Vasopressin in vasoplegic shock: A systematic review

Table 1 Trial characteristics

Ref.	Inclusion criteria	Exclusion criteria	Interventions (number of patients)	Age (yr)	Main outcomes
EI Adawy et al[25], 2015	Severe sepsis diagnosed within 72 h and septic shock diagnosed within 24 h from the time of giving norepinephrine dose of greater than or equal to 0.2 µg/kg per minute, which is required to maintain the mean arterial pressure between 70 and 90 mmHg	(1) Pregnant females; (2) Patients sensitive to Methylene blue or vasopressin; (3) Patients with known G6PD deficiency; (4) Age less than 18 yr; (5) Vasospastic diathesis (e.g., Raynaud’s syndrome); (6) Coronary artery disease; and (7) Patients receiving mono amine oxidase inhibitors	Methylene blue (20); vasopressin (20)	55.3 ± 20.9; 59.4 ± 14.5	ICU length of stay; mean arterial pressure; central venous pressure; pulmonary artery pressure
Cheng et al[23], 2018	Patients with age more than 18 yr, who had left ventricular ejection fraction ≤ 35%, left ventricular end-diastolic diameter ≥ 60 mm, and New York Heart Association ≥ III), and developing postoperative vasoplegic shock (mean arterial pressure < 65 mmHg resistant to fluid challenge and cardiac index > 2.20 L/min per meter squared)	(1) Patients with chronic obstructive pulmonary disease; and (2) Adult congenital heart disease	Norepinephrine (938); vasopressin (218)	59.43 ± 11.07; 59.25 ± 12.73	30-d mortality; mechanical ventilation more than 48 h; cardiac reoperation; postoperative extracorporeal membrane oxygenation; stroke; acute kidney injury stage II/III; infection; septic shock; atrial fibrillation; ventricular arrhythmias
Hajjar et al[24], 2017	All adult (more than 18 yr of age) patients who were scheduled for coronary artery bypass graft surgery, valve replacement, or repair surgery with cardiopulmonary bypass who required vasopressor drugs for vasodilatory shock within 48 h after coronary artery bypass surgery weaning	(1) Aortic surgery; (2) Heart transplantation; (3) Preoperative use of vasopressor therapy; (4) Presence of a ventricular assist device other than an intra-aortic balloon pump; (5) Severe hyponatremia (< 130 mEq/L); (6) Acute coronary syndrome; (7) Acute mesenteric ischemia; (8) History of Raynaud disease; (9) Pregnancy; and (10) Neoplasm	Norepinephrine (151); vasopressin (149)	55 ± 13; 54 ± 14	Days alive and free of organ dysfunction at 28 d; stroke; acute renal failure; 30 d incidence of infection, septic shock, arrhythmias (atrial fibrillation and ventricular arrhythmias); duration of mechanical ventilation; changes in hemodynamic variables; the use of dobutamine or other vasoactive agents); incidence of digital ischemia; acute mesenteric ischemia; acute myocardial; infarction; ICU and hospital lengths of stay

G6PD: Glucose-6-phosphate dehydrogenase; ICU: Intensive care unit; mEq/L: Milliequivalents per liter.

Table 2 Risk of summary bias (randomized controlled trials)

Ref.	Overall ROB	ROB from randomization process	ROB due to deviations from intended interventions	ROB due to missing outcome data	ROB in measurement of outcomes	ROB in selection of the reported results	Other (funding, conflict of interest)
El Adawy et al[25], 2016	Some concerns	Some concerns	Low risk	Low risk	Low risk	Low risk	Low risk
Hajjar et al[24], 2017	Some concerns	Some concerns	Low risk	Low risk	Low risk	Low risk	Low risk

ROB: Risk of bias.

Table 3 Risk of summary bias (cohort study)

Ref.	Overall ROB	Selection	Ascertainment of exposure	Comparability	Ascertainment of outcome	Adequacy of follow up
Cheng et al[23], 2018	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk

ROB: Risk of bias.

Table 4 Trial outcomes

Comparison	Vasopressin vs norepinephrine		Vasopressin vs methylene blue
Study	Hajjar et al[24], 2017	Cheng et al[23], 2018	El Adawy et al[25], 2016
Study design	Randomized trial	Cohort	Randomized trial
Sample size	330	338	40
30-d mortality	RR 0.97, 95%CI 0.57, 1.64; moderate	RR 3.33, 95%CI 0.93, 11.90; very low	-
Ventricular arrhythmia	RR 0.86, 95%CI 0.54, 1.35; moderate	RR 1.75, 95%CI 1.11, 2.76; very low	-
Duration of vasopressors	MD -23.00 d, 95%CI -36.12, -9.88; moderate	MD 24 d, 95%CI 16.32, 31.68; very low	-
Intensive care unit length of stay	MD -1.00 d, 95%CI -1.69, -0.31; moderate	MD 1.00 d, 95%CI 0.53, 1.47; low	MD 1.60 d, 95%CI -0.29, 3.49; very low
Stroke	RR 1.01, 95%CI 0.26, 3.98; low	RR 0.50, 95%CI 0.13, 1.97; very low	-
Acute kidney injury stage II/III	RR 0.32, 95%CI 0.21, 0.49; moderate	RR 1.12, 95%CI 0.89, 1.42; very low	-
Atrial arrhythmia	RR 0.78, 95%CI 0.67, 0.89; moderate	RR 1.70, 95%CI 1.02, 2.83; low	-
Mechanical ventilation > 48 h	RR 0.62, 95%CI 0.27, 1.46; low	RR 0.95, 95%CI 0.63, 1.42; very low	-

Data is presented as effect size, 95% confidence interval (CI), certainty of evidence. CI: Confidence interval; MD: Mean difference; RR: Relative risk.