Clinical Effectiveness and Early Goal-Directed Therapy for Severe Sepsis and Septic Shock

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We would like to thank Dr. Wolf and colleagues for their interest in our work.1Jones AE Focht A Horton JM et al.Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock.Chest. 2007; 132: 425-432Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar Their first concern was that our choice of study design resulted in unequal measured and unmeasured variables between the groups. While we agree that other study designs may produce a lower possibility of confounding, there is no guarantee of equality between groups with any study design, including a randomized controlled trial. Furthermore, as our study outlines, we made a change in the standard-of-care for all of our emergency department severe sepsis and septic shock patients, thus having a concurrent control group would simply have been unethical. We would also point out that our post-early goal directed therapy (EGDT) group had higher severity of illness and organ dysfunction scores, lower systolic BP, lower oxygen saturation, and both a higher heart and respiratory rate as compared to our pre-EGDT group. Thus, our observed survival advantage was realized in a group with a higher severity of illness and organ dysfunction. Their second concern was regarding our conclusion of demonstrating the clinical effectiveness of EGDT. Dr. Wolf is of the opinion that we overstated our findings given that the confidence interval surrounding the mortality difference “implies random error alone may account for the observed mortality benefit and that there may have been no true effect.” When examining this assertion we would offer three considerations. First, it is important to recognize that we defined clinical effectiveness a priori as a 33% relative mortality reduction, which is the same mortality reduction in the EGDT efficacy trial.2Rivers E Nguyen B Havstad S et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.The N Engl J Med. 2001; 345: 1368-1677Crossref PubMed Scopus (7424) Google Scholar Second, our findings are similar to every previous full-length EGDT effectiveness publication,3Trzeciak S Dellinger RP Abata NL et al.Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department.Chest. 2006; 129: 225-235Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar4Shapiro NI Howell MD Talmor D et al.Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol.Crit Care Med. 2006; 34: 1025-1032Crossref PubMed Scopus (289) Google Scholar5Micek ST Roubinian N Heuring T et al.Before-after study of a standardized hospital order set for the management of septic shock.Crit Care Med. 2006; 34: 2707-2713Crossref PubMed Scopus (316) Google Scholar and we are aware of no publication demonstrating a lack of effectiveness of EGDT. Finally, although we are aware of no universally accepted definition of the term random error, we would point out that random error is just what it implies, random, and therefore no study can completely account or control for randomness. In conclusion, Dr. Wolf and colleagues have every right to not agree with our findings. However, given the publications of the efficacy and effectiveness of EGDT to date, it is difficult to argue with both early resuscitation and a goal-oriented approach (whatever the goals may be) in patients with severe sepsis and septic shock. Clinical Effectiveness and Early Goal-Directed Therapy for Severe Sepsis and Septic ShockChestVol. 133Issue 2PreviewWe read the article, “Prospective External Validation of the Clinical Effectiveness of an Emergency Department-Based Early Goal-Directed Therapy Protocol for Severe Sepsis and Septic Shock,” by Jones and colleagues1 in a recent issue of CHEST (August 2007) with interest. Demonstrating clinical effectiveness is a crucial step in establishing the “real-world” benefit of therapies previously shown to be efficacious.23 Although the randomized controlled trial is considered the criterion standard, quasi-experimental study designs have been successfully used to demonstrate effectiveness. Full-Text PDF