2025 PACUPrep BCCCP Preparatory Course Pulmonary Hypertension (Acute and Chronic severe pulmonary hypertension) Acute Pharmacologic Management of Decompensated Pulmonary Hypertension
Acute Pharmacotherapeutic Strategies for Decompensated Pulmonary Hypertension

Acute Pharmacotherapeutic Strategies for Decompensated Pulmonary Hypertension in the ICU

Lesson Objective

Develop an evidence-based acute management plan for patients with decompensated pulmonary hypertension (PH) in the ICU.

I. Pathophysiologic Basis of Acute RV Failure in PH

Acute decompensation occurs when a rapid rise in pulmonary vascular resistance (PVR) overwhelms right ventricular–pulmonary artery (RV–PA) coupling, leading to low cardiac output and end-organ hypoperfusion.

Mechanisms & Hemodynamic Goals

  • Mechanisms: Sudden PVR increase, RV–PA uncoupling, RV ischemia.
  • Hemodynamic goals: Maintain mean arterial pressure (MAP) ≥65 mmHg for coronary perfusion, optimize right atrial pressure (RAP) (8–12 mmHg), support cardiac output.
  • Rationale: Early afterload reduction and inotropic support restore RV–PA coupling.
Figure 1: Pathophysiologic Cascade in Acute RV Failure
Sudden PVR Increase (e.g., hypoxia, acidosis, PE)
RV–PA Uncoupling (RV cannot overcome afterload)
RV Dilatation & Dysfunction
Reduced RV Stroke Volume & Cardiac Output
Systemic Hypotension & Reduced RV Coronary Perfusion
RV Ischemia & Worsening Failure (Downward Spiral)
End-Organ Hypoperfusion & Shock
Key Clinical Pearl

Aggressive afterload reduction within the first hours can interrupt the downward spiral of RV failure.

II. Inhaled Pulmonary Vasodilators

Inhaled agents provide selective pulmonary vasodilation, improving oxygenation and reducing RV afterload without systemic hypotension.

Agents, Mechanism, Indications, and Dosing

Table 1: Inhaled Pulmonary Vasodilators
Agent Mechanism Dosing & Titration
Inhaled Nitric Oxide (iNO) Activates soluble guanylate cyclase → ↑cGMP → vasodilation Start 20 ppm; titrate by 5–20 ppm; max 40 ppm; wean gradually
Inhaled Epoprostenol IP receptor agonism → ↑cAMP → vasodilation, anti-proliferation 10–50 ng/kg/min via continuous nebulization; increase by 10 ng/kg/min
Inhaled Iloprost IP receptor agonism → ↑cAMP → vasodilation, anti-proliferation 2.5–5 μg per dose Q4–6 h

Indications & Selection

  • Acute RV failure with high PVR and refractory hypoxemia.
  • Choice based on onset/offset, cost, and available delivery systems.

Monitoring & Safety

  • Continuous SpO₂ and invasive PAP if available.
  • Methemoglobin and NO₂ levels (for iNO).
  • Avoid abrupt discontinuation to prevent rebound PH.

Pharmacoeconomics & Formulary Considerations

  • iNO has rapid titratability but high cost and gas-delivery needs.
  • Generic inhaled prostacyclin analogs are less expensive but require nebulizer infrastructure.

III. Intravenous Prostacyclin Therapy

Continuous IV prostacyclins are the gold standard for refractory cases, offering potent pulmonary vasodilation and survival benefit but requiring meticulous titration and line care.

Mechanism, Indications, Dosing & Escalation

Table 2: Intravenous Prostacyclins
Agent Mechanism & Half-life Dosing & Escalation
Epoprostenol Potent prostacyclin analog; half-life 3–5 min Start 2 ng/kg/min; increase by 1–2 ng/kg/min every 1–2 h until goals met
Treprostinil Stable prostacyclin analog; half-life ~4 h Start 1.25 ng/kg/min; increase by 1.25 ng/kg/min Q24 h

Indications

Indicated for severe, refractory PH or RV failure unresponsive to inhaled agents.

Administration & Monitoring

  • Central line infusion with backup pump is mandatory.
  • Monitor systemic BP, PAP, CO, platelet count.
  • Contraindicated in uncontrolled hypotension or active bleeding.
Clinical Pearl

Never interrupt epoprostenol infusion abruptly; even brief gaps can precipitate life-threatening rebound PH.

