Objective To observe the effect of ulinastatin combined with glutamine on early hemodynamics in patients with severe burns. Methods Thirty-two patients with severe burns who met the inclusion criteria and hospitalized in the Affiliated Huaihai Hospital of Xuzhou Medical University from January 2016 to December 2018 were selected for conducting a prospective randomized controlled trial. According to the random number table, the patients were divided into conventional treatment group (4 males and 4 females), ulinastatin group (5 males and 3 females), glutamine group (5 males and 3 females), and ulinastatin+ glutamine group (4 males and 4 females), with ages of (36±8), (34±8), (35±9), and (38±13) years in turn. From post injury day 2, patients in the 4 groups were given nutritional support of equal nitrogen and equal calories, of which protein was 2.0 g/kg daily. In addition, patients in the ulinastatin group received intravenous injection of 100 kU ulinastatin every 8 hours for 7 consecutive days; 0.3 g/kg of protein given to patients in the glutamine group was provided by alanine glutamine for 7 consecutive days; patients in the ulinastatin+ glutamine group received corresponding treatments of both ulinastatin group and glutamine group. With the help of pulse contour cardiac output (PiCCO) monitoring technology, the cardiac index, stroke volume index (SVI), global end-diastolic volume index (GEDI), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) of patients in each group were measured on treatment day (TD) 1, 3, and 7. Data were processed with Fisher′s exact probability method, one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni method. Results The cardiac index was low and the SVI value was lower than the normal value on TD 1 in patients of the 4 groups, without statistically significant differences between any two groups (

>0.05), and then they were all gradually increased. On TD 3 and 7, compared with those of the conventional treatment group, the cardiac index and SVI of patients in the other three groups were all increased, and the cardiac index and SVI of patients in the ulinastatin+ glutamine group were significantly increased (

<0.05 or

<0.01). On TD 1, the GEDI of patients in the conventional treatment group, ulinastatin group, glutamine group, and ulinastatin+ glutamine group were at normal low levels, which were (659±58), (661±79), (659±88), and (653±71) mL/m² respectively, without statistically significant differences between any two groups (

>0.05), and then they all gradually increased. On TD 3 and 7, compared with (684±82) and (742±46) mL/m² of the conventional treatment group, the GEDI of patients in the ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all elevated, which were (732±53) and (777±33), (725±58) and (783±49), (813±65) and (849±27) mL/m² respectively, and the GEDI of patients in the ulinastatin+ glutamine group was significantly increased (

<0.05). The SVRI of patients in the four groups were all at high levels on TD 1, without statistically significant differences between any two groups (

>0.05), and then they all gradually decreased. On TD 3 and 7, compared with those of the conventional treatment group, the SVRI of patients in the other three groups were all increased, and the SVRI in the ulinastatin+ glutamine group was significantly increased (

<0.05). On TD 1, the EVLWI of patients in the conventional treatment group, ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all in the normal range, which were (6.6±0.6), (6.3±0.4), (6.5±0.4), and (6.6±0.6) mL/kg respectively, without statistically significant differences between any two groups (

>0.05), and then they all showed the increasing trend. On TD 3 and 7, compared with (7.1±0.9) and (7.9±0.5) mL/kg of the conventional treatment group, the EVLWI of patients in the ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all decreased, which were (6.2±0.6) and (7.1±0.4), (6.3±1.0) and (7.2±0.9), (5.8±0.7) and (6.7±0.6) mL/kg respectively, and the EVLWI of patients in the ulinastatin+ glutamine group was significantly decreased (

<0.05). On TD 1, the PVPI of patients in the four groups were all in the normal range, without statistically significant differences between any two groups (

>0.05), and then they all gradually decreased. On TD 3 and 7, compared with those of the conventional treatment group, the PVPI of patients in the other three groups were all decreased, and the PVPI in the ulinastatin+ glutamine group was significantly decreased (

<0.05). Conclusions Ulinastatin combined with glutamine can increase the cardiac index, SVI, GEDI, and SVRI and reduce the EVLWI and PVPI in treating patients with severe burns, thereby increasing early cardiac output after injury, promoting tissue and organ perfusion, and reducing pulmonary edema, resulting in significant improvement in early hemodynamics of patients with severe burns.