Acute decompensated pulmonary hypertension in ICU · ICU Topics

Cinematic ICU scene of a pulmonary artery pressure waveform on the monitor, an inhaled nitric oxide delivery system beside the bed, a milrinone infusion running, an echocardiogram showing a dilated right ventricle with septal shift, clinical-blue lighting, medical educational, no text, no people — FigureThe acute pulmonary hypertensive crisis — the failing right ventricle, the rising pulmonary vascular resistance, the septal shift and the LV compression. The noradrenaline for the systemic pressure, the inhaled pulmonary vasodilator, and the VA-ECMO for the refractory.

WHO PH classification

Group	Cause	Examples	Key features
1 (PAH)	Pulmonary arterial disease	Idiopathic, heritable (BMPR2), CTD (scleroderma), portal HTN, congenital heart disease, drugs	Pre-capillary, elevated PVR, responsive to PAH-specific therapy
2 (Left heart)	Post-capillary	HFrEF, HFpEF, valvular (mitral), congenital	Elevated PCWP (>15), treat underlying heart disease
3 (Lung disease)	Hypoxia-driven	COPD, ILD, OSA, chronic high altitude	Treat underlying lung disease, oxygen
4 (CTEPH)	Chronic thromboembolic	Organised thrombi in pulmonary arteries	Potentially curable: pulmonary endarterectomy
5 (Multifactorial)	Various	Sarcoidosis, haematological, metabolic, renal	Treat underlying cause

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Management of acute pulmonary hypertensive crisis

RECOGNISE — known PH patient with: hypotension (SBP <90), rising lactate, RV dysfunction on echo (dilated RV, septal shift, reduced TAPSE), rising CVP, falling cardiac output
IDENTIFY AND CORRECT PRECIPITANTS — (a) Hypoxia (SpO2 <90 → pulmonary vasoconstriction). (b) Acidosis (pH <7.3 → pulmonary vasoconstriction). (c) Hypercapnia (PaCO2 >45 → pulmonary vasoconstriction). (d) Arrhythmia (AF — common in PH, worsens RV filling). (e) Volume overload (excess fluids → RV dilatation). (f) Sepsis/infection. (g) Pulmonary embolism. (h) Non-adherence to PH medications (sildenafil, bosentan)
MAINTAIN SYSTEMIC BP — noradrenaline (alpha vasoconstriction → systemic BP ↑ → coronary perfusion to RV). Target: MAP ≥65. Avoid: pure alpha agonists (phenylephrine — may worsen PVR). Vasopressin: variable effect (may reduce PVR — some evidence)
REDUCE PVR — (a) Inhaled NO (5-20 ppm — selective pulmonary vasodilation, no systemic hypotension). (b) Inhaled epoprostenol (10-50 ng/kg/min — alternative to NO). (c) IV sildenafil (10-20 mg TDS — PDE5 inhibitor — reduces PVR). (d) IV riociguat (soluble guanylate cyclase stimulator). (e) Correct hypoxia/acidosis/hypercapnia (reduces hypoxic pulmonary vasoconstriction)
SUPPORT RV — (a) Milrinone (PDE3 inhibitor — inotropy + pulmonary vasodilation — PREFERRED). (b) Dobutamine (beta-1 — inotropy — may cause hypotension). (c) Levosimendan (calcium sensitiser — inotropy — less arrhythmia). (d) Target: cardiac index >2.0 L/min/m², mixed venous saturation >60%
AVOID EXCESS FLUIDS — volume loading >500 mL → RV dilatation → septal shift → LV compression → worse output. If hypovolaemic: cautious 250 mL bolus (assess response). If overloaded: diurese (frusemide)
MECHANICAL SUPPORT (refractory) — VA-ECMO (bridge to recovery, transplant, or decision). Reduces RV load (bypasses pulmonary circulation), supports systemic perfusion
TREAT UNDERLYING PH — restart/optimize PAH-specific therapy (sildenafil, bosentan, macitentan, riociguat, prostacyclins). Consider: lung transplant evaluation (if end-stage)

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Exam practice

SAQ — Pulmonary hypertensive crisis with right ventricular failure

10 minutes · 10 marks

A 48-year-old woman with idiopathic PAH on sildenafil 20 mg TDS, macitentan 10 mg daily, and nebulised iloprost presents with 6 hours of worsening dyspnoea and presyncope after missing her iloprost doses yesterday. She is hypotensive (BP 78/45), in new atrial fibrillation at 132/min, SpO2 86% on room air, JVP to the angle of the jaw, cool peripheries, lactate 5.2 mmol/L. Bedside echo shows a dilated RV (RV/LV ratio 1.4), D-shaped septum, TAPSE 11 mm, moderate tricuspid regurgitation.

