Pediatric Pulmonary Hypertension

Publication Date: November 3, 2015

Recommendations

Diagnostics, Assessments, and Monitoring

At the time of initial PH diagnosis, a comprehensive history and physical examination, combined with diagnostic testing for assessment of PH pathogenesis/classification and formal assessment of cardiac function, should be performed before the initiation of therapy at an experienced center. ( B , I )
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Imaging to diagnose pulmonary thromboembolic disease, peripheral pulmonary artery stenosis, pulmonary vein stenosis, pulmonary veno-occlusive disease (PVOD), and parenchymal lung disease should be performed at the time of diagnosis. (B, I)
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After a comprehensive initial evaluation, serial echocardiograms should be performed. More frequent echocardiograms are recommended in the setting of changes in therapy or clinical condition. (B, I)
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Cardiac catheterization is recommended before initiation of PAH-targeted therapy. (B, I)
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Exceptions may include critically ill patients requiring immediate initiation of empirical therapy. (B, I)
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Cardiac catheterization should include acute vasoreactivity testing (AVT) unless there is a specific contraindication. (A, I)
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The minimal hemodynamic change that defines a positive response to AVT for children should be considered as a ≥20% decrease in PAP and pulmonary vascular resistance (PVR)/systemic vascular resistance (SVR) without a decrease in cardiac output. (B, I)
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Repeat cardiac catheterization is recommended within 3 to 12 months after initiation of therapy to evaluate response or with clinical worsening. (B, I)
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Serial cardiac catheterizations with AVT are recommended as follows:

a. Serial cardiac catheterizations should be done during follow-up to assess prognosis and potential changes in therapy ( B , I )
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b. Intervals for repeat catheterizations should be based on clinical judgment but include worsening clinical course or failure to improve during treatment. ( B , I )
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Magnetic resonance imaging (MRI) can be useful as part of the diagnostic evaluation and during follow-up to assess changes in ventricular function and chamber dimensions. (B, IIa)
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Brain natriuretic peptide (BNP) or N-terminal (NT) proBNP should be measured at diagnosis and during follow-up to supplement clinical decision. (B, I)
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The 6-minute walk distance (6MWD) test should be used to follow exercise tolerance in pediatric PH patients of appropriate age. (A, I)
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The recommendations for a sleep study are the following:

a. A sleep study should be part of the diagnostic evaluation of patients with PH at risk for sleep-disordered breathing. ( B , I )
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b. A sleep study is indicated in the evaluation of patients with poor responsiveness to PAH-targeted therapies. ( B , I )
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Genetics

Genetic testing with counseling can be useful for children with IPAH or in families with heritable PAH (HPAH) to define the pathogenesis, to identify family members at risk, and to inform family planning. (C, IIa)
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Recommendations for genetic testing of first-degree relatives of patients with monogenic forms of HPAH include the following:

a. Genetic testing is indicated for risk stratification. ( B , I )
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b. Genetic testing is reasonable to screen asymptomatic carriers with serial echocardiograms or other noninvasive studies. ( B , IIa )
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Members of families afflicted with HPAH who develop new cardiorespiratory symptoms should be evaluated immediately for PAH. (B, I)
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Families of patients with genetic syndromes associated with PH should be educated about the symptoms of PH and should be counseled to seek evaluation of the affected child should symptoms arise. (B, I)
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Persistent PH of the Newborn

Inhaled nitric oxide (iNO) is indicated to reduce the need for extracorporeal membrane oxygenation (ECMO) support in term and near-term infants with persistent PH of the newborn (PPHN) or hypoxemic respiratory failure who have an oxygenation index that exceeds 25. (A, I)
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Lung recruitment strategies can improve the efficacy of iNO therapy and should be performed in patients with PPHN associated with parenchymal lung disease. (B, I)
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ECMO support is indicated for term and near-term neonates with severe PH or hypoxemia that is refractory to iNO and optimization of respiratory and cardiac function. (A, I)
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Evaluation for disorders of lung development such as alveolar capillary dysplasia (ACD) and genetic surfactant protein diseases is reasonable for infants with severe PPHN who fail to improve after vasodilator, lung recruitment, or ECMO therapy. (B, IIa)
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Sildenafil is a reasonable adjunctive therapy for infants with PPHN who are refractory to iNO, especially with an oxygenation index that exceeds 25. (B, IIa)
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Inhaled prostacyclin (PGI2) analogs may be considered as adjunctive therapy for infants with PPHN who are refractory to iNO and have an oxygenation index that exceeds 25. (B, IIb)
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Intravenous milrinone is reasonable in infants with PPHN and signs of left ventricular (LV) dysfunction. (B, IIb)
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iNO can be beneficial for preterm infants with severe hypoxemia that is due primarily to PPHN physiology rather than parenchymal lung disease, particularly if associated with prolonged rupture of membranes and oligohydramnios. (B, IIa)
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Congenital Diaphragmatic Hernia

