The demise of early goal‐directed therapy for severe sepsis and septic shock

Abstract

A protocol for the quantitative resuscitation of severe sepsis and septic shock known as early goal-directed therapy (EGDT) was published in 2001. Despite serious limitations, this study became widely adopted around the world and formed the basis of the Surviving Sepsis Campaign 6 h resuscitation bundle. Subsequently, a large number of observational before-and-after studies were published which demonstrated that EGDT reduced mortality. However, during this time period, there has been a substantial reduction in the mortality from sepsis in many Western nations that appears unrelated to EGDT. Recently, the Protocolized Care for Early Septic Shock (ProCESS) and The Australasian Resuscitation in Sepsis Evaluation (ARISE) trials failed to demonstrate any outcome benefit from EGDT. These two large, multicenter, randomized controlled studies raise serious questions regarding the validity of the original EGDT study and the scientific rigor of the uncontrolled, largely retrospective before-after clinical studies. Furthermore, accruing data suggest an association between the amount of fluid administered in the first 72 h and the mortality of patients with severe sepsis. Patients in all arms of the ProCESS and ARISE trials received substantial and nearly equivalent amounts of fluid. It is proposed that a more conservative fluid strategy and the earlier use of norepinephrine in patients with septic shock may be associated with further improvements in the outcome of patients with sepsis.

The SEP-1 quality mandate may be harmful: How to drown a patient with 30 mL per kg fluid!

“…In summary, there is now scientific evidence, supported by legal precedent that not only are the EGDT, SSC and SEP-1 protocols of limited benefit to patients if blindly followed, they are potentially harmful [3,[38][39][40]. These protocols violate the American Medical Association (AMA) and American College of Physicians (ACP) code of ethics [41,42], and the basic Hippocratic Principle of Medicine, "Primum Non Nocere".…”

A prospective quality improvement study in the emergency department targeting paediatric sepsis

“…The incorporation of early identification, early antibiotic administration and judicious targeted fluid resuscitation into standard care is thought to be responsible for the majority of this lack of observed benefit from further protocolisation in adults 13–15. If these basic interventions are given in a timely manner, adding other interventions in a protocol may make minimal difference 14. It is unclear whether these findings are generalisable to paediatric sepsis management, where EGDT and protocolisation have never been evaluated in a prospective or randomised fashion.…”

Surviving sepsis campaign in children

“…Sans être définitivement enterré, le monitorage de la ScvO 2 a toutefois été remis en question par trois grandes études menées chez des adultes en choc septique (ProCESS, ARISE, ProMISe) qui ne montrent pas de différence de mortalité entre les groupes EGDT et soins standards [65]. L'amé-lioration du pronostic du sepsis grave passe par l'application des recommandations, en considérant plusieurs étapes : la rédaction d'un protocole de traitement adapté à son environnement, la formation des personnels (auxiliaires, infirmières et médecins), l'identification des difficultés et barrières à l'implémentation du protocole, et le suivi des résultats dans le but de mettre en place les actions correctrices.…”