Purpose/Background: The Surviving Sepsis Campaign recommends norepinephrine as the first-line vasopressor in patients with septic shock to maintain a mean arterial pressure (MAP) of at least 65 mmHg. The guideline also makes a weak recommendation (2B) to use vasopressin as an adjuvant therapy to raise MAP to goal or to reduce the norepinephrine rate required to maintain the goal MAP. The recommendation is based on conflicting results of the VASST trial that showed no significant difference in 28-day all-cause mortality between patients managed with norepinephrine alone compared to norepinephrine and vasopressin. However, in subgroup analysis, the VASST trial showed mortality benefit for vasopressin in patients requiring low dose norepinephrine (5-14 mcg/min). This study will evaluate outcomes associated with the use of vasopressin in septic shock in order to validate a future protocol optimizing its utilization.
Methods: A retrospective chart review conducted at Baptist Hospital of Miami. Patients admitted from January 2018 to September 2018 with septic shock were divided into two arms based on their maximum norepinephrine equivalent rate or the norepinephrine equivalent rate at the time of vasopressin initiation. Norepinephrine equivalent rates were calculated using the equation from the VASST trial. The threshold for assignment in the severe septic shock arm was a rate greater than 0.2 mcg/kg/minute. Within each arm, patients who were administered vasopressin were compared to those who were not. Pregnant patients as well as those diagnosed with cardiogenic shock or with cardiothoracic surgery during the specific admission were excluded. Patients were also excluded if they were administered vasopressor therapy for less than 12 hours total. The primary outcome was to evaluate the in-hospital mortality in patients with both less severe and severe septic shock who were treated with vasopressin. Secondary outcomes included total time on vasopressors, number of catecholamine agents required, and length of stay. Additional data collected included age, sex, weight, APACHE II score, SOFA score, lactic acid, MAP, norepinephrine equivalent dose at time of inclusion, steroid prescribing rates, midodrine prescribing rates, time to vasopressin initiation, and duration of vasopressin administration.
Results: Of the 147 patients included, 53 were included in the low-dose vasopressor or less severe septic shock arm and 94 were included in the high-dose vasopressor or severe septic shock arm. For the patients in the less severe arm, 20 (38%) received vasopressin. Mean SOFA score at the time of inclusion was similar between those receiving vasopressin and those not, 7.9 and 8.1 respectively. Of the patients who received vasopressin on low-dose vasopressors, 7 (35%) expired prior to hospital discharge. This is compared to an in-hospital mortality of 6 (18%) among patients not administered vasopressin (p=0.17). The median time on vasopressors was 75 hours for patients receiving vasopressin compared to 33.4 hours for patients not administered vasopressin. For the patients in the high-dose vasopressor arm, 48 (51%) received vasopressin. Of the patients who received vasopressin with severe septic shock, 34 (70%) expired prior to hospital discharge. This is compared to an in-hospital mortality of 20 (44%) among patients not administered vasopressin (p=0.007). The median duration of vasopressor therapy was similar in each group, 76.5 hours for patients receiving vasopressin versus 74.2 hours for patients not administered vasopressin. Midodrine and steroid use was similar between groups in both arms.
Discussion: Vasopressin did not result in in-hospital mortality benefit for patients with less severe or severe septic shock. Vasopressin was not associated with shorter durations of vasopressor therapy. Based on the results of this study, efforts can be made to optimize vasopressin utilization in patients with septic shock in order to maximize cost-effectiveness and clinical benefit. Future studies are required to further evaluate vasopressin use in patients with less severe septic shock.
BHSF Pharmacy Residency Conference
Michael Pasqualicchio - Pharmacy Resident PGY2
Pasqualicchio, Michael; Clarke, Heidi; Kline, Jonathan; and Patel, Payal, "Evaluating the Association Between Vasopressin Use and In-Hospital Mortality in Patients with Septic Shock" (2020). All Publications. 3535.
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