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Journal of Drug Design and Research

Clinical pharmacology of Milrinone in paediatric patients

Research Article | Open Access Volume 8 | Issue 3 |

  • 1. Associate Professorof Pharmacology, Italy
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Corresponding Authors
Gian Maria Pacifici, Associate Professor of Pharmacology, via Sant’Andrea 32, 56126 Pisa, Italy.
Abstract

Milrinone inhibits human heart phosphodiesterase 3 and phosphodiesterase 4 with similar potency. By increasing cAMP concentration, they have similar actions as the β receptor agonists dobutamine and epinephrine, but tend to lower systematic and pulmonary vascular resistance more than do the catecholamines. The vasodilation due to milrinone is related to increased levels of cAMP in vascular smooth muscle. Milrinone is used for short term treatment of acute low cardiac output after cardiac surgery due to septic shock. Milrinone is administered by continuous intravenous infusion and its dosage consists in a loading dose followed by a maintenance infusion in infants and children. Milrinone is efficacy and safe in infants and children but it may induce adverse-effects. The effects of milrinone in infants and children have been extensively studied: milrinone improves oxygenation and myocardial performance, milrinone is used to treat pulmonary, ventricular dysfunction, and tachyarrhythmias. The pharmacokinetics of milrinone have been studied in infants and children and the elimination half-life is 3.1 hours in infants aged < 1 year and 1.9 hours in children. The treatment of infants and children with milrinone has been extensively studied: milrinone treats hypoxemic respiratory failure and reduces diastolic arterial pressure, milrinone has been successfully used in infants and children undergoing heart surgery, and milrinone prevents death or low cardiac output syndrome in children undergoing surgery for congenital heart disease. The aim of this study is to review the milrinone dosing, efficacy and safety, effects, adverse-effects, pharmacokinetics, and treatment in infants and children.

Citation

Pacifici GM (2021) Clinical pharmacology of Milrinone in paediatric patients. J Drug Des Res 8(3): 1087.

Keywords

• Milrinone
• Dosing
• Efficacy and safety
• Effects
• Adverse-effects
• Pharmacokinetics
• Treatment
• Infants
• Children

INTRODUCTION

Mechanism of milrinone action

Parenteral formulation of milrinone is used for short term circulation support in advanced congestive heart failure. Milrinone inhibits human heart phosphodiesterase 3 and phosphodiesterase 4 with similar potency. By increasing intracellular cAMP concentrations, they have similar actions as the β receptor agonists dobutamine and epinephrine, but tend to lower systemic and pulmonary vascular resistance more than do the catecholamines it should be kept in mind that the phosphodiesterase inhibitors potentiate the action of β receptor agonists, both beneficial and detrimental. In adults, the loading dose of milrinone is ordinarily 25 to 75 µg/kg, and the continuous infusion rate ranges from 0.375 to 0.75 µg/kg per min, and the elimination half-life of milrinone is 0.5 to 1 hour but it can be increased in patients with severe congestive heart failure [1].

Clinical use of milrinone

Milrinone lactate has been most commonly used in the postoperative care of infants with congenital heart disease to treat low cardiac output state and in near-tern and term infants with persistent pulmonary hypertension of the newborn infant as an adjunct to, or sometimes in place of nitric oxide [2]. Milrinone improves cardiac output by enhancing myocardial contractility, enhancing myocardial diastolic relaxation and decreasing vascular resistance. It acts via selective phosphodiesterase 3 inhibition that leads to increased intracellular cAMP, increased myocardial intracellular calcium, and increased reuptake of calcium after systole. Vasodilatation is related to increased levels of cAMP in vascular smooth muscle. Unlike catecholamines, myocardial oxygen consumption is not increased. Elimination is primarily via renal mechanisms. The half-life is quite variable, ranging from approximately 10 hours in extremely-low-birthweight infants to approximately 3 hours in older and more mature infants. Milrinone is used for short term (< 72 hours) treatment of acute low cardiac output after cardiac surgery or due to septic shock. It is recommended the continuous monitoring of the blood pressure and the heart rate rhythm. It should be assessed the sign of cardiac output. In addition, it should be monitored carefully the fluid and electrolyte changes, the renal function during therapy, and the platelet counts. Milrinone is incompatible with furosemide, imipenem-cilastatin, and procainamide [3]. (Figure 1)

