Dataset Information

Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial.

ABSTRACT:

Background

The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.

Methods

This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ??48?months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48?h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study.

Results

A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19-1.13; p?=?0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14-3.69, p?=?0.693), duration of mechanical ventilation (median, 47.5?h and 39.5?h, respectively; p?=?0.532), ICU stay (median, 114.5?h and 118?h, respectively; p?=?0.442), and hospital stay (median, 20?days and 20?days, respectively; p?=?0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS.

Conclusions

Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo.

Trial registration

Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass.

Trial registration number

ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx.

SUBMITTER: Wang A

PROVIDER: S-EPMC6937718 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial.

Wang Anbiao A Cui Chaomei C Fan Yiou Y Zi Jie J Zhang Jie J Wang Guanglai G Wang Fang F Wang Jun J Tan Qi Q

Critical care (London, England) 20191230 1

<h4>Background</h4>The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.<h4>Method ...[more]

PMID: 31888711

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Project description:BackgroundSmall trials suggest that levosimendan is associated with a favorable outcome in patients undergoing cardiac surgery. However, recently published larger-scale trials did not provide evidence for a similar benefit from levosimendan. We performed a meta-analysis to assess the survival benefits of levosimendan in patients undergoing cardiac surgery and to investigate its effects in subgroups of patients with preoperative low-ejection fraction (EF).MethodsWe identified randomized clinical trials through 20 April 2017 that investigated levosimendan therapy versus control in patients undergoing cardiac surgery. Individual patient data from each study were compiled. Meta-analyses were performed for primary outcomes, secondary outcomes and serious adverse events, and subgroup analyses according to the preoperative EF of enrolled patients were also conducted. The risk of bias was assessed using the Cochrane risk-of-bias tool.ResultsSeventeen studies involving a total of 2756 patients were included. Levosimendan therapy was associated with a significant reduction in 30-day mortality (RR 0.67; 95% CI, 0.49 to 0.93; p = 0.02) and reduced the risk of death in single-center trials (RR 0.49; 95% CI, 0.30 to 0.79; p = 0.004) and in subgroup trials of inferior quality (RR 0.39; 95% CI, 0.17 to 0.92; p = 0.02); however, in multicenter and in high-quality subgroup-analysis trials, no significant difference in mortality was observed between patients who received levosimendan therapy and controls (p > 0.05). However, in high-quality subgroup trials, levosimendan therapy was associated with reduced mortality in patients in a preoperative low-EF subgroup (RR 0.58; 95% CI, 0.38 to 0.88; p = 0.01). Similarly, only patients in the preoperative low-EF subgroup benefited in terms of reduced risk of renal replacement therapy (RR 0.54; 95% CI, 0.34 to 0.85; p = 0.007). Furthermore, levosimendan therapy was associated with a significant reduction in intensive care unit (ICU) length of stay (MDR -17.19; 95% CI, -34.43 to -2.94; p = 0.02).ConclusionsIn patients undergoing cardiac surgery, the benefit of levosimendan in terms of survival was not shown in multicenter or in high-quality trials; however, levosimendan therapy was associated with reduced mortality in patients with preoperative ventricular systolic dysfunction.

Project description:Clinical effects of furosemide (F) and ethacrynic acid (EA) continuous infusion on urine output (UO), fluid balance, and renal, cardiac, respiratory, and metabolic function were compared in infants undergoing surgery for congenital heart diseases.A prospective randomized double-blinded study was conducted. Patients received 0.2 mg/kg/h (up to 0.8 mg/kg/h) of either F or EA.In total, 38 patients were enrolled in the F group, and 36, in the EA group. No adverse reactions were recorded. UO at postoperative day (POD) 0 was significantly higher in the EA group, 6.9 (3.3) ml/kg/h, compared with the F group, 4.6 (2.3) ml/kg/h (P?=?0.002) but tended to be similar in the two groups thereafter. Mean administered F dose was 0.33 (0.19) mg/kg/h compared with 0.22 (0.13) mg/kg/h of EA (P?<?0.0001). Fluid balance was significantly more negative in the EA group at postoperative day 0: -43 (54) ml/kg/h versus -17 (32) ml/kg/h in the F group (P?=?0.01). Serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels and incidence of acute kidney injury did not show significant differences between groups. Metabolic alkalosis occurred frequently (about 70% of cases) in both groups, but mean bicarbonate level was higher in the EA group: 27.8 (1.5) M in the F group versus 29.1 (2) mM in the EA group (P?=?0.006). Mean cardiac index (CI) values were 2.6 (0.1) L/min/m(2) in the F group compared with 2.98 (0.09) L/min/m(2) in the EA group (P?=?0.0081). Length of mechanical ventilation was shorter in the EA group, 5.5 (8.8) days compared with the F group, 6.7 (5.9) (P?=?0.06). Length of Pediatric Cardiac Intensive Care Unit (PCICU) admission was shorter in the EA group: 14 (19) days compared with 16 (15) in the F group (P?=?0.046).In cardiac surgery infants, EA produced more UO compared with F on POD0. Generally, a smaller EA dose is required to achieve similar UO than F. EA and F were safe in terms of renal function, but EA caused a more-intense metabolic alkalosis. EA patients achieved better CI, and shorter mechanical ventilation and PCICU admission time.Clinicaltrials.gov NCT01628731. Registered 24 June 2012.

