II. Precautions

  1. Management strategies below are specific for Pulmonary Arterial Hypertension (WHO Group 1)
  2. Other Pulmonary Hypertension Causes should be specifically treated
    1. Pulmonary Hypertension associated with left heart disease
      1. Treat significant valvular disease (e.g. Mitral Stenosis)
      2. Afterload reduction for Left Ventricular Dysfunction
      3. Manage Fluid Overload with Diuretics
      4. Avoid vasodilators
    2. Pulmonary Hypertension associated with lung disease, Hypoxemia or both
      1. Screen for Sleep Apnea
        1. CPAP for Obstructive Sleep Apnea
      2. Maximize COPD Management
      3. Supplemental Oxygen for PaO2 <60 mmHg (<90% Oxygen Saturation)
      4. Avoid vasodilators
    3. Pulmonary Hypertension associated with chronic thromboembolic disease (WHO Group 4)
      1. Pulmonary endarterectomy (if surgical candidate, first-line if done at major center)
      2. Lifelong Anticoagulation
    4. Miscellaneous Pulmonary Hypertension (WHO Group 5)
      1. Maximize treatment of underlying cause (e.g. Sarcoidosis, pulmonary vessel compression)
      2. Sickle Cell Anemia may respond to Hydroxyurea, chronic transfusions

III. Management: Acute Presentation

IV. Management: Chronic

  1. General measures
    1. Prevent and promptly treat respiratory infections
    2. Regular symptom-limited Exercise
    3. Avoid pregnancy (50% mortality)
    4. Immunizations
      1. Influenza Vaccine annually
      2. Pneumococcal Vaccine
    5. Perioperative Evaluation
      1. Preoperative Echocardiogram
      2. Evaluate functional status
      3. Consider surgical alternatives
      4. Consult specialty care in the decision to approve, and the optimization before elective surgery
  2. Anticoagulation
    1. Coumadin to keep INR between 1.7 to 2.2
  3. Cardiac Output maximization
    1. Consider Digoxin to increase Cardiac Output or for tachyarrhythmias
    2. Consider parenteral inotropic medications in refractory inpatients
  4. Decrease Preload
    1. Follow low-salt diet
    2. Diuretics to reduce volume retention
  5. Treat Hypoxia
    1. Oxygen supplementation to keep Oxygen Saturation >90-92% (60 mmHg)
  6. Pulmonary Arterial Hypertension medications
    1. Low risk patient
      1. See Vasodilators below
      2. PDE-5 Inhibitors (Sildenafil) or
      3. Endothelin receptor antagonists (Bosentan, Ambrisentan)
    2. High risk patient (or low risk patient protocol fails)
      1. Epoprostenol (Flolan) IV or
      2. Selexipag (Uptravi) oral
      3. Treprostinil (Remodulin, Orenitram) Oral, IV or SQ
      4. Iloprost (Ventavis) Inhaled
  7. Other medical management
    1. Consider Calcium Channel Blocker
      1. Only indicated if positive vasoreactivity test (<5-20% of patients)
    2. Experimental options
      1. Nitric oxide
  8. Surgery (if refractory to medical management)
    1. Lung Transplantation
    2. Balloon Atrial Septoplasty

V. Management: Vasodilators (reduce vascular resistance) - Specific PAH Treatments

  1. Endothelin receptor antagonists
    1. Precautions
      1. FDA pregnancy category X (and reduce OCP efficacy)
      2. Liver Function Testing monthly (due to hepatotoxicity risk)
      3. Drug interaction with Warfarin (increased INR)
    2. Preparations
      1. Bosentan (Tracleer) 62.5 mg orally twice daily (up to maximum of 250 mg/day)
      2. Ambrisentan (Letairis) 5 mg daily (up to 10 mg/day)
      3. Sitaxsentan
  2. Phosphodiesterase-5 Inhibitors (PDE-5 Inhibitors)
    1. Precautions
      1. Avoid with nitrates (precipitous Hypotension risk)
      2. Avoid with CYP3A4 inhibitors (Clarithromycin, Itraconazole)
    2. Adverse effects
      1. Headache
      2. Flushing
      3. Epistaxis
    3. Mechanism
      1. Cyclic guanosine monophosphate (cGMP) is a vasodilator
      2. cGMP is rapidly degraded by PDE5 which present in right ventricle of PAH patients
    4. Preparations
      1. Sildenafil (Revatio) 20 mg orally three times daily ($45/month)
      2. Tedalafil (Adcirca) 40 mg daily (>$3000/month)
  3. Prostenoids (Prostacyclin)
    1. Efficacy: Highly effective
    2. Precautions
      1. Avoid stopping abruptly (risk of rebound Pulmonary Arterial Hypertension)
    3. Adverse effects
      1. Jaw pain
      2. Diarrhea
      3. Peripheral Edema
      4. Headache
    4. Mechanism
      1. Prostacyclins reduce platelet aggregation and causes vasodilation
      2. Prostacylcins are reduced in PAH
    5. Preparations
      1. Epoprostenol (Flolan) 2 ng/kg/min IV (titrate 1-2 ng/kg/min every 15 min as needed)
      2. Iloprost (Ventavis) 2.5 to 5 mcg nebulized every 2-4 hours (up to 9 doses per day)
      3. Beraprost 20 mcg three times daily (titrate up to maximum 60 mcg, over several weeks)
      4. Treprostinil (Remodulin)
        1. IV/SQ: 1.25 ng/kg/min titrated once weekly
        2. Inhaled: 18 mcg (3 breaths from 1.74 mg/2.9 ml Inhaler) four times daily
          1. Increased by 18 mcg/dose (3 breaths) every 1-2 weeks
          2. Maximum of 54 mcg/dose (9 breaths/dose)

VI. Management: Calcium Channel Blockers

  1. Do not use in non-vasodilator responders
    1. Risk of Hypotension, Syncope and right ventricular failure
  2. Effective longterm in only 5-20%
    1. Effectiveness wanes over time
  3. Requires vasodilation test as above (use only if responder)
    1. If non-responder, then do not use Calcium Channel Blocker (use other vasodilators listed above)
  4. Determine if patient responds to vasodilation (vasoreactivity study)
    1. Perform right heart catheterization (mandatory prior to using Calcium Channel Blocker)
    2. Administer vasodilator (e.g. Adenosine, epoprostenol)
    3. Responder criteria
      1. Pulmonary Artery Pressure decreases >10 mmHg and <40 mmHg
      2. Cardiac Output does not change or increases
    4. Use responder status to direct therapy
      1. Responder: Calcium Channel Blocker
      2. Non-responder: Use other vasodilators listed above
  5. Preparations (use very high dose)
    1. Diltiazem ER (max 960 mg/day)
    2. Nifedipine ER (max 240 mg/day)
    3. Amlodipine (max 30 mg/day)

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