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Adequate fluid titration during the initial resuscitation period of major burn patients is crucial. This study aimed to evaluate the feasibility and efficacy of a goal-directed fluid resuscitation protocol that used hourly urine output plus the arterial waveform analysis FloTrac (Edwards LifeSciences, Irvine, Calif) system for major burns to avoid fluid overload.We conducted a retrospective cohort study of 43 major burn patients at the Tri-Service General Hospital after the Formosa Fun Coast Dust Explosion on June 27, 2015. Because of the limited capacity of intensive care units (ICUs), 23 intubated patients were transferred from the burn wards or emergency department to the ICU within 24 hours. Fluid administration was adjusted to achieve a urine output of 30 to 50 mL/h, cardiac index greater than 2.5 L/min/m2, and stroke volume variation (SVV) less than 12%. The hourly crystalloid fluid infusion rate was titrated based on SVV and hourly urine output.Of the 23 critically burned patients admitted to the ICU, 13 patients who followed the goal-directed fluid resuscitation protocol within 12 hours postburn were included in the analysis. The mean age (years) was 21.8, and the mean total body surface area (TBSA) burned (%) was 68.0. The mean Revised Baux score was 106.8. All patients sustained inhalation injury. The fluid volumes administered to patients in the first 24 hours and the second 24 hours (mL/kg/% total body surface area) were 3.62 ± 1.23 and 2.89 ± 0.79, respectively. The urine outputs in the first 24 hours and the second 24 hours (mL/kg/h) were 1.13 ± 0.66 and 1.53 ± 0.87, respectively. All patients achieved the established goals within 32 hours postburn. In-hospital mortality rate was 0%.The SVV-based goal-directed fluid resuscitation protocol leads to less unnecessary fluid administration during the early resuscitation phase. Clinicians can efficaciously manage the dynamic body fluid changes in major burn patients under the guidance of the protocol.