This document discusses pulmonary hypertension (PH), including its definition, classification, pathophysiology, diagnosis, and management in intensive care patients. It defines PH as a mean pulmonary artery pressure >25 mmHg and outlines the various causes classified under five groups. The pathophysiology of PH involves vasoconstriction, vascular remodeling, thrombosis and endothelial dysfunction. Diagnosis involves history, physical exam, imaging like chest X-ray and ECG, as well as right heart catheterization. Management focuses on treating the underlying cause, using vasodilators, inotropes to support the right ventricle, diuretics, oxygen therapy and potentially surgery in refractory cases. PH increases mortality and deteriorations can be rapid

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

2. Definition & aetiology

3. Mean pulmonary artery pressure> 25mmHg (at rest)Systolic pulmonary artery pressure> 35mmHg

4. Pulmonary Hypertension ClassificationDana Point 2008 (WHO)

5. 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

6. Non-PAH PH in the ICUAcute/chronic PEAcute respiratory distress syndromeChronic lung diseaseAcute/chronic left heart failureMitral/aortic stenosisSevere sepsisPost cardiac or thoracic surgeryESRDThromboembolismLung diseaseHeart diseaseSpeed of onset determines tolerance to insultRV copes poorly with the acute insult

7. acute corpulmonale has very poor outcomepathophysiology

8. 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

9. Endogenous pulmonary vasoconstrictorsThromboxane A2 (TXA2)Production increased by endothelial injury Secreted by plateletsPromotes platelet aggregation and vasoconstrictionEndothelin‐1Secreted by endothelium when injured Promotes cellular proliferation and vasoconstrictionSerotoninSynthesized in endotheliumPromotes smooth muscle and fibroblast proliferation, vasoconstriction and local microthrombosis

10. Endogenous pulmonary vasodilatorsProstacyclinProstaglandinmetabolite of arachadonicacidMost powerfulendogenous inhibitor of plateletaggregationDisperses pre‐existing platelet aggregatesNitric OxideProduced in endotheliumBinds to soluble guanylatecyclaseincreasing cGMPLowers intracellular calcium, and decreases myosin cross linkingMost powerful endogenous vasodilatorDecreased synthesis allows smooth muscle proliferation responsible for remodeling

11. Haemodynamic impact of PHPFOPrice LC et al. Critical Care 2010, 14:R169 doi:10.1186/cc9264

12. Diagnostic work-up

13. Diagnostic evaluation of chronic PH

14. Diagnostic evaluation of PH in ICUTTE

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

16. Physical Exam(Carvallo’s sign)

17. Physical Exam

18. Chest X-ray FeaturesEnlargement of the main, right and left pulmonary arteries

19. Main PA diameter > 29 mm, right PA > 16 mm and left PA > 15 mm

20. Tapering of the pulmonary vasculature (‘peripheral pruning’)

21. Heart size - normal or enlarged e.g. right atrial contour

22. Underlying causes, e.g. COPD, cardiac disease

23. Loss of aortico-pulmonary windowECG 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 >7mmqRin 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

24. ECG with RVH/strain

26. Right ventricular hypertrophy

27. Tricuspid regurgitation

28. Right atrial enlargement

29. Right ventricular enlargementNormal RV:LV ratio < 0.6, severe dilation at 1:1

30. Right ventricular dysfunctionHypokinesisAkinesisSeptal dyskinesiaMcConnell’s sign: severe hypokinesis of RV mid-free wall, with normal apical contraction seen in acute PE

31. 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!

32. Clinical Impact

33. Why do we care?More patientshaveit in ICU thanyouthink!Almostanytypical ICU insult can tipthemoverThey 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 oedemaat lower PCWP

34. Independent risk factor for death

35. Prognostication in Group 1 (PAH)McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation. 2006;114:1417–31.

36. Outlook in chronic PHCHD = congenital heart disease, CTD = connective tissue diseases, IPAH = idiopathic PAH

37. therapy

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

39. Testing for vasodilator responsePulmonary artery catheterAdminister vasodilator (iNO, PG, iv adenosine, Caantag)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)

40. Established Medical Therapy for PHTreat hypoxia and left heart failureDiuretics if right heart failureCalcium channel blockersDiltiazem if HR > 100 bpmNifedipineif 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)

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

42. 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

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

45. 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).VasopressorsNoradrenalinemay 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

46. RecommendationsInotropesLow-dose dobutamine (up to 10 μg/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)Dopaminemay 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-admininstrationof pressors (Moderate-quality evidence, a STRONG recommendation) Inhaled milrinonemay be useful to minimize systemic hypotension and V/Q mismatch in pulmonary vascular dysfunction (Based on low-quality evidence, a WEAK recommendation)Levosimendanmay 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

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

48. Surgical Therapy (Refractory PH)Pulmonary EndarterectomyLung transplant (single or bilateral)Heart‐lung transplantAtrialseptostomy–make R to L shuntRightventricularassistdevice (RVAD)

49. 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%

50. 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

51. No conflicts of interest to declarethank you for your attention!

52. Appendices

53. PathogenesisRubenfire M, Bayram M, Hector-Word Z. Crit Care Clin2007; 23: 801–834

54. Diagnostic Algorithm for Acute Pulmonary HypertensionRubenfire M, Bayram M, Hector-Word Z. Crit Care Clin2007; 23: 801–834

55. 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 RespirCrit 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 CollCardiol 2009; 53: 1573-619.Pritts CD, Pearl RG. Anesthesia for patients with pulmonaryhypertension. CurrOpinAnesthesiol 2010; 23: 411-416.Guglin M, Khan H. Pulmonaryhypertension in heartfailure. J CardiacFail 2010; 16: 461-474.Price LC, Wort SJ, Finney SJ, Marino PS, Brett SJ. Pulmonaryvascular and right ventriculardysfunction in adultcriticalcare: current and emerging options for management: a systematicliteraturereview. Crit Care 2010; 14: R169.