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SAQ — Escalation of therapy in refractory pulmonary hypertension

10 minutes · 10 marks

A 55-year-old man with idiopathic PAH (WHO Group 1), chronically on tadalafil 40 mg daily, macitentan 10 mg daily, and nebulised iloprost, is admitted with syncope and NYHA IV dyspnoea despite his background therapy. PA catheter: RA pressure 18 mmHg, PCWP 12 mmHg, cardiac index 1.6 L/min/m², PVR 9 Wood units, mixed venous saturation 48%. He is on noradrenaline 0.4 mcg/kg/min, milrinone 0.5 mcg/kg/min, and inhaled NO 20 ppm, with lactate 4.8 mmol/L and MAP 58.

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Clinical pearls [1]

High-yield PH crisis points for CICM/FFICM exam

RV failure is the MAIN cause of death in PH crisis. RV pumps against high PVR → afterload too high → RV dilates → septum shifts LEFT → compresses LV → LV cannot fill → low cardiac output → cardiogenic shock → death. The vicious cycle: high PVR → RV failure → low output → ischaemia → more RV failure. MUST break the cycle by reducing PVR + supporting RV.[2] }
AVOID excess volume loading (>500 mL). In most shock states: give fluids to increase preload → increase cardiac output (Frank-Starling). BUT in PH crisis: RV is on the FLAT part of Starling curve (dilated, failing — volume doesn't increase output). MORE volume → MORE RV dilatation → MORE septal shift → LESS LV filling → LESS output → WORSE. CAREFUL fluids: 250 mL bolus, assess, don't repeat if no improvement.[2] }
Noradrenaline is FIRST-LINE vasopressor. Alpha vasoconstriction → systemic BP ↑ → coronary perfusion to RV (RV ischaemia is a major problem in PH crisis — RV needs oxygen but low output → ischaemia). Noradrenaline: slightly increases PVR (alpha on pulmonary vessels) but SYSTEMIC effect dominates (net benefit — RV perfusion preserved). Avoid: phenylephrine (pure alpha — may significantly worsen PVR).[3] }
Inhaled NO — selective pulmonary vasodilation. NO gas inhaled → reaches ventilated alveoli → diffuses to pulmonary vessels → vasodilation → reduces PVR. RAPIDLY metabolised by haemoglobin (no systemic effect — no systemic hypotension). Dose: 5-20 ppm (titrate). Response: improved cardiac output, lower PVR, better oxygenation. CAUTION: methaemoglobinaemia (monitor), rebound PH on withdrawal (taper slowly — never abrupt). COST: very expensive ($150-300/hour).[5] }
Hypoxia, acidosis, hypercapnia — pulmonary vasoconstrictors. These are POTENT pulmonary vasoconstrictors (hypoxic pulmonary vasoconstriction — normal physiological response but DANGEROUS in PH). In PH crisis: MUST correct immediately. Hypoxia: 100% FiO2 (pulmonary vasodilator — oxygen relaxes pulmonary vessels). Acidosis: correct (bicarbonate if pH <7.2 — acidosis constricts). Hypercapnia: ventilate (if intubated — increase rate, but avoid high intrathoracic pressure — see below).[2] }
Mechanical ventilation — carefully adjusted. If intubating: (1) Use LOW tidal volumes (4-6 mL/kg — high intrathoracic pressure compresses RV). (2) Low PEEP (≤5 — high PEEP increases intrathoracic pressure → reduces venous return → worsens RV output). (3) Low respiratory rate (allow long expiration — reduce intrathoracic pressure). (4) Permissive hypercapnia (if pH >7.2 — accept high CO2 to avoid high pressures). (5) Ketamine induction (maintains BP — avoid propofol/fentanyl — hypotension in PH is dangerous).[3] }
Arrhythmia — common precipitant (especially AF). PH patients: dilated RV → atrial stretch → atrial fibrillation (AF). AF → loss of atrial kick (important for RV filling in stiff RV) → reduced preload → reduced cardiac output → crisis. MANAGEMENT: (a) RATE CONTROL: amiodarone (IV — rate + rhythm), digoxin (IV — rate). Avoid: calcium channel blockers (negative inotropy — worsen RV failure), beta-blockers (negative inotropy — caution). (b) RHYTHM CONTROL: cardioversion (if haemodynamically unstable — synchronised DC shock).[3] }
