Effect of initial infusion rates of fluid resuscitation on outcomes in patients with septic shock: a historical cohort study

Abstract

Background: Fluid resuscitation has become the cornerstone of early septic shock management, but the optimal fluid rate is still not well studied. The goal of this investigation is to examine the relationship between fluid resuscitation rate and septic shock resolution.

Method: We retrospectively studied adult (≥ 18 years) patients with septic shock, defined based on sepsis III definition, from January 1, 2006, through May 31, 2018, in the medical intensive care unit (MICU) of Mayo Clinic Rochester. The fluid resuscitation time was defined as the time required to infuse the initial fluid bolus of 30 ml/kg, based on the recommendations of the 2016 surviving sepsis campaign. The cohort was divided into four groups based on the average fluid rate (group 1 ≥ 0.5, group 2 0.25-0.49, group 3 0.17-0.24, and group 4 < 0.17 ml/kg/min). The primary outcome was the time to shock reversal. Multivariable regression analyses were conducted to account for potential confounders.

Result: A total of 1052 patients met eligibility criteria and were included in the analysis. The time-to-shock reversal was significantly different among the groups (P < .001). Patients in group 1 who received fluid resuscitation at a faster rate had a shorter time to shock reversal (HR = 0.78; 95% CI 0.66-0.91; P = .01) when compared with group 4 with a median (IQR) time-to-shock reversal of 1.7 (1.5, 2.0) vs. 2.8 (2.6, 3.3) days, respectively. Using 0.25 ml/kg/min as cutoff, the higher fluid infusion rate was associated with a shorter time to shock reversal (HR = 1.22; 95% CI 1.06-1.41; P = .004) and with decreased odds of 28-day mortality (HR = 0.71; 95% CI 0.60-0.85; P < .001).

Conclusion: In septic shock patients, initial fluid resuscitation rate of 0.25-0.50 ml/kg/min (i.e., completion of the initial 30 ml/kg IV fluid resuscitation within the first 2 h), may be associated with early shock reversal and lower 28-day mortality compared with slower rates of infusion.

Keywords: Fluid resuscitation rate; Lactate clearance; Septic shock; Shock reversal; Vasopressor.

Fig. 1

Schematic representation of the study protocol. Time zero (T₀) was the starting point of septic shock fluid resuscitation and defined as the first time that MAP < 65 mmHg or serum lactate > 2 mmol/l during the ICU stay. According to the different range of initial fluid resuscitation rate (equal to the slope in the graph), the cohort was divided into four groups: group 1 (≥ 0.5 ml/kg/min), group 2 (0.25–0.5 ml/kg/min), group 3 (0.17–0.25 ml/kg/min), and group 4 (< 0.17 ml/kg/min). The “” on the timeline marked ICU admission, shock reversal time (T_r), and ICU and hospital discharge; shock reversal time (T_r), ICU discharge, and hospital discharge must be after T₀ but had no fixed time relationship with T₀. The main variables and measurements of the study are shown in the bottom half of the figure. The period of shock reversal was defined as the duration between T_r and T₀ (abbreviation: ICU = intensive care unit; T₀ = time zero; T₃ = 3 h after T₀; T_r = shock reversal time; VIS = Vasoactive-Inotropic Score; LOS = length of stay)

Fig. 2

The CONSORT flow diagram of patient enrollment (abbreviation: ICU = intensive care unit; SOFA = Sequential [Sepsis-related] Organ Failure Assessment; ICD = International Classification of Diseases; MAP = mean arterial pressure)

Fig. 3

The cumulative proportion of shock reversal and survival analysis with different initial fluid resuscitation rates (≥ 0.25 ml/kg/min vs. < 0.25 ml/kg/min). The shade indicates the confidence interval. a The cumulative proportion of shock reversal. Using Cox-model (additionally adjusted for the effects of age, gender, white race, weight, CCI, APACHE III, and SOFA), patients with ≥ 0.25 ml/kg/min rate had higher proportion of shock reversal (HR = 1.22; 95% CI 1.06–1.41; P = .007), with shorter median time (IQR) to shock reversal [1.5 (1.4, 1.7) vs. 2.3 (2.1, 2.6) days] for patients with < 0.25 ml/kg/min rate. b Survival analysis. Using Cox-model (additionally adjusted for the effects of age, gender, white race, weight, CCI, APACHE III, and SOFA), patients with ≥ 0.25 ml/kg/min rate had higher proportion of surviving (HR = 0.71; 95% CI 0.60–0.85; P < .001) for patients with < 0.25 ml/kg/min rate

Fig. 4

Association between fluid resuscitation rate (ml/kg/min) and VIS at variable time periods during the first 24 h of fluid resuscitation. Group < 0.17 ml/kg/min had significantly lower VIS at all time period. Compared to group < 0.17 ml/kg/min, *P value < 0.05, **P value < 0.01 (abbreviation: VIS = Vasoactive-Inotropic Score)