Perioperative infusion of low-dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study
Papadopoulos G, Sintou E, Siminelakis S, Koletsis E, Baikoussis NG, Apostolakis E
Journal of Cardiothoracic Surgery. 2010 Mar 5:17
Reviewer: Richa Dhawan, MD
University of Chicago Medical Center, Chicago, IL
This is a double-blinded, randomized study looking at the effects of prophylactic, continuous low dose vasopressin infusions on the effects of vasoplegic syndrome. The authors enrolled 50 patients undergoing coronary artery bypass grafting, with an ejection fraction between 30-40%, and on an angiotensin converting enzyme inhibitor (ACE-I) for at least four weeks prior to surgery. They randomized the patients into two groups. Patients in group A were infused with 0.03 IU/min vasopressin twenty minutes prior to going on cardiopulmonary bypass with a continuation of the infusion four hours after termination of bypass. Patients in group B were infused the same duration with a saline solution. The primary end points were assessment of hemodynamic status (as measured by ejection fraction, mean arterial pressures, cardiac output, and use of other vasopressors), incidence of vasodilatory shock, urine output, and blood loss at post-operative day one. Exclusion criteria included ejection fraction less than 30%, hemodynamic shock, hepatic/renal/thyroid/adrenal disease, obstructive peripheral arteriopathy, pulmonary hypertension, and chronic obstructive pulmonary disease.
There was no statistically significant difference between the two groups with regards to pre-operative general characteristics and co-morbid conditions. Vasodilatory shock was more common in group B (24%) versus group A (4%) (p= 0.042). Norepinephrine and epinephrine infusions were more likely to be initiated in group B (72% and 68%) than group A (24% and 20% respectively) (p= 0.002 and p= 0.001). Mean doses of norepinephrine were lower in group A than group B (p= 0.001). Post-operative urine output was significantly higher in group A (5600 cc) than group B (3900 cc). Post-operative blood loss (650 cc versus 975 cc) and blood (3.1 versus 4.2) and platelet transfusions (4.3 versus 5.7) were significantly lower in group A than group B (p= 0.0001).
The authors concluded that low dose vasopressin infusions appeared to be safe and potentially beneficial in this select patient population at decreasing the incidence of vasoplegic shock, improving post-operative hemodynamic profile, and decreasing blood loss and transfusion requirement.
Vasoplegic shock by definition is generally intractable to the usual modalities of resuscitation. Identification and prevention of the syndrome appears to be the best route of therapy. In this study vasodilatory shock was defined as systolic arterial pressures less than 80mmHg (or mean arterial pressure < 70mmHg) with a cardiac output more than 5L/min. Although there is no absolute range of numbers that define this clinical condition, it is clear that this is typically a high cardiac output state with decreased peripheral vascular resistance. The pathophysiology is poorly understood but there are several risk factors that have been identified, including congestive heart failure, preoperative use of angiotensin-converting enzyme inhibitors/beta-blockers/amiodarone/phosphodiesterase inhibitors, and prolonged cardiopulmonary bypass time. Previous studies have suggested that the hypotension seen clinically in these situations may respond better to therapeutic intervention with vasopressin as compared to phenylephrine or norepinephrine and the present study suggests that prophylactic vasopressin may be of benefit in patients on long-term ACE-I therapy.
This study poses an interesting question of whether we should start a pressor agent on all patients on an ACE-I who also have moderate left ventricular dysfunction prior to cardiopulmonary bypass. Vasopressin use as a bolus dose has been described extensively to increase blood pressure in patients who are on multiple antihypertensives including ARB’s and ACE-I’s, when other pressor agents do not work. In our institution that is generally how it is used.
It should be noted that this study has several limitations including: a small sample size, large exclusion criteria, and short period of follow-up. Additionally, it should be recognized that administration of vasopressin has been associated with significant risks such as bowel and peripheral extremity ischemia and these effects may limit its widespread use. Although the appropriate dose to offset undesired side-effects while maintaining efficacy is unknown, low doses, as used in this study, have been supported by other research as being safe. Future work should target larger sample sizes, less restrictive exclusion criteria (in our patient population a considerable number of patients would fit the inclusion criteria, however most would be excluded based on other co-morbid conditions), and a longer period of follow-up to better assess the use of vasopressin in this clinical scenario. The lack of other effective treatment options for refractory vasoplegic shock does make the option of empiric vasopressin infusion potentially attractive if further studies can better delineate its safety profile in broader patient populations.