Milrinone — PREFERRED inotrope for PH crisis. PDE3 inhibitor → increases cAMP → increases contractility (inotropy) + vasodilation (both systemic and pulmonary). ADVANTAGES: (a) Improves RV contractility (support failing RV). (b) REDUCES PVR (pulmonary vasodilation — reduces RV afterload). (c) Less tachycardia than dobutamine. DISADVANTAGES: (a) Systemic hypotension (vasodilation — may need noradrenaline concurrently). (b) Long half-life (2-3h — not rapidly titratable). DOSE: 0.125-0.75 mcg/kg/min.[4] }
Sildenafil (PDE5 inhibitor) — oral/IV for PH. PDE5 inhibitor → increases cGMP → pulmonary vasodilation → reduces PVR. DOSE: 10-20 mg IV TDS (or 20 mg PO TDS). RESPONSE: lower PVR, improved cardiac output, improved 6-minute walk distance (chronic). ADVANTAGE: oral available (transition from IV). CAUTION: systemic hypotension (less than milrinone). Do NOT combine with nitrates (severe hypotension).[4] }
Echo assessment in PH crisis — ESSENTIAL. (1) RV SIZE: dilated (RV/LV ratio >1 — normal <0.6). (2) SEPTAL MOTION: D-shaped LV (septum pushed into LV during diastole — from RV volume/pressure overload). (3) TAPSE (tricuspid annular plane systolic excursion): <17 mm = RV systolic dysfunction. (4) TRICUSPID REGURGITATION: velocity >2.8 m/s = elevated pulmonary pressure. (5) PERICARDIAL EFFUSION: common in PH (from RV failure). (6) IVC: dilated, non-collapsing = high RA pressure. SERIAL echo: track response to therapy (RV shrinking? septum returning to normal?).[2] }
Pulmonary embolism — common in PH. PH → venous stasis + RV dysfunction → DVT/PE risk. PE → acute increase in PVR → PH crisis. ALWAYS: DVT prophylaxis (LMWH — enoxaparin 40 mg daily — unless contraindicated). If PH crisis + suspected PE: CT pulmonary angiography (if stable enough), or empiric anticoagulation (LMWH — if unstable). THROMBOLYSIS: only if massive PE with shock (controversial in PH — bleeding risk).[2] }
Pregnancy is CONTRAINDICATED in severe PH. Pregnancy → volume overload (50% increase blood volume) + increased cardiac output + hypercoagulable → PH crisis → maternal mortality 30-50%. CONTRACEPTION: essential (effective methods — IUD, implant). If pregnant: early termination recommended (if severe PH). If continuing: multidisciplinary care (PH specialist + obstetrics + anaesthetics), planned delivery (caesarean), PAH-specific therapy throughout.[1] }
Lung transplant — definitive for end-stage PH. INDICATIONS: (1) Refractory PH despite maximal therapy (sildenafil, bosentan, prostacyclins). (2) Recurrent PH crises. (3) Declining functional capacity (NYHA IV). (4) Cardiac index <2.0, RA pressure >15, PVR >5 Wood units despite therapy. TYPES: bilateral lung transplant (preferred for PH — more room for new lungs) or heart-lung transplant (if severe RV failure — irreversible). OUTCOMES: 1-year survival 80-90%, 5-year survival 50-60%. BRIDGE: VA-ECMO (if crisis → stabilise until transplant).[6] }
CICM exam: distinguish pre-capillary from post-capillary PH. PRE-CAPILLARY (Groups 1, 3, 4, 5): PCWP ≤15 mmHg (no left heart obstruction — problem is in PULMONARY vessels). Treat: pulmonary vasodilators (NO, sildenafil, prostacyclins). POST-CAPILLARY (Group 2): PCWP >15 mmHg (left heart disease — problem is UPSTREAM). Treat: LEFT HEART (diurese, afterload reduce, treat valve). DON'T give pulmonary vasodilators to post-capillary PH (may worsen pulmonary oedema — more blood flows to lungs but can't exit through left heart).[1] }

Red flags

Prognosis

PH crisis outcomes (Price 2019)

Mortality from PH crisis in ICU: 40-60% (without prompt, targeted treatment). With early recognition + aggressive management: may improve to 20-30%. Key predictors of poor outcome: (1) Cardiac index <2.0 L/min/m². (2) RA pressure >20 mmHg. (3) Mixed venous saturation <50%. (4) Lactate >4 mmol/L. (5) Need for VA-ECMO. (6) Acute kidney injury (from low cardiac output). PAH-specific therapy (chronic): has dramatically improved survival (idiopathic PAH: median survival 2.8 years without therapy → 7+ years with sildenafil + prostacyclin). Lung transplant: 1-year survival 80-90%, 5-year 50-60%. [1]

Pregnancy with PH: maternal mortality 30-50% (contraindicated).

