A Best Practices Approach to Treating Pulmonary Hypertension for the ED and Acute Care Provider. Disclosures

Transcription

1 A Best Practices Approach to Treating Pulmonary Hypertension for the ED and Acute Care Provider Sean M. Studer, MD, MSc Chief, Pulmonary & Critical Care Director, Pulmonary Hypertension & Lung Transplantation Newark Beth Israel Medical Center Disclosures Promotional speaker: Actelion, Gilead, United Therapeutics/Lung Rx Research funding: Actelion, Gilead, United Therapeutics/Lung Rx No off label discussion of medications

2 Lecture Goals: PAH Summarize diagnosis/classification of PAH Describe lower v. higher risk patients Review current medication therapies Analyze approaches to managing emergencies in PAH Pulmonary Arterial Hypertension: Definition Mean PA pressure > 25 mmhg with PCW <15 mmhg (NIH Registry on PPH, 1987) PVR = 3 Units PVR = TPG/CO TPG = PAM-PCW??Exercise mean PA pressure > 30 mmhg

3 World Conference on Pulmonary Hypertension Revised Nomenclature and Classification Dana Point 2008 P A H Pulmonary hypertension I PAH ipah Heritable PAH Collagen vascular disease Congenital L to R shunts Portal pulmonary HTN HIV Drugs (e.g. anorexigens) PPHN II Pulmonary venous HTN Left heart disease III PH assoc with hypoxia COPD Interstitial lung disease (IPF) Sleep disordered breathing High altitude IV Thromboembolic V Multifactorial (e.g. sarcoid) At Risk Populations for PAH: WHO Gr. I

4 Impact of PAH Annual incidence: 15/million pop.; 6/mil ipah Orphan disease by US Food & Drug Admin. Demographics of affected patients: More common in women Mean age at diagnosis 36 years; All ages affected (Ann Int Med 1987;107:216-23, Chest 2007;131:5-6) Idiopathic PAH: Survival Without Treatment Survival (%) % Est. Median survival: 2.8 yrs (95% CI, 1.9 to 3.7 years) 48% 34% Years of follow up adapted from D Alonzo GE, et al. Ann Int Med 1991;115:343-49

5 Assessment of PAH: History I: Signs and Symptoms Initial signs and symptoms Dyspnea Fatigue Syncope Edema Dizziness Angina Non-specific nature of complaint can lead to: Confusion with other conditions Delayed diagnosis (~18-36 months) (Galie N, et al. Lancet 2008; 371: )

6 Assessment of PAH: Physical Examination RV lift /heave Increased P2 TR, PI murmurs Signs of congestion Right-sided extra heart sounds PHTN: Where s the Lesion? PAH-a pre-capillary arteriopathy COPD IPF MS Myxoma Cor triatriatum HTN VC RA RV PA PC PV LA LV Ao PE PPS Anomalous PV PVOD DCM HCM

7 Findings on Electrocardiogram RVH, RAE, RAD, RV strain, [RBBB]-typical Arrhythmias not typical- may need ED attn Chest X-Ray in PAH Peripheral Hypovascularity Right Decending Pulmonary Artery RV, right ventricular. McLaughlin VV et al. J Am Coll Cardiol. 2009;53: Prominent Central Pulmonary Artery RV Enlargement

8 Assessment of PAH: Echocardiography RV size and function Right atrial size Tricuspid regurgitation? Estimated RV systolic pressure Dilation, flow reversal of IVC? Pericardial effusion? Lack of left sided chamber and valve abnormalities Echocardiogram-Severe ipah

9 Pericardial Effusion in PAH Small- moderate effusions are sign of higher risk due to elevated underlying pressures. No emergent intervention generally Tamponade is not uncommon and ECG/echo may be helpful in confirming--drainage of effusion may be warranted. PAH: Diagnostic Evaluation H&P, ECG, CXR? PH Echo No evidence of PH PH; left heart dz, congenital R to L shunt Serologies CVD, HIV V/Q, chest CT, PFT, sleep study Thromboembolism, intrinsic lung dz IPAH FPAH RHC 6MWT

10 Pulmonary Arterial Hypertension: Goals of Medication Therapy Improve functional class/qol Improve exercise capacity Prevent clinical worsening Improve survival Improve hemodynamics (?)

