614 SECTION V Pediatric Critical Care Pulmonary Calcium Channel Blockers Calcium channel blockers (CCBs) are one of the drug classes used during cardiac catheterization to test vasoreactivity 52 The p[.]
614 S E C T I O N V Pediatric Critical Care: Pulmonary Calcium Channel Blockers Calcium channel blockers (CCBs) are one of the drug classes used during cardiac catheterization to test vasoreactivity.52 The potential risk of using CCBs is that they can lead to a significant drop in cardiac output, resulting in hypotension Therefore, elevated right atrial (RA) pressure and low cardiac output are contraindications Furthermore, a trial of CCB therapy should be performed only in those patients who have previously been shown to be acutely reactive to either iNO or intravenous epoprostenol CCBs are contraindicated in children who have not undergone AVT, are nonresponders to AVT, or have RV failure regardless of acute response The negative inotropic effects of CCBs are more pronounced in children younger than year; CCBs are usually not recommended in this age group The advantages of CCBs are that they not require continuous administration and are available as oral preparations Unfortunately, the majority of children with severe PAH are nonresponsive to AVT, and therapy other than a CCB is usually required Combination therapy targets multiple pathways involved in the pathogenesis of PAH striving to provide synergistic benefits compared with monotherapy Consensus is building that treating adults with combination therapy from the outset is beneficial.53 However, few studies have evaluated the safety and efficacy of combination therapy, none of them in pediatric patients Pulmonary Hypertension in the Context of Specific Diseases Group Pulmonary Arterial Hypertension Isolated Pulmonary Arterial Hypertension IPAH and HPAH are part of the group WHO classification of PAH (see Box 53.1) With an estimated incidence and prevalence of 0.7 and 4.4 per million children, respectively, isolated PAH is rare but carries high mortality.54 The hallmark of the disease is the progressive obliteration of the pulmonary vascular bed, ultimately resulting in right heart failure and death IPAH is a diagnosis of exclusion and can be made only when evaluation for all PH-associated conditions has been done and is unrevealing The WHO group also contains pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis, which can occur across the entire age spectrum PVOD is a rare disorder that is often initially misdiagnosed as IPAH owing to its similar clinical presentation.55 PVOD is diagnosed by lung biopsy, which has a high risk in patients with PAH However, a lung biopsy should be considered in a patient with a high suspicion of PVOD, as might be suggested by rapid onset or “flash” pulmonary edema during vasodilator treatment, absence of elevated PA occlusion pressure and left atrial (LA) pressure Histology of PVOD is characterized by extensive fibrous intimal proliferation that involves predominantly pulmonary venules and small veins, whereas IPAH displays frequent plexiform and possible thrombotic lesions.56 A lung transplant is the only long-term therapeutic option for PVOD Isolated abnormal pulmonary angiogenesis is the key feature of pulmonary capillary hemangiomatosis (or pulmonary microvasculopathy) Histopathologic findings of pulmonary capillary hemangiomatosis are proliferation of capillary-sized vessels within the alveolar walls, interstitium, and postcapillary venules of the lung Additionally, similar to other types of PAH, intimal thickening and medial hypertrophy of the small muscular pulmonary arteries are also present The pathogenesis of this rare disease is unknown, and there are no effective medical therapies If pulmonary capillary hemangiomatosis is suspected due to failure to respond to conventional PAH therapy, a lung biopsy should be considered to evaluate for histologic evidence of this disease Lung transplantation is the only long-term therapeutic option Case studies are suggesting that interferon-a2a might be a therapeutic option in a bridge to transplantation.57 PH due to amphetamine-methamphetamine exposure is also part of group PAH Therefore, evaluating for exposure to these medications should be part of all PH evaluations Therapeutic options include those medications currently approved for group PAH Autoimmune Disorders Adult patients with autoimmune disorders and concomitant PH fall in the category of connective tissue disorders (e.g., scleroderma in which PH is fairly common in adult patients) Connective tissue disorders are rare in the pediatric population Juvenile-onset scleroderma represents a subform of scleroderma in which the incidence of PAH before 21 years of age is low (,10%).58 In contrast with adult patients with systemic lupus erythematosus, who have a prevalence of PH of up to 10%, PH occurs only