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Meta-Analysis
. 2015 Feb 24;10(2):e0117279.
doi: 10.1371/journal.pone.0117279. eCollection 2015.

Antipyretic therapy in critically ill patients with established sepsis: a trial sequential analysis

Zhongheng Zhang  1
Affiliations
Meta-Analysis

V体育平台登录 - Antipyretic therapy in critically ill patients with established sepsis: a trial sequential analysis

Zhongheng Zhang. PLoS One. .

V体育2025版 - Abstract

Background and objective: antipyretic therapy for patients with sepsis has long been debated. The present study aimed to explore the beneficial effect of antipyretic therapy for ICU patients with sepsis VSports手机版. .

Design: systematic review and trial sequential analysis of randomized controlled trials. V体育安卓版.

Database: Pubmed, Scopus, EBSCO and EMBASE were searched from inception to August 5, 2014 V体育ios版. .

Methods: Mortality was dichotomized as binary outcome variable and odds ratio (OR) was chosen to be the summary statistic. Pooled OR was calculated by using DerSimonian and Laird method VSports最新版本. Statistical heterogeneity was assessed by using the statistic I2. Trial sequential analysis was performed to account for the small number of trials and patients. .

Main results: A total of 6 randomized controlled trials including 819 patients were included into final analysis. Overall, there was no beneficial effect of antipyretic therapy on mortality risk in patients with established sepsis (OR: 1. 02, 95% CI: 0. 50-2. 05). The required information size (IS) was 2582 and our analysis has not yet reached half of the IS. The Z-curve did not cross the O'Brien-Fleming α-spending boundary or reach the futility, indicating that the non-significant result was probably due to lack of statistical power V体育平台登录. .

Conclusion: our study fails to identify any beneficial effect of antipyretic therapy on ICU patients with established diagnosis of sepsis. Due to limited number of total participants, more studies are needed to make a conclusive and reliable analysis VSports注册入口. .

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VSports注册入口 - Conflict of interest statement

Competing Interests: The author has declared that no competing interests exist.

VSports在线直播 - Figures

Fig 1
Fig 1. Flowchart of study selection.
The initial search identified 402 citations after exclusion of duplicates. 382 of them were excluded by reviewing the titles and abstracts. The remaining 20 articles were clinical studies, in which six studies investigated hypothermia in patients with brain injury, three involved infants or children, and five were observational studies. As a result, a total of 6 randomized controlled trials were included into final analysis.
Fig 2
Fig 2. Overall effect pooled across all included trials by using random-effects model.
Only one study showed statistically beneficial effect of antipyretic therapy on mortality risk (OR: 0.44, 95% CI: 0.23–0.85), and other trials all showed neutral effect. There was significant heterogeneity among component trials as indicated by an I2 of 71.7% (p = 0.003). A total of 819 patients were included in the meta-analysis, including 411 in the treatment group and 408 in the control group. Overall, there was no beneficial effect of antipyretic therapy on mortality risk in patients with established sepsis (OR: 1.02, 95% CI: 0.50–2.05).
Fig 3
Fig 3. Meta-analysis with repeated non-superiority, non-inferiority and two-sided significance testing boundaries.
The required information size (IS) was 2582 and our analysis has not yet reached half of the IS. The Z-curve did not cross the O’Brien-Fleming α-spending boundary or reach the futility, indicating that the non-significant result was probably due to lack of statistical power.
Fig 4
Fig 4. Publication bias was assessed by using Egger’s regression test.
The standard normal deviate (SND) is regressed against the estimates precision. The intercept of the regression line is 0.76 (95% CI: -3.74–5.25), indicating no statistically significant publication bias.
Fig 5
Fig 5. Subgroup analysis by restricting to patients with septic shock.
Three trials fulfilled this criterion and the result showed there was no beneficial effect of antipyretic therapy on reducing mortality rate (OR: 1.11, 95% CI: 0.39–3.13).
Fig 6
Fig 6. Subgroup analysis stratified by the duration of antipyretic therapy.
The result showed that there was no treatment effect with antipyretic therapy in neither the subgroup with treatment<48 hours (OR: 0.73, 95% CI: 0.37–1.41) nor the subgroup with treatment>48 hours (OR: 2.01, 95% CI: 0.36–11.16).
Fig 7
Fig 7. Subgroup analysis stratified by the mode of antipyretic therapy (antipyretic medication vs. external cooling).
The result showed that there was no treatment effect with antipyretic therapy in neither the subgroup of antipyretic medication (OR: 0.90, 95% CI: 0.51–1.57) nor the subgroup of external cooling (OR: 1.38, 95% CI: 0.14–13.81).
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