Early goal-directed therapy in the management of severe sepsis or septic shock in adults: a meta-analysis of randomized controlled trials

Research article

Ling Zhang¹, Guijun Zhu², Li Han³ and Ping Fu^4*

• *
  Corresponding author: Ping Fu [email protected]

Author Affiliations

¹ Division of Nephrology and Intensive Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China

² Division of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

³ Division of Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan, China

⁴ Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China

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BMC Medicine 2015, 13:71 
doi:10.1186/s12916-015-0312-9

Published: 3 April 2015

Abstract (provisional)

Background The Surviving Sepsis Campaign guidelines have proposed early goal-directed
therapy (EGDT) as a key strategy to decrease mortality among patients with severe
sepsis or septic shock. However, its effectiveness is uncertain. Methods We searched
for relevant studies in Medline, Embase, the Cochrane Library, Google Scholar, and
a Chinese database (SinoMed), as well as relevant references from January 1966 to
October 2014. We performed a systematic review and meta-analysis of all eligible randomized
controlled trials (RCTs) of EGDT for patients with severe sepsis or septic shock.
The primary outcome was mortality; secondary outcomes were length of ICU and in-hospital
stay, mechanical ventilation support, vasopressor and inotropic agents support, fluid
administration, and red cell transfusion. We pooled relative risks (RRs) or weighted
mean differences (MDs) with 95% confidence intervals (95% CI) using Review Manager
5.2. Results We included 10 RCTs from 2001 to 2014 involving 4,157 patients. Pooled
analyses of all studies showed no significant difference in mortality between the
EGDT and the control group (RR 0.91, 95%CI: 0.79 to 1.04, P?=?0.17), with substantial
heterogeneity (?2?=?23.65, I 2?=?58%). In the subgroup analysis, standard EGDT, but
not modified EGDT, was associated with lower mortality rate in comparison with the
usual care group (RR 0.84, 95%CI: 0.72 to 0.98, P?=?0.03). However, EGDT was associated
with a higher mortality rate in comparison with the early lactate clearance group
(RR 1.52, 95%CI: 1.06 to 2.18, P?=?0.02). In the first 6 h, compared with usual care,
patients in EGDT received more inotropic agents (P?=?0.04), fluid administration (P?=?0.05),
and red cell transfusion (P?lt;?0.01). There were no significant differences in length
of ICU stay (P?=?0.73) or in-hospital stay (P?=?0.57), ventilation rate (P?=?0.53),
and vasopressor support (P?=?0.63). Conclusions EGDT was not associated with a survival
benefit among patients with severe sepsis or septic shock. Instead, EGDT was associated
with a higher mortality rate in comparison to the early lactate clearance group. Further
high-quality RCTs comparing EGDT with early lactate clearance are desirable.