Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce. Objectives: To conduct a phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults with sepsis with hypotension increases shock control by 6 hours compared with standard care. Methods: This single-center, randomized, double-blind, placebo-controlled clinical trial was conducted at Siriraj Hospital, Bangkok, Thailand. The study enrolled 310 adults diagnosed with sepsis with hypotension. The patients were randomly divided into two groups: early norepinephrine (n = 155) and standard treatment (n = 155). The primary outcome was shock control rate (defined as achievement of mean arterial blood pressure ≥65 mm Hg, with urine flow ≥0.5 ml/kg/h for 2 consecutive hours, or decreased serum lactate ≥10% from baseline) by 6 hours after diagnosis. Measurements and Main Results: The patients in both groups were well matched in background characteristics and disease severity. Median time from emergency room arrival to norepinephrine administration was significantly shorter in the early norepinephrine group (93 vs. 192 min; P < 0.001). Shock control rate by 6 hours was significantly higher in the early norepinephrine group (118/155 [76.1%] vs. 75/155 [48.4%]; P < 0.001). The 28-day mortality was not different between groups: 24/155 (15.5%) in the early norepinephrine group versus 34/155 (21.9%) in the standard treatment group (P = 0.15). The early norepinephrine group was associated with lower incidences of cardiogenic pulmonary edema (22/155 [14.4%] vs. 43/155 [27.7%]; P = 0.004) and new-onset arrhythmia (17/155 [11%] vs. 31/155 [20%]; P = 0.03). Conclusions: Early norepinephrine was significantly associated with increased shock control by 6 hours. Further studies are needed before this approach is introduced in clinical resuscitation practice. Clinical trial registered with www.clinicaltrials.gov (NCT01945983) (CENSER trial).
RCT Entities:
Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce. Objectives: To conduct a phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults with sepsis with hypotension increases shock control by 6 hours compared with standard care. Methods: This single-center, randomized, double-blind, placebo-controlled clinical trial was conducted at Siriraj Hospital, Bangkok, Thailand. The study enrolled 310 adults diagnosed with sepsis with hypotension. The patients were randomly divided into two groups: early norepinephrine (n = 155) and standard treatment (n = 155). The primary outcome was shock control rate (defined as achievement of mean arterial blood pressure ≥65 mm Hg, with urine flow ≥0.5 ml/kg/h for 2 consecutive hours, or decreased serum lactate ≥10% from baseline) by 6 hours after diagnosis. Measurements and Main Results: The patients in both groups were well matched in background characteristics and disease severity. Median time from emergency room arrival to norepinephrine administration was significantly shorter in the early norepinephrine group (93 vs. 192 min; P < 0.001). Shock control rate by 6 hours was significantly higher in the early norepinephrine group (118/155 [76.1%] vs. 75/155 [48.4%]; P < 0.001). The 28-day mortality was not different between groups: 24/155 (15.5%) in the early norepinephrine group versus 34/155 (21.9%) in the standard treatment group (P = 0.15). The early norepinephrine group was associated with lower incidences of cardiogenic pulmonary edema (22/155 [14.4%] vs. 43/155 [27.7%]; P = 0.004) and new-onset arrhythmia (17/155 [11%] vs. 31/155 [20%]; P = 0.03). Conclusions: Early norepinephrine was significantly associated with increased shock control by 6 hours. Further studies are needed before this approach is introduced in clinical resuscitation practice. Clinical trial registered with www.clinicaltrials.gov (NCT01945983) (CENSER trial).
Entities:
Keywords:
early norepinephrine administration; norepinephrine; resuscitation; sepsis with hypotension; septic shock
Authors: Anne R Levenson; Luisa Morales-Nebreda; Michael J Alexander; Clara J Schroedl Journal: Am J Respir Crit Care Med Date: 2020-10-01 Impact factor: 21.405
Authors: Jan Bakker; Eduardo Kattan; Djillali Annane; Ricardo Castro; Maurizio Cecconi; Daniel De Backer; Arnaldo Dubin; Laura Evans; Michelle Ng Gong; Olfa Hamzaoui; Can Ince; Bruno Levy; Xavier Monnet; Gustavo A Ospina Tascón; Marlies Ostermann; Michael R Pinsky; James A Russell; Bernd Saugel; Thomas W L Scheeren; Jean-Louis Teboul; Antoine Vieillard Baron; Jean-Louis Vincent; Fernando G Zampieri; Glenn Hernandez Journal: Intensive Care Med Date: 2021-12-15 Impact factor: 17.440
Authors: Jessika Stefanie Kreß; Marc Rüppel; Hendrik Haake; Jürgen Vom Dahl; Sebastian Bergrath Journal: Anaesthesist Date: 2021-04-08 Impact factor: 1.041