Abstract
BackgroundOptimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock.MethodsA total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h.ResultsPatients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0–510] vs. 1500[650–2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500–1900] vs. 2600[1600–3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17–0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h.ConclusionA very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.
Highlights
Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance
Since the optimal timing of the introduction of vasopressors remains unknown and whether the benefits or harm of vasopressor introduction even preceding fluid resuscitation has not been still answered, we evaluated the impact of very early and the concurrent start of vasopressor support and fluid resuscitation on clinical outcomes in patients with septic shock
Time elapsed between the first hypotension episode and the start of VP support (FHypo-to-VPs interval) was significantly longer in the delayed vasopressor start (D-VPs) group
Summary
Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. Fluid administration is widely accepted as the first-line therapy followed by Ospina-Tascón et al Critical Care (2020) 24:52 recommendation on the timing to start vasopressor support was not clearly stated [1]. Recent experimental data suggested that fluid resuscitation preceding the start of vasopressors is associated with higher lactate levels and a paradoxical increase in vasopressor requirements when compared with an immediate start of vasopressor therapy without previous fluid administration [11]. Other data indicates that vasopressors should be administered in combination with fluids since isolated vasopressors can improve arterial pressure but not regional blood flow [25]
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