Is early goal-directed therapy associated with a higher risk of adverse events?

Area of Science:

• Critical Care Medicine
• Emergency Medicine
• Clinical Practice Guidelines

Background:

• The 2016 Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock recommended against early goal-directed therapy (EGDT).
• This recommendation was based on the ProCESS, ARISE, and ProMISe trials, which found no significant mortality difference between EGDT and usual care.
• The guidelines cited potential harms of EGDT outweighing benefits.

Purpose of the Study:

• To re-evaluate the evidence regarding early goal-directed therapy (EGDT) in septic shock management.
• To analyze potential benefits and harms of EGDT beyond mortality, considering subgroups and adverse events.

Main Methods:

• Analysis of data from three large-scale randomized controlled trials: ProCESS, ARISE, and ProMISe.
• Assessment of mortality and serious adverse events in patients receiving EGDT versus usual care.
• Subgroup analysis focusing on disease severity and physiological parameters like central venous oxygen saturation.

Main Results:

• While overall mortality showed no significant difference, a trend towards reduced serious adverse events was observed with EGDT (risk difference = -1%, 95% CI: -2% to 0%, P=0.05).
• EGDT may offer benefits in specific patient populations, including those with high disease severity and low central venous oxygen saturation.
• Potential benefits may be more pronounced when managed by less experienced healthcare staff.

Conclusions:

• The established guidelines against EGDT may not fully capture the nuanced benefits observed in specific septic shock patient subgroups.
• Further investigation into the role of EGDT in high-risk septic shock patients and under specific clinical conditions is warranted.
• Reconsideration of EGDT recommendations may be necessary based on a comprehensive analysis of risks and benefits, including serious adverse events.