Critical Care Management of Decompensated Right Heart Failure in Pulmonary Arterial Hypertension Patients – An Ongoing Approach
, , oraz | 05 sie 2021
O artykule
Article Category: Review
Data publikacji: 05 sie 2021
Zakres stron: 170 - 183
Otrzymano: 30 maj 2021
Przyjęty: 21 cze 2021
DOI: https://doi.org/10.2478/jccm-2021-0020
Słowa kluczowe
© 2021 Ioan Tilea, Andreea Varga, Anca-Meda Georgescu, Bianca-Liana Grigorescu, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Fig. 1
Fig. 2
The main hemodynamic and oxygenation parameters considered in diagnosis and monitoring PAH patients (adapted from [34, 35])
| Hemodynamic parameters | Equation | Normal range |
|---|---|---|
| Systolic blood pressure (SBP) | 90-140 mmHg | |
| Diastolic blood pressure (DBP) | 60-90 mmHg | |
| Mean arterial pressure (MAP) | [SBP + (2 x DBP)]/3 | 70–100 mmHg |
| Heart rate (HR) | 60–100 bpm | |
| Right atrial pressure (RAP) | ≤6 mmHg | |
| Right ventricular systolic pressure (RVSP) | 15-30 mmHg | |
| Right ventricular diastolic pressure (RVDP) | 1-8 mmHg | |
| Pulmonary artery systolic pressure (PASP) | 15-30 mmHg | |
| Pulmonary artery diastolic pressure (PADP) | 6-12 mmHg | |
| Mean (mPAP) pulmonary artery pressure | [PASP + (2 x PADP)]/3 | 9-18 mmHg |
| Pulmonary capillary wedge pressure (PCWP) | ≤12 mmHg | |
| Cardiac output (CO) | HR x SV/1000 | 4-8 L/min |
| Cardiac index (CI) | CO/BSA | 2.6-4.2 L/min/m2 |
| Stroke volume (SV) | CO/HR x 1000 | 60-120 mL/beat |
| Stroke volume index (SVI) | CI/HR x 1000 | 40-50 mL/beat/m2 |
| Systemic vascular resistance (SVR) | (MAP-mean RA/CO) x 80 | 800-1200 dynes x s/cm5 10-15 WU |
| Systemic vascular resistance index (SVRI) | 80 x (MAP - RAP)/CI | 1970-2390 dynes x s/cm5/m2 24.6-29.8 WU |
| Pulmonary vascular resistance (PVR) | (mPAP-mean PCWP/CO) x 80 | 120-250 1.5dynes -3.1 WU x s/cm5 |
| Pulmonary vascular resistance index (PVRI) | 80 x (MPAP - PAWP)/CI | 255-285 3.2dynes -3.6 x WU s/cm5/m2 |
| Partial pressure of arterial oxygen (PaO2) | 80-100 mmHg | |
| Partial pressure of arterial CO2 | 35-45 mmHg | |
| (PaCO2) | ||
| Bicarbonate (HCO3) | 22-28 mEq/L | |
| pH | 7.38-7.42 | |
| Arterial oxygen saturation(SaO2) | 95-100% | |
| Mixed venous saturation (SvO2) | 60-80% | |
| Oxygen delivery (DO2) | CaO2 x CO x 10 | 950-1150 mL/min |
| Oxygen delivery index (DO2I) | CaO2 x CI x 10 | 500-600 mL/min/m2 |
| Oxygen consumption (VO2) | (C(a - v)O2) x CO x 10 | 200-250 mL/min |
| Oxygen consumption index (VO2I) | (C(a - v)O2 x CI x 10 | 120-160 mL/min/m2 |
| Oxygen extraction ratio (O2ER) | [(CaO2 - CvO2)/CaO2] x 100 | 22-30% |
| Oxygen extraction Index (O2EI) | [SaO2 - SvO2)/SaO2 x 100 | 20-25% |
Vasopressors and inotropes effects on hemodynamics
| Effect | CO | HR | SVR | PVR |
|---|---|---|---|---|
| ↑↑ | Dobutamine Milrinone Levosimendan Epinephrine | Dopamine Epinephrine | Epinephrine Norepinephrine Vasopressin | - |
| ↑ | Dopamine Norepinephrine | Dobutamine Norepinephrine | Dopamine | Dopamine Norepinephrine |
| ↑/↓ | Vasopressin | - | - | Epinephrine Vasopressin |
| ↓ | - | - | Dobutamine Milrinone Levosimendan | Dobutamine Milrinone Levosimendan |
Currently approved agents for PAH patients.(adapted after [14,51,52]). Abbreviations: PDE-5-phosphodiesterase-5, ERA-endothelin receptor antagonist, sGC-soluble guanilat cyclase, OD-omne in die (once daily), BID-bis in die (twice daily), TID-ter in die (three times a day)
| Administration route | Class | Drug | settings Acute | Dosing | Major side-effects | Important precautions |
|---|---|---|---|---|---|---|
| PDE-5 inhibitor | Sildenafil | N/A | 20mg TID | Hypotension, headache, epistaxis, visual changes, diziness | Contraindicated sGC with nitrates and stimulators | |
| PDE-5 inhibitor | Tadalafil | N/A | 40mg OD | Headache, flushing, hypotension, epistaxis, visual changes | Contraindicated with nitrates and sGC stimulators | |
| ERA | Bosentan | N/A | Initial 62.5mg BID then up-titration to 125mg BID | Anemia, fluid retention | Potential hepatotoxicity, decrease in hemoglobin concentrations, teratogenicity, avoid administration with CYP3A4 and | |
