Norepinephrine

Abstract

The study was designed to assess whether high dosages of norepinephrine are associated with increased death rate and to determine the dosage of norepinephrine associated with an intensive care unit (ICU) death rate greater than 90%. We conducted a retrospective, noninterventional, observational study in a single ICU (15 beds) of an academic hospital. From January 2009 to May 2013, data of all patients with a diagnosis of septic shock were extracted from our database. Data were collected at the time of the admission in ICU, at the onset of septic shock, and when the maximal posology of norepinephrine was reached. Mortality was assessed in ICU, in hospital, and at day 90. Among the 324 patients with septic shock, the death rate was 48%. The death rate reached 90% for the quantile of patients receiving more than 1 μg/kg per minute of norepinephrine. In our cohort, four independent factors associated with mortality were identified: age (odds ratio, 1.02 [95% confidence interval, 1.00-1.04]; P = 0.02), thrombocytopenia (odds ratio, 3.8 [95% confidence interval, 1.8-8.5]; P < 0.001), urine output less than 500 mL (odds ratio, 8.7 [95% confidence interval, 3.6-25]; P < 0.001), and dosage of norepinephrine greater than 1 μg/kg per minute (odds ratio, 9.7 [95% confidence interval, 4.5-23]; P < 0.001). However, because of the study's design, unmeasured confounding factors should be taken into account in our findings.

Outcome of patients with septic shock and high-dose vasopressor therapy

“…Given the lack of common definition for refractory shock and high-dose vasopressor per se, there is considerable variability in administered dosages reported in the literature, ranging from 0.5 to 4 µg/kg/min [18, 19, 22, 24, 25]. Martin et al [16] recently established a refractory dosage of 1 µg/kg/min with a 90% mortality rate at D90.…”

“…Depending on the studies, high doses have been defined by a cutoff value ranging from 0.5 µg/kg/min to 2 µg/kg/min [14], although converging evidence has recently confirmed the dose of 1 µg/kg/min [15, 16]. However, mortality at these doses is substantial, from 80 to 100% [17–19].…”

Vasopressor-Refractory Shock From Clozapine Overdose Treated With Synthetic Angiotensin II Infusion

“…The immediate objective during resuscitative efforts is to restore the perfusion pressure to maintain oxygenation of vital tissues and organs, by administration of intravascular fluids and vasopressors. Vasodilatory shock that is refractory to vasopressors is highly morbid, and in cases where norepinephrine dosing requirements reach 1 µg/kg/min, mortality is as high as 90% ( 5 ). Historically available vasopressors include catecholamines, which produce vasoconstriction by direct stimulation of alpha-adrenergic receptors in the vasculature and arginine vasopressin that produces vasoconstriction by stimulation of V 1 receptors in the vasculature.…”

Differential Effects of Selective and Nonselective Potassium Channel Inhibitors in Ovine Endotoxemic Shock (Macrocirculation) and in a Rat Model of Septic Shock (Microcirculation)

“…Catecholamines(in combination with adequate fluid resuscitation) are the first line drugs for the treatment of vasodilatory shock in sepsis (4,5).However, they may be associated with several deleterious side effects especially in high doses (7,6).This "catecholamine resistant" shock andhigh dosages of catecholamines are independently associated with mortality (8,9,6).Therefore, alternative, non-adrenergic vasoconstrictors are necessary.…”