FRCA Notes

Pulmonary Hypertension

This topic features in a concisely described curriculum item: 'demonstrates knowledge of hypertension - systemic and pulmonary'.

It was an SAQ in September 2017, where marks were available for definition, aetiology, goals of anaesthesia, and pharmacological treatments.

Resources

  • Pulmonary hypertension is defined as:

    • Elevated mean pulmonary arterial pressure ≥25mmHg at rest (as measured by PA catheter)

  • It is more likely in females, Caucasians and those in the fifth decade of life
  • The high pressure within the pulmonary vessels leads to strain on the (usually low-pressure) right ventricle and, eventually, right ventricular failure

Group Description
1 Pulmonary arterial hypertension
2 Pulmonary HTN due to left heart disease
3 Pulmonary HTN due to lung disease or chronic hypoxia
4 Pulmonary HTN due to chronic thromboembolism (CTEPH)
5 Pulmonary HTN due to multisystem disorders

Classification by aetiology

  • Group 1
    • Idiopathic PAH
    • Hereditary or familial (e.g. BMPR2 mutations)
    • Connective tissue diseases e.g. SLE, systemic sclerosis, Sjogren's syndrome, RA, polymyositis
    • Congenital systemic-to-pulmonary shunts inc. Eisenmenger syndrome
    • HIV-associated
    • Drug- and toxin-induced e.g. aminorex (weight loss stimulant), fenfluramine, chemotherapy agents, cocaine, SSRIs

  • Group 2

  • Group 3
    • Idiopathic pulmonary fibrosis
    • COPD

  • Group 4
    • Thromboemboli
    • Includes other obstructing processes of the pulmonary vasculature e.g. tumours

  • Group 5
    • Sarcoidosis
    • Haematological diseases e.g. polycythaemia vera, essential thrombocytopaenia, CML, sickle cell disease, thalassaemia, MAHA
    • Schistosomiasis
    • Glycogen storage diseases

  • The key pathophysiological process in pulmonary hypertension is the development of increased PVR
  • In pulmonary hypertension associated with other disease processes, the precise changes in the vasculature depend on the underlying cause
    • E.g. in thromboembolic disease, there is a reduced cross-sectional area of the pulmonary vascular bed due to occlusion

Idiopathic PAH

  • There are a number of pathogenic pathways:

    1. Reduced expression and activity of endothelial nitric oxide synthetase
      • There is reduced NO production, and subsequently reduced cGMP levels and reduced smooth muscle relaxation
      • This is also causes an increase in cell proliferation

    2. Increased production / decreased clearance of endothelin-1
      • This is a potent vasoconstrictor
      • It also stimulates cell proliferation

    3. Reduced production of prostacyclin synthase and therefore prostacyclin
      • Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation and smooth muscle proliferation

  • This results in:
    • Tunica media smooth muscle hypertrophy
    • Tunica intima thickening/fibrosis
  • As such, there is increased pulmonary vascular resistance and raised RV afterload

RV sequelae

  • Chronically raised RV afterload can impair right coronary artery perfusion due to the impact of myocardial adaptive changes on the coronary vessels
  • The hypertrophic RV (increased wall thickness and reduced internal radius) makes it susceptible to acute elevations in PA pressure
  • Such elevations may precipitate:
    • Macroscopic RV overdistension i.e. bulging of the interventricular septum, with RV failure and associated LV failure
    • Microscopic RV overdistension i.e. sarcomere overstretching, moving down the Starling curve and into RV failure

Symptoms

  • Clinical features may present late and/or be non-specific

  • The cardinal symptom is dyspnoea, although this may already be present as part of the underlying disease process
  • Fatigue
  • Hoarse voice from dilation of the pulmonary arterial trunk and compression of the left recurrent laryngeal nerve
  • Symptoms relating to the underlying aetiology

  • Late symptoms arise from RV failure and low cardiac output state, and include:
    • (Worsening) dyspnoea
    • Chest pain
    • (Pre-) Syncope
    • Fluid overload/weight gain

Signs (i.e. those of RV failure)

  • Raised JVP
  • Peripheral oedema
  • Hepatomegaly
  • Ascites

  • RV heave
  • Pansystolic murmur due to TR
  • Loud P2
  • Irregular HR (or atrial flutter)