sporadically in pediatric patients Though PH is a rare complication of connective tissue disorders in childhood, it carries high morbidity and mortality; thus, screening echocardiography is recommended Currently, there is insufficient data to provide evidence-based recommendations of PH-specific drug therapies versus modifying the antiinflammatory therapy of the underlying autoimmune disorder Infectious Diseases PH as a complication of an infectious disease occurs most commonly in the human immunodeficiency virus (HIV) and schistosomiasis, which has now been recognized in the most recent iteration of the WHO classification of PH1 (see Box 53.1) The incidence of PAH in patients with HIV infection is estimated to be 0.5% and has not been reduced by the increasing availability of highly active retroviral therapy PH due to HIV infection has been linked to alveolar macrophages that produce specific angioproliferative proteins.59,60 Schistosomiasis is endemic in Africa, Southeast Asia, China, and some parts of Brazil Some 5% to 10% of infected patients develop hepatosplenic disease; of these patients, 7% to 10% develop PAH Published literature describing PAH in pediatric patients with HIV and schistosomiasis is sparse, and there is little information evaluating PAH pharmacotherapy in these children Group Pulmonary Arterial Hypertension (Cardiac Disease) Group PH is caused by left heart disease that may be secondary to left heart failure (with or without reduction of the left ventricular [LV] ejection fraction), valvular heart disease, or cardiovascular conditions leading to postcapillary PH A detailed description of those conditions and treatment is beyond the scope of this chapter CHAPTER 53 Diseases of the Pulmonary Circulation • BOX 53.2 Developmental Lung Diseases Associated With Pulmonary Hypertension Bronchopulmonary dysplasia Congenital diaphragmatic hernia Alveolar capillary dysplasia with misalignment of veins Lung hypoplasia Surfactant protein abnormalities • Surfactant protein B deficiency • Surfactant protein C deficiency ABCA3 • ABCA3 deficiency • TTF-1/Nkx2 deficiency or mutation Pulmonary interstitial glycogenosis Pulmonary alveolar proteinosis Pulmonary lymphangiectasia Group Pulmonary Arterial Hypertension (Intrinsic Pulmonary Diseases) Pulmonary Arterial Hypertension Due to Parenchymal Lung Disease Parenchymal lung disease associated with PAH may occur owing to genetic disorders or originate from disturbances in fetal or early postnatal lung development (Box 53.2) These disorders are either present at birth or become symptomatic in the first months to years of life, with BPD and lung hypoplasia due to congenital diaphragmatic hernia (CDH) being the most common Alveolar capillary dysplasia (ACD) is a rare disorder characterized by misalignment of pulmonary veins and severe hypoplasia of the alveolar capillaries Many cases of ACD are caused by mutations of the FOXF1 gene ACD is usually fatal; lung transplantation is the only therapeutic option Pulmonary Hypertension Secondary to Bronchopulmonary Dysplasia BPD is a chronic lung disease of infancy that occurs predominantly in infants born prematurely It is the sequelae of inadequate pulmonary development in conjunction with injury associated with oxygen and ventilator therapy required to support the immature lungs Despite significant progress in the management of acute infant respiratory disease over the last decades, BPD continues to have a high prevalence in premature infants, with PH contributing significantly to the morbidity and mortality in these patients.61,62 Even in the postsurfactant era, PH persisting beyond the first few months of life continues to be strongly linked with poor survival.63 Reduced size of small pulmonary arteries and an abnormal distribution pattern are characteristic signs of pulmonary vascular disease in BPD.64,65 The consequence of the dysmorphic pulmonary vascular system is a decrease in alveolar-capillary surface area, leading to impaired gas exchange and a prolonged need for oxygen supplementation and ventilator support Animal models of BPD suggest that the ventilator-induced lung injury inflicted on the developing lung can impair angiogenesis, which leads to decreased alveolarization, creating a vicious cycle of lung injury.64 PAH in BPD is not exclusively due to abnormal growth and remodeling of the small pulmonary vessels, as vascular tone and reactivity are abnormal as well Patients with BPD are reported to display an exaggerated vasoconstrictive response to hypoxia,66,67 even in infants with only modest PH at baseline PVD in BPD can be present in the absence of baseline PH, which likely contributes to the increase in pulmonary artery 615 pressure in response to hypoxia and respiratory infections In addition, there is growing evidence that prematurity has long-term effects on the pulmonary and cardiovascular