BACKGROUND: Conventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients\' recovery.
METHODS: In total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2-0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2-0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome.
RESULTS: Blood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05).
CONCLUSIONS: Our findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin.
BACKGROUND: ChiCTR2200056891,first registered on 22/02/2022.

Background: The potential harm and clinical benefits of inotropic therapy in patients with decompensated heart failure with reduced ejection fraction or advanced heart failure were debated for three decades. Nonetheless, confronted with a dismal quality of life in the last months to years of life, continuous home inotropic therapy has recently gained traction for palliative therapy in patients who are not candidates for left ventricular mechanical circulatory support or heart transplantation. Methods: As continuous inotropic therapy is only considered for patients who experience symptomatic relief and display objective evidence of improvement, clinical equipoise is no longer present, and randomized controlled trials are hard to conduct. Results: We first outline the transient use of inotropic therapy in patients with decompensated heart failure with reduced ejection fraction and emphasize the hemodynamic requisite for inotropic therapy, which is a demonstration of a low cardiac output through a low mixed venous oxygen saturation. Lastly, we review the current experience with the use of home inotropic therapy in patients who are not candidates or are awaiting mechanical circulatory support or heart transplantation. Conclusions: Evidence-based clinical data are needed to guide inotropic therapy for refractory decompensated heart failure with reduced ejection fraction in patients who are ineligible or awaiting mechanical circulatory support or heart transplantation.

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16-12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09-6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64-0.75) and 0.67 (95% CI 0.62-0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.

UNASSIGNED: Pregnancy in a patient with pulmonary hypertension carries a high risk of mortality. It poses multiple problems in the management of pregnancy, labor, and postpartum, thereby emphasizing the need for a multidisciplinary team for a successful outcome. We describe the successful management of a case of Eisenmenger syndrome who developed pre-eclampsia during her 28 weeks of pregnancy. As far as our knowledge, this is the first case report that describes the use of milrinone in a parturient for a successful outcome.

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The \"before\" period included 277 patients, and the \"after\" one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the \"after\" period. Conversely, the occurrence of DCIn was reduced with the \"after\" management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, p = 0.001 ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, p < 0.001 ) and associated with superior hemodynamics. The present study from a large cohort of aSAH patients suggests, for one part, the interest of CTP in early diagnosis of vasospasm and DCI, and for the other the efficacy of CT perfusion-guided systemic administration of milrinone in both preventing and treating DCIn.

Milrinone, a phosphodiesterase III inhibitor with contractile and vasodilatory effects, is widely used in acute decompensated heart failure and medically refractory end-stage heart failure (HF). The adverse reactions of milrinone have been extensively explored clinically, but its possible toxicities and underlying molecular mechanisms in embryo development need further understanding as its clinical applications increase. Herein, we assessed the milrinone toxicity using the zebrafish embryotoxicity test (ZET), with a view of providing evidence and guidance for gravidas medicine. We carried out ZET by exposing embryos to a milrinone culture with a series concentration gradients since 1.5 hours post fertilization (hpf) and observed and assessed mortality and hatching rates of drug-treated zebrafishes at 24, 48, 72, and 96 hpf. No significant lethal effect was found in milrinone-treated zebrafish, but hatching rate of eggs at 48 hpf was up-regulated with the increase of milrinone concentration. The impact of milrinone on embryogenesis was assessed through body length, eye area, yolk sac area, swim bladder inflation area, pericardial area and venous congestion area at 96hpf. 150 μg/mL or higher milrinone treatment showed significant effects in the indicators. Organ disorders including enlarged pericardium, liver atrophy and decreased blood vessels were observed in dysplasia individuals versus controls. TUNEL assay suggested the ability of milrinone to induce apoptosis in malformation embryos. Quantitative real-time PCR showed aberrant expressions of transcription factors associated with heart development and genes related to liver development and apoptosis regulation. Therefore, ZET is feasible for the milrinone toxicity test, and high-dose milrinone causes harm to the embryonic development of zebrafish, especially in embryonic carcinogenesis, vasculogenesis, and hepatogenesis.