  • Bloods:
    • FBC
    • U&E; cardiorenal syndrome may be present
    • BNP (raised)

ECG

  • May be normal, and lacks sensitivity/specificity in the diagnosis of pulmonary hypertension
ECG features of RV hypertrophy from PAH
Right axis deviation
RBBB
RV strain pattern; TWI/ST↓ in right anterior, or inferior, leads
Short QRS
P pulmonale from RA dilation
Dominant R wave V1
Dominant S wave V6

Pulmonary investigations

  • CXR: may reveal an underlying cause, although cardiomegaly and prominent pulmonary arteries may be specific signs of PAH

  • Lung function tests
    • May reveal underlying respiratory disease
    • May demonstrate relatively normal lungs and disproportionate dyspnoea, which is a feature of PAH

Echocardiography

  • Commonest and least invasive method of demonstrating pulmonary hypertension
    • Can estimate systolic PA pressure from the velocity of the tricuspid regurgitant jet
  • Can estimate RA pressure using the modified Bernoulli equation
  • Helps elucidate RV function
  • May identify underlying cause e.g. valvular disease, congenital heart disease, LV dysfunction

PA catheter

  • Is the definitive gold standard method of diagnosing pulmonary hypertension
  • Allows direct measurement of PA pressure, RA pressure, pulmonary artery wedge pressure (PCWP), PVR, cardiac output/index, RA and RV pressures
  • Can be used to assess response to vasodilator therapy by administering a short-acting vasodilator e.g. adenosine

  • Prominent v wave on CVC waveform

Exercise capacity testing

  • Provides prognostic information via measuring functional capacity

  • CPET may be difficult in patients due to functional limitations
  • Reduced VO2 peak and VE/VCO2 are associated with increased perioperative morbidity and mortality

  • Six minute walk test is an alternative

General measures

  • Oxygen therapy - aim SpO2 >90% to reduce HPV
  • Diuretics to prevent RV overload; loop diuretics, thiazides, and mineralocorticoid receptor antagonists are all viable as monotherapy or in combination
  • Treat underlying disease process
  • Anticoagulation if the underlying aetiology is thromboembolic, or in severe disease as they are at high risk of thromboembolism
  • Treat iron-deficiency anaemia
  • Exercise therapy can improve quality of life
  • Vaccinations: pneumococcal, 'flu and Covid

Specific drug therapies

Class Examples Notes
Calcium channel blockers Amlodipine
Felodipine		 In those who demonstrate vasodilator response during PA catheterisation (∽10%)
Prostacyclin (PGI2) analogues Epoprostenol (IV infusion)
Treprostinil (IV infusion)
Iloprost (IV or nebulised)
Beraprost
Selexipag		 Reduce PVR
Selexipag is a selective PGI receptor agonist
Endothelin receptor analogues Bosentan (PO)
Ambrisentan (PO)
Macitentan		 Bind endothelin-1 and prevent pulmonary vascular vasoconstriction
PDE-V inhibitors Sildenafil (PO or IV)
Tadafil (PO)		 Increase cGMP levels, causing vasodilation via the NO pathway
Guanylate cyclase activators Riociguat Stimulates cGMP similarly to nitric oxide
Nitric oxide 20-40ppm Direct pulmonary vascular vasodilation by stimulating cGMP production

Invasive therapies

  • Pulmonary endarterectomy in Group 5 pulmonary hypertension
  • ECMO (as a bridge to transplant)
  • Lung transplant

Perioperative management of the patient with pulmonary hypertension


  • Patients with pulmonary HTN undergoing elective, non-cardiac surgery have a high peri-operative morbidity and mortality (up to 7%)
  • Patients should be discussed at an MDT, which should explore non-operative and local/regional options for performing surgery
  • Surgery should be performed in specialist centres used to dealing with pulmonary hypertensive patients in the peri-operative period

Assessment

  • History and examination elucidating diseases features as above
  • Investigations as above
  • Risk assessment using functional capacity testing

Optimisation

  • Aggressive treatment of underlying conditions and optimisation of risk
  • Aggressive treatment of exacerbating conditions e.g. infections with antibiotics

