Early versus delayed administration of norepinephrine in patients with septic shock

Abstract

IntroductionThis study investigated the incidence of delayed norepinephrine administration following the onset of septic shock and its effect on hospital mortality.MethodsWe conducted a retrospective cohort study using data from 213 adult septic shock patients treated at two general surgical intensive care units of a tertiary care hospital over a two year period. The primary outcome was 28-day mortality.ResultsThe 28-day mortality was 37.6% overall. Among the 213 patients, a strong relationship between delayed initial norepinephrine administration and 28-day mortality was noted. The average time to initial norepinephrine administration was 3.1 ± 2.5 hours. Every 1-hour delay in norepinephrine initiation during the first 6 hours after septic shock onset was associated with a 5.3% increase in mortality. Twenty-eight day mortality rates were significantly higher when norepinephrine administration was started more than or equal to 2 hours after septic shock onset (Late-NE) compared to less than 2 hours (Early-NE). Mean arterial pressures at 1, 2, 4, and 6 hours after septic shock onset were significantly higher and serum lactate levels at 2, 4, 6, and 8 hours were significantly lower in the Early-NE than the Late-NE group. The duration of hypotension and norepinephrine administration was significantly shorter and the quantity of norepinephrine administered in a 24-hour period was significantly less for the Early-NE group compared to the Late-NE group. The time to initial antimicrobial treatment was not significantly different between the Early-NE and Late-NE groups.ConclusionOur results show that early administration of norepinephrine in septic shock patients is associated with an increased survival rate.

Arterial blood pressure and heart rate regulation in shock state

“…A recent retrospective cohort demonstrated a positive association between earlier administration of norepinephrine and improved outcomes in septic shock [19]. Although it is not entirely clear whether this benefit is derived from better care, less fluids, or improved perfusion, this trial does highlight the benefits of the timing of vasopressor administration in addition to solely the target MAP [20].…”

Early Liberal Fluid Therapy for Sepsis Patients Is Not Harmful: Hydrophobia Is Unwarranted but Drink Responsibly

“…The more frequent administration of vasopressors in ProCESS, ARISE, and ProMISe may result in a hemodynamic phenotype of “vasodilatory septic shock” which is associated with a lower mortality risk as described by Hernandez et al (50). These findings may further indicate that early vasopressor administration instead of continued fluid therapy may be beneficial once the resuscitation is complete (51). Thus, it seems that ProCESS, ARISE, and ProMISe showed us that 4–6 L of fluid is generally required for early hemodynamic optimization.…”

Evaluation of Perfusion Index as a Predictor of Vasopressor Requirement in Patients with Severe Sepsis

“…The importance of timing vasopressor therapy appropriately was recently emphasized in a report on the protocolized management of septic shock (9). Bai et al (9) analyzed 213 patients admitted to the ICU and found a strong relationship between delayed initial noradrenaline administration and 28-day mortality.…”

“…More recently, a retrospective study (9) identified a strong association between the early initiation of vasopressor therapy and reduced mortality in these patients. These findings raise an important question: can the requirement for vasopressor therapy be predicted in patients with severe sepsis?…”