De Backer, Daniel

OBJECTIVE: A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN: Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING: Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS: A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS: A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS: A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.

Purpose of review The diuretic agents are commonly used in ICUs for various purposes. Despite the widespread utilization of diuretics, there remains substantial ambiguity regarding their indications, ICU-related changes in their pharmacodynamics and pharmacokinetics, dosing, form, and timing of administration, the differences in their utilities based on each organ failure, and their monitoring and safety issues. Recent findings In the recent past, there have been several clinical trials and large registries or systematic reviews with a focus on the use of diuretic agents in ICUs. Summary In this review article, we outline the essential changes in drug behavior during critical illnesses and organ failures, describe the indications of their use in ICUs (management of fluid overload, electrolyte imbalances, or diagnostic or prognostic tests), assess the impact of different organ failures on the utility and effectiveness of diuretics, review major recent clinical trials related to diuretic comparison, use of multiple classes of diuretics, and monitoring and safety of their use. We also provide some information regarding the safety and adverse effects of diuretic use in the ICU and outline the importance of individualizing their use during critical illnesses.