Minimizing peak inspiratory pressure and avoiding large tidal volumes is recommended to reduce ventilator-associated acute lung injury in infants with congenital diaphragmatic hernia (CDH). (B, I)
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High-frequency oscillatory ventilation is a reasonable alternative mode of ventilation for subjects with CDH when poor lung compliance, low volumes, and poor gas exchange complicate the clinical course. (A, IIa)
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iNO therapy can be used to improve oxygenation in infants with CDH and severe PH but should be used cautiously in subjects with suspected LV dysfunction. (B, IIa)
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ECMO is recommended for patients with CDH with severe PH who do not respond to medical therapy. (B, I)
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Prostaglandin E1may be considered to maintain patency of the ductus arteriosus and to improve cardiac output in infants with CDH and suprasystemic levels of PH or RV failure to improve cardiac output. (C, IIb)
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Evaluation for long-term PAH-specific therapy for PH in infants with CDH should follow recommendations for all children with PH, which include cardiac catheterization. (B, I)
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Longitudinal care in an interdisciplinary pediatric PH program is recommended for infants with CDH who have PH or are at risk of developing late PH. (B, I)
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Bronchopulmonary Dysplasia

Screening for PH by echocardiogram is recommended in infants with established BPD. (B, I)
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Evaluation and treatment of lung disease, including assessments for hypoxemia, aspiration, structural airway disease, and the need for changes in respiratory support, are recommended in infants with BPD and PH before initiation of PAH-targeted therapy. (B, I)
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Evaluation for long-term therapy for PH in infants with BPD should follow recommendations for all children with PH and include cardiac catheterization to diagnose disease severity and potential contributing factors such as LV diastolic dysfunction, anatomic shunts, pulmonary vein stenosis, and systemic collaterals. (B, I)
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Supplemental oxygen therapy is reasonable to avoid episodic or sustained hypoxemia and with the goal of maintaining O2saturations between 92% and 95% in patients with established BPD and PH. (C, IIa)
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PAH-targeted therapy can be useful for infants with BPD and PH on optimal treatment of underlying respiratory and cardiac disease. (C, IIa)
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Treatment with iNO can be effective for infants with established BPD and symptomatic PH. (C, IIa)
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Serial echocardiograms are recommended to monitor the response to PAH-targeted therapy in infants with BPD and PH. (B, I)
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Pharmacotherapy

Supportive care with digitalis and diuretic therapy is reasonable with signs of right heart failure but should be initiated cautiously. (C, IIb)
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Recommendations for long-term anticoagulation with warfarin include the following:

a. Warfarin may be considered in patients with IPAH/HPAH, patients with low cardiac output, those with a long-term indwelling catheter, and those with hypercoagulable states. ( C , IIb )
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b. Targeting the therapeutic range for an international normalized ratio between 1.5 and 2.0 is recommended for young children with PAH. ( C , I )
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c. Anticoagulation should not be used in young children with PAH because of concerns about harm from hemorrhagic complications. ( C , III (harm) )
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Oxygen therapy is reasonable for hypoxemic PAH patients who have oxygen saturations <92%, especially with associated respiratory disease. (B, IIa)
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Recommendations for calcium channel blockers (CCBs) include the following:

a. CCBs should be given only to those patients who are reactive as assessed by AVT and >1 year of age. ( C , I )
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b. CCBs are contraindicated in children who have not undergone or are nonresponsive to AVT and in patients with right-sided heart dysfunction owing to the potential for negative inotropic effects of CCB therapy. ( C , III (harm) )
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Oral PAH-targeted therapy in children with lower-risk PAH is recommended and should include either a phosphodiesterase type 5 (PDE5) inhibitor or an endothelin (ET) receptor antagonist (ERA). (B, I)
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A goal-targeted therapy approach in which PAH-specific drugs are added progressively to achieve specified therapeutic targets can be useful. (C, IIa)
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Intravenous and subcutaneous PGI2or its analogs should be initiated without delay for patients with higher-risk PAH. (B, I)
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Recommendations for the transition from parenteral to oral or inhaled therapy include the following:

a. This transition may be considered in asymptomatic children with PAH who have demonstrated sustained, near-normal pulmonary hemodynamics. ( C , IIb )
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b. The transition requires close monitoring in an experienced pediatric PH center. ( B , I )
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Idiopathic PAH

