II. Precautions
- Management strategies below are specific for Pulmonary Arterial Hypertension (WHO Group 1)
- Other Pulmonary Hypertension Causes should be specifically treated
- Pulmonary Hypertension associated with left heart disease
- Treat significant valvular disease (e.g. Mitral Stenosis)
- Afterload reduction for Left Ventricular Dysfunction
- Manage Fluid Overload with Diuretics
- Avoid vasodilators
- Pulmonary Hypertension associated with lung disease, Hypoxemia or both
- Screen for Sleep Apnea
- Maximize COPD Management
- Supplemental Oxygen for PaO2 <60 mmHg (<90% Oxygen Saturation)
- Avoid vasodilators
- Pulmonary Hypertension associated with chronic thromboembolic disease (WHO Group 4)
- Pulmonary endarterectomy (if surgical candidate, first-line if done at major center)
- Lifelong Anticoagulation
- Miscellaneous Pulmonary Hypertension (WHO Group 5)
- Maximize treatment of underlying cause (e.g. Sarcoidosis, pulmonary vessel compression)
- Sickle Cell Anemia may respond to Hydroxyurea, chronic transfusions
- Pulmonary Hypertension associated with left heart disease
III. Management: Acute Presentation
IV. Management: Chronic
-
General measures
- Prevent and promptly treat respiratory infections
- Regular symptom-limited Exercise
- Avoid pregnancy (50% mortality)
- Immunizations
- Perioperative Evaluation
- Preoperative Echocardiogram
- Evaluate functional status
- Consider surgical alternatives
- Consult specialty care in the decision to approve, and the optimization before elective surgery
-
Anticoagulation
- Coumadin to keep INR between 1.7 to 2.2
-
Cardiac Output maximization
- Consider Digoxin to increase Cardiac Output or for tachyarrhythmias
- Consider Parenteral inotropic medications in refractory inpatients
- Decrease Preload
- Follow low-salt diet
- Diuretics to reduce volume retention
- Treat Hypoxia
- Oxygen Supplementation to keep Oxygen Saturation >90-92% (60 mmHg)
-
Pulmonary Arterial Hypertension medications
- Low risk patient
- See Vasodilators below
- PDE-5 Inhibitors (Sildenafil) or
- Endothelin receptor Antagonists (Bosentan, Ambrisentan)
- High risk patient (or low risk patient protocol fails)
- Epoprostenol (Flolan) IV or
- Selexipag (Uptravi) oral
- Treprostinil (Remodulin, Orenitram) Oral, IV or SQ
- Iloprost (Ventavis) Inhaled
- Low risk patient
- Other medical management
- Consider Calcium Channel Blocker
- Only indicated if positive vasoreactivity test (<5-20% of patients)
- Experimental options
- Nitric oxide
- Consider Calcium Channel Blocker
- Surgery (if refractory to medical management)
- Lung Transplantation
- Balloon Atrial Septoplasty
V. Management: Vasodilators (reduce vascular resistance) - Specific PAH Treatments
- Endothelin receptor Antagonists
- Precautions
- FDA pregnancy category X (and reduce OCP efficacy)
- Liver Function Testing monthly (due to hepatotoxicity risk)
- Drug Interaction with Warfarin (increased INR)
- Preparations
- Bosentan (Tracleer) 62.5 mg orally twice daily (up to maximum of 250 mg/day)
- Ambrisentan (Letairis) 5 mg daily (up to 10 mg/day)
- Sitaxsentan
- Precautions
- Phosphodiesterase-5 Inhibitors (PDE-5 Inhibitors)
- Precautions
- Avoid with nitrates (precipitous Hypotension risk)
- Avoid with CYP3A4 inhibitors (Clarithromycin, Itraconazole)
- Adverse effects
- Mechanism
- Cyclic guanosine monophosphate (cGMP) is a vasodilator
- cGMP is rapidly degraded by PDE5 (Phosphodiesterase 5) which present in right ventricle of PAH patients
- Preparations
- Sildenafil (Revatio) 20 mg orally three times daily ($45/month)
- Tedalafil (Adcirca) 40 mg daily (>$3000/month)
- Precautions
- Prostenoids (Prostacyclin)
- Efficacy: Highly effective
- Precautions
- Avoid stopping abruptly (risk of rebound Pulmonary Arterial Hypertension)
- Adverse effects
- Jaw pain
- Diarrhea
- Peripheral Edema
- Headache
- Mechanism
- Prostacyclins reduce Platelet aggregation and causes vasodilation
- Prostacylcins are reduced in PAH
- Preparations
- Epoprostenol (Flolan) 2 ng/kg/min IV (titrate 1-2 ng/kg/min every 15 min as needed)
- Iloprost (Ventavis) 2.5 to 5 mcg nebulized every 2-4 hours (up to 9 doses per day)
- Beraprost 20 mcg three times daily (titrate up to maximum 60 mcg, over several weeks)
- Treprostinil (Remodulin)
- IV/SQ: 1.25 ng/kg/min titrated once weekly
- Inhaled: 18 mcg (3 breaths from 1.74 mg/2.9 ml Inhaler) four times daily
- Increased by 18 mcg/dose (3 breaths) every 1-2 weeks
- Maximum of 54 mcg/dose (9 breaths/dose)
VI. Management: Calcium Channel Blockers
- Do not use in non-vasodilator responders
- Risk of Hypotension, Syncope and Right Ventricular Failure
- Effective longterm in only 5-20%
- Effectiveness wanes over time
- Requires vasodilation test as above (use only if responder)
- If non-responder, then do not use Calcium Channel Blocker (use other vasodilators listed above)
- Determine if patient responds to vasodilation (vasoreactivity study)
- Perform right heart catheterization (mandatory prior to using Calcium Channel Blocker)
- Administer vasodilator (e.g. Adenosine, epoprostenol)
- Responder criteria
- Pulmonary Artery Pressure decreases >10 mmHg and <40 mmHg
- Cardiac Output does not change or increases
- Use responder status to direct therapy
- Responder: Calcium Channel Blocker
- Non-responder: Use other vasodilators listed above
- Preparations (use very high dose)
- Diltiazem ER (max 960 mg/day)
- Nifedipine ER (max 240 mg/day)
- Amlodipine (max 30 mg/day)
VII. Complications
VIII. References
- Meter (2013) Crit Dec Emerg Med 27(5): 2-10
- Dunlap (2016) Am Fam Physician 94(6):463-9 [PubMed]
- Gaine (2000) JAMA 284:3160-8 [PubMed]
- Galie (2009) Eur Heart J 30(20): 2493-537 [PubMed]
- Nauser (2001) Am Fam Physician 63(9):1789-98 [PubMed]
- Rubin (1997) N Engl J Med 336:111-7 [PubMed]
- Rubin (1993) Chest 104:236-50 [PubMed]
- Ryerson (2010) Respir Res 11:12 [PubMed]
- McLaughlin (2009) Circulation 119(16): 2250-94 [PubMed]
- Stringham (2010) Am Fam Physician 82(4): 370-7 [PubMed]