Reassessing the role of milrinone in the treatment of heart failure and pulmonary hypertension in neonates and children: a systematic review and meta-analysis

Matsushita, Felipe Yu; Krebs, Vera Lúcia Jornada; de Campos, Carolina Vieira; de Vincenzi Gaiolla, Paula Vieira; de Carvalho, Werther Brunow

doi:10.1007/s00431-023-05342-0

Cited by 4 publications

(5 citation statements)

References 48 publications

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“…In children, milrinone can decrease arterial and central venous pressure (CVP) by increasing vessel distensibility ( 5 ). Therefore, it has been suggested that its predominant effect is more systemic vasodilatory than inotropic ( 8 ). At the microcirculation level, milrinone’s effects could be related to the reduction of venule pressure (due to a decrease in CVP), thereby optimizing the capillary driving pressure and thus convective flow.…”

Section: Discussionmentioning

confidence: 99%

“…These inodilator effects have been found in children with septic shock, including patients with meningococcal sepsis and severe peripheral vasoconstriction ( 6 ). It has recently been suggested that the effects of milrinone in improving cardiac function are mediated by its systemic vasodilating effect, with little inotropic effect ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…In sepsis, inotropes or inodilators are recommended when there is myocardial dysfunction with signs of low cardiac output, increased filling pressures or persistent signs of tissue hypoperfusion ( 1 , 7 , 8 ). However, the strongest evidence supporting the use of inodilators is mainly based on physiological studies.…”

Section: Introductionmentioning

confidence: 99%

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Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock

Sarta-Mantilla,

Fernández-Sarmiento,

Acevedo

et al. 2024

Transl Pediatr

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Background The goal of fluid resuscitation and the use of inotropes in septic shock has traditionally focused on improving blood pressure and cardiac output, without considering the microcirculatory changes. Reaching macrocirculatory goals but with persistent microcirculatory abnormalities (hemodynamic incoherence) in septic shock has been associated with greater organ dysfunction and mortality. The objective of this study was to evaluate the microcirculation (flow and capillary density) and endothelial glycocalyx changes associated with the use of milrinone in children with septic shock, as well as their relationship with clinical variables and organ dysfunction. Methods A prospective cohort study from February 2022 to January 2023 at a university hospital (Fundación Cardioinfantil-Instituto de Cardiología). Sublingual video microscopy was used to evaluate capillary density, microvascular flow rates and perfused boundary region (PBR—inverse parameter of glycocalyx thickness—abnormal if >2.0 microns). The primary outcome was the association between microcirculation and endothelial glycocalyx changes related to the use of milrinone. Results A total of 140 children with a median age of two years [interquartile range (IQR) 0.58–12.1] were included. About 57.9% (81/140) of the patients received milrinone infusions. Twenty-four hours after receiving milrinone, the patients maintained functional capillary density (P<0.01) and capillary recruitment capacity (P=0.04) with no changes in capillary blood volume versus those who did not receive milrinone. Children under two years old who received milrinone had better 4–6-micron capillary density than older children [odds ratio (OR) 0.33; 95% confidence interval (95% CI): 0.12–0.89; P=0.02] and less endothelial glycocalyx degradation [adjusted OR (aOR) 0.34 95% CI: 0.11–0.99; P=0.04]. These changes persisted despite elevated ferritin (aOR 0.41; 95% CI: 0.18–0.93; P=0.03). Prolonged capillary refill and elevated lactate were correlated with microcirculation changes in both groups. The patients who died had the highest PBR levels (P=0.04). Conclusions Children with septic shock who receive milrinone infusions have microcirculation changes compared with those who do not receive them. The group that received milrinone was found to maintain functional capillary density and capillary recruitment capacity and have less endothelial glycocalyx degradation 24 hours after administration. These changes were present despite the inflammatory response and were more significant in those under two years of age.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock

Sarta-Mantilla,

Fernández-Sarmiento,

Acevedo

et al. 2024

Transl Pediatr

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“…STE requires high frame rate and good image quality for analysis, which may be difficult to obtain in the critical care setting due to tachycardia, poor echocardiographic windows and limited timeframe to acquire images (55, 56). Data interpretation of STE values is also confounded by varied loading conditions including fluid status and inotropic support (57–60), as well as a lack of established normative data for LV diastolic dysfunction in children (43, 61). There are small trials and an ongoing study investigating the impact of milrinone and levosimendan on GLS (59, 60, 62).…”

Section: Speckle-tracking Echocardiographymentioning

confidence: 99%

“…Data interpretation of STE values is also confounded by varied loading conditions including fluid status and inotropic support (57–60), as well as a lack of established normative data for LV diastolic dysfunction in children (43, 61). There are small trials and an ongoing study investigating the impact of milrinone and levosimendan on GLS (59, 60, 62). STE-based strain measurement is also affected by variability between ultrasound machines and image analysis platforms (63).…”

Section: Speckle-tracking Echocardiographymentioning

confidence: 99%

Use of Speckle-Tracking Echocardiography in Septic Cardiomyopathy in Critically Ill Children: A Narrative Review

Chan,

Menon,

Rotta

et al. 2024

Critical Care Explorations

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OBJECTIVES: In critically ill children with severe sepsis, septic cardiomyopathy (SCM) denotes the subset of patients who have myocardial dysfunction with poor response to fluid and inotropic support, and higher mortality risk. The objective of this review was to evaluate the role of speckle-tracking echocardiography (STE) in the diagnosis and prognosis of pediatric SCM in the PICU setting. DATA SOURCES: We performed detailed searches using PubMed, Scopus, Web of Science, and Google Scholar. Reference lists of all included studies were also examined for further identification of potentially relevant studies. STUDY SELECTION: Studies with the following medical subject headings and keywords were selected: speckle-tracking echocardiography, strain imaging, global longitudinal strain, echocardiography, sepsis, severe sepsis, septic shock, septic cardiomyopathy, and myocardial dysfunction. DATA EXTRACTION: The following data were extracted from all included studies: demographics, diagnoses, echocardiographic parameters, severity of illness, PICU management, and outcomes. DATA SYNTHESIS: STE is a relatively new echocardiographic technique that directly quantifies myocardial contractility. It has high sensitivity in diagnosing SCM, correlates well with illness severity, and has good prognosticating value as compared with conventional echocardiographic parameters. Further studies are required to establish its role in evaluating biventricular systolic and diastolic dysfunction, and to investigate whether it has a role in individualizing treatment and improving treatment outcomes in this group of patients. CONCLUSIONS: STE is a useful adjunct to conventional measures of cardiac function on 2D-echocardiography in the assessment of pediatric SCM in the PICU.

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Milrinone in pediatric heart failure and pulmonary hypertension: Is meta-analyses the answer?

Lone,

Kanthimathinathan

2023

Eur J Pediatr

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Reassessing the role of milrinone in the treatment of heart failure and pulmonary hypertension in neonates and children: a systematic review and meta-analysis

Cited by 4 publications

References 48 publications

Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock

Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock

Use of Speckle-Tracking Echocardiography in Septic Cardiomyopathy in Critically Ill Children: A Narrative Review

Milrinone in pediatric heart failure and pulmonary hypertension: Is meta-analyses the answer?

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