system,68 which is particularly important as more infants are surviving extreme prematurity and growing to adulthood Diagnostic PH Evaluation in BPD arly echocardiograms for the diagnosis of PH are recommended E in preterm infants with severe respiratory distress syndrome who require high levels of ventilator support and supplemental oxygen.4 Of note, preterm infants born at less than 26 weeks’ gestation are at especially high risk for late-onset PH.69 Additionally, infants with a persistent or progressive need for high levels of respiratory support should be assessed for PH, especially if the oxygen required is disproportionate to their degree of lung disease Serial ECGs may not be an adequate screening tool for PH, as some patients can have significant RVH and PH despite normal ECGs The 2015 AHA/ATS guidelines recommend echocardiograms to screen for PH in patients with BPD, with follow-up studies performed at 4- to 6-month intervals depending on changes in clinical course, such as recurrent respiratory exacerbations, persistent oxygen requirement, severity of PH, and changes in drug therapy However, it should not be used as the sole measure to assess the presence or severity of PH There is a poor correlation between echocardiogram and subsequent cardiac catheterization in infants with BPD, which is considered to be the gold standard.70 In the absence of a measurable tricuspid regurgitation (TR) jet, qualitative echocardiogram findings of PH—including RA enlargement, RV hypertrophy, RV dilation, pulmonary artery dilation, and septal flattening—have relatively weak predictive value However, due to its noninvasive nature, echocardiography remains the best available screening tool for PH in patients with BPD despite its limitations In summary, in their 2015 consensus review, the AHA/ATS guidelines recommend cardiac catheterizations for patients with BPD and an echocardiographic diagnosis of PH in the following settings: (1) persistent signs of severe cardiorespiratory disease or clinical deterioration not directly related to airway disease; (2) clinical suspicion of significant PH despite optimal management of lung disease and associated morbidities; (3) candidates for long-term PH drug therapy; and (4) patients with unexplained, recurrent pulmonary edema BPD-Specific Therapies ptimal management of the underlying lung disease is key in inO fants with BPD and PH Patients should be evaluated and treated for associated comorbidities, such as reflux, reactive airway disease, and aspiration and evaluated for structural airway abnormalities (e.g., tonsillar and adenoidal hypertrophy, vocal cord paralysis, subglottic stenosis, and tracheomalacia) Periods of acute hypoxia, whether intermittent or prolonged, are common causes of persistent PH in BPD.71 Due to the variability of oxygen saturation, pulse oximetry should be monitored over an extended period to determine whether supplemental oxygen is needed Targeting oxygen saturation of 92% to 94% is sufficient to balance the adverse effects of hypoxia with the increased risk of hyperoxia-induced lung injury Pulmonary vasodilators are increasingly being used in the therapy of PH secondary to BPD However, these agents should be used cautiously and only after a thorough diagnostic evaluation, as data demonstrating efficacy are extremely limited Current therapies used for PH in infants with BPD generally include iNO, sildenafil, endothelin receptor antagonists, and calcium channel blockers 616 S E C T I O N V Pediatric Critical Care: Pulmonary Congenital Diaphragmatic Hernia CDH occurs in about of every 2500 births and is characterized by marked lung hypoplasia with PH, which results in impaired cardiac performance Of note, concomitant structural cardiac defects occur in 11% to 15% of children born with a CDH.72 The severity of PH is a major determinant of survival in children with a CDH Severe PH is present in about 63% of CDHs and carries a mortality of 45%73,74 and contributes to the overall poor outcome of CDH beyond the immediate postnatal period throughout childhood PVR often remains at suprasystemic levels in newborns with CDH, with the resulting R to L shunt causing profound hypoxemia High PVR in CDH is the result of a combination of vasoconstriction, pulmonary vascular remodeling, and LV dysfunction.75,76 General Management of CDH S urgical management of CDH has undergone marked changes over the last decades (mostly in regard to the timing of the repair from being an immediate after birth surgical emergency to delayed surgery for at least 24 hours to allow stabilization) However, most of the changes have not been studied in randomized controlled trials (RCTs) Equally, mechanical ventilation management strategies vary widely between centers and are not guided by evidencebased studies Infants with CDH are at high risk for chronic lung disease due to severe