Vasopressor therapy in critically ill patients with shock

Abstract

Background: Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock.

Objectives: The objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, β1-blockers, and directions for research.

Methods: The quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).

Results: Vasopressors bind adrenergic: α1, α2, β1, β2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin).

Conclusions: Norepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge.

Keywords: Angioensin II; Esmolol; Norepinephrine; Septic shock; Vasopressin; Vasopressors.