Literature search

The literature search was performed electronically using PubMed database as search engine and the following key words were used: “milrinone dosing infants, children”, “milrinone efficacy, safety, infants, children”, “milrinone effects infants, children”, “milrinone adverse-effects infants, children”, “milrinone pharmacokinetics infants, children”, and “milrinone treatment infants, children”. In addition, the books: The pharmacological Basis of Therapeutics [1], Neonatal Formulary [2], NEOFAX® by Young and Mangum [3], and The British National Formulary for Children [4] are consulted.

RESULTS

Administration schedules of milrinone to infants and children

Administration by intravenous infusion to infants [2]:

  1. Preterm infants. Give a loading dose of 0.75 µg/kg per min for 3 hours, and then a maintenance infusion of 0.2 µg/kg per min for 18 hours.
  2. Term infants and older infants. Give a loading dose of 50 to 75 µg/kg over 30 to 60 min, and then a continuous intravenous infusion of 30 to 45 µg/kg per hour for 2 to 3 days (usually for 12 hours after cardiac surgery). Hypotension may occur while the loading dose is being given because the drug causes some vasodilation. Volume expansion and/or low-dose dopamine will usually counteract this.
  3. Administration by intravenous infusion to children [4]: Give initially 50 to 75 µg/kg over 30 to 60 min, reduce or omit the initial dose if there is the risk of hypotension, and then (by continuous infusion) give 30 to 45 µg/kg per hour for 2 to 3 days (usually for 12 hours after cardiac surgery).

 Efficacy and safety of milrinone in infants and children: Preterm infants undergoing a post-ligation cardiac syndrome were treated with milrinone as a bolus infusion of 0.75 µg/kg per min for 3 hours followed by a 0.16 µg/kg per min maintenance infusion and this treatment is efficacy and safe [5]. Milrinone is found safe in hospitalized infants [6]. Milrinone is found efficacy and safe in children undergoing low cardiac output syndrome [7]. The use of milrinone for ≥ 3 days is effective and safe in preventing low cardiac output in children after cardiac surgery [8].

Effects of milrinone in infants and children: Milrinone improves both oxygenation and myocardial performance in preterm infants with pulmonary hypertension [9]. Milrinone is a useful therapy for preterm infants with echocardiography findings of pulmonary hypertension and/or ventricular dysfunction [10]. Administration of milrinone to infants with low cardiac output leads to improved postoperative stability [11]. Intravenous milrinone produces early improvements in oxygenation in infants without compromising systemic blood pressure [12]. Administration of milrinone in infants with low cardiac output after cardiac surgery lowers filling pressures, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistances, while improving cardiac index [13]. Perioperative milrinone infusion improved the mortality after the Norwood-Sano procedure in children [14]. Milrinone is found to have several beneficial hemodynamic effects in children during critical illness when used at usual clinical doses [15]. Milrinone is used by the vast majority of caregivers following congenital heart surgery in children [16]. Milrinone use is an independent risk factor for clinically significant tachyarrhythmias in the early postoperative period after congenital heart surgery in children [17]. Milrinone is beneficial in the optimization of cardiovascular function after cardiac surgery and in children with septic shock [18]. Low dose of milrinone has anti-inflammatory properties and potentially can improve splanchnic perfusion in children [19]. Bolus milrinone consistently decreases pulmonary vascular resistance in children with pulmonary hypertension secondary to severe heart failure [20].

Adverse-effects which are common or very common in infants and children [4]: Arrhythmia supraventricular (increased risk in patients with pre-existing arrhythmias), arrhythmias, headache, and hypotension.

Adverse-effects which are uncommon in infants and children [4]: Angina pectoris, chest pain, hypokalaemia, thrombocytopenia, and tremor.

Adverse-effects which are rare or very rare in infants and children [4]: Anaphylactic shock, bronchospasm, and skin eruption.

Adverse-effects whose frequency is not known in infants and children [4]: Intraventricular haemorrhage and renal failure.

Contra-indications [4]: Severe hypovolaemia.