lung hypoplasia Additional pulmonary injury due to ventilator-induced lung injury further increases the risk of chronic lung disease Therefore, avoiding lung overdistension by minimizing ventilation volumes and pressure is critically important for reducing lung overdistention and improving outcomes Lung protective strategies often result in permissive hypercapnia, which has been thought to improve outcomes in regard to the development of chronic lung disease However, this needs to be balanced with the fact that sustained hypercapnia increases baseline PVR and the subsequent hypoxic response.77 No RCTs of permissive hypercapnia have been conducted in CDH; furthermore, permissive hypercapnia has not been shown to reduce chronic lung disease in premature infants.78 Small clinical trials have shown that high-frequency oscillatory ventilation can be useful in the management of severe CDH when used as rescue.79 PH-Specific Therapy in CDH espite the fact that severe PH is a common complication in D children with CDH, the management of PH in CDH remains controversial, perhaps because (1) there are very few well designed and powered RCTs and (2) several therapies were not primarily studied in CDH but rather extrapolated from PPHN iNO has been shown to decrease the need for extracorporeal membrane oxygenation (ECMO) in PPHN.80 However, in patients with CDH, two RCTs of iNO did not show improvement in mortality or progression to ECMO, despite the fact that iNO improved oxygenation in children with CDH in earlier studies.81 Failure of iNO treatment in newborns with CDH can likely be attributed to LV dysfunction combined with a relatively small LV size in CDH Increasing the preload via iNO to an LV that is unable to respond properly by increasing the stroke volume can lead to pulmonary venous hypertension and thus worsening pulmonary edema Therefore, therapies resulting in pulmonary vasodilation such as iNO must be used judiciously in infants with CDH, with close monitoring of LV function Some patients with severely impaired LV function might profit from the enhancement of right to left ductal shunt by prostaglandin infusion to maintain ductal patency, as in this setting the RV can be used to maintain cardiac output Prostacyclin, prostaglandin E1, ethyl nitrite, sodium nitroprusside, and sodium nitrite have been used in pilot studies in infants with CDH but not in controlled clinical trials The concerns are that, similarly to iNO, the impaired LV function in severe CDH might limit the utility of vasodilator drugs (although they might be useful as a temporizing measurement in severe preductal hypoxemia to facilitate ECMO cannulation Cystic Fibrosis PH can occur in advanced pulmonary cystic fibrosis (CF) PH in pediatric patients with CF is rare; PH is more commonly seen in adult CF patients with end-stage lung disease.82 However, even in pediatric patients, especially those with severe pulmonary manifestations of CF leading to hypoxemia, PH can be present and contribute to poor exercise tolerance and negatively affect the quality of life There are no controlled clinical studies of PH pharmacotherapy in CF patients, but ERA therapy or PDE5 inhibitor therapy have been described in case reports Diffuse Lung Disease PVD can masquerade as diffuse lung disease (e.g., surfactant protein, pulmonary interstitial glycogenosis, pulmonary alveolar proteinosis, pulmonary lymphangiectasia; see Box 53.2) Therefore, screening for PAH is clinically indicated in all infants and children with these diseases, especially as PAH is associated with a worse outcome in patients with interstitial lung disease.83 Pulmonary Hypertension Secondary to Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) is an acute lung injury due to direct lung injury, such as pneumonia or aspiration, or extrapulmonary causes, such as sepsis PH can occur as a complication of ARDS, but the frequency is unknown Himebauch et al performed screening echocardiograms on 103 children within 24 hours of their diagnosis of ARDS Of those, 21% met echocardiographic criteria for PH, which was associated with higher morbidity.84 In adult patients, a meta-analysis of 16 studies85 found that 23% of patients with ARDS showed evidence of PH PVD in ARDS is caused by areas of lung over- and underdistension, resulting in areas with significantly increased PVR It is further exacerbated by changing flow-pressure dynamics due to the heterogeneity of pulmonary blood flow throughout the lungs This acquired pulmonary vascular disease is clinically apparent in 22% to 50% of adults with ARDS and is independently associated with a higher risk of mortality.86 The incidence and risk factors for acquired PVD associated with pediatric ARDS is less well delineated A small, retrospective cohort study estimates that 26% to 40% of children with ARDS show evidence of acquired PVD Importantly, the