Lung biopsy may be considered for children with PAH suspected of having PVOD, pulmonary capillary hemangiomatosis, or vasculitis. (C, IIb)
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Referral to lung transplantation centers for evaluation is recommended for patients who are in World Health Organization (WHO) functional class III or IV on optimized medical therapy or who have rapidly progressive disease. (A, I)
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Referral to a lung transplantation center for evaluation is recommended for patients who have confirmed pulmonary capillary hemangiomatosis or PVOD. (B, I)
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Pediatric Heart Disease

In children with significant structural heart disease (ie, atrial septal defect [ASD], ventricular septal defect [VSD], and patent ductus arteriosus [PDA]) who have not undergone early repair (as generally defined as by 1 to 2 years of age, depending on the lesion and overall clinical status), the following are recommended:

a. Cardiac catheterization should be considered to measure PVR index (PVRI) and to determine operability. ( B , IIa )
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b. Repair should be considered if PVRI is <6 Wood units (WU)·m2 or PVR/SVR <0.3 at baseline. ( B , I )
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In children with evidence of right-to-left shunting and cardiac catheterization revealing a PVRI ≥6 WU·m2 or PVR/SVR ≥0.3, repair can be beneficial if AVT reveals reversibility of PAH (absolute PVRI <6 WU·m2 and PVR/SVR <0.3). (C, IIa)
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If cardiac catheterization reveals a PVRI ≥6 WU·mor PVR/SVR ≥0.3 and minimal responsiveness to AVT, the following are recommended:

a. Repair is not indicated. ( A , III (harm) )
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b. It is reasonable to implement PAH-targeted therapy followed by repeat catheterization with AVT after 4 to 6 months and to consider repair if the PVRI is <6 WU. ( C , IIb )
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PH Crises/Acute RV Failure

General postoperative strategies for avoiding PH crises (PHCs), including avoidance of hypoxia, acidosis, and agitation, should be used in children at high risk for PHCs. (B, I)
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Induction of alkalosis can be useful for the treatment of PHCs. (C, IIa)
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Administration of opiates, sedatives, and muscle relaxers is recommended for reducing postoperative stress response and the risk for or severity of PHCs. (B, I)
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In addition to conventional postoperative care, iNO and/or inhaled PGI2 should be used as the initial therapy for PHCs and failure of the right side of the heart. (B, I)
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Sildenafil should be prescribed to prevent rebound PH in patients who have evidence of a sustained increase in PAP on withdrawal of iNO and require reinstitution of iNO despite gradual weaning of iNO dose. (B, I)
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In patients with PHCs, inotropic/pressor therapy should be used to avoid RV ischemia caused by systemic hypotension. (B, I)
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Mechanical cardiopulmonary support should be provided in refractory cases. (B, I)
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Atrial septostomy (AS) is recommended for patients with RV failure, recurrent syncope, or PHCs that persist despite optimized medical management but must be performed in an experienced PH center. (B, I)
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Lung Diseases

Children with chronic diffuse lung disease should be evaluated for concomitant cardiovascular disease or PH by echocardiogram, especially those with advanced disease. (B, I)
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Echocardiography is recommended to assess PH and RV function in patients with severe obstructive sleep apnea (OSA). (B, I)
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For exercise-limited patients with advanced lung disease and evidence of PAH, the following are recommended:

a. A trial of PAH-targeted therapy is reasonable. ( C , IIa )
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b. Catheterization of the right side of the heart may be considered. ( B , IIb )
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Hypobaric Hypoxia

Patients with symptomatic high altitude–related PH may be encouraged to move to low altitude. (C, IIb)
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CCB therapy (with amlodipine or nifedipine) may be reasonable for high-altitude pulmonary edema (HAPE) prophylaxis in children with a previous history of HAPE. (C, IIb)
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Therapy for symptomatic HAPE should include supplemental oxygen therapy and consideration of immediate descent. (B, I)
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Children with HAPE should undergo evaluation to rule out abnormalities of pulmonary arteries or pulmonary veins, lung disease, or abnormal control of breathing. (B, I)
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Systemic Disease

