A commentary on “Milrinone is better choice for controlled low central venous pressure during hepatectomy: A randomized, controlled trial comparing with nitroglycerin” [Int. J. Surg. (2021) 94: 106080]

Dear Editor, We are deeply impressed with the innovative article published by Peng Yang and colleagues [1]. The authors emphasized that infusion of milrinone during open liver resection was associated with less intraoperative bleeding, shorter times of hepatectomy and hepatic hilum occlusion, better hemodynamic stability, and a more favorable recovery pattern in the postoperative period when compared to nitroglycerin-induced low central venous pressure (CVP) technique. To our knowledge, this is the first report on the comprehensive perioperative clinical characteristics regarding the use of milrinone that resulted in a low CVP condition during hepatectomy in the literature. Milrinone is well-known as a phosphodiesterase III inhibitor that facilitates cardiac inotropy (systolic contraction), lusitropy (diastolic relaxation), and peripheral vasodilatation by increasing cyclic adenosine monophosphate [2]. Preference is commonly given to using milrinone in individuals with severe pulmonary hypertension because of the potential mechanism of decreasing pulmonary artery pressures and ameliorating right ventricular function [3]. From the perspective of hepatectomy, milrinone administration is helpful because systemic vasodilatation causes relative hypovolemia and low CVP. Lowering the pressure of the right heart reduces the pressure of the inferior vena cava, hepatic vein, and sinusoids, thereby reducing back pressure bleeding in the anatomic parenchyma [4]. Furthermore, enhanced cardiac inotropy and lusitropy accelerate venous drainage leading to dynamic decrease of vena cava pressures and CVP [5]. However, there is little medical evidence which has been reported on its favorable properties for hepatectomy with milrinone-induced low CVP technique. The current clinical trial conducted by the authors has confirmed the hypothesis that controlling a low CVP with milrinone during liver resection would benefit patients, in particular on blood loss. Nonetheless, this randomized clinical trial of milrinone compared with nitroglycerin in patients with liver diseases is not without limitations. First, as described in the study, the authors only demonstrated that hemodynamic parameters including CVP, cardiac index, and stroke volume index showed better properties using milrinone infusion than nitroglycerin administration. Other hemodynamic changes were similar within the two groups. The existing evidence provided in this study did not find any significant advantage of milrinone over nitroglycerin concerning hemodynamic stability. Second, the goal of maintaining a low CVP with milrinone during hepatic resection is to reduce blood loss, and thus increase the chances of obtaining a better surgical field. In addition, the difference in the postoperative hospital stay may be due to the more meticulous surgery provided by the clean and dry operation area. The primary outcome on the status of the surgical field should be used in this randomized trial. With reference to a previous study, two independent surgeons were blinded in assessing the condition of the surgical field during hepatectomy using a four-point grading scale [6]. Third, recruitment of patients into this simple clinical trial was from a single center, which can limit external generalizability. Studies with large sample sizes and multi-center trials should be performed in the future to study not only the short-term outcomes in open hepatectomy but also the long-term prognosis in minimally invasive surgery. Although the loading dose of milrinone infusion with 0.5 μg/kg/min in patients without a history of cardiac diseases seems unlikely to induce any intra- or postoperative heart complications, potential adverse effects associated with a low CVP need to be considered. Extremely low CVP can lead to an increased risk of air embolism, unstable hemodynamics, and renal injury. In addition, caution should be taken when employing the present results to other patients, such as those with liver transplantation or chronic cardiovascular diseases. Further studies on the safety of milrinone-induced low CVP are required. Provenance and peer review Commentary, internally reviewed. Funding None. Ethical approval No Ethical Approval was given because this is a comment. Author contribution Wang Hu: writing. Zhangzhen Li: literature research. Zeming Hu: study design and critically reviewing. Guarantor Zeming Hu. Declaration of competing interest The authors declare that they have no competing interests.