Safety and Efficacy of the Off-Label Use of Milrinone in Pediatric Patients with Heart Diseases

Abstract

Background and ObjectivesMilrinone is often used in children to treat acute heart failure and prevent low cardiac output syndrome after cardiac surgery. Due to the lack of studies on the long-term milrinone use in children, the objective of this study was to assess the safety and efficacy of the current patterns of milrinone use for ≥3 days in infants and children with heart diseases.Subjects and MethodsWe retrospectively reviewed the medical records of patients aged <13 years who received milrinone for ≥3 days from January 2005 to December 2012. Patients' characteristics including age, sex, height, weight, and body surface area were recorded. The following parameters were analyzed to identify the clinical application of milrinone: initial infusion rate, maintenance continuous infusion rate, total duration of milrinone therapy, and concomitantly infused inotropes. The safety of milrinone was determined based on the occurrence of adverse events such as hypotension, arrhythmia, chest pain, headache, hypokalemia, and thrombocytopenia.ResultsWe assessed 730 admissions (684 patients) during this period. Ventricular septal defects were the most common diagnosis (42.4%) in these patients. Milrinone was primarily used after cardiac surgery in 715 admissions (97.9%). The duration of milrinone treatment varied from 3 to 64.4 days (≥7 days in 149 admissions). Ejection fraction and fractional shortening of the left ventricle improved in patients receiving milrinone after cardiac surgery. Dose reduction of milrinone due to hypotension occurred in only 4 admissions (0.5%). Although diverse arrhythmias occurred in 75 admissions (10.3%), modification of milrinone infusion to manage arrhythmia occurred in only 3 admissions (0.4%). Multivariate analysis indicated that the development of arrhythmia was not influenced by the pattern of milrinone use.ConclusionMilrinone was generally administered for ≥3 days in children with heart diseases. The use of milrinone for ≥3 days was effective in preventing low cardiac output after cardiac surgery when combined with other inotropes, suggesting that milrinone could be safely employed in pediatric patients with heart diseases.

Experience with Mechanical Circulatory Support for Medically Intractable Low Cardiac Output in a Pediatric Intensive Care Unit

“…Infection, neurological problems, and hemorrhage were significant predictors of poor outcome, which could be caused by long-term use of mechanical circulatory support and abnormal coagulation systems. 19) Survivors with complications normally stayed longer in the hospital than survivors without complications. Meticulous attention to patients and prepared management of known complications can be beneficial for early diagnosis, treatment, and survival without sequelae.…”

The effect of milrinone on hemodynamic and gas exchange parameters in children

“…A total of six studies including 791 patients were included in the analyses (Fig 1). [11][12][13][14][15][16] Studies were published between the years 2013 and 2018. A majority, four, of the six studies included patients in the first month of life.…”

“…A total of five studies with data from 219 patients were included in the pooled analysis of left ventricular shortening fraction. [11][12][13][14][15] Heterogeneity analysis resulted in a Q-statistic with a p value of less than 0.001 and an I 2 value of 75%, indicating the presence of significant heterogeneity. Thus, a random-effects model was used.…”

Vasopresores e inotrópicos: uso en pediatría

“…Hoffman et al encontraron que el SBGC en posquirúrgicos de cirugía cardiaca afecta aproximadamente al 25% de los pacientes, y evaluaron el uso de milrinona profiláctica para pacientes posquirúrgicos de cirugía cardiaca, donde se encuentra que se puede reducir hasta el 64% del riesgo en el desarrollo de SBGC con el uso profiláctico de la milrinona 43 . Sin embargo, Burkhard et al en su revisión de Cochrane donde valoran el uso profiláctico de la milrinona para prevención del SBGC en cirugía de cardiopatías congénitas concluyeron que la evidencia actual es insuficiente para valorar el efecto de la milrinona como prevención en mortalidad y SBGC; solo se ha observado que disminuye la aparición de este síndrome en el periodo posoperatorio inmediato comparado con el placebo 44,45 . En cuanto a los efectos adversos se encontró que la hipotensión, la trombocitopenia y las arritmias que se han reportado en pacientes adultos ocurren infrecuentemente en pediatría 43 .…”

“…El desarrollo de trombocitopenia se presentó en el 0.5% de los casos y la mayoría de los casos fueron pacientes con un tiempo de bomba incrementado. Se concluye que la milrinona es eficaz y segura en pacientes pediátricos; sin embargo se debe monitorizar la aparición de arritmias principalmente en pacientes que tienen algún factor de riesgo para la aparición de las mismas 45 . La milrinona puede utilizarse en dosis de carga de 50-75 g/kg por vía intravenosa para 15-60 min; pudiendo disminuir la dosis de carga hasta 25 g/kg en pacientes con alto riesgo de hipotensión.…”