Early evaluation for PH, including a Doppler echocardiogram, is reasonable for children with hemolytic hemoglobinopathies or hepatic, renal, or metabolic diseases who develop cardiorespiratory symptoms. (C, IIa)
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In children with chronic hepatic disease, an echocardiogram should be performed to rule out portopulmonary hypertension (PPHTN) and pulmonary arteriovenous shunt before they are listed for liver transplantation. (B, I)
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It is reasonable for children with SCD to undergo an echocardiogram to screen for PH and associated cardiac problems by 8 years of age or earlier in patients with frequent cardiorespiratory symptoms. (C, IIa)
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For children with SCD who have evidence of PH by echocardiogram, the following are recommended:

a. Children with SCD should undergo further cardiopulmonary evaluation, including pulmonary function testing, polysomnography, assessment of oxygenation, and evaluation for thromboembolic disease. ( C , I )
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b. Children with SCD should undergo cardiac catheterization before the initiation of PAH-specific drug therapy. ( C , I )
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BNP and NT-proBNP measurements can be useful in screening for PH in patients with SCD. (C, IIa)
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With the diagnosis of PH in children with SCD, optimization of SCD-related therapies (eg, blood transfusions, hydroxyurea, iron chelation, and supplemental oxygen) is recommended. (C, I)
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PAH-targeted therapy should not be used empirically in SCD-associated PH because of potential adverse effects. (C, III (harm))
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PAH-targeted therapy may be considered in patients with SCD in whom there is confirmation of PH with marked elevation of PVR without an elevated pulmonary capillary wedge pressure by cardiac catheterization. (C, IIb)
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A trial of a PGI2 agonist or an ERA is preferred over PDE5 inhibitors in patients with markedly elevated PVR and SCD. (B, IIa)
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Outpatient Care of Children With PH

Children with PH should be evaluated and treated in comprehensive, multidisciplinary clinics at specialized pediatric centers. (C, I)
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Outpatient follow-up visits at 3- to 6-month intervals are reasonable, with more frequent visits for patients with advanced disease or after initiation of or changes in therapy. (B, IIa)
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The following preventive care measures for health maintenance are recommended for pediatric patients with PH:
  • Respiratory syncytial virus prophylaxis (if eligible)
  • Influenza and pneumococcal vaccinations
  • Rigorous monitoring of growth parameters
  • Prompt recognition and treatment of infectious respiratory illnesses
  • Antibiotic prophylaxis for the prevention of subacute bacterial endocarditis in cyanotic patients and those with indwelling central lines.
(C, I)
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Careful preoperative planning, consultation with cardiac anesthesia, and plans for appropriate postprocedural monitoring are recommended for pediatric patients with PH undergoing surgery or other interventions. (C, I)
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Elective surgery for patients with pediatric PH should be performed at hospitals with expertise in PH and in consultation with the pediatric PH service and anesthesiologists with experience in the perioperative management of children with PH. (C, I)
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As a result of significant maternal and fetal mortality associated with pregnancy in patients with PH, it is recommended that female adolescents with PH be provided with age-appropriate counseling about pregnancy risks and options for contraception. (C, I)
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Because of the risks of syncope or sudden death with exertion, it is recommended that a thorough evaluation, including cardiopulmonary exercise testing (CPET) and treatment, be performed before the patient engages in athletic (symptom-limited) activities. (C, I)
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Pediatric patients with severe PH (WHO functional class III or IV) or recent history of syncope should not participate in competitive sports. (C, III (harm))
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During exercise, it is recommended that pediatric patients with PH engage in light to moderate aerobic activity, avoid strenuous and isometric exertion, remain well hydrated, and be allowed to self-limit as required. (C, I)
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During airplane travel, supplemental oxygen use is reasonable in pediatric patients with PH. (B, IIa)
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Given the impact of childhood PAH on the entire family, children, siblings, and caregivers should be assessed for psychosocial stress and be readily provided support and referral as needed. (C, I)
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Recommendation Grading

Disclaimer

Overview

Title

Pediatric Pulmonary Hypertension

Authoring Organizations

Publication Month/Year

November 3, 2015

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Child, Infant

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Diagnosis

Diseases/Conditions (MeSH)

D006976 - Hypertension, Pulmonary

Keywords

pulmonary hypertension, PAH

Supplemental Methodology Resources

Evidence Tables, Data Supplement