Cautions [4]: Correct hypokalaemia, heart failure associated with hypertrophic cardiomyopathy, stenosis or obstructive valvular disease or other outlet obstruction.

Pregnancy [4]: The manufactory advises the use of milrinone only the potential benefit outweighs the risk.

Pharmacokinetics of milrinone in infants and children: Hornik et al. [21] studied the pharmacokinetics of milrinone in 74 infants, children, and adolescents whose demographic characteristics are reported in table 1. The subjects received milrinone by continuous intravenous infusion at median dose of 0.5 µg/kg per min (range, 0.1 to 41) for a median duration of 12 hours (range, 0.02 to 2,647) (Table 1& 2).

This table shows that the distribution volume is similar to the water volume and there is a remarkable interindividual variability in the total body clearance and in the distribution volume. Such variability is accounted by the wide variability of the subject characteristics.

Ramamoorthy et al. [22] investigated the pharmacokinetics of milrinone in 19 infants and children after open heart surgery. Table 3 summarizes the demographic characteristics of the subject included in the study. (Table 3)

Subjects were divided in two groups to receive milrinone as follows: 11 subjects were treated with an initial bolus dose of 25 µg/kg followed by a maintenance infusion dose of 0.25 µg/ kg per min started at the end of the first dose. Thirty min later, a second 25 µg/kg bolus was given, and the infusion was increased to 0.5 µg/kg per min (small dose). Eight subjects received a 50 µg/kg bolus administered over 10 min, and an infusion of 0.5 µg/ kg per min was started at the end of the bolus. A 25 µg/kg bolus was given 30 min after the first bolus, and the final rate infusion was increased to 0.75 µg/kg per min (large dose). In addition, the subjects in both groups received a third bolus dose of milrinone of 25 µg/kg. (Table 4)

This table shows that the distribution volume is similar to the water volume, milrinone is rapidly eliminated and there is a remarkable variability in the pharmacokinetic parameters. Such variability accounts for the wide variability of the demographic characteristics and also for the heart disease. (Table 5)

This table shows that the distribution volume is larger in infants and the total body clearance is higher in children. Milrinone is mainly eliminated by the renal route and the renal function increases with the infant maturation and child development.

Treatment of infants and children with milrinone: Milrinone treats infants with hypoxemic respiratory failure and hypoxic ischemic encephalopathy and develops profound reduction in diastolic arterial pressure [23]. Dobutamine and milrinone, two primary medicines that can be used in the treatment of cases with postligation cardiac syndrome in infants, possess similar therapeutic efficacy on this pathology [24]. Intravenous milrinone used in conjunction with infants treated with nitric oxide will result in a reduction in the time spent on infants treated with nitric oxide only [25]. Intravenous milrinone is a commonly used medication in neonatal/paediatric intensive care units and is currently used in 17% of patients with congenital diaphragmatic hernia [26]. Milrinone treatment is effective in children with cardiac dysfunction and in the therapy for cardiac transplant, or as palliative therapy for cardiomyopathy [27]. Milrinone treatment prevents death or low cardiac output syndrome in children undergoing surgery for congenital heart disease [28]. Milrinone, epinephrine, dopamine, and dobutamine are mostly used, and should be prioritised for future research on low cardiac output syndrome treatment in children [29]. A loading dose of 75 µg/kg milrinone lactate and starting infusion rates of 0.75 to 1.0 µg/kg per min for children with normal renal function should be used and the infusion rate should then be titrated to effect [30]. Intravenous administration of milrinone is used in paediatric patients with non-hyperdynamic septic shock [31].

Table 1: Demographic characteristics of subjects included in the study. Figures are the number and (%), by Hornik et al. [21].

Characteristic Median (range) or number (%)
Age (years) 2.9 (0.04, 18)
≤ 28 days 13 (8%)
>28 days to ≤ 2 years 19 (26%)
>2 years to ≤ 12 years 29 (39%)
>12 years 13 (18%)
Gestational age (weeks) 39 (37 - 41)
Postmenstrual age (weeks) 192 (37 - 977)
Body-weight 13.1 (2.6 - 158)
Male 39 (53%)
Serum creatinine (mg/dl) 0.5 (0.1 - 3.1)
Creatinine clearance (ml/min/1.73 m2) 118 (1.1 - 261)

Table 2: Parameter estimates and bootstrap results for the final population pharmacokinetic model, by Hornik et al. [21].

