Introduction
Causes of pulmonary hypertension in ICU | Causes of RV failure in ICU |
---|---|
1) PAH (for example, preexisting PAH; PoPH (8.5% ESLD) | 1) RV Pressure overload, pulmonary hypertension, any cause |
2) Elevated LAP: RV pressure overload (left-sided myocardial infarction/cardiomyopathy; mitral regurgitation; pulmonary stenosis) | 2) Reduced RV contractility |
3) PH due to hypoxia: acute (for example, ARDS)/preexisting lung disease (for example, COPD, IPF) | RV infarction; sepsis; RV cardiomyopathy; myocarditis; pericardial disease; LVAD; after CPB; after cardiac surgery/transplantation |
4) Thromboembolic (for example, acute PE; chronic (CTEPH); other causes of emboli (AFE, air, cement) | 3) RV-volume overload |
5) Mechanical (for example, increased Pplat - IPPV | Cardiac causes: tricuspid and pulmonary regurgitation; intracardiac shunts |
The pulmonary circulation and pathophysiology of right ventricular failure
Factors increasing pulmonary vascular tone | Additional contributors to elevated PVR in ARDS |
---|---|
High pulmonary arterial pCO2/low pH | Vasoconstrictor: vasodilator imbalance |
Low mixed venous pO2 | |
High sympathetic tone; α-adrenoceptor agonism | Reduced NO, prostanoids [20] |
Mechanical effects: | |
High airway Pplat; gravity; increased flow (for example, one-lung ventilation) | Endothelial injury [363] |
Relating to CPB: | |
Pulmonary vascular remodeling [1] |
1. Optimize volume status: avoid filling (± offload) if RV volume-overloaded |
2. Augment CO |
3. Reduce PVR |
a) Use pulmonary vasodilators (preferably inhaled: less systemic hypotension and V/Q mismatch) |
b) Treat reversible factors that may increase PVR |
Metabolic state: correct anemia, acidosis, hypoxemia |
Treat respiratory failure: treat hypoxia; limit Pplat by using lung-protective ventilatory strategies, but beware of high pCO2 increasing PVR |
Reduce sympathetic overstimulation |
4. Maintain adequate systemic vascular resistance (SVR): keep PVR well below SVR; use pressors if necessary |
Materials and methods
Systematic review of ICU management of pulmonary vascular and RV dysfunction
Subtype of treatment for pulmonary vascular dysfunction | Number of studies in initial search | Number of suitable studies included in review |
---|---|---|
Volume therapy | 113 | 5 |
Vasopressors | 388 | 28 |
Sympathetic inotropes | 565 | 8 |
Inodilators | 280 | 17 |
Levosimendan | 172 | 12 |
Pulmonary vasodilators | 586 | 121 |
Mechanical devices | 47 | 19 |
Results and Discussion
ICU management of pulmonary vascular and RV dysfunction
Management of volume and use of vasopressors
Volume management
GRADE RECOMMENDATION 1
Vasopressors
CI | PVR | SVR | PVR/SVR | Tachycardia | Renala/metabolic | |
---|---|---|---|---|---|---|
Vasopressors | Dose related | |||||
NE | + | + | ++ | +/- | + | Lactic acidosis |
PHE | - | ++ | + | + | - | - |
Low-dose AVP | +/- | +/- | ++ | - | - | Diuresis ++ |
Inotropes | ||||||
Dobutamine | ++ | - | - | - | + | |
< 5 μg/kg/min | ||||||
Dopamine | + | +/- | + | + | ++ | Natriuresis |
Epinephrine | ++ | - | ++ | - | ++ | Lactic acidosis |
Inodilators | ||||||
PDE IIIs | ++ | - | - | - | +/- | - |
Levosimendan | ++ | - | - | - | - | - |
Sympathomimetic pressors
Norepinephrine
GRADE RECOMMENDATION 2
Nonsympathomimetic pressors: Vasopressin
GRADE RECOMMENDATION 3
Inotropic augmentation of RV myocardial function
Inotropes
Sympathomimetic inotropes
Dobutamine
Inodilators
PDE3 inhibitors
Levosimendan
GRADE RECOMMENDATION 4
GRADE RECOMMENDATION 5
GRADE RECOMMENDATION 6
Reduction of right ventricular afterload
Drug | Dose | Half-life (duration of action) | Potential adverse effects |
---|---|---|---|
Intravenous | |||
Prostacyclin (Epoprostenol, Flolan) | Start at 1 ng/kg/min; titrate upward in 2-ng/kg/min increments according to effect | 3-5 minutes (10 minutes) | Systemic hypotension, worsening oxygenation (increased V/Q mismatch), antiplatelet effect, headache, flushing, jaw pain, nausea, diarrhea |