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Triggers and precipitants

Common precipitants of acute PH decompensation

Trigger	Mechanism of decompensation	Key management point
Hypoxia / hypercapnia / acidosis	Hypoxic pulmonary vasoconstriction + acidosis directly constrict pulmonary arterioles → PVR rises sharply	Correct immediately: 100% FiO2, ventilate to normocapnia, bicarbonate if pH <7.2[2] }
Arrhythmia (new AF/flutter)	Loss of atrial kick → loss of ~25-30% RV preload → RV output collapses; atrial stretch from dilated RA is the substrate	Urgent rhythm/rate control — synchronised cardioversion if unstable; amiodarone; AVOID CCB/beta-blocker monotherapy[9] }
Sepsis / systemic infection	Sepsis-induced myocardial depression + vasodilation (low systemic BP → RV ischaemia) + pulmonary neutrophil activation ↑ PVR + iNOS downregulation	Early antibiotics, source control, careful vasopressor support (noradrenaline); restrictive fluids[14] }
Acute pulmonary embolism	Acute obstruction of pulmonary vasculature → sudden PVR spike on already-compromised RV	Empiric anticoagulation if unstable; CTPA if stable; thrombolysis for massive PE with shock (weigh bleeding)[11] }
Withdrawal of PH-specific therapy	Sudden cessation of PDE5i/ERA/prostacyclin → rebound pulmonary vasoconstriction; missed doses are a leading avoidable cause of crisis	NEVER interrupt background PAH therapy — confirm and restart sildenafil, bosentan, prostacyclin immediately on admission; NG/IV route if NPO[3] }
Pregnancy	50% increase in blood volume + ↑ cardiac output + hypercoagulability + labour-related surges → RV cannot adapt → crisis; maternal mortality 30-50%	Contraception mandatory; if pregnant: multidisciplinary PH-OB-anaesthesia clinic, planned caesarean, epidural (avoid GA), continue PAH therapy[1] }
Volume overload / aggressive fluid resuscitation	RV on flat Starling curve → dilates further → septal shift → LV compression → output falls	Cautious 250 mL boluses with reassessment; diurese if overloaded; target RA pressure 5-10 mmHg[9] }
Perioperative / procedural	Anaesthetic vasodilation + positive-pressure ventilation + withdrawal of PAH drugs intra-op	Highest-risk period: continue PAH therapy peri-op, avoid hypotension, plan post-op ICU admission[10] }
Anaemia / blood loss	Reduced oxygen-carrying capacity → worsens RV ischaemia; tachycardia ↑ RV demand	Transuse to keep Hb ≥90-100 g/L in decompensated PH (RV oxygen supply/demand is critical)[12] }
High-altitude exposure / air travel	Hypobaric hypoxia → hypoxic pulmonary vasoconstriction	Supplemental oxygen for all flights; avoid altitude in uncontrolled PH

Identifying the trigger — a systematic approach

BEDSIDE — exclude immediate killers: Airway/breathing (hypoxia? SpO2, ABG — acidosis/hypercapnia?), Circulation (arrhythmia? 12-lead + rhythm strip — new AF/VT?), Disability (sepsis? temperature, lactate, cultures)
DRUG HISTORY — the single most common avoidable trigger: Confirm the patient has received their usual sildenafil/tadalafil, bosentan/macitentan, riociguat, and prostacyclin (inhaled iloprost, SC/IV treprostinil). A missed dose or stopped infusion can precipitate crisis within hours. Check adherence, supply, and whether any were withheld (e.g., for procedures)
INFECTION SCREEN — pneumonia (most common infection trigger), line infection, UTI, bacteraemia. Send cultures, CXR, procalcitonin, lactate. Treat early and broadly
EXCLUDE PE — D-dimer (low utility in PH), CTPA if haemodynamically stable; bedside echo (acute RV dilatation with McConnell sign suggests PE). Empiric LMWH if suspicion high
ECHO — compare to prior: worsening RV dilatation, new septal shift, change in TAPSE, new pericardial effusion, new TR jet velocity
VOLUME STATUS — clinical (JVP, oedema, hepatomegaly), echo (IVC, RA size), and if available PA catheter (RA pressure, PCWP, cardiac index, PVR). A common error is over-resuscitating the failing RV