IV. Inotropes and Vasopressors

Optimize RV contractility and maintain systemic pressure to support coronary perfusion.

Table 3: Inotropes and Vasopressors in RV Failure
Agent Mechanism & Key Effects Typical Dose Range Key Considerations
Dobutamine β₁ agonist 2–10 μg/kg/min Enhances contractility; watch for tachyarrhythmias, hypotension.
Milrinone PDE-3 inhibitor 0.25–0.75 μg/kg/min (no bolus) Inotropy + pulmonary vasodilation; can cause hypotension, arrhythmias. Renal dose adjustment.
Norepinephrine α₁ > β agonist Titrate to MAP ≥65 mmHg Increases SVR to preserve coronary perfusion pressure; may increase PVR at high doses.
Vasopressin V₁ agonist (non-adrenergic) 0.01-0.04 units/min Raises SVR without significantly increasing PVR; useful adjunct.

V. Volume Management with Diuretics

Optimize RV preload to improve RV function without causing hypovolemia, which can compromise cardiac output in a preload-dependent RV.

Table 4: Volume Management Strategies
Strategy Details Monitoring & Considerations
Loop Diuretics Furosemide 20–40 mg IV bolus or continuous infusion (e.g., 5-10 mg/hr) Adjust to urine output, daily weights, CVP/RAP, IVC diameter (POCUS), renal function, electrolytes.
Fluid Challenge (Cautious) Small boluses (e.g., 250 mL crystalloid) ONLY if clear evidence of hypovolemia and low RAP. Monitor RAP, CI, BP response. High risk of worsening RV failure if euvolemic or hypervolemic.
Ultrafiltration Consider in cases of severe volume overload refractory to high-dose diuretics. Requires specialized equipment and expertise; monitor hemodynamic stability.

Key Principles

  • Avoid over-diuresis: The failing RV is often preload-dependent. Excessive volume removal can lead to a drop in cardiac output.
  • Goal: Achieve euvolemia, relieving congestion while maintaining adequate RV filling.

VI. Oxygenation and Ventilatory Strategies

Prevent hypoxemia and hypercapnia, as both can worsen PVR. Minimize intrathoracic pressure to optimize venous return and RV function.

Table 5: Oxygenation and Ventilation Targets
Parameter Target/Strategy Rationale/Considerations
Oxygen Saturation (SpO₂) >90% (PaO₂ >60 mmHg) Prevent hypoxic pulmonary vasoconstriction.
Arterial CO₂ (PaCO₂) 35–45 mmHg (normocapnia) Avoid hypercapnia (vasoconstriction) and significant hypocapnia (cerebral vasoconstriction).
Mechanical Ventilation (if needed) Low tidal volume (6 mL/kg ideal body weight) Minimize barotrauma and high airway pressures.
PEEP Minimal PEEP compatible with oxygenation (e.g., 5-8 cm H₂O) High PEEP can decrease venous return and increase RV afterload.
Adjuncts Adequate sedation and analgesia. Neuromuscular blockade if severe dyssynchrony. Minimize oxygen consumption and improve ventilator synchrony.

VII. Identification and Management of Precipitants

A crucial step in managing decompensated PH is to actively search for and treat reversible triggers that may have led to the acute deterioration.

Table 6: Common Precipitants and Management
Precipitant Management Approach
Infections (e.g., pneumonia, sepsis) Prompt broad-spectrum antibiotics based on likely source and local epidemiology; obtain cultures; source control if applicable.
Arrhythmias (especially atrial tachyarrhythmias) Rate control (e.g., digoxin, cautious beta-blocker/calcium channel blocker if tolerated). Cardioversion if hemodynamically unstable. Maintain sinus rhythm if possible to optimize RV filling and atrial contribution to CO.
Acidosis (metabolic or respiratory) Correct metabolic acidosis (e.g., bicarbonate if severe, treat underlying cause). Adjust ventilation to normalize PaCO₂ (avoiding high airway pressures).
Pulmonary Embolism (PE) Systemic thrombolysis or catheter-directed therapy for massive/submassive PE causing RV strain. Anticoagulation.
Non-adherence to PH medications Restart or optimize home PH regimen as appropriate once stabilized. Patient education.
Volume Overload / Anemia Judicious diuresis for volume overload. Transfuse packed red blood cells for symptomatic anemia (target Hb typically >8-9 g/dL).