Iloprost | 1-5 ng/kg/min | 30 minutes | Similar to Flolan; also syncope (5%) |
Sildenafil [325] (NB off-license use in hemodynamically unstable patients) | Low dose, 0.05 mg/kg; high dose, 0.43 mg/kg) (comes as 0.8 mg/ml) | 3-5 hours | Hypotension: caution if fluid depleted, severe LV-outflow obstruction, autonomic dysfunction. Hypoxemia due to V/Q mismatch. Common: headache, flushing, diarrhea, epistaxis, tremor. Rare but important: anterior ischemic optic neuropathy |
Milrinone | 50 μg/kg over 10 minutes followed by 0.375-0.75 μg/kg/min infusion | 1-2 hours | Tachyarrhythmias, hypotension |
Adenosine | 50-350 μg/kg/min, titrate up in 50 μg/kg/min increments | 5-10 seconds (2 minutes) | Bradycardia, bronchospasm, chest pain |
Inhaled (preferred; Note variable absorption likely) | |||
0.2-0.3 ml/min of 10-20 μg/ml nebulized into inspiratory limb of ventilator circuit (30-40 ng/kg/min) | 3-5 minutes | As above but less hypotension and improved oxygenation compared with intravenous use | |
Iloprost [275] | 2.5-5 μg 6-9 times/day, 1 mg/ml milrinone into the ventilator circuit at 0.2-0.3 ml/min for 10-20 minutes | 30 minutes | As above and bronchospasm |
5-80 ppm continuously | 1-2 hours | Less systemic hypotension than with IV milrinone | |
NO | 15-30 seconds (5 minutes) | Methemoglobinemia; withdrawal PH | |
ORAL (rarely in ICU) | |||
Bosentan | 62.5-125 mg b.d. | 5 hours | Liver-function test abnormalities; drug interactions; edema |
Sildenafil | 0.25-0.75 mg/kg 4 hrly | 3-4 hours | As above; less hypotension and hypoxemia in stable patients |
Pulmonary vasodilator therapy
Adenosine
Inhaled nitric oxide
Prostanoids
PDE5 inhibitors
GRADE RECOMMENDATION 7
Nonpharmacologic Management
Ventilatory strategies
Mechanical support
GRADE RECOMMENDATION 8
Conclusions
Key messages
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Pulmonary hypertension (PH) and associated right ventricular (RV) failure are associated with worse outcomes in critical care, and because of nonspecific presenting symptoms and signs, may be difficult to recognize: echocardiography is a very useful initial test, and invasive monitoring may be helpful in some cases for more continuous monitoring and accurate measurement of pulmonary vascular resistance.
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Volume loading of the right ventricle may worsen its performance: all fluid challenges should be closely monitored.
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It is essential to maintain adequate aortic root pressure to prevent the onset of RV ischemia. Vasopressors are useful in this setting, including low-dose norepinephrine as a first-line agent. Low-dose vasopressin may also be useful in some resistant cases but has adverse myocardial effects at higher doses. Potentially useful inotropes in RV failure include dobutamine and those with additional pulmonary vasodilating effects, including PDE III inhibitors, although co-administration with pressors is often necessary. The effects of any vasoactive drug may be unpredictable in an individual and require close clinical observation of circulatory performance, potentially assisted by echocardiography.
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Pulmonary vasodilators are useful to reduce RV afterload in several ICU settings, including PH and RV failure after cardiac surgery. Systemic administration may worsen systemic hemodynamics and oxygenation because of ventilation-perfusion mismatching.
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The use of mechanical therapies to manage acute PH and enhance RV performance is expanding, although with evidence currently limited to case series, and may be useful in experienced centers to ameliorate RV failure while awaiting definitive therapy.