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Right ventricular failure pathophysiology — the vicious spiral

Pathophysiology of acute RV failure in pulmonary hypertension: rising PVR, RV dilation, septal bowing, falling LV preload and cardiac output — FigurePressure overload dilates the thin-walled RV; septal bowing starves LV filling — the RV failure spiral.

The decompensation spiral: how RV failure becomes irreversible

TRIGGER raises PVR (hypoxia, acidosis, PE, sepsis, arrhythmia) → pulmonary artery pressure rises acutely
RV cannot eject against high afterload → RV end-systolic and end-diastolic volume INCREASE → RV dilates. The normal RV is a thin-walled, low-pressure, volume-tolerant chamber that CANNOT acutely generate high pressures (unlike the LV)
RV wall stress rises (Laplace: T = P × r / 2h) → RV oxygen demand rises sharply at the same time that coronary perfusion is falling. RV myocardium becomes ischaemic — RV infarction patterns (ST elevation in V4R) can develop[12] }
RV ISCHAEMIA — uniquely vulnerable: the RV receives coronary perfusion in BOTH systole and diastole (low-pressure chamber normally), but as RV pressure rises, systolic perfusion is lost; falling systemic BP (from low output) reduces diastolic perfusion. Supply-demand mismatch → RV dysfunction worsens → lower output → worse perfusion — a true vicious cycle[12] }
SEPTAL SHIFT — RV dilatation pushes the interventricular septum LEFTWARD into the LV cavity (paradoxical/D-shaped septum on echo). This is the central mechanical lesion of PH crisis
LV COMPRESSION — the septum compresses the LV during diastole → LV cannot fill adequately → LV preload falls → LV stroke volume falls (despite a normal LV). LV end-diastolic volume may be tiny
LOW CARDIAC OUTPUT → systemic hypotension → coronary hypoperfusion (both LV and RV) → worsening biventricular ischaemia → further RV failure. The patient is now in cardiogenic shock
TRICUSPID REGURGITITATION WORSENS — RV annular dilatation from RV enlargement → functional TR → further reduction in forward RV output → worsening venous congestion
VENOUS CONGESTION & ENDO-ORGAN FAILURE — high RA pressure → congested liver (ischemic hepatitis), kidneys (pre-renal + congestive nephropathy → AKI), gut (ileus, malabsorption). This is the clinical face of irreversible RV failure
DEATH if the spiral is not broken by reducing PVR + restoring RV perfusion + mechanical support (VA-ECMO)

RV–LV interdependence — the concept examiners love

The RV and LV share the interventricular septum and pericardial space. They are not independent pumps — what happens in one directly constrains the other. This is RV–LV interdependence (ventricular coupling). In PH crisis, the failing RV IMPRISIONS the LV via septal shift and pericardial constraint.[11] }
Why the normal RV cannot cope with acute afterload. The RV is crescent-shaped, thin-walled (3-5 mm), and adapted to ejecting into a low-resistance circuit (normal PVR ~1-2 Wood units). It has little contractile reserve against acute pressure. The LV, by contrast, is conical, thick-walled, and pressure-adapted. When PVR rises suddenly, the RV decompensates at an afterload the LV would tolerate easily.[11] }
RV coronary perfusion is bivascular and phase-dependent. The RV free wall is supplied by the right coronary artery (RCA) branches. Normally perfused in BOTH systole and diastole (because RV pressure is low). As RV systolic pressure rises toward systemic, systolic perfusion is LOST. Combined with falling systemic diastolic pressure (shock), RV ischaemia develops. This is why maintaining systemic BP with noradrenaline is RV-protective — it preserves coronary driving pressure.[12] }
The 'suicide RV'. Once the spiral is established (high PVR → RV failure → low output → ischaemia → more RV failure), it becomes self-sustaining and the RV is said to be 'committed to failure' — only mechanical unloading (VA-ECMO) or dramatic PVR reduction can break it. Recognise and intervene EARLY before this point.[3] }

ICU management — drug-by-drug

ICU management of PH crisis: optimise preload, reduce PVR with oxygen and inhaled vasodilators, support RV with milrinone or dobutamine, maintain SVR with vasopressin, escalate to VA-ECMO — FigurePH crisis: careful preload, lower PVR (O₂, iNO/prostacyclin), support RV inotropy, defend coronary perfusion pressure, escalate MCS early.

