. 2022 May 25;8(3):185–199.

Table 2. Narrative summary of included studies.

Study ID	Population	Intervention	Comparisons	Outcome
Patel et al., 2002 [8] Prospective, double blind, randomized, and controlled trial	Patients experiencing septic shock that required high dose vasopressor support N=24 (C=11, T=13) Male: T=77% C=73% Female T=23% C=27% Value (Median, Q1, Q3D) C: 68 (58,75) T: 68 (58,70)	The starting volume of the vasopressin infusion was 7 ml/h. This corresponded to a vasopressin infusion of 0.01 units/min. The maximum rate of infusion allowed in this study protocol was 56 ml/h of blinded study drug, which corresponded to a vasopressin infusion rate of 0.08 units/min	The starting volume of the norepinephrine infusion was 7 ml/h. This corresponded to a norepinephrine infusion of 2 mg/min. The maximum rate of infusion allowed in this study protocol was 56 ml/h of blinded study drug, which corresponded to a norepinephrine infusion rate of 16 mg/min	Mean arterial pressure: Median (q1, q3) T: Baseline 69 (65,72) After 4 h 69 (65,70) mm of Hg C: Baseline 68 (65,70) After 4 h 67 (61,70) mm of Hg Urine output: Mean T: Baseline: 32.5 ml.h After 4 h: 65 ml/h C: Baseline: 25 ml/h After 4 h: 15 ml/h Cardiac index: Median (q1, q3) T: Baseline 4.8 (3.5,5.5), After 4 h: 4.4 (3.1,5.3) C: Baseline 5.0 (3.8, 5.6) After 4 h: 4.0 (3.2, 5.1) Heart rate: Median (q1, q3) T: Baseline: 102 (90, 110) bpm after 4 : 93 (91, 100) bpm C: baseline :97 (89, 110) bpm after 4 :92 (83, 100) bpm Systemic vascular ressitance index: Median (q1, q3) T: Baseline: 905 (838, 1044), After 4 hours: 948 (864,1130) C: Baseline 750 (681, 1173) After 4 hours: 781 (662, 1263)
Morelli et al., 2009 [24] Prospective randomized controlled trial	Patients with septic shock with mean arterial pressure below 65 mm of Hg despite adequate volume resuscitation N=45 (T1=15/45, C=15, 45, T2=15/45) Male T1=67%, C=80%, T2=73% Female T1=33%, T2=27%, C – 20%) Value (median, Q1, Q3) Age: T1: 66 (60,74) T2: 67 (69,71) C: 64 (59,72)	T1: Vasopressin (0.03 units/min) T2: Terlipressin (1.3 mgkg^-1 h^-1) All three groups received open-label norepinephrine and intravenous hydrocortisone as a continuous infusion	C: Norepinephrine (15 mg/min^-1)	ICU mortality T1: 8/15 T2: 7/15 C: 10/15 ICU length of stay (Median, q1, q3) T1: 17 (5,27) T2: 14 (9,25), C: 17 (7, 23) Norepinephrine requirement at 48 h T1: 0.8 mgkg^-1 min^-1 T2: 0.2 mgkg^-1 min^-1 C: 1.2 mgkg^-1 min^-1 Urine output (ml/h) T1: Baseline: 42.3±46.9; 24 h: 42±41.6; 48 h: 43.3±58.7 T2: Baseline: 34.6±31.3; 24 h: 49.2±49.5; 48 h: 46.6±33.3 C: Baseline: 38.6±34.3; 24 h: 66±77; 48 h: 58.6±63.8 Mean arterial pressure T1: Baseline: 53±4; 24 h: 70±3; 48 h: 71±3 mmHg T2: Baseline: 53±4; 24 h: 71±3; 48 h: 71±4 mm Hg C: Baseline: 54±3; 24 h: 71±2; 48 h: 71±3 mmHg Heart rate T1: Baseline: 100±22 At 48 h: 93±25 bpm T2: Baseline: 95±16 At 48 h: 71±16 bpm C: Baseline: 97±21 At 48 h: 96±21 bpm Cardiac index T1: Baseline: 4.0±1.1 At 48 h: 4.2±1.9 L/min/m T2: Baseline: 4.0±1.0 At 48 h: 4.2±1.9 L/min/m C: Baseline: 4.0±1.0 At 48 h: 3.9±1.5 L/min/m Systemic vascular resistance index: T1: Baseline: 41±12 At 48 h: 43±12 ml/beats/m T2: Baseline: 46±13 At 48 h: 50±10 ml/beats/m C: Baseline: 4.0±1.0 At 48 h: 3.9±1.5 ml/beats/m
