“… Some drugs are known to have an additive effect due to different mechanisms of action on distinct pathways. This has been observed in various animal studies or clinical reports describing patients of any age [ 12 – 14 , 20 , 25 , 28 , 29 , 31 , 35 , 37 , 38 , 60 – 68 ] and is of utmost importance for the choice of drugs to treat refractory PPHN (Fig. 1 ).…”
Section: The Available Weaponrymentioning
confidence: 72%
“…Therefore, it has a weaker and less consistent pulmonary vasodilatory action compared to the other drugs. However, it may be useful if a restrictive or recently closed ductus arteriosus is associated with right ventricular failure or pulmonary overflow (see below) [ 28 , 70 ]. Fig.…”
Section: The Available Weaponrymentioning
confidence: 99%
“…@ Trepostinil is administered subcutaneously with particularly designed micro-infusion pumps and specific dilutions. Abbreviations: B : bolus; C : continuous infusion; cAMP : cyclic adenosine monophosphate; cGMP : cyclic guanosine monophosphate; IV : intra-venous; PDE : phosphodiesterase; ROP : retinopathy of prematurity; SC : sub-cutaneous Drug Route Dose Mechanism of action Possible side effects Adenosine [ 26 , 31 , 33 , 34 ] IV C: 50 mcg/kg/min cAMP precursor None Alprostadil (PGE 2 ) [ 18 , 27 , 28 , 41 , 43 , 50 ] IV C: 0.0125-0.05 mcg/kg/min ↑↓intracellular cAMP ‡ Keep the ductus arterious open Hypo- and hypertension, respiratory arrest, fever, bleeding, ductal aneurysm, bone cortical bone proliferation (for long-term therapy), worsening inflammation. Aerosol † C: 25-300 ng/Kg/min Beraprost [ 25 , 32 , 49 ] Per os 1 mcg/Kg/6h Prostacyclin analog (↑intracellular cAMP) Hypotension Bosentan [ 14 , 17 , 25 , 29 , 36 – 38 , 46 ] Per os 1 mg/kg/12h Endothelin pathway inhibition None Iloprost* [ 6 , 12 , 21 , 22 ] Aerosol † 1-2 mcg/kg/2-4h # Prostacyclin ...…”
Persistent pulmonary hypertension of the neonate (PPHN) refractory to inhaled nitric oxide still represents a frequent clinical challenge with negative outcomes in neonatal critical care. Several pulmonary vasodilators have become available thanks to improved understanding of pulmonary hypertension pathobiology. These drugs are commonly used in adults and there are numerous case series and small studies describing their potential usefulness in neonates, as well. New vasodilators act on different pathways, some of them can have additive effects and all have different pharmacology features. This information has never been summarized so far and no comprehensive pathobiology-driven algorithm is available to guide the treatment of refractory PPHN.
Conclusion
: We offer a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge.
What is Known:
•
Refractory PPHN occurs in 30–40% of iNO-treated neonates and represents a significant clinical problem. Several pulmonary vasodilators have become available thanks to a better understanding of pulmonary hypertension pathobiology.
What is New:
•
Available vasodilators have different pharmacology, mechanisms of action and may provide additive effect. We provide a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge
.
“… Some drugs are known to have an additive effect due to different mechanisms of action on distinct pathways. This has been observed in various animal studies or clinical reports describing patients of any age [ 12 – 14 , 20 , 25 , 28 , 29 , 31 , 35 , 37 , 38 , 60 – 68 ] and is of utmost importance for the choice of drugs to treat refractory PPHN (Fig. 1 ).…”
Section: The Available Weaponrymentioning
confidence: 72%
“…Therefore, it has a weaker and less consistent pulmonary vasodilatory action compared to the other drugs. However, it may be useful if a restrictive or recently closed ductus arteriosus is associated with right ventricular failure or pulmonary overflow (see below) [ 28 , 70 ]. Fig.…”
Section: The Available Weaponrymentioning
confidence: 99%
“…@ Trepostinil is administered subcutaneously with particularly designed micro-infusion pumps and specific dilutions. Abbreviations: B : bolus; C : continuous infusion; cAMP : cyclic adenosine monophosphate; cGMP : cyclic guanosine monophosphate; IV : intra-venous; PDE : phosphodiesterase; ROP : retinopathy of prematurity; SC : sub-cutaneous Drug Route Dose Mechanism of action Possible side effects Adenosine [ 26 , 31 , 33 , 34 ] IV C: 50 mcg/kg/min cAMP precursor None Alprostadil (PGE 2 ) [ 18 , 27 , 28 , 41 , 43 , 50 ] IV C: 0.0125-0.05 mcg/kg/min ↑↓intracellular cAMP ‡ Keep the ductus arterious open Hypo- and hypertension, respiratory arrest, fever, bleeding, ductal aneurysm, bone cortical bone proliferation (for long-term therapy), worsening inflammation. Aerosol † C: 25-300 ng/Kg/min Beraprost [ 25 , 32 , 49 ] Per os 1 mcg/Kg/6h Prostacyclin analog (↑intracellular cAMP) Hypotension Bosentan [ 14 , 17 , 25 , 29 , 36 – 38 , 46 ] Per os 1 mg/kg/12h Endothelin pathway inhibition None Iloprost* [ 6 , 12 , 21 , 22 ] Aerosol † 1-2 mcg/kg/2-4h # Prostacyclin ...…”
