Clinical study of central venous-to-arterial carbon dioxide difference (Pcv-aCO2 gap) guiding the use of milrinone in patients with septic shock:a randomized controlled trial
Authors: Wang Jing , Yang Peng-Lei , Li Xiang-Hui , Yu Jiang-Quan , Zheng Rui-Qiang 
Published: July 2023

Abstract
Background: For septic shock patients with elevated Pcv-aCO2 and no volume response, the treatment scheme is still controversial. In this study, milrinone was used to intervene it to explore whether milrinone can reduce Pcv-aCO2, thus increasing tissue perfusion and reducing mortality.
Methods: This study was a single-center, open-label, randomized clinical trial. Patients with confirmed septic shock who were admitted to the intensive care medicine department of Northern Jiangsu People’s Hospital between February 2021 and May 2022 were selected, and patients were initially therapy according to the SSC guidelines. The Pcv-aCO2 was measured 3 hours after admission to the ICU, and septic shock patients with gap≥6 mmHg were included in the study, and those who met the inclusion criteria were randomly assigned to the experimental and control groups. Patients in the experimental group without volume responsiveness were given milrinone intervention, while the control group was treated by clinicians according to the 2016 SSC guidelines, using positive inotropic drugs other than milrinone if needed.
Results: 51 patients were included in the analysis. At 3 hours of ICU admission, Pcv-aCO2 was 9.1mmHg and 8.1mmHg in the experimental and control groups, respectively, with no statistical difference (p=0.295); The Pcv-aCO2 was higher than 6mmHg in 26 patients in the experimental group, of which 23.07% (6/26) added milrinone for intervention; 25 patients in the control group had a Pcv-aCO2 higher than 6mmHg, of which 4% (1/25) used positive inotropic drugs, and there was a statistical difference between the drug use in the two groups (P=0.048). At 6 hours of admission to the ICU, Pcv-aCO2 was measured again in both groups, and the results showed that 46.15% (12/26) of patients in the experimental group still had Pcv-aCO2 higher than 6mmHg, 80% (20/25) of patients in the control group had Pcv-aCO2 higher than 6mmHg,There is a statistical difference(p=0.012).42.3%(11/26) of patients in the experimental group were intervened with milrinone and 8%(2/25) of patients in the control group were treated with orthomimetic drugs, There was a statistical difference between the two groups of patients in terms of drug use (p < 0.05).The Pcv-aCO2 was 6.07±2.11mmHg and 7.25±1.80mmHg in the experimental and control groups, respectively (p=0.037). There were no significant differences in baseline characteristics、ICU mortality risk and 28-Days mortality. Compared to controls, patients in the experimental group had higher cardiac output, significantly lower levels of the inflammatory factor interleukin-6, and higher lactate clearance.
Conclusions: The use of milrinone in patients with septic shock whose Pcv-aCO2 remains high after adequate fluid resuscitation, although not reducing mortality, is effective in increasing cardiac output and lactate clearance and reducing the inflammatory response.
Trial registration China Clinical Trial Registry(ChiCTR2100044523;March 23,2021)