Lauzier et al., 2006 [10] Multicenter randomized non-blinded trial	Patients with early hyperdynamic septic shock N=23 (T=13/23, C=10/23) Male T=46%, C=80% Female T=54%, C=20% Age, median (IQR): T=51.2±17.2 C=58.1±17.5	Vasopressin (0.04–0.20 Umin^–1) as a single agent for 48 hours	Norepinpehrine (0.1–2.8 mgkg^–1 min^–1) as a single agent for 48 hours	Urine output Baseline: T: 1420±656 ml C: 1146±700 ml 24h: T: 2049±562 ml C: 1895±1292 ml 48h: T: 3051±1666 ml C: 2644±1060 ml Mean arterial pressure mean, SD Baseline: T: 72±7 C: 68±10 mm Hg 1 h: T: 74±8 C: 72±5 mm Hg 24 h: T: 81±11 C: 77±6 mm Hg 48 h: T: 78±12 C: 81±9 mm Hg Heart rate mean, SD Baseline: T: 118±16 C: 109±23 bpm 1 h: T: 105±16 C: 108±22 bpm 6 h: T: 100±15 C: 104±22 bpm 48 h: T: 93±21 C: 96±18 bpm Cardiac index mean, SD Baseline: T: 4.6±1.0 C: 4.4±1.4 1 h: T: 3.6±1.1 C: 4.3±1.4 6 h: T: 3.7±0.7 C: 4.3±1.7 48 h: T: 3.7±0.9 C: 3.7±1.6 Mortality ICU T: 2/13 C: 1/10 Acute coronary syndrome T: 1/13 C: 1/10
Russell et al., 2008 [11] Multicenter, randomized, double-blind trial	Patients older than 16 years of age who had septic shock that was resistant to fluids (as defined by lack of response to 500 ml of normal saline or a requirement for vasopressors and low-dose norepinephrine N=778 (T=396, C=382) Male: T=62%, C=59.9% Female T=38%, C=40.1% Age: T: 59.3±16.4, C=61.8±16	Blinded vasopressin infusion was started at 0.01 U per minute and titrated to a maximum of 0.03 U per minute	Blinded norepinephrine infusion was started at 5 mg per minute and titrated to a maximum of 15 mg per minute	28-day mortality Randomization: T=144/404 C=154/395 Randomization and infusion: T=140/396 C=150/382 90 day mortality Randomization T=177/400 C=194/391 Randomization and infusion T=172/392 C=188/379 Length of ICU stay median, IQR T (396) =15 (7-29); C (382) =16 (8-32) Length of Hospital stay median, IQR T (396)=27 (13-52), C (382)=26 (15-53) Serious adverse events T=41/396 C=40/382 Acute myocardial infarction T=8/396 C=7/382 Cardiac arrest T=3/396 C=8/382 Life-threatening arrhythmia T=8/396 C=6/382 Acute mesenteric ischemia T=9/396 C=13/382 Hyponatremia T=1/396 C=1/382 Digital ischemia T=8/396 C=2/382 Cerebrovascular accident T=1/396 C=1/382
Russell et al., 2018 [19] Retrospective cohort study using propensity based matching SPH 1 : 2001-2007 SPH 2: 2008-2012	Patients admitted to Intensive care unit who had two of four SIRS criteria who had suspected or proven infection and who were unresponsive to fluid resuscitation and received infusion of norepinephrine or vasopressin. SPH 1: Before matching T: 165 C: 558 Age: T: 56.1±15.7 C: 60.7±16.2 Male: T: 73.3% C: 61.8% After matching T: 158 C: 158 Age: T: 56.4±15.4 C: 57.1±15.1 Male: T: 72.8% C: 67.1% SPH 2: Before matching T: 525 C: 145 Age: T: 60.9±13.9 C: 61.4±16.8 Male: T: 62.4% C: 66.4% After matching T: 93 C: 93 Age: T: 60.9±13.9 C: 61.4±14.5 Male: T: 37.6% C: 30.1%	Vasopressin as per local practice	Nor epinephrine as per local practice	28 day mortality SPH 1: After matching T: 96/158 C: 73/158 SPH 2: After matching T: 29/93 C: 25/93
Gordon et al., 2016 [12] Double blind, randomized clinical trial	Adult patients (≥16 years) who had sepsis and required vasopressors despite adequate intravenous fluid resuscitation. N=409 T1=101 T2=104 C1=101 C2=103 Male: T1=58%, T2=52%, C1=62%, C2=65% Female: T1=42%, T2=48%, C1=38%, C2=35% Age (median, IQR) T1: 66 (57-76), T2: 67 (59-77), C1: 63 (52-76), C2: 66 (54-76)	T1=Vasopressin and hydrocortisone T2=Vasopressin and placebo T=Vasopressin with placebo or hydrocortisone Vasopressin (titrated upto 0.06 U/min) as the initial vasopressor infusion. Once maximum infusion rate of vasopressin was reached, either 50 mg of