development of PVD was not related to severity of lung disease but was associated with outcomes such as mortality and duration of mechanical ventilation.84 The reversibility of this pulmonary vascular injury and associated strain on the RV is unclear, but is likely related to the severity and duration of perturbed physiology as well as the reversibility and cessation of the inciting injury iNO has been studied extensively in pediatric ARDS mainly with the underlying hypothesis that it would improve the ventilation/perfusion mismatch and lead to better clinical outcomes Furthermore, in patients with preexisting risk factors for PH (e.g., patients with BPD or Down syndrome), ARDS can acutely worsen preexisting PH Three RCTs failed to demonstrate improved mortality, duration of mechanical ventilation, ventilator-free days, or length of ICU or hospital stay with iNO treatment.87–89 CHAPTER 53 Diseases of the Pulmonary Circulation Therefore, iNO is not recommended for routine use in pediatric ARDS.90 However, it is important to note that those studies did not specifically investigate patients with ARDS and PH iNO may have a role in patients with documented PH or severe RV dysfunction Inhaled PGI2 (epoprostenol or iloprost) has been used in ARDS in a manner similar to iNO, but data in pediatric patients are scant In summary, PH is associated with diverse intrinsic lung diseases in the pediatric population that can manifest from birth to late childhood The exact incidence of PH in these disorders is unknown, and the role of PAH pharmacotherapy has not been rigorously studied However, the link between PH and significantly increased morbidity and mortality is well established Therefore, it is critical for clinicians to consider PH and evaluate using appropriate screening tests based on their clinical suspicion Group Pulmonary Hypertension Chronic Hemolytic Anemia Although PH can occur in many chronic hemolytic anemias, it has been most rigorously studied in sickle cell disease (SCD) and is associated with increased mortality in adults with SCD.91 However, even though increased tricuspid regurgitant jet velocity (TRJV) is present in 10% to 20% of children with SCD, PH itself is rare and does not have the clear impact on mortality seen in adults.92,93 It is also important to note that, in pediatric SCD, increased TRJV does not correlate well with PAP measured by cardiac catheterization.94 Furthermore, TRJV is unable to differentiate precapillary from postcapillary PH, which is critical to differentiate since PAH-specific drug therapy in children, with postcapillary PH vasodilation, can lead to pulmonary edema and worsening hypoxemia Therefore, the 2012 AHA guidelines recommend against PAH-targeted therapy except for patients who have a high PVR and normal pulmonary capillary wedge pressure In those cases, the recommendation is for a trial of ERA or PGI2 analog Based on adult data that associate higher mortality risk with an elevated TRJV (.2.5 m/s), high NT-proBNP greater than 160 pg/mL, or mPAP greater than 25 mm Hg by cardiac catheterization, more aggressive treatment of the underlying SCD is recommended Acute Pulmonary Hypertension Crisis/Right Ventricular Failure Pathophysiology and management of acute pulmonary hypertensive crises (PHCs) in critical care settings have focused mainly on the perioperative period after CHD surgery In pulmonary hypertensive vascular disease, the adaptation of the RV to an increased afterload is critical in determining symptoms and outcome rather than the absolute increase in PVR or PAP This explains why children with Eisenmenger syndrome, who have long-standing RV overload and adaptation, can remain stable with PH over many years PHCs are sudden and potentially lethal increases in PAP and PVR that result in acute RV failure and ultimately lead to systemic hypotension, myocardial ischemia, and, at times, bronchoconstriction (Fig 53.6) PHCs can be triggered by various stimuli, such as pain, anxiety, tracheal suctioning, hypoxia, and acidosis Although most commonly described after cardiac surgery, PHCs can also occur after rapid withdrawal of PH-specific therapy (such as iNO) and may be precipitated outside the perioperative period by intercurrent illness or noncardiac interventions, such as acute lung injury or infection Specific patient populations, such as children with trisomy 21 or BPD, are particularly prone to exacerbation of Inciting event (hypoxia, agitation, acidosis) PAP ↑ PVR ↑ Metabolic acidosis RV Failure lschemia Cardiac output RVEDP ↑ RVEDV ↑ Hypoxia respiratory acidosis V/Q mismatch Dead space ventilation ↑ Arrhythmia Septal shift LVEDV ↑ • Fig 53.6 Mechanism 617 PBF ↑ Small and large airway obstruction Systemic hypotension of acute pulmonary hypertension crisis and subsequent right ventricular failure LVEDV, Left ventricular end-diastolic pressure; PAP, positive