  • Patients should be established on optimal dose regimens of drug therapies in specialist clinics
    • These drugs should be continued in the peri-operative period
    • May need to switch from enteral to IV routes to ensure continuation in the peri-operative period
    • NB prostacyclin analogues will cause potent inhibition of platelet aggregation

  • Patients should be counselled about risks including need for ECMO, death and limitations on treatment

Monitoring and access

  • AAGBI
  • Arterial line pre-induction

  • CVC, especially in those with preserved LV function
    • Allows measurement of CVP i.e. changes in RV preload/filling pressure/RV performance
    • Allows ScvO2 monitoring
  • PA catheters may be required in some patients

  • Minimally invasive cardiac output monitoring e.g. transoesophageal Doppler or pulse contour analysis
    • Have the advantage of avoiding the major complications of PA catheters and still allow monitoring for low-CO states
    • Are unable to measure RV and pulmonary vasculature haemodynamic changes
  • Intra-operative TOE/TTE allows visualisation of RV filling and contractility

Anaesthetic technique

  • The choice of technique will ultimately depend on patient, surgical and anaesthetic factors
Technique Advantages Disadvantages
Regional anaesthesia No cardiorespiratory depression
Opioid-sparing analgesia		 Not always suitable depending on surgery
Timing of anticoagulants
Need for sedation may mitigate some benefits
Neuraxial anaesthesia Opioid-sparing analgesia
Avoids GA
 Not always suitable depending on surgery
Timing of anticoagulants
Patient may not be able to lie flat
Sympathetic blockade and CV sequelae
General anaesthesia Facilitates controlled ventilation
Titratable, familiar		 Cardiorespiratory depression
PONV
Analgesia requirements

Haemodynamic goals

  • The overall goal is to prevent RV decompensation or RV coronary ischaemia
Cardiovascular feature Goal of management Rationale
Heart rate Avoid tachycardia
Heart rhythm Maintain sinus rhythm with rapid treatment of arrhythmia Ensures atrial systole contributes maximally to RV preload
Preload Maintain preload but avoid overload Maintains RV filling
PVR Avoid increases & reduce as much as possible
Aggressively treat factors increasing PVR		 Increased RV afterload causes RV dilation and dysfunction
RV dilation also compromises LV function through septal bulging
SVR Maintain SVR Rapid reduction can reduce venous return and RV output
Large increases in SVR as can reduce LV cardiac output
Contractility Avoid negative inotropy and provide inotropic support Aim CI ≥2.2L/min/m2
Blood pressure MAP ≥65mmHg
SBP ≥90mmHg		 Maintain RV coronary perfusion pressure

General anaesthesia

  • Premedication
    • May reduce sympathetic drive and avoid tachycardia
    • May increase PVR if causes respiratory depression and hypercarbia
    • Potential to depress RV contactility

  • Balanced induction technique
    • Aim to limit tachycardia and reductions in SVR
    • Typically involves high-dose opioids (2-7μg/kg fentanyl)
    • Propofol + vasopressor e.g. metaraminol, phenylephrine, noradrenaline, vasopressin
    • Ketamine can increase PVR although also positive sympathetic effect improves RV performance and maintains SVR
    • May increase PVR through hypercarbia, hypoxia, sympathetic stimulation and high ventilatory pressures

  • Optimise RV preload
    • Maintain sinus rhythm to allow atrial emptying to contribute maximally to RV preload
    • Use goal-directed fluid therapy to ensure optimal preload and contractility
    • May require use of diuretics

  • Maintenance of anaesthesia
    • Both TIVA and volatile maintenance can cause cardiorespiratory depression, although at standard doses have negligible effects on PVR
    • Although both techniques can reduce ventilatory drive, patients are often mechanically ventilated

  • Reduce RV afterload by preventing increases in PVR
    • Aggressively treat factors increasing PVR e.g. hypoxia, hypercarbia, acidosis, pain, hypothermia, stress
    • Use selective pulmonary vasodilator e.g. NO, prostaglandin analogue, PDE-V inhibitor, endothelin receptor analogue

