Abstract: Objective To explore the influence of inhalation injury on fluid resuscitation of massive burn patients during shock stage. Methods A total of 74 massive burn patients (65 males and 9 females, aged 21 to 65 years) admitted to the Second Affiliated Hospital of Air Force Medical University (n=57) and Yan′an University Affiliated Hospital (n=17) from May 2009 to December 2019 were enrolled in this retrospective cohort study. Patients were divided into inhalation injury group (n=56) and non-inhalation injury group (n=18) based on clinical symptoms, vital signs, and results of bronchofibroscopy. Then 26 patients in inhalation injury group and 13 patients in non-inhalation injury group were 1∶2 matched by case-control matching based on the difference of total burn surface area. The total fluid replacement coefficient, crystalloid replacement coefficient, colloid replacement coefficient, glucose input volume, ratio of crystalloid to colloid, urine volume, and cumulative ratio of input to output volume during the first 24 h post injury, the second 24 h post injury, and the third 24 h post injury, heart rate, respiratory rate, mean arterial pressure (MAP), and hematocrit (HCT) at post injury hour (PIH) 24, 48, and 72 were recorded and compared between the two groups. Data were statistically analyzed with analysis of variance for repeated measurement and Bonferroni correction, t test, Fisher′s exact probability test, and Mann-Whitney U test. Results (1) After matching, during the first to third 24 h post injury, the total fluid replacement coefficient and glucose input volume of patients in inhalation injury group were significantly higher than those in non-inhalation injury group (F=4.202, 10.671, P<0.05 or P<0.01). During the first, second, and third 24 h post injury, the total fluid replacement coefficient, crystalloid replacement coefficient, colloid replacement coefficient, and ratio of crystalloid to colloid were similar between the patients in two groups(t=-1.336, -1.452, -1.998; -0.148, 0.141, 0.561; 0.916, -0.046, -0.509; -1.024, 0.208, 0.081, P>0.05). During the first, second, and third 24 h post injury, the glucose input volume of patients in inhalation injury group were respectively (2 996±1 176), (2 659±1 030), and (2 680±1 509) mL, which were significantly higher than (2 125±898), (1 790±828), and (1 632±932) mL in non-inhalation injury group (t=-2.334, -2.639, -2.297, P<0.05). (2) After matching, in overall comparison between groups, during the first to third 24 h post injury, the urinary output volumes and cumulative ratios of input to output volume of patients in inhalation injury group were significantly lower or higher than those in non-inhalation injury group, respectively (F=12.158, 9.111, P<0.01). At PIH 24, 48, and 72, heart rate of patients in inhalation injury group were significantly higher than those in non-inhalation injury group (F=4.675, P<0.05). There were no statistically significant differences in heart rate, respiratory rate, MAP, and HCT between patients in the two groups at PIH 24 and 48 (t=-0.039, -1.688, 1.399, 1.299, -1.741, 0.754, -0.677, 0.037, P>0.05). During the first and second 24 h post injury, the urine volume and cumulative ratio of input to output volume of patients in inhalation injury group were respectively significantly lower and higher than those in non-inhalation injury group (t_{urine volume}=2.421, 2.876, t_{cumulative ratio of input to output volume}=-2.687、-2.943, P<0.05 or P<0.01). At PIH 72, the heart rate and HCT of patients in inhalation injury group ( (114±13) times/min, 0.42±0.06) were significantly higher than those in non-inhalation injury group ( (98±18) times/min, 0.38±0.06, t=-3.182, -2.123, P<0.05 or P<0.01), there were no statistically significant differences in respiratory rate and MAP between the patients in two groups (t=0.359, 1.722, P>0.05). During the third 24 h post injury, there were no statistically significant differences in urine volume and cumulative ratio of input to output volume between the patients in two groups (t=1.664, -1.895, P>0.05). Conclusions The presence of inhalation injury can lead to increased fluid requirement in massive burn patients during shock stage. An appropriate increase of fluid volume in the fluid resuscitation of burn patients combined with inhalation injury would be beneficial for maintaining ideal urine output.