Protocolized Care for Early Septic Shock (ProCESS), a new multicenter research consortium, is beginning a large-scale study to determine whether specific interventions can halt the progression to severe sepsis or septic shock. Every year, about 750,000 people in the United States are affected with severe sepsis and about 200,000 people die from it. Sepsis is a syndrome characterized by a systemic response to infection that can rapidly lead to death. It is the leading cause of death in noncoronary intensive care units.
The University of Pittsburgh School of Medicine has been awarded an $8.4 million five-year grant by the National Institute of General Medical Sciences, part of the National Institutes of Health, to lead the multidisciplinary, multicenter consortium.
Sepsis can be fatal within a few hours, and it is often not diagnosed until it is too late. "Septic patients present with various underlying disease states, infecting pathogens, and degrees of inflammatory response," stated Ty Kiser, Pharm.D., BCPS, assistant professor, department of clinical pharmacy at the University of Colorado Health Sciences Center. "Sepsis is still difficult to diagnose and treat, because we still have much to learn about the pathogenesis of sepsis itself. Our understanding of the causes and course of sepsis has improved drastically, but many of our most plausible experimental therapies have fallen short in clinical trials. To date, there is no magic bullet that we can use to treat all patients with septic shock. We have to use our best interpretation of the literature and try to apply the most appropriate care to each individual patient."
All patients will be followed for a full year after their recovery to detect any long-term differences in health and mortality rates. "This is an effective protocol," said Martin J. Ohlinger, Pharm.D., assistant professor of pharmacy practice at the University of Toledo College of Pharmacy. "Rivers and his colleagues proved that in their study. It may not be perfect, and all research is subject to critique, especially within the 'real-world' setting, but it's the best evidence we have supporting early aggressive therapy in septic shock."
According to Kiser, the program will help establish the crucial time line for appropriately assessing and managing patients with sepsis, evaluating more than one approach to early resuscitation. "Additionally, the program will establish cost-effectiveness of the resources utilized in early goal-directed treatment [EGDT] and look at many different biomarkers of sepsis and may help delineate their usefulness," he said.
In the original trial conducted by Rivers, 263 patients were randomly assigned to receive either six hours of EGDT or standard treatment before admission to the ICU. In-hospital mortality was 30.5% in the patients who received EGDT, compared with 46.5% in the standard treatment group.
"The protocol requires intensive monitoring and the coordination of many healthcare team members," stated Kiser. It also calls for healthcare facilities to utilize standard "sepsis bundles" or develop their own protocols to ensure that patients receive appropriate care, he added.
"The protocol is very resource-demanding," said Kiser. "It requires physicians, nurses, pharmacists, respiratory therapists, and other healthcare providers to work closely together to ensure patients are adequately assessed and monitored, given appropriate fluid resuscitation, started on appropriate antimicrobial therapy and vasoactive agents, and receive appropriate oxygenation and ventilation. The questions in the real world will be: How well are institutions doing with replicating the care that was provided in Rivers' protocol? and, If institutions are unable to maximize their adherence to the protocol, will they still see the impressive morbidity and mortality benefits?"