Therapeutics
In septic shock, early goal-directed or standard protocol-based therapy did not reduce mortality
ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-93.
Clinical impact ratings: E ★★★★★★★ I ★★★★★★✩ c ★★★★★★★ Questions In early septic shock, is protocol-based resuscitation better than usual care for reducing in-hospital mortality? Is protocol-based, early goal-directed therapy [EGDT] better than protocol-based standard therapy?
Methods Design: Randomized controlled trial (Protocolized Care for Early Septic Shock [ProCESS] trial). ClinicalTrials.gov NCT00510835. Allocation: Concealed.* Blinding: Blinded* {data analysts and central coordinating group}¶. Follow-up period: In hospital, 90 days, and 1 year. Setting: 31 emergency departments in the USA. Patients: 1351 patients ≥ 18 years of age (mean age 61 y, 56% men) who had suspected sepsis and were enrolled ≤ 12 hours after arrival in the emergency department and ≤ 2 hours after shock was detected, met ≥ 2 systemic inflammatory response syndrome criteria, and had refractory hypotension (systolic blood pressure < 90 mm Hg or needing vasopressors to maintain 90 mm Hg) or a serum lactate level ≥ 4 mmol/L. Interventions: Protocol-based EGDT, including placement of central venous catheters to monitor pressure and oxygen saturation and administer protocol-directed treatments (n = 445); protocolbased standard therapy, including adequate peripheral venous access (n = 448); or usual care (n = 458), each for 6 hours. Outcomes: Primary outcome was 60-day in-hospital mortality, comparing protocol-based resuscitation with usual care, and whether adding EGDT enhanced protocol-based therapy. Other outcomes included 90-day and 1-year mortality and serious adverse events (SAEs). Patient follow-up: 99% for in-hospital mortality (intention-totreat analysis).
Main results Overall, protocol-based therapy did not differ from usual care for 60-day in-hospital mortality (20% vs 19%, P = 0.83). Protocolbased EGDT and protocol-based standard therapy did not differ Protocol-based early goal-directed therapy (EGDT) vs protocolbased standard therapy (ST) vs usual care (UC) in patients with early septic shock† Outcomes
Event rates ST
UC
21%
18%
19%
21%
18%
—
EGDT In-hospital mortality at 60 d
RRI (95% CI) 4% (−18 to 31)‡ 15% (−12 to 51)
P value across 3 groups§ Mortality at 90 d|| Serious adverse events
32% 5.2%
31% 4.9%
34% 8.1%
0.66 0.32
†Abbreviations defined in Glossary. RRI and CI calculated from relative risk in article. ‡EGDT and ST combined vs UC. §Comparisons among individual groups were not reported for overall P > 0.05. ||n = 1232.
17 June 2014 | ACP Journal Club | Volume 160 • Number 12
from usual care or each other for 60-day in-hospital mortality (Table); groups did not differ for 90-day mortality or SAEs (Table) or 1-year mortality (P = 0.92).
Conclusion In patients with septic shock in the emergency department, protocol-based therapy, either early goal-directed or standard, did not reduce mortality compared with usual care. *See Glossary. ¶Information provided by author.
Source of funding: National Institute of General Medical Sciences. For correspondence: Dr. D.C. Angus, University of Pittsburgh, Pittsburgh, PA, USA. E-mail [email protected]. ■
Commentary In 1969, Dr. Jeremy Swan was watching sailboats off the California coast deploy their spinnakers when he envisaged how a flowdirected balloon catheter could similarly navigate deep into the cardiopulmonary circuit to guide resuscitation of critically ill patients (1). And so began the pendulum swings of how aggressively we should manage severe sepsis. At the millennium, many experts were calling for a moratorium on use of the Swan-Ganz catheter. After Rivers and colleagues published a landmark study on EGDT and validated an aggressive, interventional approach to sepsis (2), guidelines emerged (3), tripling the use of central venous lines. Now, with the results of the ProCESS trial, the approach will move back toward conservative, noninvasive management. That EGDT did not show superiority over “usual care” should not surprise given that the Rivers study (2), along with widespread sepsis awareness and recognition campaigns it inspired, undoubtedly contributed to the 15% to 20% absolute reduction of sepsis mortality in the past decade (4). The results of the trial again highlight that “usual care” is simply much more aggressive than it was 10 years ago. In April 2014, the National Quality Forum downgraded use of central venous lines to be at the discretion of clinicians (5). The next round of Surviving Sepsis guidelines will probably follow suit. With 2 major studies of protocolled sepsis management nearing completion, we may not have seen the last swing of the resuscitation pendulum that began on that beach 45 years ago. Kevin M. King, FACEP, MD Bruce D. Adams, FACEP, MD Department of Emergency Medicine University of Texas Health Science Center at San Antonio San Antonio, Texas, USA References 1. Swan HJ. Anesthesiology. 2005;103:890-3. 2. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. N Engl J Med. 2001;345:1368-77. 3. Dellinger RP, Carlet JM, Masur H, et al; Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med. 2004;32:858-73. 4. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Crit Care Med. 2014;42:625-31. 5. National Quality Forum. www.qualityforum.org/News_And_Resources/ Press_Releases/2014/Statement_from_NQF_on_Review_of_Sepsis_ Measure.aspx (accessed 5 May 2014). © 2014 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/930364/ by a NYU Medical Center Library User on 03/03/2017
JC9
In septic shock, early goal-directed or standard protocol-based therapy did not reduce mortality
ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-93.