VIII. Escalation Pathways and Advanced Therapies

Combine therapies sequentially based on response and disease severity. Consider mechanical or interventional support for refractory cases, always involving multidisciplinary discussion.

Therapeutic Escalation Strategy

Figure 2: Escalation Pathway for Decompensated PH
Initial Stabilization: Oxygen, Diuretics, Treat Precipitants
Inhaled Pulmonary Vasodilators (e.g., iNO, inhaled prostacyclin)
Inotropes (e.g., Dobutamine, Milrinone) + Vasopressors (e.g., Norepinephrine) for MAP & CO support
IV Prostacyclins (e.g., Epoprostenol, Treprostinil) if refractory
VA-ECMO Candidacy Evaluation
Balloon Atrial Septostomy (Palliative/Bridge)
Goals of Care Discussion / Palliative Care Consultation

Specific Advanced Therapies

Table 7: Advanced Therapies and Considerations
Therapy Description & Indication Key Considerations
Oral PH Agents PDE-5 inhibitors (sildenafil, tadalafil), Endothelin Receptor Antagonists (bosentan, ambrisentan), Riociguat. Typically added or optimized after acute stabilization, as part of long-term management. Not primary acute therapies for decompensation.
VA-ECMO (Veno-Arterial Extracorporeal Membrane Oxygenation) Provides biventricular circulatory and respiratory support. For refractory cardiogenic shock despite maximal medical therapy. Multidisciplinary team evaluation for candidacy. Bridge to recovery, decision, or transplant. High risk, resource-intensive.
Balloon Atrial Septostomy (BAS) Creates an interatrial right-to-left shunt to decompress the RV and improve LV preload/systemic CO. High-risk palliative procedure in expert centers for refractory RV failure, often as a bridge to transplant or in end-stage disease. Can worsen hypoxemia.
Goals-of-Care Discussions Essential throughout, especially when considering high-burden interventions. Align interventions with patient values, prognosis, and quality of life. Involve palliative care early.

VExUS Score: Assessing Venous Congestion

The Venous Excess Ultrasound (VExUS) score is a point-of-care ultrasound (POCUS)-based system used to grade the severity of systemic venous congestion, which is a strong predictor of acute kidney injury and other organ dysfunction in critically ill patients.

Figure 3: Simplified VExUS Score Components for Assessing Venous Congestion. This diagram illustrates the three core components of the VExUS score, providing a visual representation of the parameters used to grade venous congestion.

VExUS Score Components for Assessing Venous Congestion

1. IVC Diameter

Plethoric (>2 cm)

2. Hepatic Vein

~

Pulsatile (S > D wave)

3. Portal Vein

~

Pulsatility Index >30%

References

  1. Barst RJ, Rubin LJ, Long WA, et al. Continuous IV epoprostenol vs conventional therapy in primary pulmonary hypertension. N Engl J Med. 1996;334:296–302.
  2. Hoeper MM, Benza RL, Corris P, et al. Intensive care, RV support, and transplant in PH. Eur Respir J. 2019;53:1801906.
  3. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for pulmonary hypertension. Eur Respir J. 2023;61(1):2200879.
  4. Olschewski H, Simonneau G, Galiè N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347:322–329.
  5. Tello K, Kremer N, Richter MJ, et al. Inhaled iloprost improves RV contractility independent of afterload. Am J Respir Crit Care Med. 2022;206(1):111–114.
  6. Vizza CD, Lang IM, Badagliacca R, et al. Aggressive afterload lowering in PAH. Am J Respir Crit Care Med. 2022;205(7):751–760.
  7. Boucly A, Savale L, Jaïs X, et al. Initial treatment strategy and long-term survival in PAH. Am J Respir Crit Care Med. 2021;204(7):842–854.
  8. Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P. The prostacyclin pathway in PAH: clinical review. Expert Rev Respir Med. 2017;11(7):491–503.
  9. Kapur NK, Esposito ML, Bader Y, et al. Mechanical support for acute RV failure. Circulation. 2017;136:314–326.
  10. Khan MS, Memon MM, Amin E, et al. Balloon atrial septostomy in advanced PAH: meta-analysis. Chest. 2019;156:53–63.
  11. Rosenkranz S, Howard LS, Gomberg-Maitland M, et al. Systemic consequences of PH and RV failure. Circulation. 2020;141:678–693.
  12. Wen L, Sun ML, An P, et al. Supraventricular arrhythmias in idiopathic PAH. Am J Cardiol. 2014;114:1420–1425.
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