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Clinical Trial
. 2020 Feb 14;24(1):52.
doi: 10.1186/s13054-020-2756-3.

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

Gustavo A Ospina-Tascón  1   2 , Glenn Hernandez  3 , Ingrid Alvarez  4 , Luis E Calderón-Tapia  4 , Ramiro Manzano-Nunez  4 , Alvaro I Sánchez-Ortiz  4 , Egardo Quiñones  4 , Juan E Ruiz-Yucuma  4 , José L Aldana  4   5 , Jean-Louis Teboul  6 , Alexandre Biasi Cavalcanti  7 , Daniel De Backer  8 , Jan Bakker  3   9   10   11
Affiliations
Clinical Trial

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

Gustavo A Ospina-Tascón et al. Crit Care. .

Abstract

Background: 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.

Methods: A 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.

Results: Patients 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.

Conclusion: A 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.

Keywords: Clinical outcomes; Norepinephrine; Septic shock; Vasopressor support.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Cumulative resuscitation fluids for very early- (VE-VPs) and delayed-vasopressor support (D-VPs). a Cummulative resuscitation fluids (in mL) at the start of vasopressor, 2,4, 6, and 8 h after. b Cummulative resuscitation fluids (in mL/kg) at the start of vasopressor, 2,4, 6, and 8 h after. Very early VPs, vasopressor support initiated before or within the next hour of the first fluid resuscitation (FRLoad). Delayed VPs, vasopressor support initiated > 1 h of the first fluid resuscitation (FRLoad). VPs, start of vasopressor support
Fig. 2
Fig. 2
Cox proportional hazard model for risk of death at day 28 for very early- (VE-VPs) and delayed-vasopressor support (D-VPs). The Cox proportional hazards model was adjusted by SOFA score at day 1, the presence of hyperlactatemia (septic shock according to Sepsis 3.0 definition), delay time of antibiotic administration, and the net fluid balance at 24 h. Very early VPs, vasopressor support initiated before or within the next hour of the first fluid resuscitation (FRLoad). Delayed VPs, vasopressor support initiated > 1 h of the first fluid resuscitation (FRLoad). VPs, start of vasopressor support
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