From 6159 records identified through literature search, we included 51 RCTs with a total of 5715 patients (Table 1 and Fig. 1) [5, 6, 12,13,14, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69]. The major exclusions and reasons for exclusion are shown in Table S2. The predominant population investigated was septic shock in 30 studies [5, 6, 12, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50], cardiac surgery in 11 studies [13, 14, 51,52,53,54,55,56,57,58,59], and non-cardiac surgery in 10 studies [60,61,62,63,64,65,66,67,68,69]. The non-adrenergic agent assessed was vasopressin in 16 studies [26, 29,30,31,32, 34, 37, 39, 45, 52, 54, 56, 57, 59, 61, 68], terlipressin in 15 studies [24, 25, 28, 33, 38, 42, 46, 48,49,50, 62, 65,66,67, 69], selepressin in two studies [36, 44], angiotensin II in five studies [12,13,14, 27, 51], methylene blue in 11 studies [5, 35, 40, 41, 47, 53, 55, 58,