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The current Surviving Sepsis Campaign guidelines recommend that patients with septic shock shall receive vasopressors (norepinephrine as the first choice) for hypotension refractory to initial fluid resuscitation to maintain a mean arterial pressure (MAP) ≥65 mm Hg, and that this shall be completed within six hours.1 In clinical practice, healthcare practitioners sometimes wait before starting a vasopressor and this may cause prolonged hypotension and hence irreversible damage to some vital organs.2, 3 The authors of this study therefore sought to examine the relationship between delay in initial norepinephrine administration and hospital mortality.4

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The study is a retrospective cohort study that was conducted in two ICUs in a tertiary care hospital in China. All adults (≥18 years of age) with a diagnosis of septic shock were included. Septic shock was defined as sepsis-induced persisting hypotension (defined as systolic blood pressure <90 mm Hg, a decrease of 40 mm Hg in systolic pressure from the patient’s baseline or MAP <65 mm Hg).  An episode of hypotension was a representative of septic shock when the following were present: hypotension persisted from the onset despite adequate fluid resuscitation (30 mL/kg crystalloid fluids) or hypotension was ONLY transiently improved (for <1 hour) with adequate fluid resuscitation.4

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The authors analyzed a total of 213 patients. The mean time to initial norepinephrine administration was 3.1 ± 2.5 hours. A total of 18.8% of all patients received norepinephrine administration within 1 hour after the onset of septic shock, 40.4% within 2 hours and 9.9% of patients received norepinephrine ≥6 hours after the first occurrence of septic shock. Mortality was 27.5% if norepinephrine administration was initiated <1 hour after the onset of septic shock, 30.4% if initiated from 1 to 2 hours after the onset and 65.2% if initiated ≥6 hours after the onset. Furthermore, the 28-day mortality increased when receiving norepinephrine ≥ 2 hours compared to those who received it <2 hours after onset (OR of death was 2.16 (1.23 to 3.81, P =0.007)).4

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The authors of the study conclude that the early administration of norepinephrine for septic shock is associated with improved survival.  Limitations of this study include the retrospective design that does not establish any causation.  In addition, the sample size of the study is relatively small. It is crucial to confirm the results of this study by conducting multicenter cohort studies.

1. Dellinger RP, Levy MM, Rhodes A, et al: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013, 41:580–637.   [PubMed: 23353941]
2. LeDoux D, Astiz ME, Carpati CM, et al: Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000, 28:2729–2732.   [PubMed: 10966242]
3. Ruokonen E, Takala J, Kari A, et al: Regional blood flow and oxygen transport in septic shock. Crit Care Med 1993, 21:1296–1303.   [PubMed: 8370292]
4. Bai, et al: Early versus delayed administration of norepinephrine in patients with septic shock. Critical Care 2014, 18:532.   [PubMed: 25277635]

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