This chapter is dedicated to the dissection of perhaps the most famous randomised controlled trial in the management of sepsis, the 2001 Rivers trial titled "Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock".
Why is it important to dedicate an entire page to Rivers-bashing?
Well. Certainly, our illustrious college has already dedicated two past paper questions to interrogating their candidate's understanding of this trial, their ability to recall the "goals", and their familiarity with the controversy which has enveloped this topic. Given the influence of this paper, it is not surprising that even now it is being waved around in ICU exit exams: Question 16 from the second paper of 2013 and Question 28 from the first paper of 2015 are certainly not where it is going to end.
The most important resources for answering all questions of this nature would have to include the following:
In brief summary:
Classical goals as per Rivers et al. (2001)
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Disadvantages of EGDT
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Rationale and advantages of EGDT
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Evidence against EGDT |
When one embarks upon a course of "early goal-directed therapy", if one is faithful to the standards of the original paper, one commits to achieving a series of physiological parameters:
Rivers used a protocolised pathway of interventions to achieve the abovementioned goals. These interventions consisted of:
The rationale for an early aggressive assault on oxygen delivery is grounded in some fairly sensible assertions.
The official answer to the CICM question adds a parallel to EGDT. If ealy goal-directed therapy for myocardial infarction, stroke and trauma works, then why not for sepsis? This is an unusual leap to make, as the abovementioned "early management" strategies all rely on the correction of very different physiological abnormalities, eg. the coronary artery thrombus or catastrophic exsanguination. However, the uniting feature is the suggestion that perhaps critically ill patients should be managed in a rapid, attentive and coordinated manner, rather than being allowed to fester in the corner of the emergency department.
Though previously this section was brief and to the point, Question 28 from the first paper for 2015 has generated the need for indepth dissection of the evidence. The ProCESS, ARISE and ProMISE studies were quoted by the examiners. Even though "candidates were not expected to provide specific details of the trials", the college model answer provides these details in abundance, and so shall I.
ProCESS trial (2013): n=1341; multicentre RCT (31 US hospitals)
ARISE trial (2014): n=1600; multicentre RCT (50 Australian hospitals)
ProMISE trial (2015): n=1260; multicentre RCT (56 UK hospitals)
Meta-analysis (2015) - Angus, Barnato, Bell, Bellomo et al...
Rivers, Emanuel, et al. "Early goal-directed therapy in the treatment of severe sepsis and septic shock." New England Journal of Medicine 345.19 (2001): 1368-1377.
Jones, Alan E., et al. "The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis." Critical care medicine 36.10 (2008): 2734.
Kumar, Anand, et al. "Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock*." Critical care medicine 34.6 (2006): 1589-1596.
Early Goal-Directed Therapy Collaborative Group of Zhejiang Province. "The effect of early goal-directed therapy on treatment of critical patients with severe sepsis/septic shock: A multi-center, prospective, randomized, controlled study." Zhongguo wei zhong bing ji jiu yi xue= Chinese critical care medicine= Zhongguo weizhongbing jijiuyixue 22.6 (2010): 331.
Yealy, Donald M., et al. "A randomized trial of protocol-based care for early septic shock." The New England journal of medicine 370.18 (2014): 1683-1693.
Power, GSarah, et al. "The Protocolised Management in Sepsis (ProMISe) trial statistical analysis plan." Critical Care and Resuscitation 15.4 (2013): 311.
Delaney, Anthony P., et al. "The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan." Critical Care and Resuscitation 15.3 (2013): 162.
Marik, Paul E. "Early Management of Severe Sepsis: Concepts and Controversies." CHEST Journal 145.6 (2014): 1407-1418.
Peake, Sandra L., et al. "Goal-directed resuscitation for patients with early septic shock." The New England journal of medicine 371.16 (2014): 1496.
Yealy, Donald M., et al. "A randomized trial of protocol-based care for early septic shock." The New England journal of medicine 370.18 (2014): 1683-1693.
Mouncey, Paul R., et al. "Trial of early, goal-directed resuscitation for septic shock." New England Journal of Medicine 372.14 (2015): 1301-1311.
Angus, D. C., et al. "A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators." Intensive care medicine (2015): 1-12.
Jones, Alan E., et al. "Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial." Jama 303.8 (2010): 739-746.