DOI: 10.1097/01.CCM.0000092458.16716.EE
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PMID: 14605551
Issn Print: 0090-3493
Publication Date: 2003/11/01
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Excerpt
In this issue, Dr. Klinzing and colleagues (13) evaluated vasopressin in septic shock by replacing norepinephrine with vasopressin to maintain blood pressure constant (mean vasopressin dose was 0.47 IU/min; range, 0.06–1.8 IU/min). Vasopressin decreased cardiac index, oxygen delivery, and oxygen uptake. Fractional splanchnic blood flow increased, yet the gastric Pco2 gap increased. The authors conclude, and I agree, that “it would not appear beneficial to directly replace norepinephrine with vasopressin in septic shock.” Dr. Klinzing and colleagues’ study is important because it shows that simply replacing norepinephrine with vasopressin has deleterious consequences on global blood flow and complex effects on splanchnic perfusion. The dose of vasopressin was relatively high, making comparisons to low-dose vasopressin studies difficult. The unique strengths of Dr. Klinzing and colleagues’ study include crossover from norepinephrine to vasopressin and measurement of splanchnic blood flow. Potential limitations are the small sample size (n = 12), lack of randomization, and controversy regarding the indocyanine green determination of splanchnic blood flow and the gastric Pco2 gap.
Persistent vasodilation and failure to increase mean arterial pressure and cardiac output in response to resuscitation characterize nonsurvivors of septic shock. Oxygen delivery must be maintained above a critical threshold, and arterial pressure must be adequate. Catecholamines are most often used. Recent studies favor norepinephrine (14), but norepinephrine has important adverse effects. Norepinephrine’s α- adrenergic effects decrease cardiac output, and norepinephrine at higher doses decreases renal blood flow and may decrease gut and myocardial perfusion. Norepinephrine increases pulmonary vascular resistance, and vascular responsiveness to norepinephrine diminishes.
Norepinephrine infusion results in nonphysiologic, high serum concentrations of norepinephrine. Yet mechanisms of cardiovascular dysfunction during sepsis are not directly related to catecholamines. For example, excessive activation of adenosine triphosphate-sensitive K+ channels (15), which close voltage-dependent Ca2+ channels, decreases calcium entry and leads to widespread dilation of arterial smooth muscle independent of catecholamines.
Vasopressin has little effect on arterial pressure normally. Vasopressin acts primarily as an antidiuretic hormone. During hypotension, vasopressin levels increase and maintain arterial blood pressure by vasoconstriction (16). Vasopressin is secreted by the posterior pituitary. Activation of V1 receptors on vascular smooth muscle causes vasoconstriction by blocking adenosine triphosphate-sensitive K+ channels (17). Activation of V2 receptors on renal tubules is responsible for water resorption, vasopressin’s antidiuretic effect. Activation of V3 pituitary receptors increases adrenocorticotropic hormone production (18). Vasopressin stimulates oxytocin receptors, which mediate vasodilation by stimulation of nitric oxide. Thus, there is organ-specific heterogeneity in the vascular responsiveness to vasopressin, and this vascular profile may be beneficial in septic shock. The study of Dr. Klinzing and colleagues (13) suggests potentially important differences between norepinephrine and vasopressin in gut blood flow distribution; however, the clinical impact is not clear in part because vasopressin increased gastric Pco2 gap, which may indicate redistribution of blood flow away from the gut mucosa.
Patients with septic shock are sensitive to vasopressin (1, 4). Vasopressin stimulates V1-mediated vasoconstriction and blocks adenosine triphosphate-sensitive K+ channels (17). Vasopressin potentiates effects of catecholamines. Vasopressin-induced vasoconstriction spares cerebral, coronary, pulmonary, and afferent glomerular capillary circulations (19, 20).
Human studies of vasopressin in vasodilatory shock are summarized in Table 1. There are studies in patients who had septic shock (1–5, 13), in postbypass patients (6–10), and in organ donors with vasodilatory shock (11).