Parameter Estimate (RSE) Bootstrap median (5th, 95th percentile)
Total body clearance70kg (L/h) 15.9 (23%) 15.9 (12.2, 33.5)
Distribution volume70kg (L) 32.2 (30%) 31.6 (12.4, 154)
Exponent for power function characterizing the effect of CrCl on TBC) 0.522 (27%) 0.54 (0.30, 0.82)
TM50 (weeks PMA) 67.7 (64%) 68.4 (39.5, 1,159)
Hill Coefficient 1.12 (70%) 1.1 (0.44, 24.7)
Interindividual variation of TBC (CV%) 70 (27%) 67 (48, 83)
Residual proportional error (%) 32 (29%) 26 (20, 30)
TBC = total body clearance. %RSE = %relative standard error. CrCl = creatinine clearance. PMA = postmenstrual age in weeks. CV = coefficient of variation. The total body clearance and the distribution volume are standardized to a body-weight of 70 kg.

Table 3: Demographic characteristics of the subjects included in the study. Figures are the minimum, maximum, mean, and standard deviation (+SD), by Ramamoorthy et al. [22].

Value Age (year) Body-weight (kg) CPB ICU (arrival to milrinone start (min) Duration of infusion (h)
Minimum 0.36 4.4 52 55 16
Maximum 11.8 42.0 164 192 91
Mean 3.0 12 120 107 40
SD +3.7 +12 +24 +34 +20
ICU = intensive care unit.

Table 4: Pharmacokinetic parameters of milrinone which are obtained in 19 infants and children. Figures are the mean and standard deviation (+SD), by Ramamoorthy et al. [22].

Parameter Mean+SD
Concss (Small dose) 113+39
Concss (Large dose) 206+74
Total body clearance (L/h) 4.0+4.9
Total body clearance (ml/kg/min) 4.5+1.8
β (h) 0.45+0.34
Elimination half-life (h) 2.7+2.1
DVβ (L) 8.4+7.2
DVβ (L/kg) 0.83+0.40
Concss = steady-state plasma milrinone concentration. β = terminal elimination rate constant. DV = distribution volume

Table 5: Comparison of the pharmacokinetic parameters which are obtained in 12 infants and 7 children. Figures are the mean and the standard deviation (+SD), by Ramamoorthy et al. [22].

Parameter Infants aged < 1 year (N = 12) Children aged > 1 year (N = 7)
Distribution volumeβ (L/kg) 0.9+0.4 0.7+0.2*
TBL (ml/kg/min) 3.8+1.0 5.9+2.0*
Elimination half-life (h) 3.1+2.0 1.9+2.0*
β = terminal elimination rate-constant. *P-value (Student test) < 0.05.

 