Clinical impact ratings: E ★★★★★★★ I ★★★★★★✩ c ★★★★★★★ Questions In early septic shock, is protocol-based resuscitation better than usual care for reducing in-hospital mortality? Is protocol-based, early goal-directed therapy [EGDT] better than protocol-based standard therapy?
Methods Design: Randomized controlled trial (Protocolized Care for Early Septic Shock [ProCESS] trial). ClinicalTrials.gov NCT00510835. Allocation: Concealed.* Blinding: Blinded* {data analysts and central coordinating group}¶. Follow-up period: In hospital, 90 days, and 1 year. Setting: 31 emergency departments in the USA. Patients: 1351 patients ≥ 18 years of age (mean age 61 y, 56% men) who had suspected sepsis and were enrolled ≤ 12 hours after arrival in the emergency department and ≤ 2 hours after shock was detected, met ≥ 2 systemic inflammatory response syndrome criteria, and had refractory hypotension (systolic blood pressure < 90 mm Hg or needing vasopressors to maintain 90 mm Hg) or a serum lactate level ≥ 4 mmol/L. Interventions: Protocol-based EGDT, including placement of central venous catheters to monitor pressure and oxygen saturation and administer protocol-directed treatments (n = 445); protocolbased standard therapy, including adequate peripheral venous access (n = 448); or usual care (n = 458), each for 6 hours. Outcomes: Primary outcome was 60-day in-hospital mortality, comparing protocol-based resuscitation with usual care, and whether adding EGDT enhanced protocol-based therapy. Other outcomes included 90-day and 1-year mortality and serious adverse events (SAEs). Patient follow-up: 99% for in-hospital mortality (intention-totreat analysis).
Main results Overall, protocol-based therapy did not differ from usual care for 60-day in-hospital mortality (20% vs 19%, P = 0.83). Protocolbased EGDT and protocol-based standard therapy did not differ Protocol-based early goal-directed therapy (EGDT) vs protocolbased standard therapy (ST) vs usual care (UC) in patients with early septic shock† Outcomes
Event rates ST
UC
21%
18%
19%
21%
18%
—
EGDT In-hospital mortality at 60 d
RRI (95% CI) 4% (−18 to 31)‡ 15% (−12 to 51)
P value across 3 groups§ Mortality at 90 d|| Serious adverse events
32% 5.2%
31% 4.9%
34% 8.1%
0.66 0.32
†Abbreviations defined in Glossary. RRI and CI calculated from relative risk in article. ‡EGDT and ST combined vs UC. §Comparisons among individual groups were not reported for overall P > 0.05. ||n = 1232.
17 June 2014 | ACP Journal Club | Volume 160 • Number 12
from usual care or each other for 60-day in-hospital mortality (Table); groups did not differ for 90-day mortality or SAEs (Table) or 1-year mortality (P = 0.92).
Conclusion In patients with septic shock in the emergency department, protocol-based therapy, either early goal-directed or standard, did not reduce mortality compared with usual care. *See Glossary. ¶Information provided by author.
Source of funding: National Institute of General Medical Sciences. For correspondence: Dr. D.C. Angus, University of Pittsburgh, Pittsburgh, PA, USA. E-mail [email protected]. ■
Commentary In 1969, Dr. Jeremy Swan was watching sailboats off the California coast deploy their spinnakers when he envisaged how a flowdirected balloon catheter could similarly navigate deep into the cardiopulmonary circuit to guide resuscitation of critically ill patients (1). And so began the pendulum swings of how aggressively we should manage severe sepsis. At the millennium, many experts were calling for a moratorium on use of the Swan-Ganz catheter. After Rivers and colleagues published a landmark study on EGDT and validated an aggressive, interventional approach to sepsis (2), guidelines emerged (3), tripling the use of central venous lines. Now, with the results of the ProCESS trial, the approach will move back toward conservative, noninvasive management. That EGDT did not show superiority over “usual care” should not surprise given that the Rivers study (2), along with widespread sepsis awareness and recognition campaigns it inspired, undoubtedly contributed to the 15% to 20% absolute reduction of sepsis mortality in the past decade (4). The results of the trial again highlight that “usual care” is simply much more aggressive than it was 10 years ago. In April 2014, the National Quality Forum downgraded use of central venous lines to be at the discretion of clinicians (5). The next round of Surviving Sepsis guidelines will probably follow suit. With 2 major studies of protocolled sepsis management nearing completion, we may not have seen the last swing of the resuscitation pendulum that began on that beach 45 years ago. Kevin M. King, FACEP, MD Bruce D. Adams, FACEP, MD Department of Emergency Medicine University of Texas Health Science Center at San Antonio San Antonio, Texas, USA References 1. Swan HJ. Anesthesiology. 2005;103:890-3. 2. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. N Engl J Med. 2001;345:1368-77. 3. Dellinger RP, Carlet JM, Masur H, et al; Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med. 2004;32:858-73. 4. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Crit Care Med. 2014;42:625-31. 5. National Quality Forum. www.qualityforum.org/News_And_Resources/ Press_Releases/2014/Statement_from_NQF_on_Review_of_Sepsis_ Measure.aspx (accessed 5 May 2014). © 2014 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/930364/ by a NYU Medical Center Library User on 03/03/2017
JC9
