Steven Q Simpson1, Melissa Gaines2, Youness Hussein3, Robert G Badgett4. 1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kansas University School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66160. Electronic address: ssimpson3@kumc.edu. 2. Kansas University School of Medicine - Wichita, Department of Internal Medicine, 1010 N Kansas, Wichita, KS 67214-3199. Electronic address: mgaines@kumc.edu. 3. Kansas University School of Medicine - Wichita, Department of Internal Medicine, 1010 N Kansas, Wichita, KS 67214-3199. 4. Kansas University School of Medicine - Wichita, Department of Internal Medicine and Department of Preventive Medicine and Public Health, 1010 N Kansas, Wichita, KS 67214-3199.
Abstract
Studies and meta-analyses conflict regarding the use of early goal-directed therapy (EGDT) for septic shock. We sought to clarify the conflict by performing a living systematic review and meta-regression. METHODS: We performed a meta-analysis and explored heterogeneity with meta-regression. We conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and qualified strength of evidence with a Grading of Recommendations Assessment, Development and Evaluation profile. RESULTS: Overall, EGDT did not significantly reduce mortality compared with usual care (relative risk, 0.85; 95% confidence interval, 0.67-1.08); however, heterogeneity was substantial (I2=64%; 95% confidence interval, 12%-85%). Illness severity did not correlate with mortality reduction; however, there were significant correlations with control rate mortality and the strategy employed by the control group. Benefit was confined to trials with a control mortality greater than 35%. Compared with monitoring of lactate clearance and central venous pressure, EGDT mortality was higher. CONCLUSION: The benefit of EGDT is evident in populations with high mortality, in line with reported global mortality rates. In settings with low mortality the recent trials challenge the need for 6-hour goals; however, most patients in these trials met 3-hour resuscitation goals as defined by the Surviving Sepsis Campaign. In settings with higher mortality, EGDT or normalization of lactate/central venous pressure may be viable therapeutic options.
Studies and meta-analyses conflict regarding the use of early goal-directed therapy (EGDT) for septic shock. We sought to clarify the conflict by performing a living systematic review and meta-regression. METHODS: We performed a meta-analysis and explored heterogeneity with meta-regression. We conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and qualified strength of evidence with a Grading of Recommendations Assessment, Development and Evaluation profile. RESULTS: Overall, EGDT did not significantly reduce mortality compared with usual care (relative risk, 0.85; 95% confidence interval, 0.67-1.08); however, heterogeneity was substantial (I2=64%; 95% confidence interval, 12%-85%). Illness severity did not correlate with mortality reduction; however, there were significant correlations with control rate mortality and the strategy employed by the control group. Benefit was confined to trials with a control mortality greater than 35%. Compared with monitoring of lactate clearance and central venous pressure, EGDT mortality was higher. CONCLUSION: The benefit of EGDT is evident in populations with high mortality, in line with reported global mortality rates. In settings with low mortality the recent trials challenge the need for 6-hour goals; however, most patients in these trials met 3-hour resuscitation goals as defined by the Surviving Sepsis Campaign. In settings with higher mortality, EGDT or normalization of lactate/central venous pressure may be viable therapeutic options.
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