Project description:BackgroundBlood-based cardioplegia is the standard myocardial protection strategy in pediatric cardiac surgery. Custadiol (histidine-tryptophan-ketoglutarate), an alternative, may have some advantages but is potentially less effective at myocardial protection. This study aimed to test whether custadiol is not inferior to blood-based cardioplegia in pediatric cardiac surgery.MethodsThe study was designed as a randomized controlled trial with a blinded outcome assessment. All pediatric patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegia, including neonates, were eligible. Emergency surgery was excluded. The primary outcome was a composite of death within 30 days, an ICU stay longer than 5 days, or arrhythmia requiring intervention. Secondary endpoints included total hospital stay, inotropic score, cardiac troponin levels, ventricular function, and extended survival postdischarge. The sample size was determined a priori for a noninferiority design with an expected primary outcome of 40% and a clinical significance difference of 20%.ResultsBetween January 2018 and January 2021, 226 patients, divided into the Custodiol cardioplegia (CC) group (n = 107) and the blood cardioplegia (BC) group (n = 119), completed the study protocol. There was no difference in the composite endpoint between the CC and BC groups, 65 (60.75%) vs. 71 (59.66%), respectively (P = 0.87). The total length of stay in the hospital was 14 (Q2-Q3: 10-19) days in the CC group vs. 13 (10-21) days in the BC group (P = 0.85). The inotropic score was not significantly different between the CC and BC groups, 5 (2.6-7.45) vs. 5 (2.6-7.5), respectively (P = 0.82). The cardiac troponin level and ventricular function did not differ significantly between the two groups (P = 0.34 and P = 0.85, respectively). The median duration of follow-up was 32.75 (Q2-Q3: 18.73-41.53) months, and there was no difference in survival between the two groups (log-rank P = 0.55).ConclusionsCustodial cardioplegia is not inferior to blood cardioplegia for myocardial protection in pediatric patients. Trial registration The trial was registered in Clinicaltrials.gov, and the ClinicalTrials.gov Identifier number is NCT03082716 Date: 17/03/2017.

Project description:BackgroundLevosimendan has pharmacologic and hemodynamic advantages over conventional intravenous inotropic agents. It has been used mainly as a rescue drug in the pediatric intensive care unit or in the operating room. We present the largest single-center experience of levosimendan in children.MethodsRetrospective analysis of all children who received levosimendan infusions between July 5, 2001 and July 4, 2010 in a pediatric intensive care unit. The results of a questionnaire for physicians (anesthesiologist/intensivists, cardiologists and cardiac surgeons) concerning their clinical perceptions of levosimendan are evaluatedResultsDuring the study period a total of 484 infusions were delivered to 293 patients 53% of whom were male. The median age of the patients was 0.4 years (4 hours-21.1 years) at the time of levosimendan administration. A majority of levosimendan infusions were administered to children who were undergoing cardiac surgery (72%), 14% to children with cardiomyopathy and 14% to children with cardiac failure. Eighty-nine out of the 293 patients (30.4%) received repeated doses of levosimendan (up to 11 infusions). The most common indication for the use of levosimendan (94%) was when the other inotropic agents were insufficient to maintain stable hemodynamics. Levosimendan was especially used in children with cardiomyopathy (100%) or with low cardiac output syndrome (94%). A majority (89%) of the respondents believed that levosimendan administration postponed the need for mechanical assist devices in some children with cardiomyopathy. Moreover, 44% of respondents thought that the mechanical support was totally avoided in some patients undergoing cardiac surgery after receiving levosimendan.ConclusionLevosimendan is widely used in our institution and many physicians believe that its use could decrease the need for mechanical support in children undergoing cardiac surgery or in children with decompensated heart failure. However, there is a lack of good empirical evidence in children to support this perception.

Project description:Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding.To evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery.Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery.The primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding.The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 ?g/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor.Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition.clinicaltrials.gov Identifier: NCT00767507.

Dataset Information

Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial.

Background

Methods

Results

Conclusions

Trial registration

Trial registration number

Publications

Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial.

Similar Datasets

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