scholarly journals Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn

2017 ◽  
Vol 34 (08) ◽  
pp. 749-758 ◽  
Author(s):  
Annie Giaccone ◽  
Athena Zuppa ◽  
Beena Sood ◽  
Meryl Cohen ◽  
Michael O'Byrne ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pilot Study ◽  
Drug Exposure ◽  
Structural Model ◽  
Standard Dose ◽  
Oxygenation Index ◽  
Persistent Pulmonary Hypertension ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Open Label ◽  
The Impact

Objective To describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition. Design Randomized, open label pilot study. Setting Multicenter; level 3 and level 4 neonatal intensive care units. Patients Six infants ≥34 weeks' gestational age and <10 days of life with persistent hypoxemia receiving inhaled nitric oxide. Intervention Intravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0.2 mcg/kg/minute, and (2) standard dose, 50 mcg/kg bolus followed by 0.5 mcg/kg/minute. Measurements and Main Results The final structural model was a two-compartment disposition model with interindividual variability estimated on clearance (CL). The estimated value of CL is 7.65 mL/minute/3.4 kg (3.05 mL/minute/kg). The addition of age improved the precision of the CL estimate, and CL increased with chronological age in days. The oxygenation index was highly variable within each participant and improved with time. There were no observed safety concerns in either dosing group. Conclusion The CL of milrinone in newborns with PPHN is reduced and increases with age. In this pilot study, we did not see significant pharmacodynamic or safety effects associated with drug exposure.

Four Patterns of Response to Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn

PEDIATRICS ◽  
1996 ◽  
Vol 98 (4) ◽  
pp. 706-713 ◽  
Author(s):  
Allan P. Goldman ◽  
Robert C. Tasker ◽  
Sheila G. Haworth ◽  
Paul E. Sigston ◽  
Duncan J. Macrae
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Time Course ◽  
Pulmonary Hypoplasia ◽  
Oxygenation Index ◽  
Pediatric Intensive Care ◽  
Inhaled Nitric Oxide ◽  
Persistent Pulmonary Hypertension ◽  
Clinical Role ◽  
Initial Trial

Objective. To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). Study Design. Prospective open observational clinical study. Setting. A regional cardiac and pediatric intensive care unit. Methods. Twenty-five consecutive near-term neonates (&gt;35 weeks gestation) with severe PPHN (oxygenation index [OI]&gt; 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in Pao 2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy. Results. Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO—one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to &gt;40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days—all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy. Conclusions. Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.

scholarly journals Intravenous epoprostenol improves oxygenation index in patients with persistent pulmonary hypertension of the newborn refractory to nitric oxide

2018 ◽  
Vol 38 (9) ◽  
pp. 1212-1219 ◽  
Author(s):  
Kaashif Aqeeb Ahmad ◽  
Jesse Banales ◽  
Cody Lance Henderson ◽  
Susanne Erika Ramos ◽  
Katherine Marie Brandt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Oxygenation Index ◽  
Persistent Pulmonary Hypertension

scholarly journals Hydrocortisone Improves Oxygenation Index and Systolic Blood Pressure in Term Infants With Persistent Pulmonary Hypertension

2019 ◽  
Vol 13 ◽  
pp. 117955651988891 ◽  
Author(s):  
Mahdi Alsaleem ◽  
Aysha Malik ◽  
Satyan Lakshminrusimha ◽  
Vasantha HS Kumar
Keyword(s):  
Blood Pressure ◽  
Pulmonary Hypertension ◽  
Systolic Blood Pressure ◽  
Animal Studies ◽  
Oxygenation Index ◽  
Retrospective Chart Review ◽  
Meconium Aspiration Syndrome ◽  
Persistent Pulmonary Hypertension ◽  
Term Infants ◽  
Near Term

