Therapeutics
Early goal-directed therapy did not reduce mortality more than usual care in early septic shock 多多多多多多多
Clinical impact ratings:
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The ARISE Investigators and the ANZICS Clinical Trials Group. Goaldirected resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-506.
多多多多多多夞
Question
Main results
In patients who present to the emergency department (ED) with early septic shock, does early goal-directed therapy (EGDT) reduce mortality more than usual care?
The main results are in the Table.
Methods Design: Randomized controlled trial (RCT) (Australasian Resuscitation in Sepsis Evaluation [ARISE] study). ClinicalTrials.gov NCT00975793. Allocation: Concealed.*
Conclusion In patients who presented to the emergency department with early septic shock, early goal-directed therapy did not reduce 90-day mortality more than usual care. *See Glossary. Sources of funding: National Health and Medical Research Council of Australia and Alfred Foundation.
Blinding: Unblinded.* Follow-up period: 90 days. Setting: 51 hospitals in Australia, New Zealand, Finland, Hong Kong, and the Republic of Ireland that did not have sepsis resuscitation protocols or resuscitation guided by ScvO2 measurement. Patients: 1600 adults ≥ 18 years of age (mean age 63 y, 60% men) who had suspected or confirmed infections; evidence of refractory hypotension or hypoperfusion; and ≥ 2 of core temperature > 38° C or < 36° C, heart rate > 90 beats/min, respiratory rate > 20 breaths/min or PaC02 < 32 mm Hg or need for invasive mechanical ventilation for an acute process, or white cell count > 12.0 x 109/L or < 4.0 x 109/L or > 10% immature band forms. Exclusion criteria included hemodynamic instability due to active bleeding, inpatient transfer from another acute health care facility, contraindication to blood products or central venous catheter insertion in the superior vena cava, death imminent and inevitable or expected within 90 days, or inability to begin EGDT within 1 hour of randomization or to deliver EGDT for 6 hours. Eligibility criteria had to be met within 6 hours of ED presentation. Intervention: EGDT (n = 796) or usual care (n = 804). EGDT was delivered in the ED and/or intensive care unit by a study team trained in its delivery. Arterial and central venous catheters capable of continuous measurement of ScvO2 were inserted. Resuscitation followed an EGDT algorithm. Outcomes: Mortality at 90 days. Secondary outcomes included use of invasive mechanical ventilation, vasopressor support, and renal replacement therapy. The study had 85% to 90% power to detect a relative risk reduction of 20% from a baseline 90-day mortality rate of 28% (␣ = 0.05).
For correspondence: Ms. B. Howe, Australian and New Zealand Intensive Care Research Center, Melbourne, Victoria, Australia. E-mail [email protected].
Commentary EGDT was introduced in 2001 and changed how sepsis would be treated (1). The ARISE trial showed that EGDT and standard therapy did not differ. However, ARISE, like the ProCESS trial (2), does not disprove the efficacy of EGDT as much as it reaffirms that standard therapy has been fundamentally transformed to include many of the core principles of EGDT. Usual care today looks like EGDT and is much different than standard sepsis treatment in 2001. Mortality from sepsis has decreased 2% to 3% per year over the past decade (3). Early recognition and aggressive fluid resuscitation are now standard, and the fluid volume used in the usual care group in ARISE was closer to the volume used in the EGDT group than it was to the standard therapy in the original 2001 EGDT study (1). Vasopressor use is much more prevalent now. Notably, early use of antibiotics is no longer in question (4). While the 2001 EGDT study evaluated the percentage of antibiotics administered within 6 hours, it is now assumed that antibiotics will be administered rapidly; in ARISE, time to administration was measured in minutes. This publicly funded RCT, which was done in various health care settings around the world, clarifies which features of EGDT are important and provides insight into how far we've come in sepsis management. However, EGDT as a protocol does not seem to increase survival. Andrew Muck, MD Bruce D. Adams, MD Department of Emergency Medicine University Hospital, San Antonio UT School of Medicine San Antonio San Antonio, Texas, USA
Patient follow-up: 99% for primary outcome (intention-to-treat analysis).
Early goal-directed therapy (EGDT) vs usual care in septic shock† Outcomes
EGDT
Usual care
RRR (95% CI)
NNT (CI)
Mortality at 90 d
18.6%
18.8%
2% (⫺21 to 20)
Not significant
30%
32%
5% (⫺11 to 18)
Not significant
13.4%
13.5%
1% (⫺27 to 23)
Not significant
RRI (CI)
NNH (CI)
76%
66%
16% (9 to 24)
10 (7 to 17)
Invasive mechanical ventilation Renal replacement therapy
Vasopressor support
†Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from relative risks and usual care event rates in article.
姝 2015 American College of Physicians
JC4
References 1. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77. 2. ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014; 370:1683-93. 3. Lagu T, Rothberg MB, Shieh MS, et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40:754-61. 4. Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goaldirected therapy was initiated in the emergency department. Crit Care Med. 2010;38:1045-53.
