There is no consensual definition of refractory shock, and many cut-offs were used in diverse clinical scenarios (). Norepinephrine (NE) doses > 0.5
mcg/kg/min or need for rescue therapy with vasopressin generally is associated with mortality rates higher than 50%, while 94% of patients requiring concentrations above 100
mcg/min of NE or epinephrine died in one study [4
Summary of studies on high-dose vasopressor dependente shock.
The threshold of approximately 0.5
mcg/kg/min of NE is often used in clinical trials as a definition of refractory shock [8
]. In 2011, Benbenishty et al. used a ROC analysis to determine the correlation between maximum dose of vasopressors and death. The area under the curve was high (0.85), and the administration of concentrations above 0.5
NE or epinephrine demonstrated sensitivity of 96% and a specificity of 76% for the likelihood of mortality [2
]. Interestingly, the same dose was the inflexion point of the mortality curve in the study by Luckner et al. [14
]. In the recent study by Brown et al., high-dose vasopressor therapy was defined as use of more than 1
mcg/kg/min of norepinephrine equivalents [12
]. Mortality at 90 days was 83%, which may suggest that rescue therapies could be considered earlier in the evolution of shock.
Regarding the incidence of refractory shock, Mayr et al. described the causes of death and outcomes of critically ill patients and attributed 17.8% of deaths to refractory cardiovascular failure, while the main cause of death in the ICU was acute multiple organ failure [16
]. In the recent randomized SOAP 2 study including 1,679 patients with shock from diverse etiologies, 43% of deaths were due to refractory shock [1
]. Kumar et al. attributed 55% of deaths to this entity in their retrospective analysis of 4,662 patients with septic shock, a finding similar to the SOAP 2 one [17
]. However, a clear limitation of this type of analysis is the inclusion only of non-survivors. Thus, some efforts to specifically evaluate the epidemiology of refractory shock were done. In the study by Benbenishty et al., 7% of patients required >0.5
mcg/kg/minute NE or epinephrine during ICU stay [2
]. Jenkins et al. found that 6% of their ICU patients required concentrations above 100
mcg/min of NE or epinephrine [4
]. Despite the difference in dosages, taking together these data suggest that approximately 6-7% of critically ill patients will develop refractory shock.