Vasopressors in PH crisis — effect on systemic vs pulmonary vasculature

Agent	Systemic effect	Pulmonary effect	Role in PH crisis
Noradrenaline (FIRST-LINE)	α1 vasoconstriction → ↑ SVR, ↑ MAP	Mild α1 on pulmonary vessels → slight ↑ PVR, but NET beneficial (systemic effect dominates)	FIRST-LINE: restores systemic BP → restores RV coronary perfusion. Titrate to MAP ≥65[3] }
Adrenaline	α + β → ↑ SVR + inotropy + chronotropy	Modest ↑ PVR, ↑ RV O2 demand (tachycardia, arrhythmia)	Second-line if noradrenaline inadequate; adds inotropy. Caution: lactate rise, arrhythmia
Vasopressin	V1 → ↑ SVR (peripheral)	Pulmonary vasculature relatively INSPARIED; may REDUCE PVR:PVR ratio (favourable)	USEFUL ADD-ON: can reduce PVR relative to SVR. Consider in refractory shock with rising PVR[8] }
Phenylephrine (AVOID)	Pure α1 → ↑ SVR	Significant ↑ PVR (no β2 offset) → WORSENS RV afterload	AVOID — pure afterload rise on RV can precipitate or worsen crisis[7] }
Metaraminol	α1 (some β1) → ↑ SVR	Variable ↑ PVR	CAUTION — common peri-induction agent but can spike PVR; use only short-term, transition to noradrenaline

Inotropes in PH crisis — supporting the failing RV

Agent	Mechanism	RV effect	PVR effect	Cautions
Milrinone (PREFERRED)	PDE3 inhibitor → ↑ cAMP	↑ RV contractility	↓ PVR (pulmonary vasodilation)	Systemic hypotension (often need noradrenaline concurrently); long half-life (2-3 h); thrombocytopenia; cannot rapidly titrate off[3] }
Dobutamine	β1 agonist → ↑ cAMP	↑ RV (and LV) contractility	Mild ↓ PVR (β2) at low doses	Tachycardia, arrhythmia, hypotension at higher doses; ↑ myocardial O2 demand; less pulmonary-selective than milrinone
Levosimendan	Cardiac myofilament Ca²⁺ sensitizer (no cAMP)	↑ contractility without ↑ O2 demand	↓ PVR	Cost, limited availability; QT prolongation; less tachyarrhythmia than dobutamine — consider if tachyarrhythmia limits catecholamines
Digoxin	Na-K ATPase inhibition → ↑ intracellular Ca²⁺	Modest inotropy	None	Mainly for RATE CONTROL of AF, not primary inotrope in crisis; narrow therapeutic window

Pulmonary vasodilators — selective vs non-selective

Agent	Route	Selectivity	Onset/dose	Key advantages	Key cautions
Inhaled nitric oxide (iNO)	Inhaled gas	HIGHLY SELECTIVE pulmonary (inhaled → ventilated alveoli only; bound by Hb systemically → no systemic vasodilation)	5-20 ppm; onset seconds	Gold standard for selective pulmonary vasodilation; rapid; no systemic hypotension	Methaemoglobinaemia; rebound PH on withdrawal (taper slowly); cost ($150-300/h); NO2 toxicity at high dose; V/Q matching improved (only ventilated units vasodilate)
Inhaled epoprostenol (PGI2)	Nebulised	SELECTIVE pulmonary	10-50 ng/kg/min; nebulised continuously	Cheaper than iNO; equipotent; avoids methaemoglobinaemia	Requires continuous nebuliser; abrupt interruption causes rebound; systemic leak possible at high doses
Inhaled iloprost (PGI2 analogue)	Nebulised 6-9×/day	SELECTIVE pulmonary	2.5-5 mcg/inhaled dose	Oral/inhaled chronic formulation available; useful for step-down from iNO	Frequent dosing; cough; reversible with cessation
IV epoprostenol / treprostinil	Continuous IV	NON-SELECTIVE (pulmonary AND systemic)	Eoprostenol 1-12 ng/kg/min; titrate slowly	Potent background therapy for Group 1 PAH	Systemic hypotension (dangerous in crisis); central line sepsis risk; cannot abruptly stop; prostacyclin withdrawal can precipitate crisis
Sildenafil (PDE5i)	IV or oral	Pulmonary-selective (lung PDE5-rich)	10-20 mg IV TDS; 20 mg PO TDS	Oral available; smooth step-down from iNO; well-tolerated	Systemic hypotension (mild); NEVER with nitrates (profound hypotension); onset slower than inhaled
Riociguat (sGC stimulator)	Oral	Pulmonary	1-2.5 mg TDS	Alternative cGMP pathway	Hypotension; not combined with PDE5i (both ↑ cGMP — additive hypotension)
SYSTEMIC vasodilators — GTN, SNP, hydralazine	IV	NON-SELECTIVE (systemic > pulmonary)	—	None in crisis	DANGEROUS — systemic hypotension → RV ischaemia → worsening crisis. CONTRAINDICATED in acute decompensated PH