Persistent pulmonary hypertension of the newborn (PPHN) is an essential cause for hypoxic respiratory failure with significant morbidity and mortality in term and near-term neonates. Hydrocortisone has been shown to decrease oxygen dependency and pulmonary hypertension in neonates with meconium aspiration syndrome and animal studies, respectively. We hypothesize that hydrocortisone will improve oxygenation in term and near-term infants with pulmonary hypertension. We performed a retrospective chart review of all infant with PPHN who received intravenous hydrocortisone therapy as a rescue for severe PPHN. Clinical response was objectively measured using, oxygenation index (OI), PaO2/FiO2 ratio, and inotrope score before, during, and after the hydrocortisone course. We found that hydrocortisone administration resulted in significant improvement of systolic blood pressure, OI, and PaO2/FiO2. In conclusion, hydrocortisone increased systolic blood pressure and improved oxygenation in term and near-term infants with persistent pulmonary hypertension. Prospective randomized trials are required to evaluate these findings further.

scholarly journals Pharmacokinetics of intravenous sildenafil in children with palliated single ventricle heart defects: effect of elevated hepatic pressures

2015 ◽  
Vol 26 (2) ◽  
pp. 354-362 ◽  
Author(s):  
Kevin D. Hill ◽  
Mario R. Sampson ◽  
Jennifer S. Li ◽  
Robert D. Tunks ◽  
Scott R. Schulman ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Structural Model ◽  
Single Ventricle ◽  
Heart Defects ◽  
Model Development ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Population Pharmacokinetic ◽  
Mixed Effect ◽  
The Impact

AbstractAimsSildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures, which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects.MethodsA population pharmacokinetic model was developed using data from 20 single ventricle children receiving single-dose intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect modelling was used for model development, and covariate effects were evaluated based on estimated precision and clinical significance.ResultsThe analysis included a median (range) of 4 (2–5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of des-methyl-sildenafil (1.94×(hepatic pressure/9)−1.33 L/hour/kg) was predicted to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ⩾10 versus <10 mmHg (median area under the curve=533 versus 792 µg*h/L).DiscussionElevated hepatic pressure delays clearance of the sildenafil metabolite – des-methyl-sildenafil – and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessments in patients with unique cardiovascular physiology that may affect drug metabolism.

Persistent pulmonary hypertension of the newborn in extremely preterm infants: a Japanese cohort study

2018 ◽  
Vol 103 (6) ◽  
pp. F554-F561 ◽  
Author(s):  
Hidehiko Nakanishi ◽  
Hideyo Suenaga ◽  
Atsushi Uchiyama ◽  
Satoshi Kusuda
Keyword(s):  
Pulmonary Hypertension ◽  
Cohort Study ◽  
Preterm Infants ◽  
Research Network ◽  
Persistent Pulmonary Hypertension ◽  
Neurodevelopmental Outcomes ◽  
Significant Independent Risk Factor ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
The Impact

ObjectiveTo investigate the characteristics of persistent pulmonary hypertension of the newborn (PPHN) in extremely preterm infants and its impact on neurodevelopmental outcomes at 3 years of age.DesignA retrospective multicentre cohort study.Settings202 tertiary perinatal centres registered in the Neonatal Research Network of Japan (NRNJ).PatientsInfants born at <28 weeks of gestational age (GA), between 2003 and 2012, were extracted from tertiary perinatal centres participating in NRNJ.Main outcome measuresDemographic characteristics, morbidity, interventions and mortality were compared for infants with and without PPHN. Multivariable logistic analysis was performed to evaluate the impact of PPHN on long-term neurodevelopmental outcomes (the prevalence rate of cerebral palsy, need for home oxygen therapy, and visual, hearing and cognitive impairment) at 3 years of age.ResultsThe prevalence of PPHN among the 12 954 extremely preterm infants enrolled was 8.1% (95% CI 7.7% to 8.6%), with the trend increasing annually, and a higher proportion as GA decreased: 18.5% (range, 15.2% to 22.4%) for infants born at 22 weeks compared with 4.4% (range, 3.8% to 5.2%) for those born at 27 weeks. Clinical chorioamnionitis and premature rupture of membranes were associated with PPHN. On multivariate analysis of the data from 5923 infants followed up for 3 years, PPHN was a significant independent risk factor for visual impairment (adjusted OR, 1.42, 95% CI 1.03 to 1.97).ConclusionsThe prevalence of PPHN in extremely preterm infants has been increasing over the past decade in Japan. Clinicians should be aware of visual impairments as a neurodevelopmental abnormality among infants with PPHN.

Sign in / Sign up

Export Citation Format

Share Document