airway pressure; PBF, pulmonary blood flow; PVR, pulmonary vascular resistance; RV, right ventricular; RVEDP, right ventricular end-diastolic pressure; RVEDV, right ventricular end-diastolic volume; V/Q, ventilation/perfusion ratios 618 S E C T I O N V Pediatric Critical Care: Pulmonary Activate GO Inhibit FAO, glutaminolysis, or PDK Increased RVSP initiates RVH adaptive and maladaptive RVH Reduced RV function = Reduced RCA perfusion pressure Altered metabolism Reduced GO/glycolysis Adrenergic remodeling β1 receptor downregulation Vicious Cycle of RVH Capillary rarefaction Maladaptive RVH RV inflammation Fibrosis RV lschemia • Fig 53.7 Cycle of right ventricular failure including metabolic changes and right ventricular ischemia FAO, fatty acid oxidation; GO, glucose oxidation; RCA, right coronary artery; RVH, right ventricular hypertrophy; RVSP, right ventricular systolic pressure preexisting, often underrecognized, elevated PAP They warrant close monitoring in the setting of an acute illness (e.g., bronchiolitis) Hypoxia out of proportion to the severity of lung disease should trigger suspicion for PHC Right Ventricular Dysfunction in Pulmonary Hypertension RV function determines the functional capacity and prognosis of infants and children with many forms of PH and CHD The adequacy of the response of the RV to pressure-volume overload relates to factors including alterations in contractile proteins, angiogenesis, metabolism, b-adrenergic signaling, and fibrotic responses (Fig 53.7) Adaptive Versus Maladaptive Right Ventricular Hypertrophy RV hypertrophy (RVH) triggered by pressure overload is initially compensatory but can progress to RV failure Despite similar RV afterload and mass, some patients develop adaptive RVH (concentric with retained RV function), while others develop maladaptive RVH characterized by dilation, fibrosis, and RV failure.95 It is useful to differentiate adaptive RVH (loosely defined by relatively preserved function, compensatory hypertrophy, the absence of severe dilation, and freedom from premature morbidity/ mortality) from maladaptive RVH (dilated, hypokinetic RVs with adverse functional and survival consequences) PH patients with congenital heart disease (Eisenmenger syndrome) or patients with pulmonic stenosis often retain concentrically hypertrophied, contractile (adaptive) RVs for decades.96 In contrast, patients with PAH often decompensate within the first years after diagnosis (maladaptive) However, even within the relatively defined syndrome of group PH, there are patients with well-preserved RV function and others with RV failure despite similar disease duration, PVR, and RV mass.97 For example, patients with scleroderma and PAH, despite lower PA pressures, have worse RV function and a higher incidence/severity of RVF than patients with idiopathic PH.98 At the molecular level, maladaptive RVH displays greater impairment of angiogenesis,99 adrenergic signaling,100,101 and metabolism102–104 than adaptive RVH and these disorders often involve the LV Clinically, maladaptive RVH is characterized by increased NT-proBNP levels,105 troponin release,106 elevated catecholamine levels,107 RV dilation,97 and late gadolinium enhancement on MRI,108 increased 18fluorodeoxyglucose uptake on PET,102 and QTc prolongation on the ECG.109 In maladaptive RVH, there is reduced inotrope responsiveness because of G-protein receptor kinase-mediated downregulation, desensitization, and uncoupling of b-adrenoreceptors While none of these has yet to shape the practice of pediatric cardiology, each offers great opportunities for research and suggests new therapeutic strategies for clinical trials Sympathetic Activation in Pulmonary Arterial Hypertension b1-AR inhibition is not currently indicated for the management of RVH or PAH However, in left heart failure, inhibition of excessive sympathetic activation and b1-AR downregulation/ desensitization is achieved with b1-AR antagonists, such as carvedilol, with marked improvement in survival.110 Circulating catecholamines are also elevated in PAH patients with RVF.107 In a canine pulmonary artery banding (PAB) model, b1-AR are downregulated.111 There are interesting preclinical reports of the a-/b-blocker carvedilol and the b-blocker propranolol regressing ... decades.96 In contrast, patients with PAH often decompensate within the first years after diagnosis (maladaptive) However, even within the relatively defined syndrome of group PH, there are patients... enhancement of right to left ductal shunt by prostaglandin infusion to maintain ductal patency, as in this setting the RV can be used to maintain cardiac output Prostacyclin, prostaglandin E1, ethyl... the frequency is unknown Himebauch et al performed screening echocardiograms on 103 children within 24 hours of their diagnosis of ARDS Of those, 21% met echocardiographic criteria for PH, which