11 Therapeutic Targets for PAH Endothelin pathway Endothelin cells Nitric oxide pathway Vessel lumen Prostacyclin pathway Arachidonic acid Prostaglandin I 2 Pre-proendothelin Proendothelin Endothelin receptor A Endothelin receptor antagonists Endothelin 1 Endothelin receptor B Vasodilation and antiproliferation L-arginine L-citrulline Phosphodiesterase type 5 Nitric oxide cgmp + Exogenous nitric oxide Vasodilation and antiproliferation Prostacyclin (prostaglandin I 2 ) camp + Vasodilation and antiproliferation Prostacyclin derivatives Smooth muscle cells Phosphodiesterase type 5 inhibitor Humbert M, Sitbon O, Simonneau G. N Engl J Med 2004;351: PAH Determinants of Risk Lower Risk Determinants of Risk Higher Risk No Clinical evidence of RV failure Yes Gradual Progression Rapid II, III WHO class IV Longer (>400 m) 6MW distance Shorter (<300 m) Minimally elevated BNP Very elevated Minimal RV dysfunction Normal/near normal RAP and CI Echocardiographic findings Hemodynamics Pericardial effusion, significant RV dysfunction High RAP, low CI McLaughlin and McGoon. Circulation 2006;114:

12 Emergency issues on therapy: General considerations Involve specialty pharmacy early- if infusion drug pump will usually be labeled with toll-free phone # Contact PAH program for more information re: patient Emergency issues not well studiedpatients use support group rec s; we ll review by type of therapy

13 Clozel. Ann Med. 2003: 35; 1-5. Endothelin is a Key Pathogenic Mediator * Proliferation vascular smooth muscle fibroblasts ET Fibrosis fibroblast proliferation extracellular matrix proteins collagenase production Vasoconstriction direct or via facilitation of other vasoconstrictor systems (renin angiotensin system, sympathetic) Hypertrophy cardiac/vascular Inflammation vascular permeability neutrophil / mast cell activation promotes cellular adhesion cytokine production * Based on animal, in-vitro, and human hemodyamic models Endothelin Receptor Antagonists Bosentan (Tracleer) Improves walk distance and functional class FDA approved for class II-IV PAH LFTs, pregnancy concerns Ambrisentan (Letairis) Once daily dosing, Class II-IV PAH Improves six minute walk distance LFTs, pregnancy concerns

14 Emergency Issues-ERAs Liver enzyme abnormalities (AST/ALT)-few cases of unexplained hepatic failure Lower extremity edema- usually not an emergency but can be misinterpreted as sign of another condition Worsening of disease can present as low cardiac output; may need more therapy PDE 5 inhibitors Sildenafil (Viagra, Revatio) FDA approved for class II-IV PAH Oral, well-tolerated Usual PDE 5 inhibitor concerns Tadalafil (Cialis, Adcirca) Oral, once daily dosing FDA approved for class II-IV PAH

15 Emergency issues: PDE-5i Priapism Visual changes- often reversible with drug cessation Hypotension with nitrate therapy Worsening of PAH may present with reduced cardiac output Epoprostenol (Flolan & generic) and RTS- Epoprostenol Continuous IV Rx, half life of minutes Expensive, Requires ice packs unless RTS-epo utilized Significant adverse effects- GI, Musc-skel. AutoCadd Legacy Pump

16 Room temp. stable epoprostenol (Veletri) Does not require ice packs at room temp (77 degrees F) Reconstituted with saline or sterile H 2 O For NYHA Class III-IV patients Same half life of minutes Treprostinil (Remodulin ) Stable at room temperature; longer half-life Continuous IV or SQ Smaller pump (SQ) Limiting factor traditionally was site pain Typical prostacyclin side effects

17 Emergency issues: Infusion Prostacyclin Therapy Deliver system complications: Catheter-related blood stream infection Catheter-related thrombosis, bleeding, etc Abrupt cessation may result in rebound PAHalways try to continue infusion- peripheral IV is OK GI adverse effects may lead to volume depletion; High output cardiac state not uncommon Iloprost Inhalation Solution: Dosage and Administration 6-9 inhalations daily during waking hours No more than once every two hours-most patients ~5 x daily Dose: 2.5 or 5 mcg delivered Dosed via prodose AAD system Adverse effects (with rate >5% placebo subtracted) include flushing, cough, headache, trismus, insomnia, hypotension, vomiting, increased alkaline phosphatase

18 Optineb-ir Device Overview for inhaled treprostinil Tyvaso inhalation system Inhaled tre. dosing 4x daily (~2-3 minutes per treatment) Repetitive-breath system Patient must manually time each inhalation Inhaled Rx: Emergency Issues Abrupt withdrawl is not a consideration In absence of delivery device usually not advisable to use alternative nebulizer device Ask family/friends to get patient s device or consider alternative treatment option

19 Summary: Emergencies in PAH on Medication Therapy #1. Obtain current treatment to identify risks; e.g. no nitrates with PDE-5 Rx #2. Infusions are almost never abruptly discontinued and require special handling- contact specialty pharmacy and patient s PAH prescriber #3. Acute risks include pericardial effusion and low cardiac output- echocardiography often essential Conclusions: Best practices for PAH Proper diagnosis and classification of PAH is critical to best practice Titrate approach for high vs. low risk pts Understanding current therapies will improve emergency response Focused testing, involving specialty pharmacy /PAH program quickly will add information and promote best decisions

20 Thanks for your attention! Newark Beth Israel Medical Center Pulmonary Hypertension & Lung Transplant 888-NJ-LUNG-1