ACP Journal Club
Annals of Internal Medicine
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/933569/ by a Fudan University User on 03/03/2017
17 March 2015
Early goal-directed therapy did not reduce mortality more than usual care in early septic shock 多多多多多多多
Clinical impact ratings:
多多多多多夞夞
多多多多多多夞
The ARISE Investigators and the ANZICS Clinical Trials Group. Goaldirected resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-506.
多多多多多多夞
Question
Main results
In patients who present to the emergency department (ED) with early septic shock, does early goal-directed therapy (EGDT) reduce mortality more than usual care?
The main results are in the Table.
Methods Design: Randomized controlled trial (RCT) (Australasian Resuscitation in Sepsis Evaluation [ARISE] study). ClinicalTrials.gov NCT00975793. Allocation: Concealed.*
Conclusion In patients who presented to the emergency department with early septic shock, early goal-directed therapy did not reduce 90-day mortality more than usual care. *See Glossary. Sources of funding: National Health and Medical Research Council of Australia and Alfred Foundation.
Blinding: Unblinded.* Follow-up period: 90 days. Setting: 51 hospitals in Australia, New Zealand, Finland, Hong Kong, and the Republic of Ireland that did not have sepsis resuscitation protocols or resuscitation guided by ScvO2 measurement. Patients: 1600 adults ≥ 18 years of age (mean age 63 y, 60% men) who had suspected or confirmed infections; evidence of refractory hypotension or hypoperfusion; and ≥ 2 of core temperature > 38° C or < 36° C, heart rate > 90 beats/min, respiratory rate > 20 breaths/min or PaC02 < 32 mm Hg or need for invasive mechanical ventilation for an acute process, or white cell count > 12.0 x 109/L or < 4.0 x 109/L or > 10% immature band forms. Exclusion criteria included hemodynamic instability due to active bleeding, inpatient transfer from another acute health care facility, contraindication to blood products or central venous catheter insertion in the superior vena cava, death imminent and inevitable or expected within 90 days, or inability to begin EGDT within 1 hour of randomization or to deliver EGDT for 6 hours. Eligibility criteria had to be met within 6 hours of ED presentation. Intervention: EGDT (n = 796) or usual care (n = 804). EGDT was delivered in the ED and/or intensive care unit by a study team trained in its delivery. Arterial and central venous catheters capable of continuous measurement of ScvO2 were inserted. Resuscitation followed an EGDT algorithm. Outcomes: Mortality at 90 days. Secondary outcomes included use of invasive mechanical ventilation, vasopressor support, and renal replacement therapy. The study had 85% to 90% power to detect a relative risk reduction of 20% from a baseline 90-day mortality rate of 28% (␣ = 0.05).
For correspondence: Ms. B. Howe, Australian and New Zealand Intensive Care Research Center, Melbourne, Victoria, Australia. E-mail [email protected].
Commentary EGDT was introduced in 2001 and changed how sepsis would be treated (1). The ARISE trial showed that EGDT and standard therapy did not differ. However, ARISE, like the ProCESS trial (2), does not disprove the efficacy of EGDT as much as it reaffirms that standard therapy has been fundamentally transformed to include many of the core principles of EGDT. Usual care today looks like EGDT and is much different than standard sepsis treatment in 2001. Mortality from sepsis has decreased 2% to 3% per year over the past decade (3). Early recognition and aggressive fluid resuscitation are now standard, and the fluid volume used in the usual care group in ARISE was closer to the volume used in the EGDT group than it was to the standard therapy in the original 2001 EGDT study (1). Vasopressor use is much more prevalent now. Notably, early use of antibiotics is no longer in question (4). While the 2001 EGDT study evaluated the percentage of antibiotics administered within 6 hours, it is now assumed that antibiotics will be administered rapidly; in ARISE, time to administration was measured in minutes. This publicly funded RCT, which was done in various health care settings around the world, clarifies which features of EGDT are important and provides insight into how far we've come in sepsis management. However, EGDT as a protocol does not seem to increase survival. Andrew Muck, MD Bruce D. Adams, MD Department of Emergency Medicine University Hospital, San Antonio UT School of Medicine San Antonio San Antonio, Texas, USA
Patient follow-up: 99% for primary outcome (intention-to-treat analysis).
Early goal-directed therapy (EGDT) vs usual care in septic shock† Outcomes
EGDT
Usual care
RRR (95% CI)
NNT (CI)
Mortality at 90 d
18.6%
18.8%
2% (⫺21 to 20)
Not significant
30%
32%
5% (⫺11 to 18)
Not significant
13.4%
13.5%
1% (⫺27 to 23)
Not significant
RRI (CI)
NNH (CI)
76%
66%
16% (9 to 24)
10 (7 to 17)
Invasive mechanical ventilation Renal replacement therapy
Vasopressor support
†Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from relative risks and usual care event rates in article.
姝 2015 American College of Physicians
JC4
References 1. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77. 2. ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014; 370:1683-93. 3. Lagu T, Rothberg MB, Shieh MS, et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40:754-61. 4. Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goaldirected therapy was initiated in the emergency department. Crit Care Med. 2010;38:1045-53.
ACP Journal Club
Annals of Internal Medicine
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/933569/ by a Fudan University User on 03/03/2017
17 March 2015