DISCUSSION

Parenteral formulation of milrinone is used for term circulation support in advanced congestive heart failure. Milrinone inhibits human heart phosphodiesterases 3 and 4 with similar potency. By increasing intracellular cAMP concentrations, they have similar actions as the β receptor agonists dobutamine and epinephrine, but tend to lower systemic pulmonary vascular resistance more than do the catecholamines and the phosphodiesterase inhibitors potentiate the action of β receptor agonists, both beneficial and detrimental [1] and the vasodilatation is related to increased levels of cAMP in vascular smooth muscle [3]. Milrinone is administered by continuous intravenous infusion and the dosage of milrinone consists in a loading dose followed by a maintenance infusion in infants [2] and children [4]. The efficacy and safety of milrinone have been described in infants and in children [5-8]. Preterm infants undergoing postligation cardiac syndrome were treated with milrinone and this treatment is efficacy and safe [5]. Milrinone has been found safe in hospitalized infants [6] and in children undergoing low cardiac output syndrome [7]. Milrinone is efficacy and safe in preventing low cardiac output in children after cardiac surgery [8]. The effects of milrinone have been reported in infants and children [9-20]. Milrinone improves both oxygenation and myocardial performance in preterm infants with pulmonary hypertension [9], milrinone is a useful therapy for preterm infants with pulmonary hypertension and/or ventricular dysfunction [10], and milrinone improves postoperative stability in infants with low cardiac output [11]. Administration of milrinone improves oxygenation in infants without compromising systemic blood pressure [12], and administration of milrinone in infants with low cardiac output after cardiac surgery lowers filling pleasures, systemic and pulmonary arterial, and systemic and pulmonary vascular resistances [13]. Milrinone improves the mortality-rate after Norwood-Sano procedure in children [14], milrinone has beneficial hemodynamic effect in children during critical illness [15], milrinone is used in children following congenital heart surgery [16], milrinone treats tachyarrhythmias in children during early postoperative period after cardiac surgery and in children with septic shock [17], and milrinone optimizes cardiovascular function in children after cardiac surgery and in children with septic shock [18]. Low dose of milrinone has antiinflammatory properties [19], and milrinone decreases vascular resistance in children with pulmonary hypertension [20]. Milrinone may cause adverse effects in infants and children [4]. The pharmacokinetics of milrinone have been studied in infants and children [21-22]. The elimination half-life of milrinone is 3.1 hours in infants aged < 1 year and 1.9 hours in children [22] and the distribution volume is similar to the water volume [21- 22]. Milrinone is mainly eliminated by renal route and the renal function increases with infant maturation and child development. This consideration explains the longer elimination half-life of milrinone in infants than in children. The total body clearance, the distribution volume, and the elimination half-life range in a wide interindividual variability and this variability is accounted by the wide variation in the demographic characteristics of subjects and by the heart disease. The treatment of infants and children with milrinone has been extensively reported [23-31]. Milrinone treats infants with hypoxemic respiratory failure and hypoxic ischemic encephalopathy and reduces the diastolic arterial pressure [23]. Dobutamine and milrinone can be used in the treatment of infants with postligation cardiac syndrome and possess similar therapeutic efficacy on this pathology [24]. Intravenous milrinone is used in combination with nitric oxide and reduces the time spent on infants treated with nitric oxide only [25], and intravenous milrinone is used in infants and children with congenital diaphragmatic hernia [26]. Treatment with milrinone is effective in children with cardiac dysfunction or as palliative therapy for cardiomyopathy [27]. Milrinone treatment prevents death or low cardiac output syndrome in children undergoing surgery for congenital heart disease [28]. Milrinone, epinephrine, dopamine, and dobutamine are used for the treatment of low cardiac output syndrome in children undergoing surgery for congenital heart disease [29]. The treatment of children with milrinone lactate requires a loading dose of 75 µg/kg followed by an infusion of 0.75 to 1.0 µg/kg per min [30], and intravenous milrinone is used in paediatric patients with non-hyperdynamic septic shock [31].

In conclusion, milrinone inhibits human heart phosphodiesterases 3 and phosphodiesterases 4 with similar potency. By increasing intracellular cAMP concentrations, they have similar actions as the β receptor agonists dobutamine and epinephrine, but tend to lower systematic and pulmonary vascular resistance more than do the catecholamines. The phosphodiesterase inhibitors potentiate the action of β receptor agonists, both beneficial and detrimental. The vasodilatation induced by milrinone is related to increased levels of cAMP in vascular smooth muscle. Milrinone is used for short term (< 72 hours) treatment of acute low cardiac output after cardiac surgery or due to septic shock. Milrinone is administered by continuous intravenous infusion and it is administered by a loading dose followed by a maintenance infusion in infants and children. Milrinone has been found efficacy and safe in infants and children but it may induce adverse-effects. The effects operated by milrinone and the pharmacokinetics of milrinone have been extensively studied in infants and children. In infants aged < 1 year, the elimination half-life of milrinone is 3.1 hours and it is 1.9 hours in children. Milrinone is mainly eliminated by renal route and the renal function increases with infant maturation and child development. The treatment of infants and children with milrinone has been extensively studied. The aim of this study is to review the clinical pharmacology of milrinone in infants and children.

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2. Neonatal Formulary (2020). Milrinone. Oxford University Press. 2020; 522-524.