OBJECTIVE: Pulmonary hypertension (PH) is a common cause of postoperative mortality in cardiac surgery that is commonly treated with conventional inhaled therapies, specifically nitric oxide and prostacyclin. Alternative therapies include inhaled milrinone and levosimendan, which are receiving more research interest and are increasing in clinical use as they may cut costs while allowing for easier administration. We sought to conduct a scoping review to appraise the evidence base for the use of these two novel inhaled vasodilators as an intervention for PH in cardiac surgery.
METHODS: We searched Embase and MEDLINE for relevant articles from 1947 to 2022.
RESULTS: We identified 17 studies including 969 patients. The included studies show that inhaled milrinone and levosimendan are selective pulmonary vasodilators with potential benefits ranging from ease of weaning from cardiopulmonary bypass to reduction in ventricular dysfunction. Nevertheless, high-quality data are limited, and study design and comparators are extremely heterogeneous, limiting the potential validity and generalizability of findings.
CONCLUSIONS: The findings of this scoping review suggest that milrinone and levosimendan may be effective alternatives to current inhaled therapies for cardiac dysfunction in the setting of PH. Nevertheless, randomized trials have focused on specific agents and consistent outcome measures are needed to better validate the early-stage promise of these agents.
BACKGROUND: Open Science Framework ( https://osf.io/z3k6f/ ); first posted 21 July 2022.
RéSUMé: OBJECTIF: L’hypertension pulmonaire (HTP) est une cause fréquente de mortalité postopératoire en chirurgie cardiaque généralement traitée par des thérapies inhalées conventionnelles, en particulier le monoxyde d’azote et la prostacycline. Les thérapies alternatives comprennent la milrinone et le lévosimendan inhalés, qui suscitent de plus en plus d’intérêt dans la recherche et sont de plus en plus utilisés en clinique car ils peuvent réduire les coûts tout en permettant une administration plus facile. Nous avons cherché à réaliser une étude de portée afin d’évaluer la base de données probantes concernant l’utilisation de ces deux nouveaux vasodilatateurs inhalés comme intervention pour l’HTP en chirurgie cardiaque.
METHODS: Nous avons cherché des articles pertinents dans Embase et MEDLINE de 1947 à 2022.
UNASSIGNED: Nous avons identifié 17 études incluant 969 patient·es. Les études incluses montrent que la milrinone et le lévosimendan inhalés sont des vasodilatateurs pulmonaires sélectifs possédant des avantages potentiels allant de la facilité de sevrage de la circulation extracorporelle à la réduction de la dysfonction ventriculaire. Néanmoins, les données de haute qualité sont limitées, et la conception des études et les comparateurs sont extrêmement hétérogènes, ce qui limite la validité potentielle et la généralisabilité des résultats.
CONCLUSIONS: Les résultats de cette étude de portée suggèrent que la milrinone et le lévosimendan pourraient être des solutions de rechange efficaces aux traitements inhalés actuels pour le dysfonctionnement cardiaque dans un contexte d’HTP. Néanmoins, les études randomisées se sont concentrées sur des agents spécifiques et des mesures cohérentes des résultats sont nécessaires pour mieux valider les promesses de ces agents à un stade précoce. ENREGISTREMENT DE L’éTUDE: Open Science Framework ( https://osf.io/z3k6f/ ); première publication le 21 juillet 2022.

Background: Various inotropes and inodilators have been utilized to treat low cardiac output syndrome after the arterial switch operation. The use of levosimendan, a calcium sensitizer has been limited in this setting. This study compares the effects of levosimendan with milrinone in managing low cardiac output after the arterial switch operation. Methods: A retrospective, comparative study was conducted in a tertiary care hospital on patients weighing up to 3 kg undergoing the arterial switch operation between January 2017 and January 2022. Patients received a loading dose followed by continuous infusion of either levosimendan or milrinone. Echocardiographic, hemodynamic and biochemical parameters were compared. Results: Forty-three patients received levosimendan and 42 patients received milrinone as the primary test drug. Cardiac index of less than 2.2 L/min/m2 on postoperative day 1 and 2 was found in 9.3% and 2.3% of patients receiving levosimendan versus 26.2% and 11.9% in those receiving milrinone, respectively (P = .04 and .08, respectively). Early lactate-clearance and better central venous oxygen saturations were noted in the levosimendan group. Prevalence of acute kidney injury was higher in the milrinone group (50% vs 28%; P = .03). Use of peritoneal dialysis in the milrinone group versus levosimendan was 31% and 16.3%, respectively (P = .11). There was no difference in hospital mortality between the groups (milrinone, 3; levosimendan, 2, P = .62). Conclusions: Levosimendan is safe and as effective as milrinone to treat low cardiac output syndrome occurring in neonates after the arterial switch operation. In addition we found that levosimendan was renal protective when compared with milrinone.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation.
METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group\'s sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth.
RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153).
CONCLUSIONS: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

OBJECTIVE: A single centre experience with chylothorax in post cardiac surgical patients.
METHODS: Retrospective review.
RESULTS: Chylothorax developed in 55 out of 873 operated patients (6.3%). Median age of the chylothorax cohort was 95 days (range 1-995). Neonates constituted 36% and 49% were infants. Group-1(35 patients-treated during the years 2011-2015) included those who were managed with low fat diet initially with other standard measures including steroid, octreotide, pleurodesis, lymphangiogram or thoracic duct ligation whenever required.Group-2 (20 patients, treated between year 2016-2018) were managed with nil per oral, total parenteral nutrition, extended use of milrinone and no use of chest tube suction with other above standard measures when required.Group-1 and group-2 were comparable in terms of their age and weight (p > 0.05).We observed lower volume of chest drainage, shorter intubation time, length of intensive care stay and hospital stay in group-2 compared to group-1 though they were statistically not significant (p > 0.05). Occurrence of massive chylothorax (>20 ml/kg/day) in group-1 was significantly higher [18 patients (51%) in group-1 vs 4 patients in group-2 (20%) (Chi-square 5.25, p = 0.02)]. In hospital mortality in group-1 was higher compared to group-2 (5/35 = 14.5% vs 1/20 = 5%), however, it was statistically not significant [risk ratio 2.86; 95% CI 0.36, 22.77; p = 0.59)]. Acute kidney injury was observed in about 25% of patients who had chylothorax. A higher mortality was observed in patients with chylothorax who had acute kidney injury [5/14 (35%)] compared to those who did not have acute kidney injury [1/41 (2.4%)] (Chi-square 11.89, p = 0.001)].
CONCLUSIONS: In a heterogenous cohort of post-cardiac surgical patients who developed chylothorax, our suggested new regime (nil per oral, parenteral nutrition, extended use of milrinone and no suction applied to the chest drains) contributed to reduce the frequency of massive chylothorax occurrence significantly.