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Vasoactive drug selection — exam-grade reasoning

Why noradrenaline over phenylephrine. Both raise SVR. But phenylephrine is a PURE α1 agonist with no β2 — it constricts the pulmonary bed disproportionately and removes the favourable β2 pulmonary vasodilation that noradrenaline's modest β activity provides. In ex-vivo human pulmonary artery rings, phenylephrine produces greater pulmonary vasoconstriction than noradrenaline at equi-systemic doses. Net: phenylephrine raises PVR more per unit SVR gained — harmful.[7] }
Vasopressin — the dark horse. Pulmonary vasculature expresses little V1 receptor activity, so vasopressin raises SVR without proportionally raising PVR — the PVR:SVR ratio FALLS. In animal models of severe PH, vasopressin improved RV perfusion without worsening PVR. Use as an add-on when noradrenaline alone is insufficient or PVR is rising.[8] }
The milrinone + noradrenaline 'combo' is the workhorse. Milrinone lowers PVR and supports RV inotropy but causes systemic hypotension; noradrenaline restores SVR. Together they achieve the therapeutic goal: low PVR + adequate systemic BP + supported RV. This combination is the most frequently used vasoactive strategy in PH crisis.[3] }
SYSTEMIC vasodilators are CONTRAINDICATED. Glyceryl trinitrate, sodium nitroprusside, hydralazine, and high-dose dobutamine alone all lower SVR → systemic hypotension → RV ischaemia → spiral worsens. They may 'open' the pulmonary bed slightly but the systemic cost is catastrophic. The exception is when used as part of a deliberately balanced strategy WITH a vasopressor backing SVR — but this is advanced, not routine.[9] }
Inhaled vs IV prostacyclin. Inhaled epoprostenol/iloprost vasodilates only ventilated alveoli (improves V/Q matching) with no systemic spillover. IV prostacyclin vasodilates the entire pulmonary tree AND the systemic tree → hypotension. In crisis, prefer INHALED (or iNO) for selective pulmonary vasodilation. Reserve IV prostacyclin for patients already established on it chronically — and NEVER stop it abruptly (withdrawal crisis).[5] }
The iNO withdrawal trap. Abrupt cessation of iNO causes rebound pulmonary hypertension that can be WORSE than baseline and fatal. ALWAYS taper iNO slowly (e.g., reduce by 5 ppm every few hours) while transitioning to an oral agent (sildenafil) or inhaled prostacyclin. Plan the exit before you start iNO.[3] }

Mechanical ventilation in PH crisis

Ventilation strategy to protect the RV (lung-protective AND RV-protective)

