Polling and commenting remain open until June 2018. As of June 28, 2017, we received 987 responses to the poll and posted 51 of your comments. An interim analysis of the poll results appears below.
– Edward W. Campion, Executive Editor
Editor’s Comment
Management of Septic Shock — Polling Results
Rebecca E. Berger, M.D., and Julie R. Ingelfinger, M.D.
Management of septic shock was transformed in 2001 with the publication of the randomized, controlled trial, “Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock,” by Emanuel Rivers and colleagues.[1] That study showed that patients assigned to an early, goal-directed therapy (EGDT) protocol that involved monitoring central venous pressure, urine output, and central venous oxygen saturation (ScvO2) and performing interventions that included administration of fluid boluses, early administration of antibiotics, administration of inotropes, and blood transfusions to achieve target ranges of these variables were significantly less likely to die than those who were randomly assigned to standard care. That trial catalyzed a transformation in the treatment of sepsis, and protocols aimed at prompt diagnosis and early, aggressive intervention for patients with septic shock were widely implemented. As a result, mortality associated with septic shock has decreased. Three recent multicenter, randomized trials — the ProCESS (Protocolized Care for Early Septic Shock),[2] ARISE (The Australasian Resuscitation in Sepsis Evaluation),[3] and ProMISe (Protocolized Management in Sepsis)[4] trials — compared EGDT with current usual care, which now includes early fluid resuscitation and early administration of antibiotics; all three trials showed no differences in mortality between the groups. In June 2017, the Journal published a meta-analysis of individual patient-level data from these three trials, as the Protocolized Resuscitation in Sepsis Meta-Analysis (PRISM) study; this study also showed no significant effect of EGDT, as compared with usual care, on 90-day mortality.[5] Length of stay in the intensive care unit was longer in the EGDT group, but otherwise there were no significant differences in secondary outcomes.
In the same issue of the Journal, we presented the case of Ms. Jones, a 65-year-old woman with a history of hypertension who presented to the emergency department with chills and dysuria.[6] She had leukocytosis, acute kidney injury, an elevated lactate level, and urinalysis results consistent with a urinary tract infection. Progressive hypotension developed, and a diagnosis of septic shock from a presumed urinary source was made. Despite crystalloid fluid resuscitation, hypotension and oliguria progressed, and vasopressor therapy was initiated.
Readers were invited to vote on their preferred management strategy. Option 1 was to follow the classic EGDT protocol, with serial measurement of central venous pressure, ScvO2, and hemoglobin and specified targets for the initiation of inotropic agents or transfusion of red cells. Option 2 was to continue antibiotic and vasopressor therapy and determine further management by monitoring clinical signs, including blood pressure and urine output, without serial central venous pressure monitoring, serial ScvO2 monitoring, transfusion of red cells, or administration of inotropic agents. Two experts offered supporting views of the two treatment options.
During the first 3 weeks of polling, more than 80,000 readers viewed the Clinical Decisions article, and 987 readers from 86 countries participated in the informal poll; 32% of the respondents were from the United States or Canada. A total of 231 voters (23%) recommended option 1 (following the EGDT protocol), and 756 (77%) recommended option 2 (using clinical signs without strict targets for central venous pressure and ScvO2).
In these first 3 weeks, 51 readers provided comments with their votes. Commenters included students and physicians in the fields of internal medicine, critical care medicine, cardiology, respiratory and pulmonary medicine, immunology, nephrology, anesthesiology, infectious diseases, emergency medicine, geriatric medicine, and family medicine. Many readers commented on the importance of always tailoring a treatment plan to the specific patient, whether the plan involved following a strict protocol or monitoring clinical signs alone. Some noted differences in patient populations and trial design between the original EGDT and the three newer randomized, controlled trials that were included in the PRISM study. Some readers suggested using methods for measuring volume responsiveness, including passive leg raising, dynamic (rather than static) central venous pressure measurement, and bedside ultrasonography, and measurement of the inferior vena cava collapsibility index. Others suggested using additional diagnostic tools, such as critical care echocardiography, to monitor cardiac function and assess the need for adding inotropic agents. One reader noted the importance of considering the risks of blood transfusions, including transfusion-associated lung injury and pulmonary edema. Many commenters suggested adjunctive therapies for the patient’s septic shock, including established therapies, such as the addition of vasopressin to norepinephrine, and controversial or experimental therapies, such as early renal-replacement therapy or administration of intravenous vitamin C, thiamine, or glucocorticoids. Some readers noted that both option 1 and option 2 could be reasonable approaches, given the equivalence of the methods in the trials, and stated that decisions might depend on staff, resources, and accepted local practices.
So does the PRISM study signify the end of EGDT? As one reader asked, referring to EGDT, “Can we finally let this go?” The results of this informal Clinical Decisions poll indicate that although many Journal readers believe that the PRISM study is the end of EGDT, the jury may still be out. The votes and the range of comments reflect the variability in existing clinical practice and the controversy surrounding the validity and generalizability of new data.
REFERENCES
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Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
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The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93.
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The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506.
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Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015;372:1301-11.
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The PRISM Investigators. Early, goal-directed therapy for septic shock — a patient-level meta-analysis. N Engl J Med 2017;376:2223-34.
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Berger RE, Rivers E, and Levy MM. Management of septic shock. N Engl J Med 2017;376:2282-5.