hydrocortisone phosphate or placebo was administered as an intravenous bolus every 6 h for 5 days, every 12 h for 3 days and then once daily for 3 days	C1=Norepinephrine and hydrocortisone C2=Norepinephrine and placebo C=Norepinephrine with or without placebo Norepinephrine titrated upto 12 mg/min as the initial vasopressor infusion. Once maximum infusion rate of norepineprhine was reached, either 50 mg of hydrocortisone phosphate or placebo was administered as an intravenous bolus every 6 for 5 days, every 12 h for 3 days and then once daily for 3 days	Hospital Mortality T=68/204 C=60/204 Requirement of RRT T=52/205 C=72/204 ICU length of stay median (IQR) T=7 (3 to 11) C=5 ( 3 to 13) Hospital length of stay median (IQR) T=16 (7 – 36) days C=16 (8-38) days Serious adverse events T=22/205 C=17/204 Acute coronary syndrome T=7/205 C=4/204 Digital ischemia T=11/205 C=3/204 Mesenteric ischemia T=5/205 C=5/204 Life-threatening arrhythmia T=2/205 C=5/204 Urine output mean, SD Day 1 T (205): 737±3813 ml C (204): 1010±2455 Day 2 T (189): 1521±2204 ml C (198): 1628±1733 Day 7 T (114): 2314±1150 C (99): 1906±1363
Hall et al., 2004 [20] Retrospective cohort single left study	Critically ill patients who were receiving continuous intravenous infusion of vasopressin, norepinephrine and dopamine N=50, T1=50, T2=51 and C=49 Male: T1=60%, C=57% and T2=55% Female: T1=40%, C=43% and T2=45% Age: T1=67.1±17.1, T2=62.5±17.7 and C: 61.1±18.0	T1: Fixed dosage of intravenous vasopressin 0.04 U/min T2: Titrated intravenous infusion of dopamine (6.7±5.5 mg/kg/min)	C: Titrated intravenous infusion of norepinephrine (0.28±0. mg/kg/min)	28-day mortality T1: 23/44 T2: 28/51 C: 30/46 Hospital stay mean, SD T1 (50): 36±34 days T2 (51): 29±29 days C (49): 36±40 days ICU length of stay mean, SD T1 (50): 14±55 days T2 (51): 20±26 days C (49): 29±40 days Serious adverse events T1: 36/50 T2: 36/51 C: 39/49 MI T1: 2/50 T2: 2/51 C: 4/49 ARDS T1: 10/50 T2: 12/51 CL 17/49 Atrial arrhythmia T1: 6/50, T2: 6/51, C=15/49 Acute renal insufficiency T1: 3/50, T2: 3/51, C: 3/49 Venous thromboembolism T1: 7/50, T2: 4/51, C=1/49 Peripheral vascular necrosis T1: 3/50, T2: 2/51, C=3/49 Urine output: mean, SD T1 (44): Baseline: 3437±4618, 24 h: 2898±4103 T2 (44): Baseline: 3215±2958 24 h: 4210±6350 C (43): Baseline: 2495±1960 24 h: 2810±2193 Cardiac index mean, SD T1: Baseline: 4.1±1.6; 1 h: 3.5±1.3 T2: 2.8±1.0; 1 h: 2.6±1.2 C: 3.6±1.3; 1 h: 3.3±1.0 MAP T1: Baseline: 63.3±13.3 mm Hg 1 h: 74.4±11.3 mm Hg T2: Baseline: 58.7±9.5 mm Hg 1 h: 70.5±11.6 mm Hg C: Baseline: 56.8±8.5 mm Hg 1 h: 72.9±8.9 mm Hg
Daley et al., 2013 [21] Retrospective cohort study	Patients with septic shock with mean arterial pressure less than 65 mm Hg. N=130 T=65 C=65 Male T=52.3%, C=53.8% Female T=47.7%, C=46.2% Age mean (SD) T=61 (17.7) C=56 (17.7)	Administration of vasopressin 1 h after the onset of septic shock	Administration of norepinephrine 1 h after the onset of septic shock	Mortality T=29/65 C=32/65 Length of hospital stay (Median, Interquartile range) T=15 (8-34) C=15 (7-31) ICU length of stay: Median, Interquartile range T=7 (4-24) C=7 (3-15) Requirement of renal replacement therapy T=19/65 C=21/65 MAP mean, SD (mm Hg) T: Baseline: 57.3 (5.9), 0-6 h: 75.0 (9.6); 12-24 h: 71.7 (10.3) C: Baseline: 56.8 (6.4) 0-6 h: 76 (8.2); 12-24 h: 73.4 (11.1) Urine output mean, SD (ml/kg/h) T: 0-6 h: 0.84 (1) 6-12 h: 0.72 (0.9) 12-24 h: 0.77 (0.9) C: 0-6 h: 0.63 (1) 6-12 h: 0.66 (0.8) 12-24 h: 0.51 (0.6)