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Vasopressin for Vasodilatory Shock
Abstract & Commentary
Synopsis: The combined infusion of AVP and NE was superior to NE alone in catecholamine-resistant vasodilatory shock.
Source: Dunser MW, et al. Circulation. 2003;107: 2313-2319.
Vasodilatory shock frequently complicates sepsis and can occur after cardiopulmonary bypass requiring surgery. The value of arginine vasopressin (AVP) vs norepinephrine (NE) alone or in combination is not fully understood. Thus, Dunser and colleagues randomized 48 patients with mean arterial pressure (MAP) < 70 mm Hg despite volume resuscitation and NE requirements > 0.5 mg/kg/min to continued NE or the addition of AVP at a constant infusion of 4 U/h. In the NE group, when the NE infusion to keep MAP > 70 mm Hg exceeded 2.26 mg/kg/h, NE was discontinued and AVP was infused. In both groups, if cardiac index remained < 2 L/min/m2, then a milrinone infusion was added. The primary end point was the difference in hemodynamic parameters between the groups at 48 hours. Secondary end points focused on single organ function, such as gastric tonometry. The patient groups were well matched: about 60% had inflammatory or septic shock and 40% had postcardiotomy shock. AVP was associated with higher MAP and cardiac index and lower heart rate and NE requirements vs NE. New tachyarrhythmias were less with AVP vs NE (8% vs 54%; P < .001). Acid base status was improved more by AVP, but platelet counts were lower and bilirubin levels were higher on AVP. There was no difference in myocardial, skin, or intestinal ischemic events. In both groups, 75% of the patients also received a milrinone infusion. Almost all patients in both groups were on hemofiltration. Overall mortality was 70% for both groups. Dunser et al concluded that the combined infusion of AVP and NE was superior to NE alone in catecholamine-resistant vasodilatory shock.
Comment by Michael H. Crawford, MD
Previous small studies have shown beneficial hemodynamic effects of AVP in vasodilatory shock. AVP is a potent constrictor of peripheral resistance vessels and raises MAP even in patients no longer responsive to catecholamines. The receptors for AVP seem to be preserved during hypoxia and acidosis, unlike the catecholamine receptors. Based upon this limited information, critical care specialists have been using AVP for shock patients, but little is known about specific organ perfusion and adverse effects in the shock patient.
This study showed that myocardial performance was enhanced perhaps because the use of AVP allowed NE to be down-titrated. Alternatively, the increase in MAP may have increased coronary blood flow. Also, there were less tachyarrhythmias in the AVP group. Whether AVP has a positive inotropic effect as has been shown in animals is difficult to determine in the clinical setting. Only 3 patients developed myocardial ischemia or infarction in this study, but all were in the NE group.
Ischemic skin injury occurred in about one-quarter of patients but was similar in both groups. Tonometric assessment of the gastric mucosa showed improved perfusion in the AVP group. One patient in the NE group died of intestinal ischemia. However, bilirubin was higher in the AVP group, which may indicate that hepatic blood flow was reduced. Finally, platelet counts were lower in the AVP group.
Clearly, this was a sick group of patients who were not doing well on NE infusions and 75% of whom required a continuous milrinone infusion. Although many parameters of organ perfusion appeared better on AVP and significant complications were less, the over-all mortality was no different between the 2 groups and was high (70%). This trial was not powered for mortality and major morbidity differences, but the results are encouraging enough to support the use of AVP in selected patients until a larger trial is conducted.
Dr. Crawford is Professor of Medicine, Mayo Medical School; Consultant in Cardiovascular Diseases, and Director of Research, Mayo Clinic, Scottsdale, AZ.