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Sepsis & Septic Shock

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The results of the CLOVERS trial are now released at NEJM and revealed that 90-day mortality is not different between conservative fluid strategy with early vasopressor use and liberal fluid strategy with fluid-predominant approach. All patients had sepsis-induced hypotension refractory to the intravenous administration of at least 1000 ml of fluid (up to 3 liters). It is important to know that the study protocol excluded the following patients:

  • Patients with an elapse of more than 4 hours since the meeting of the criteria.

  • Patients with an elapse of more than 24 hours since presentation at the hospital.

  • Previous receipt of more than 3000 ml of intravenous fluid during this episode (including prehospital administration of fluid by emergency medical services).

  • Patients with the presence of fluid overload, and severe volume depletion from nonsepsis causes.


Thus the results cannot be generalized to any population other that those included in the study. However,



The CLASSIC trial investigated the difference between a conservative and liberal approach to fluid therapy on septic shock patients already admitted in the intensive care unit. No differences were noted in 90-day all-cause mortality between the two group. The CLOVERS trial is distinctive in its patient population, since it mostly included those who initially visited an emergency room with sepsis. In contrast, the CLASSIC trial included a substantial portion of patients (34%) who previously received care on hospital wards and another 23% from operating rooms prior to ICU admission.




The CLOVERS trial period was only 24 hours compared to duration of hospitalization in the CLASSIC trial. The "rescue fluid" criteria was more stringent in the CLASSIC trial compared to the CLOVERS trial.


90-day Mortality rate was much higher in the CLASSIC trial (42.3%) compared to 14% in the CLOVERS trial reflecting much more sicker population in the CLASSIC trial.


So it is clear that these two trials represented two different population, nevertheless, no difference in 90-day mortality with restrictive approach in either one.


Based on CLASSIC and CLOVERS trials, which approach would you use?

  • Restrictive fluid strategy

  • Liberal fluid strategy

  • Undecided yet!


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