Early, Goal-Directed Therapy Doesn’t Improve Mortality in Patients with Early Septic Shock

Clinical question: Does early goal-directed therapy (EGDT) improve mortality in patients presenting to the ED with early septic shock?

Background: EGDT (achieving central venous pressure of 8-12 mmHg, superior vena oxygen saturation (ScvO2) of > 70%, mean arterial pressure ≥ 65mmHg, and urine output ≥ 0.5 mL/kg/h) has been endorsed by the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients with septic shock, but its effectiveness is uncertain and has been questioned by a recent randomized trial.

Study design: Prospective, randomized, parallel group trial.

Setting: Fifty-one tertiary and non-tertiary care metropolitan and rural hospitals, mainly in Australia and New Zealand.

Synopsis: Researchers randomized 1,600 patients who presented to the ED with early septic shock (evidence of refractory hypotension or hypoperfusion) to receive EGDT or usual care for six hours. All patients received antimicrobials and fluid resuscitation (approximately 2.5 liters) before randomization. There was no significant difference between the groups for the primary outcome (all-cause mortality at 90 days), but the EGDT group was more likely to receive vasopressor support and red blood cell transfusions and to have invasive monitoring.

Analysis for the whole group and various patient subgroups (location, age, APACHE II score, and others) did not show any benefit from using EGDT for any outcomes (including length of stay in ICU and hospital, invasive mechanical ventilation, and use of renal replacement therapy).

This study confirms that early diagnosis and aggressive treatment of sepsis is crucial. EGDT might be less important when fluid resuscitation and antimicrobials are started early after sepsis is suspected. With continuous improvement in these areas, monitoring of certain parameters as required in EGDT (like ScvO2, which requires a special catheter) might not be as important.

Bottom line: Early-goal directed therapy is not associated with improved mortality in sepsis in patients treated early with antimicrobials and aggressive fluid resuscitation.

Citation: ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Eng J Med. 2014;371(16):1496-1506.

Clinical question: Does early goal-directed therapy (EGDT) improve mortality in patients presenting to the ED with early septic shock?

Background: EGDT (achieving central venous pressure of 8-12 mmHg, superior vena oxygen saturation (ScvO2) of > 70%, mean arterial pressure ≥ 65mmHg, and urine output ≥ 0.5 mL/kg/h) has been endorsed by the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients with septic shock, but its effectiveness is uncertain and has been questioned by a recent randomized trial.

Study design: Prospective, randomized, parallel group trial.

Setting: Fifty-one tertiary and non-tertiary care metropolitan and rural hospitals, mainly in Australia and New Zealand.

Synopsis: Researchers randomized 1,600 patients who presented to the ED with early septic shock (evidence of refractory hypotension or hypoperfusion) to receive EGDT or usual care for six hours. All patients received antimicrobials and fluid resuscitation (approximately 2.5 liters) before randomization. There was no significant difference between the groups for the primary outcome (all-cause mortality at 90 days), but the EGDT group was more likely to receive vasopressor support and red blood cell transfusions and to have invasive monitoring.

Analysis for the whole group and various patient subgroups (location, age, APACHE II score, and others) did not show any benefit from using EGDT for any outcomes (including length of stay in ICU and hospital, invasive mechanical ventilation, and use of renal replacement therapy).

This study confirms that early diagnosis and aggressive treatment of sepsis is crucial. EGDT might be less important when fluid resuscitation and antimicrobials are started early after sepsis is suspected. With continuous improvement in these areas, monitoring of certain parameters as required in EGDT (like ScvO2, which requires a special catheter) might not be as important.

Bottom line: Early-goal directed therapy is not associated with improved mortality in sepsis in patients treated early with antimicrobials and aggressive fluid resuscitation.

Citation: ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Eng J Med. 2014;371(16):1496-1506.

Clinical question: Does early goal-directed therapy (EGDT) improve mortality in patients presenting to the ED with early septic shock?

Background: EGDT (achieving central venous pressure of 8-12 mmHg, superior vena oxygen saturation (ScvO2) of > 70%, mean arterial pressure ≥ 65mmHg, and urine output ≥ 0.5 mL/kg/h) has been endorsed by the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients with septic shock, but its effectiveness is uncertain and has been questioned by a recent randomized trial.

Study design: Prospective, randomized, parallel group trial.

Setting: Fifty-one tertiary and non-tertiary care metropolitan and rural hospitals, mainly in Australia and New Zealand.

Synopsis: Researchers randomized 1,600 patients who presented to the ED with early septic shock (evidence of refractory hypotension or hypoperfusion) to receive EGDT or usual care for six hours. All patients received antimicrobials and fluid resuscitation (approximately 2.5 liters) before randomization. There was no significant difference between the groups for the primary outcome (all-cause mortality at 90 days), but the EGDT group was more likely to receive vasopressor support and red blood cell transfusions and to have invasive monitoring.

Analysis for the whole group and various patient subgroups (location, age, APACHE II score, and others) did not show any benefit from using EGDT for any outcomes (including length of stay in ICU and hospital, invasive mechanical ventilation, and use of renal replacement therapy).

This study confirms that early diagnosis and aggressive treatment of sepsis is crucial. EGDT might be less important when fluid resuscitation and antimicrobials are started early after sepsis is suspected. With continuous improvement in these areas, monitoring of certain parameters as required in EGDT (like ScvO2, which requires a special catheter) might not be as important.

Bottom line: Early-goal directed therapy is not associated with improved mortality in sepsis in patients treated early with antimicrobials and aggressive fluid resuscitation.

Citation: ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Eng J Med. 2014;371(16):1496-1506.