Pulmonary Hypertension

Pulmonary Hypertensionand the IntensivistDr. Andrew FergusonConsultant in Anaesthetics and Intensive Care MedicineCraigavon Area Hospital

Definition & aetiology

Systolic pulmonary artery pressure> 35mmHgMean pulmonary artery pressure> 25mmHg (at rest)

Pulmonary Hypertension ClassificationDana Point 2008 (WHO)

Group 1 Pulmonary Arterial HypertensionIdiopathicFamilialAssociated conditionsConnective tissue diseases e.g. sclerodermaCongenital systemic-pulmonary shuntsPortal hypertensionHIVDrugs and toxinsOther e.g. thyroid disease, myeloproliferative or glycogen storage diseasesSignificant venous or capillary involvementPulmonary veno-occlusive disease (PVOD)Pulmonary capillary hemangiomatosis (PCH)Persistent pulmonary hypertension of the newborn

Non-PAH PH in the ICUAcute/chronic PEAcute respiratory distress syndromeChronic lung diseaseAcute/chronic left heart failureMitral/aortic stenosisSevere sepsisPost cardiac or thoracic surgeryESRD ThromboembolismLung diseaseHeart disease

Speed of onset determines tolerance to insultRV copes poorly with the acute insult acute cor pulmonale has very poor outcome

pathophysiology

PathophysiologyPAHMainly pre-capillary arteries and arteriolesIncreased vasoconstriction (ET-1 etc.)Vascular remodeling (smooth muscle proliferation/neointima) In situ thrombosisEndothelial dysfunctionLung disease with hypoxia e.g. ILD, COPDHypoxic vasoconstrictionVascular destructionALI/ARDSHypoxic vasoconstrictionIncreased vasoconstriction (ET-1 etc.)Intravascular fibrin and cell debris

Endogenous pulmonary vasoconstrictorsThromboxane A2 (TXA2)Production increased by endothelial injury Secreted by plateletsPromotes platelet aggregation and vasoconstrictionEndothelin1 Secreted by endothelium when injured Promotes cellular proliferation and vasoconstrictionSerotoninSynthesized in endotheliumPromotes smooth muscle and fibroblast proliferation, vasoconstriction and local microthrombosis

Endogenous pulmonary vasodilatorsProstacyclinProstaglandin metabolite of arachadonic acidMost powerful endogenous inhibitor of platelet aggregationDisperses preexisting platelet aggregatesNitric OxideProduced in endotheliumBinds to soluble guanylate cyclase increasing cGMPLowers intracellular calcium, and decreases myosin cross linkingMost powerful endogenous vasodilatorDecreased synthesis allows smooth muscle proliferation responsible for remodeling

Haemodynamic impact of PHPFO

Price LC et al. Critical Care 2010, 14:R169 doi:10.1186/cc9264

Diagnostic work-up

Diagnostic evaluation of chronic PH

Diagnostic evaluation of PH in ICU

TTE

Clinical HistoryDyspnoea esp. SOBOEFatigueChest painLoss of appetiteAngina PalpitationsSyncope or near syncopeOedemaHoarseness

Physical Exam

(Carvallos sign)

Physical Exam

Chest X-ray Features

Enlargement of the main, right and left pulmonary arteriesMain PA diameter > 29 mm, right PA > 16 mm and left PA > 15 mmTapering of the pulmonary vasculature (peripheral pruning)Heart size - normal or enlarged e.g. right atrial contourUnderlying causes, e.g. COPD, cardiac diseaseLoss of aortico-pulmonary window

ECG Features (insensitive)Right atrial enlargementP wave >2.5 mm tall in II and/or >1.5 mm in V1 (P pulmonale)Right ventricular hypertrophy or strainR/S ratio > 1 in lead V1R/S > 1 in V3R or V4RR wave lead V1> 7mmqR in V1rSR' in V1 with R' >10mmIncomplete RBBBST depression or T inversion in V1-3 +/- II, III, aVF (if STRAIN)Right axis deviation of QRSRight axis deviation of > +90 degrees

ECG with RVH/strain

Echo Features of Pulmonary HypertensionRight ventricular hypertrophySignificant tricuspid regurgitation - Using TR jet estimated RVSP is 4V2 + RAPRight atrial enlargementRight ventricular enlargement/dilatation - D-shaped LV on short axisRight ventricular dysfunctionPulmonary regurgitation - Using PR jet estimated PAEDP is 4V2 + RAPReduced RV outflow tract velocity, short acceleration timeDilated IVC not collapsing with respiration (if patient not ventilated)Patent foramen ovale (bubble contrast used)Pericardial effusionDilated pulmonary arteries