| CYP2C9 inhibitors | ||||||
| ERA | Macitentan | N/A | 10mg OD | Anemia, edema, nasopharyngitis, moderate elevation in liver tests | Teratogenicity | |
| Oral | ERA | Ambrisentan | N/A | Initial 5mg OD then up-titration to 10mg OD | Edema, headache, migraine, nasopharyngitis, moderate elevation in liver test | Severe hepatic impairment (with or without cirrhosis), teratogenicity |
| Stimulator of sGC | Riociguat | N/A | Initial 0.5mg TID then up-titration to 2.5mg TID | Hypotension, anemia, gastrointestinal distress, headache, gastritis, hemoptysis | Contraindicated with nitrates and PDE-5 inhibitors, teratogenicity | |
| Synthetic analogue of prostacyclin | Treprostinil | N/A | Initial 0.25mg BID or 0.125mg TID, then up-titration to 0.25-0.5mg BID or 0.125mg TID every 3-4 days to the highest tolerated dose | Hypotension, gastrointestinal distress, headache | ||
| Selective prostacyclin receptor agonist | Selexipag | N/A | Initial 200mcg BID, then up-titration weekly with 200mcg BID to a maximum tolerated dose of 1600mcg BID | Hypotension, gastrointestinal distress, myalgias | ||
| Synthetic analogue of prostacyclin | Epoprostenol (Flolan®) | YES | Continuous intravenous, in acute setting starting at 1-2ng/kg/min, step by step dose escalation at an interval of minimum 15 minutes 1- to 2- ng/kg/min depending on clinical response | Tachycardia, flushing, hypotension, headache, diarrhoea, jaw pain, muscle aches, dizziness | Short half-time (3-5 minutes) At 25°C old formula is stable for only 8 hours; new formula is stable for up to 72h | |
| Synthetic analogue of prostacyclin | Epoprostenol (Veletri®) | YES | Continuous intravenous, in acute setting: 1-2 ng/kg/min and increased by increments of 2 ng/kg/min every 15 minutes or longer depending on clinical response | Hypotension, headache, jaw pain, muscle aches, agitation, anxiety, flushing, anorexia, photosensitivity, catheter-related infection | Stable at 25°C for 48h at concentrations of 3000<60000 ng/ mL and for 72h at concentrations >60000 ng/mL | |
| Parenteral | Synthetic analogue of prostacyclin | Treprostinil | N/A | Continuous intravenous or subcutaneously initiated at 1.25ng/ kg/min, rising the dose by 1.25 ng/kg/min per week during the first month and then 2.5ng/kg/ min per week, depending on the clinical response | Flushing, hypotension, headache, gastrointestinal distress, diarrhoea, jaw pain, myalgias; infusion site pain (subcutaneously administration) | Stable at room temperature |
| PDE-5 inhibitor | Sildenafil | YES | In acute setting bolus 0.05-0.43mg/kg, usually 10-20mg, then continuous infusion starts at 1.25 mg/ hour with a maximum effect in 20 minutes | Similar as in orally administration | Similar as in orally administration | |
| Synthetic analogue of prostacyclin | Epoprostenol | YES | In acute setting 30-40ng/kg/min, over 10-20 minutes, inhaled or nebulisation | |||
| Inhaled | Synthetic analogue of prostacyclin | lloprost | YES | In acute setting 2.5-5 mg 6-9 times per day | Cough, headache, hemoptysis, gastrointestinal distress | |
| analogue Synthetic of prostacyclin | Treprostinil | N/A | 18-54 mg 4 times a day | Cough, headache, hemoptysis, gastrointestinal distress | ||
Pharmacological options in acute right heart failure PAH patients
| Drugs | Dosage | Duration of action (t1/2) |
|---|---|---|
| Noradrenaline | 0.2 - 1.0 μg/kg/min | 1-2 min |
| Vasopressin | 20 units/ml dose 1-4 units/hour | 4- 20 min |
| Dopamine | 2 – 20 μg/kg/min | 2 min |
| Dobutamine | 2 – 20 μg/kg/min | 2-3 min |
| Milrinone | 0.375 - 0.75 μg/kg/min | 1-2 hours |
| Levosimendan | 0.1–0.2 μg/kg/min (Optional bolus of 6–12 μg/kg bolus in 10 min; not recommended if SBP<90 mmHg) | 1 hour |
| Epoprostenol | 5 – 20 μg/kg/min | 2-3 min |
| Iloprost |
2.5 – 5 μg 6-9 times/day | 30 min |
| Epoprostenol | Titrate upward in 2 ng/kg/min increments according to effect | 2-3 min |
| Iloprost | 1 – 5 ng/kg/min | 30 min |