of Recommenda- clearance-guided therapy was associ-
Electronic supplementary material tion, Assessment, Development and ated with a reduction in mortality (RR
The online version of this article
(doi:10.1007/s00134-015-3955-2) contains Evaluation) approach to evaluate the 0.65, 95 % CI 0.49–0.85, p = 0.002,
supplementary material, which is available quality of evidence. The primary I2 = 0 %, Fig. 1). TSA showed that
to authorized users. outcome was all-cause mortality. 34.5 % of the required information
Secondary outcomes included length size of 1586 patients were accrued.
of hospital stay and length of inten- The cumulative z curve crossed the
sive care unit (ICU) stay. We conventional boundary for benefit but
Dear Editor, calculated risk ratios (RRs) or mean did not cross the trial sequential
Sepsis represents a global problem differences (MDs) and 95 % confi- monitoring boundary for benefit,
with high economic burden for health dence intervals (CIs) using a random- showing that currently cumulative
care systems. Since 2002, the Sur- effects model. A two-tailed p value evidence is inconclusive, as shown in
viving Sepsis Campaign has less than 0.05 was considered a sig- Fig. 3 (ESM). For secondary out-
recommended early quantitative nificant level except for where a comes, early lactate clearance-guided
resuscitation for patients with severe certain p value has been given. All therapy had no effect on length of
sepsis and septic shock with a recent statistical analyses were performed hospital stay (weighted mean differ-
update [1]. However, the optimal using RevMan 5.2 (Nordic Cochrane ence, WMD –0.13 days, 95 %
goals for quantitative resuscitation Centre). We conducted trial sequen- CI –4.58 to 4.31, three RCTs [2, 3, 5])
remain uncertain. Lactate clearance, tial analysis (TSA) using a diversity- and length of ICU stay (WMD
defined by the change of lactate levels adjusted required information size –1.54 days, 95 % CI –3.22 to 0.15,
between two points in time, as a more calculated from an alpha error of four RCTs [2–5]), as shown in Fig. 2
rapid and less costly parameter, has 0.05, a beta error of 0.20, a control (ESM). The GRADE evidence

Fig. 1 Forest plot depicting mortality

profiles for the primary and secondary 2. Jansen TC, van Bommel J, J. Bakker ())
outcomes are summarized in Table 3 Schoonderbeek FJ et al (2010) Early Department of Intensive Care Adults,
lactate-guided therapy in intensive care Erasmus MC University Medical Centre,
(ESM). The GRADE level of evi- unit patients: a multicenter, open-label, P.O. Box 2040, Room H625, 3000CA
dence was moderate for all-cause randomized controlled trial. Am J Respir Rotterdam, The Netherlands
mortality, and low for length of hos- Crit Care Med 182:752–761 e-mail: jan.bakker@erasmusmc.nl
pital stay and length of ICU stay. 3. Jones AE, Shapiro NI, Trzeciak S et al
(2010) Lactate clearance vs central
In summary, the use of lactate venous oxygen saturation as goals of J. Bakker
clearance as a goal to guide early early sepsis therapy: a randomized Department of Intensive Care, Pontificia
therapy is associated with a reduction clinical trial. JAMA 303:739–746 Universidad Católica de Chile, Santiago,
in the risk of death in adult patients 4. Tian HH, Han SS, Lv CJ et al (2012) The Chile
with sepsis. However, caution should effect of early goal lactate clearance rate
on the outcome of septic shock patients J. Bakker
be used to translate these findings to with severe pneumonia. Zhongguo Wei Division of Pulmonary and Critical Care,
clinical protocols, because data were Zhong Bing Ji Jiu Yi Xue 24:42–45 Columbia University College for Physicians
limited by insufficient information 5. Yu B, Tian HY, Hu ZJ et al (2013) and Surgeons/New York Presbyterian
size. Further, the underlying mecha- Comparison of the effect of fluid
resuscitation as guided either by lactate Hospital, New York, USA
nisms by which lactate clearance- clearance rate or by central venous
guided therapy benefits these patients oxygen saturation in patients with sepsis.
remain to be investigated. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
25:578–583
Compliance with Ethical Standards

Conflicts of interest The authors declare to W.-J. Gu

References Z. Zhang
Department of Critical Care Medicine,
1. Dellinger RP, Levy MM, Rhodes A et al Jinhua Municipal Central Hospital, Jinhua
(2013) Surviving Sepsis Campaign: Hospital of Zhejiang University, Jinhua,
international guidelines for management China
of severe sepsis and septic shock, 2012.
Intensive Care Med 39:165–228