Right ventricular hypertrophy

Tricuspid regurgitation

Right atrial enlargement

Right ventricular enlargement

Normal RV:LV ratio < 0.6, severe dilation at 1:1

Right ventricular dysfunctionHypokinesisAkinesisSeptal dyskinesiaMcConnells sign: severe hypokinesis of RV mid-free wall, with normal apical contraction seen in acute PE

Right heart catheterisationYES!Challenging!Severe TRElevated PAPCO measurement may be inaccurate (TR & low CO)Tachyarrhythmias (even AF) can be disastrous!One time when it may actually help!

Clinical Impact

Why do we care?More patients have it in ICU than you think!Almost any typical ICU insult can tip them overThey can deteriorate VERY rapidlyToo much or too little fluid = BIG changes in cardiac index and gas exchangeAltered LV shape causes diastolic dysfunction and reduces LV stroke volumeDevelop interstitial oedema at lower PCWP

Independent risk factor for death

Prognostication in Group 1 (PAH)DeterminantLow risk (good prognosis)High risk (bad prognosis)Clinical RV failureNOYESWHO functional classII/IIIIV6 min walk distance> 400m< 300mCPET resultsVO2 max > 10.4 ml/kg/minVO2 max < 10.4 ml/kg/minEchoMinimal RV dysfunctionPericardial effusionRV enlarged or dysfunctionRA enlargedHaemodynamicsRAP < 10 mmHgCI > 2.5 L/min/m2RAP > 20 mmHgCI < 2.0 L/min/m2BNPMinimal elevationSignificant elevation

McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006;114:141731.

Outlook in chronic PH

CHD = congenital heart disease, CTD = connective tissue diseases, IPAH = idiopathic PAH

therapy

Therapeutic goalsReduce pulmonary artery pressureReduce pulmonary vascular resistanceImprove RV functionImprove CIBEFORE RV failure becomes irreversibleMaintain adequate preloadMaintain SVRAvoid acidosis, hy[ercapnia, hypothermia, hypoxia

Testing for vasodilator responsePulmonary artery catheterAdminister vasodilator (iNO, PG, iv adenosine, Ca antag)Look for positive response> 10 mmHg drop in MPAPsPAP < 40 mmHgSide effectsPulmonary oedemaWorsening ABGHypotensionDo not test if CI < 2.0, pulmonary oedema, PCWP > 15 (i.e. frank LVF)

Established Medical Therapy for PHTreat hypoxia and left heart failureDiuretics if right heart failureCalcium channel blockersDiltiazem if HR > 100 bpmNifedipine if HR < 100 bpmProstacyclin analogs (mortality benefit in chronic)iv epoprostanol, inhaled iloprost, s/c TrepostinilPhosphodiesterase (PDE-5) inhibitorsSildenafil, TadalafilEndothelin receptor antagonists e.g. BosentanNitric oxide (inhaled, continuous)

Price LC et al. Critical Care 2010, 14:R169 doi:10.1186/cc9264

Inotropes & pressors in RV dysfunctionDobutamine (best studied)Up to 5 mg/kg/min PVR falls, CI climbs5-10 mg/kg/min tachycardia with no change in PVRCan combine with NO inhalationNoradrenalineIncreases mPAP and PVRSustains CIMay be needed to offset hypotension with dobutamineDopamineNo convincing benefit on PVRTachycardia dangerousPhenylephrineIncreases mPAP and PVRDrops CO and HR therefore AVOID IT!AdrenalineNot widely studied although fairly widely usedVasopressinNot studied in low doses (as used in sepsis)Doses > 1 unit/kg/hour increase mPAP and PVRMilrinoneDecreases mPAP and PVR (but less than PDE-5 inhibitors)Increases CO BUT often causes hypotensionLevosimendanDecreases mPAP and PVRImproves RV/PA coupling

Price LC et al. Critical Care 2010, 14:R169 doi:10.1186/cc9264

RecommendationsVolume managementClose monitoring of fluid status according to effects on RV function is recommended. Initial carefully monitored limited volume loading may be useful after acute PE, but may also worsen RV performance in some patients with pulmonary vascular dysfunction, and vasoactive agents may be required (very-low-quality evidence, WEAK recommendation).VasopressorsNoradrenaline may be an effective systemic pressor in patients with acute RV dysfunction and RV failure, as it improves RV function both by improving SVR and by increasing CO, despite potential increases in PVR at higher doses (mostly low-quality evidence,WEAK recommendation).In patients with vasodilatory shock and pulmonary vascular dysfunction, low-dose AVP (vasopressin) may be useful in difficult cases that are resistant to usual treatments, including norepinephrine (low-quality evidence, WEAK recommendation).

