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The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials.

Gu WJ, Wang F, Bakker J, Tang L, Liu JC - Crit Care (2014)

Bottom Line: The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis.GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I 2 = 56%).However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial showed no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality due to sepsis.

Methods: We searched the PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases and reference lists of extracted articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.

Results: In total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I 2 = 56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that a mortality benefit was seen only in the subgroup of early GDT within the first 6 hours (seven trials; RR, 0.77; 95% CI, 0.67 to 0.89; P =0.0004; I 2 = 40%), but not in the subgroup with late or unclear timing of GDT (six trials; RR, 0.92; 95% CI, 0.69 to 1.24; P =0.59; I 2 = 56%). GDT was significantly associated with the use of dobutamine (five trials; RR, 2.71; 95% CI, 1.20 to 6.10; P =0.02).

Conclusions: The results of the present meta-analysis suggest that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

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Related in: MedlinePlus

Risk of bias summary.
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Fig2: Risk of bias summary.

Mentions: The details of risk of bias are summarized in Figure 2. Five trials were judged to be at low risk of bias [6,7,19,21,22], and eight trials were judged to be at unclear risk of bias [16-18,20,23-26]. Adequate randomized sequences were generated in eight trials [6,7,17-19,21,22,26], and the investigators in five trials reported appropriate allocation concealment [6,7,19,21,22]. Among the 13 RCTs, none were double-blinded. However, blinding of patients and clinicians was extremely difficult in these trials to evaluate a complex intervention such as a GDT protocol, and we judged that the primary outcome (that is, overall mortality) was not likely to be influenced by lack of blinding.Figure 2


The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials.

Gu WJ, Wang F, Bakker J, Tang L, Liu JC - Crit Care (2014)

Risk of bias summary.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232636&req=5

Fig2: Risk of bias summary.
Mentions: The details of risk of bias are summarized in Figure 2. Five trials were judged to be at low risk of bias [6,7,19,21,22], and eight trials were judged to be at unclear risk of bias [16-18,20,23-26]. Adequate randomized sequences were generated in eight trials [6,7,17-19,21,22,26], and the investigators in five trials reported appropriate allocation concealment [6,7,19,21,22]. Among the 13 RCTs, none were double-blinded. However, blinding of patients and clinicians was extremely difficult in these trials to evaluate a complex intervention such as a GDT protocol, and we judged that the primary outcome (that is, overall mortality) was not likely to be influenced by lack of blinding.Figure 2

Bottom Line: The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis.GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I 2 = 56%).However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial showed no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality due to sepsis.

Methods: We searched the PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases and reference lists of extracted articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.

Results: In total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I 2 = 56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that a mortality benefit was seen only in the subgroup of early GDT within the first 6 hours (seven trials; RR, 0.77; 95% CI, 0.67 to 0.89; P =0.0004; I 2 = 40%), but not in the subgroup with late or unclear timing of GDT (six trials; RR, 0.92; 95% CI, 0.69 to 1.24; P =0.59; I 2 = 56%). GDT was significantly associated with the use of dobutamine (five trials; RR, 2.71; 95% CI, 1.20 to 6.10; P =0.02).

Conclusions: The results of the present meta-analysis suggest that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

Show MeSH
Related in: MedlinePlus