Protocol-based resuscitation did not reduce sepsis deaths or morbidity, compared with usual care, in the Protocolized Care for Early Septic Shock study conducted at 31 U.S. academic hospitals.
Among 1,341 evaluable patients, the primary endpoint of 60-day in-hospital mortality was 21% with protocol-based early goal-directed therapy (EGDT), 18.2% with protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions, and 18.9% with usual care according to the treating physician’s judgment.
The difference was not statistically significant between the protocol-based interventions and usual care (relative risk, 1.04; P = .83) or between protocol-based EGDT and protocol-based standard therapy (RR, 1.15; P = .31), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published in the New England Journal of Medicine (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1401602]).
The three groups also did not differ significantly with regard to 90-day mortality, incidence of cardiovascular or respiratory failure, length of hospital stay, or discharge disposition.
The results from ProCESS differ from those reported more than a decade ago in the pivotal, single-center Rivers et al. study, in which mortality was significantly reduced for patients with severe sepsis or septic shock treated with 6 hours of EGDT therapy versus standard therapy (N. Engl. J. Med. 2001;345:1368-77).
Though both trials used the same EGDT protocol delivered by a trained, dedicated team at each site, possible reasons for the discordance are that the Rivers study showed nearly perfect adherence to protocol and that its cohort was slightly older, had higher rates of preexisting heart and liver disease, and had a higher initial serum lactate level, noted Dr. Derek Angus, ProCESS principal investigator and chair of critical care medicine at the University of Pittsburgh.
In addition, changes in the management of critically ill patient in the ensuing decade, including use of lower hemoglobin levels as a threshold for transfusion, use of lung-protection strategies, and tighter blood sugar control, "may have helped lower the overall mortality and may have reduced the marginal benefit of alternative resuscitation strategies," he observed.
Dr. Angus received grant support from the National Institutes of General Medical Sciences and nonfinancial support from Edwards Inc. during the trial, grant support to his university from Eisai, and personal fees from Pfizer and MedImmune outside this trial.