Price LC et al. Critical Care 2010, 14:R169 doi:10.1186/cc9264

RecommendationsInotropesLow-dose dobutamine (up to 10 g/kg/min) improves RV function and may be useful in patients with pulmonary vascular dysfunction, although it may reduce SVR (Low-moderate-quality evidence, a WEAK recommendation)Dopamine may increase tachyarrhythmias and is not recommended in the setting of cardiogenic shock (STRONG recommendation based on high-quality evidence level)PDE III inhibitors improve RV performance and reduce PVR in patients with acute pulmonary vascular dysfunction, although systemic hypotension is common, usually requiring co-admininstration of pressors (Moderate-quality evidence, a STRONG recommendation) Inhaled milrinone may be useful to minimize systemic hypotension and V/Q mismatch in pulmonary vascular dysfunction (Based on low-quality evidence, a WEAK recommendation)Levosimendan may be considered for short-term improvements in RV performance in patients with biventricular heart failure (low-quality evidence, a WEAK recommendation)

Price LC et al. Critical Care 2010, 14:R169 doi:10.1186/cc9264

Examplar evaluation and treatment algorithm

Zamanian, Roham T., et al. "Management strategies for patients with pulmonary hypertension in the intensive care unit." Critical care medicine 35.9 (2007):2037-2050.

Surgical Therapy (Refractory PH)Pulmonary EndarterectomyLung transplant (single or bilateral)Heartlung transplantAtrial septostomy make R to L shuntRight ventricular assist device (RVAD)

Mechanical ventilation in PHRV afterload and pulmonary vascular resistance increased byHigh lung volumes/over-distensionDecreased functional residual capacity/underinflation/atelactasisInadequate recruitment/PEEP can be just as bad as overinflation, risking fatal decreases in cardiac outputPEEP 3-8 cmH2O better than < 3 or > 8 in one small studySuggests best approach is low tidal volume with minimum PEEP consistent with acceptable balance of FiO2 and PaO2Permissive hypercapnia is problematic as it increases PVR and may decrease cardiac output e.g. post-cardiac surgery hypercapnia increased PVR by 54% and mPAP by 30%

SummaryCritical clinical problem to understandIndex of suspicion and early diagnosis neededTreat underlying causes where possibleConsider right heart catheterisationVasodilator options (evidence lacking in ICU)Aggressive treatment of RV dysfunctionMortality remains high

thank you for your attention!No conflicts of interest to declare

Appendices

Pathogenesis

Rubenfire M, Bayram M, Hector-Word Z. Crit Care Clin 2007; 23: 801834

Diagnostic Algorithm for Acute Pulmonary HypertensionRubenfire M, Bayram M, Hector-Word Z. Crit Care Clin 2007; 23: 801834

Selected referencesRubenfire M, Bayram M, Hector-Wood Z. Pulmonary hypertension in the critical care setting: classification, pathophysiology, diagnosis, and management. Crit Care Clin 2007; 23: 801-834.Stamm J, Mathier M, Donahoe M, Saul M, Gladwin MT. Pulmonary hypertension in the medical intensive care unit population: retrospective investigation of risk factors and impact on survival. Am J Respir Crit Care Med 2010; 181: A6832.ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2009; 30: 2493-2537.ACCF/AHA 2009 Expert consensus document on pulmonary hypertension. J Am Coll Cardiol 2009; 53: 1573-619.Pritts CD, Pearl RG. Anesthesia for patients with pulmonary hypertension. Curr Opin Anesthesiol 2010; 23: 411-416.Guglin M, Khan H. Pulmonary hypertension in heart failure. J Cardiac Fail 2010; 16: 461-474.Price LC, Wort SJ, Finney SJ, Marino PS, Brett SJ. Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit Care 2010; 14: R169.