Review Note

Last Update: 02/17/2025 02:33 AM

Current Deck: ACG Part 2::Thoracic SSU

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SS_TS 1.4 Discuss the pathophysiology of pulmonary hypertension and methods available to the anaesthetist to manipulate pulmonary vascular resistance and pulmonary artery pressures
PH defined as PAP at rest >25mmHg
  • Mild 25-40
  • Mod 41-55
  • Severe >55 

Pathophysiology

  • (i) Group 1 - pulmonary arterial hypertension (PAH)
  • (ii) Group 2 - PH caused by left-sided heart disease (PH-LHD)
  • (iii) Group 3 - PH caused by lung diseases, hypoxia, or both (PH-LD)
  • (iv) Group 4 - PH caused by pulmonary artery obstructions (chronic thromboembolic pulmonary hypertension [CTEPH])
  • (v) Group 5 - PH with unclear or multifactorial mechanisms
Can be classified by pre-capillary, post-capillary and combined.

Diagnosis
  • Gold standard for diagnosis and classification = right heart catheter
  • TTE can be used to estimate likelihood of PH
    • TR velocity
    • TAPSE/sPAP ratio

Methods to manipulate PVR and PAPs


Drugs reducing PVR 
  • Calcium channel blockers e.g. nifedipine, diltiazem 
    • MOA: competitive antagonism of VGCC (L type) à reduces calcium influx à reduces intracellular calcium
    • Heart effects reduces SAN automaticity, AVN conductivity and inotropy 
    • Vessel effects arterial vasodilation
    • Side effects 
      • CVS may precipitate cardiac failure (from reduced CO), hypotension, reflex tachycardia
      • Resp worsening of hypoxic pulmonary vasoconstriction 
  • Prostacyclin (PGI2) 
    • IV epoprostenol via CVL 
      • MOA: increases adenylate cyclase -> increases cAMP-> reduces calcium -> vasodilator and  inhibits platelet aggregation 
      • Side effects hypotension, tachycardia, facial flushing, headache
    • Inhaled iloprost selective for lung vasculature;   requires 6-9x/day administrations 
  • Endothelin-1 receptor antagonist e.g. bosentan 
    • Endothelin-1 is a potent vasoconstrictor, which affects ETA receptors and GqPCR to cause vasoconstriction 
      • Side effects hepatotoxicity (requires monthly LFTs), teratogen, oedema 
  • Phosphodiesterase-5 inhibitors e.g.sildenafil 
    • MOA inhibits cGMP breakdown-> reduces calcium-> reduces arteriolar smooth muscle tone -> vasodilation
    • Side effects hypotension, flushing, headache, visual disturbance, erect penis
  • Nitric oxide Inorganic gas produced by L-arginine 
    • MOA activates adenylate cyclase -> increased cGMP-> reduces calium, arteriolar smooth muscle -> vasodilation 
    • Side effects worsening of HPV with increasing shunt, increases CBF, inhibits platelet aggregation, metHb 
  • Inhalational anaesthetic agents 
  • GTN 
    • MOA prodrug metabolized to NO ->activates guanylate cyclase -> increased cGMP -> reduced intracellular calcium 
    • Effects venous and arterial vasodilation
  • Sodium nitroprusside 
    • MOA produces NO -> venous and arterial vasodilation  

Drugs increasing PVR 
  • N2O 
  • Adrenaline, noradrenaline, dopamine 
  • Other factors increasing PVR 
    • Hypoxia 
    • Hypercapnoea 
    • Acidosis 
    • Extremes of lung volume 
    • PGE2, PGF2a, thromboxane A2, histamine

(Gold Coast Notes)