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6. Samiee-Zafarghandy S, Raman SR, van den Anker JN, McHutchison K, Hornik CP, Clark RH, et al. Safety of milrinone use in neonatal intensive care units. Early Hum Dev. 2015; 91: 31-35.

7. Hoffman TM, Wernovsky G, Atz AM, Bailey JM, Akbary A, Kocsis JF, et al. Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics. Am Heart J. 2002; 143: 15-21.

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13. Chang AC, Atz AM, Wernovsky G, Burke RP, Wessel DL. Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med. 1995; 23: 1907-1914.

14. Kanazawa T, Shimizu K, Iwasaki T, Baba K, Otsuki S, et al. Perioperative Milrinone Infusion Improves One-Year Survival After the NorwoodSano Procedure. J Cardiothorac Vasc Anesth. 2021; 35: 2073-2078.

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16. Roeleveld PP, de Klerk JCA. The Perspective of the Intensivist on Inotropes and Postoperative Care Following Pediatric Heart Surgery: An International Survey and Systematic Review of the Literature. World J Pediatr Congenit Heart Surg. 2018; 9: 10-21.

17. Smith AH, Owen J, Borgman KY, Fish FA, Kannankeril PJ. Relation of milrinone after surgery for congenital heart disease to significant postoperative tachyarrhythmias. Am J Cardiol. 2011; 108: 1620-1624.

18. Meyer S, Gortner L, Brown K, Abdul-Khaliq H. The role of milrinone in children with cardiovascular compromise: review of the literature. Wien Med Wochenschr. 2011; 161: 184-191.

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20. Givertz MM, Hare JM, Loh E, Gauthier DF, Colucci WS. Effect of bolus milrinone on hemodynamic variables and pulmonary vascular resistance in patients with severe left ventricular dysfunction: a rapid test for reversibility of pulmonary hypertension. J Am Coll Cardiol. 1996; 28: 1775-1780.

21. Hornik CP, Yogev R, Mourani PM, Watt KM, Sullivan JE, Atz AM, et al. Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents. J Clin Pharmacol. 2019; 59(12): 1606-1619.

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23. Bischoff AR, Habib S, McNamara PJ, Giesinger RE. Hemodynamic response to milrinone for refractory hypoxemia during therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. J Perinatol. 2021.

24. Korkmaz L, Ozdemir A, Pamukçu Ö, Güne? T, Ozturk MA. Which Inotropic Drug, Dobutamine or Milrinone, Is Clinically More Effective in the Treatment of Postligation Cardiac Syndrome in Preterm Infants? Am J Perinatol. 2020.

25. El-Khuffash A, McNamara PJ, Breatnach C, Bussmann N, Smith A, et al. The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1): study protocol and review of literature. Matern Health Neonatol Perinatol. 2018; 4: 24.

26. Lakshminrusimha S, Keszler M, Kirpalani H, Van Meurs K, Chess P, et al. Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study protocol, review of literature and survey of current practices. Matern health neonatol perinatol. 2017; 3: 27.

27. Curley M, Liebers J, Maynard R. Continuous Intravenous Milrinone Therapy in Pediatric Outpatients. J Infus Nurs. 2017; 40: 92-96.

28. Burkhardt BEU, Rücker G, Stiller B. Prophylactic milrinone for the prevention of low cardiac output syndrome and mortality in children undergoing surgery for congenital heart disease. Cochrane Database Syst Rev. 2015; (3): CD009515.

29. Vogt W, Läer S. Treatment for paediatric low cardiac output syndrome: results from the European EuLoCOS-Paed survey. Arch Dis Child. 2011; 96: 1180-1186.

30. Lindsay CA, Barton P, Lawless S, Kitchen L, Zorka A, et al. Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock. J Pediatr. 1998; 132: 329-334.

31. Barton P, Garcia J, Kouatli A, Kitchen L, Zorka A, et al. Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled, interventional study. Chest. 1996; 109: 1302-1312.

Pacifici GM (2021) Clinical pharmacology of Milrinone in paediatric patients. J Drug Des Res 8(3): 1087

Received : 07 Sep 2021
Accepted : 20 Sep 2021
Published : 22 Sep 2021
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Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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