Vasopressors or Fluids in Early Septic Shock

The optimal approach to early resuscitation in septic shock remains uncertain, with ongoing equipoise between the use of larger volumes of intravenous fluids to restore perfusion and the use of early vasopressor therapy with smaller fluid volumes to minimize potential harm from excess fluid.

Investigators compared an approach centered on restricted intravenous fluid administration with early vasopressor therapy against a strategy using larger fluid volumes followed by later vasopressor initiation in adults presenting to the emergency department with septic shock. The study evaluated whether either approach resulted in a greater number of days alive and out of the hospital through day 90.

A total of 1,000 patients underwent randomization, with 499 assigned to the early vasopressor group and 501 to the higher-fluid group. After informed consent was not obtained for 37 patients, 963 patients were included in the intention-to-treat analysis, comprising 481 patients in the vasopressor group and 482 in the fluids group. Three patients in the fluids group were lost to follow-up for the primary outcome.

During the first 24 hours after randomization, the two treatment strategies produced differences in early management. Patients assigned to restricted fluids and early vasopressors received less intravenous fluid than those managed with the higher-fluid approach, with a median difference of 1,108 mL. Vasopressor use was also more common in the restricted-fluid group, with an absolute increase of 18.9 percentage points compared with the higher-fluid group.

The primary outcome was the same between the groups. The median number of days alive and out of the hospital at day 90 was 76 days in both treatment arms. Statistical analysis demonstrated no difference between the strategies, with an estimated difference of 0.0 days and a P value of 1.00.

Adverse events occurred in similar percentages of patients in both groups, with one exception. Pulmonary edema occurred less frequently in the restricted-fluid and early vasopressor group than in the higher-fluid group, affecting 0.6% and 5.0% of patients, respectively (P<0.001).

The investigators concluded that among adults presenting to the emergency department with septic shock, a strategy involving restricted fluid volume and early vasopressor therapy did not result in a greater number of days alive and out of the hospital at day 90 than an approach involving greater fluid volume and later administration of vasopressors.