Persistent pulmonary hypertension of the neonate (PPHN) refractory to inhaled nitric oxide still represents a frequent clinical challenge with negative outcomes in neonatal critical care. Several pulmonary vasodilators have become available thanks to improved understanding of pulmonary hypertension pathobiology. These drugs are commonly used in adults and there are numerous case series and small studies describing their potential usefulness in neonates, as well. New vasodilators act on different pathways, some of them can have additive effects and all have different pharmacology features. This information has never been summarized so far and no comprehensive pathobiology-driven algorithm is available to guide the treatment of refractory PPHN.
Conclusion
: We offer a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge.
What is Known:
•
Refractory PPHN occurs in 30–40% of iNO-treated neonates and represents a significant clinical problem. Several pulmonary vasodilators have become available thanks to a better understanding of pulmonary hypertension pathobiology.
What is New:
•
Available vasodilators have different pharmacology, mechanisms of action and may provide additive effect. We provide a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge
.
“…It is difficult to compare our rates of complications with other studies, even if our population was comparable with other studies in terms of gestational age and birth weight [ 9 , 37 ]. We only assessed neonatal complications occurring before the first hospital discharge while most other studies have reported a long-term follow up of CDH patients [ 10 , 12 , 38 ].…”
Background: Congenital diaphragmatic hernia (CDH) is a rare disease associated with major nutritional and digestive morbidities. Oral feeding autonomy remains a major issue for the care and management of these patients. The aim of this study was to specify the perinatal risk factors of delayed oral feeding autonomy in patients treated for CDH. Methods: This monocentric cohort study included 138 patients with CDH. Eighty-four patients were analyzed after the exclusion of 54 patients (11 with delayed postnatal diagnosis, 5 with chromosomal anomaly, 9 with genetic syndrom, 13 with right-sided CDH, and 16 who died before discharge and before oral feeding autonomy was acquired). They were divided into two groups: oral feeding autonomy at initial hospital discharge (group 1, n = 51) and nutritional support at discharge (group 2, n = 33). Antenatal, postnatal, and perisurgical data were analyzed from birth until first hospital discharge. To remove biased or redundant factors related to CDH severity, statistical analysis was adjusted according to the need for a patch repair. Results: After analysis and adjustment, delayed oral feeding autonomy was not related to observed/expected lung-to-head ratio (LHR o/e), intrathoracic liver and/or stomach position, or operative duration. After adjustment, prophylactic gastrostomy (OR adjusted: 16.3, IC 95%: 3.6–74.4) and surgical reoperation (OR adjusted: 5.1, IC 95% 1.1–23.7) remained significantly associated with delayed oral feeding autonomy. Conclusions: Delayed oral feeding autonomy occurred in more than one third of patients with CDH. Both prophylactic gastrostomy and surgical reoperation represent significant risk factors. Bowel obstruction might also impact oral feeding autonomy. Prophylactic gastrostomy seems to be a false “good idea” to prevent failure to thrive. This procedure should be indicated case per case. Bowel obstruction and all surgical reoperations represent decisive events that could impact oral feeding autonomy.
“…Prostaglandin E1 (PGE1) is used globally in neonatal medicine to maintain patency of the ductus arteriosus in duct-dependent congenital heart disease. Due to its non-selective pulmonary vasodilator effect and its role in offloading the pressure on the right ventricle via the ductus arteriosus, PGE1 has been increasingly used in the management of neonatal pulmonary hypertension, especially in those patients with congenital diaphragmatic hernia (CDH) 1 2. Gastric outlet obstruction (GOO) has been described as a side effect of PGE1 in populations with congenital heart disease, most commonly secondary to hypertrophic pyloric stenosis (HPS) or antral foveolar hyperplasia (AFH) 3…”
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