There is no consensual definition of refractory shock. The use of more than 0.5？mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hypoperfusion signs persist after initial resuscitation. Arginine vasopressin is frequently used in refractory shock, although definite evidence to support this practice is still missing. Its associations with corticosteroids improved outcome in observational studies and are therefore promising alternatives. Other rescue therapies such as terlipressin, methylene blue, and high-volume isovolemic hemofiltration await more evidence before use in routine practice. 1. Introduction In-hospital mortality of circulatory shock requiring vasopressors exceeds 50% and nearly 40% of these deaths are caused by progressive hypotension despite support [1]. There is no consensual definition of refractory shock. Increasing doses of vasopressors are associated with unfavorable outcomes [2] and there is a wide range of cut-offs used to identify doses associated with higher mortality, including 15 to 100 micrograms per minute of norepinephrine (NE), for example [3, 4]. High-dose vasopressor-dependent shock is often seen as a terminal event in the intensive care unit. On one hand, it is commonly argued as futile to administer high-dose vasopressors in the critically ill patient with multiple organ failure [5]. On the other hand, survival is up to 50% in “severe” septic shock patients receiving early treatment with a specific algorithm [6]. Unfortunately, high-quality data to guide therapy in this situation are scarce. While several rescue strategies were described, few studies compared them. The objective of this narrative review is to summarize part of this evidence to help clinicians in the management of this extreme condition. 2. Definition and Epidemiology There is no consensual definition of refractory shock, and many cut-offs were used in diverse clinical scenarios (Table 1). 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]. Table 1: Summary of studies on high-dose vasopressor
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