  • Ventilatory strategy
    • Avoid hyperinflation as PVR lowest at FRC e.g. use a low tidal volume (5 - 7ml/kg IBW) ventilatory strategy
    • Low (or zero) PEEP
    • Aim PaCO2 4-4.5kPa

  • Maintain systemic perfusion pressures through use of vasoconstrictors to counteract the vasodilatory effects of anaesthetic drugs e.g. noradrenaline

  • Support RV contractility
    • Use inodilators to reduce PVR and support the RV e.g. dobutamine, milrinone, levosimendan although may need to combine them with a vasopressor to limit reductions in SVR

Neuraxial anaesthesia

  • If neuraxial blockade is administered, use slowly-titrated epidural, CSE or low-dose spinal rather than standard spinal anaesthesia
  • Risks include:
    • Reduced SVR and consequently RV preload
    • Increase PVR through stress
    • Depressed RV contractility
    • Neuraxial haematoma

  • Sedation alongside neuraxial anaestheisa:
    • May reduce sympathetic drive and avoid tachycardia
    • Potential to reduce RV contractility
    • May increase PVR if causes respiratory depression and hypercarbia

Surgical stimulis

  • There may be increases in PVR and heart rate due to stimuli such as knife to skin or tourniquet pain
  • Release of anaerobic metabolites following tourniquet release may further increase PVR
  • Sympathetic stimulation can increase RV contractility
  • Pneumoperitoneum risks reducing RV contractility, increasing PVR

Obstetrics

  • Pulmonary hypertension is a WHO Class IV cardiac disease i.e. pregnancy is 'contraindicated'

  • Labour pain, anxiety and neuraxial intervention may cause tachycardia, although high block may cause bradycardia
  • Fluid shifts at the time of delivery can impair RV contractility through fluid overload
  • Placenta removal can generate micro-emboli, increasing PVR

  • Book HDU/ICU bed for 48-72hrs post-operatively as most perioperative events relate to RV dysfunction during this period
  • Early extubation is desirable to reduce intrathoracic pressure and RV stress

  • Ongoing management of PVR and SVR, using haemodynamic interventions as necessary
  • Supraventricular tachyarrhythmias are common; may necessitate prophylactic anti-arrhythmics (those with minimal negative inotropic impact)

  • Multi-modal analgesia to avoid:
    • Excessive sympathetic drive (↑PVR)
    • Excess opioid-related sedation and hypercapnoea (↑PVR)
  • Multi-modal anti-emesis to ensure minimal interruption to existing medication regimen

  • Post-operative physiotherapy and early mobilisation
  • Recommence full anticoagulation as soon as possible; may requiring bridging therapy

Critical care management of pulmonary hypertension (pulmonary hypertensive crisis)


  • Characterised by acute elevation in PVR and is associated with significant (up to 50%) mortality

Aetiology of deterioration

  • Exacerbation of co-existing chronic conditions
  • Infection (/sepsis)
  • Anaemia
  • Thromboembolism
  • Cardiac arrhythmia
  • Metabolic abnormalities
  • Post-operative fluid shifts, inflammation

Pathophysiology

  • Increased PVR causes raised RV filling pressures
  • Failure of RV to maintain cardiac output against increased afterload
  • Reduced LV preload and therefore cardiac output
  • This reduces diastolic coronary perfusion pressure
  • There is subsequent myocardial ischaemia
  • This leads to spiralling cardiovascular collapse

  • Treat underlying cause

Treat systemic hypotension to prevent RV ischaemia

  • E.g. noradrenaline or vasopressin
  • Do not stop pulmonary vasodilators

Optimise RV function

  • Preload
    • Aim CVP 8 - 12cmH2O
    • Diuresis (furosemide ± spironolactone ± bendro.) or CVVH if refractory overload

  • Contractility
    • Dobutamine
    • Dopamine
    • PDE-III inhibitors e.g. milrinone
    • Levosimendan

  • Afterload: reduce PVR
    • Pulmonary vasodilators (see management, above)
    • Oxygen therapy
    • Ventilatory management to control oxygen, carbon dioxide and pH levels

Invasive management

  • V-A ECMO may be an option to support the RV as a bridge to recovery or transplantation
  • Percutaneous RV assist devices