AVOID INTUBATION if possible. Non-invasive ventilation may avoid the haemodynamic collapse that accompanies intubation in PH (anaesthetic vasodilation + loss of sympathetic tone + positive pressure → RV failure). Use NIV/HHF if the patient can protect their airway and oxygenation/ventilation failure is reversible
IF INTUBATING — anticipate cardiovascular collapse. Have noradrenaline, milrinone, and inhaled NO RUNNING BEFORE induction. Use a haemodynamically neutral induction: ketamine (maintains SVR, sympathetic preservation) or etomidate. AVOID propofol (profound vasodilation). AVOID high-dose opiates as sole agent. Full-stomach precautions; RSI with minimal apnoea
LUNG-PROTECTIVE + RV-PROTECTIVE settings: (a) Low tidal volumes 4-6 mL/kg PBW. (b) Lowest PEEP that maintains oxygenation (≤5-8 cmH2O — high PEEP raises intrathoracic pressure → compresses pulmonary vessels → raises transpulmonary pressure → raises RV afterload). (c) Plateau pressure <30 cmH2O. (d) Allow permissive hypercapnia if pH >7.2 (avoid hypercapnia that causes pulmonary vasoconstriction, but do not chase normocapnia at the cost of high pressures). (e) Lowest mean airway pressure possible
MINIMISE INTRATHORACIC PRESSURE — this is the cardinal rule. High intrathoracic pressure: (i) reduces venous return (preload falls), (ii) raises PVR (compresses alveolar vessels), (iii) reduces RV coronary perfusion. Use short inspiratory time, long expiratory time, low rate if possible
CORRECT THE GAS EXCHANGE FIRST — 100% FiO2 (pulmonary vasodilator), normalise pH, target SpO2 >92% and PaCO2 35-40 (or permissive up to 55 if pH >7.2)
AVOID DYNAMIC HYPERINFLATION / AUTO-PEEP — in COPD-Group 3 PH especially, trapped gas raises intrathoracic pressure catastrophically. Slow rate, long expiratory time
EXTUBATE EARLY — once the trigger is corrected and PVR-controlled, wean to spontaneous breathing/NIV as soon as possible. Positive-pressure ventilation is haemodynamically hostile to the PH RV

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Mechanical circulatory support (MCS)

Mechanical support options for refractory PH crisis

Modality	Mechanism	Indication	Limitations
VA-ECMO (preferred MCS)	Drains RA → oxygenates → returns to femoral artery; bypasses RV AND lung → unloads RV, supports systemic perfusion, restores coronary perfusion	Refractory cardiogenic shock from RV failure despite maximal medical therapy; bridge to transplant / recovery / decision	Bleeding, stroke, infection, limb ischaemia (femoral), LV distension (afterload from retrograde flow) — may need LV vent; can worsen pulmonary congestion if LV failing
Pulmonary artery pulsatility / RV assist device (RVAD)	Surgically or percutaneously (TandemHeart, ProtekDuo) unloads RA/RV directly → drains RA, returns to PA	RV failure without severe lung disease (need native lung gas exchange); bridge in selected centres	Requires functional lungs; not suitable if hypoxia is the driver; cannulation expertise needed
V-AV ECMO	Adds venous return to support both RV (VA) and oxygenation (VV)	Combined RV failure + severe hypoxaemia	Complexity, more cannulae, higher anticoagulation burden
IABP (intra-aortic balloon pump)	↓ LV afterload, ↑ coronary perfusion	Largely UNHELPFUL for primary RV failure — no direct RV support. Only if concomitant LV failure	Not first-line for PH crisis

[1]

VA-ECMO in PH crisis — when and how

INDICATION — PH crisis with refractory cardiogenic shock (rising lactate despite inotropes/vasopressors, MAP <65 on two pressors, cardiac index <1.8) despite: (a) maximal vasoactive therapy (noradrenaline + milrinone ± vasopressin), (b) inhaled pulmonary vasodilator (iNO or epoprostenol), (c) corrected triggers, (d) lung-protective ventilation
GOAL — unload the RV (rest), restore systemic perfusion and coronary perfusion, break the ischaemia spiral, allow time for reversibility or bridge to lung transplant
CANNULATION — femoro-femoral VA-ECMO is fastest; central cannulation if post-cardiotomy or for transplant bridge. Consider LV venting if LV distension (septal shift means LV is small — assess by echo; some need IABP or pigtail vent)
ANTICOAGULATION — unfractionated heparin to ACT 1.5× baseline (balance bleeding vs clotting; PH patients often on background anticoagulation)
MANAGE THE LUNG — on VA-ECMO, continue lung-protective ventilation (rest settings), keep iNO/pulmonary vasodilators running (to lower PVR for when ECMO is weaned), avoid high PEEP
DE-ESCALATION — as the trigger reverses (infection treated, PE anticoagulated, PAH therapy restarted), taper vasoactives, then trial off VA-ECMO by reducing flows while monitoring RV function (echo) and lactate. Wean iNO last (after ECMO decannulation)
DESTINATION — recovery (rare in fixed PAH), lung transplant (bridge to transplant in decompensated end-stage PAH — awake VA-ECMO preferred), or palliation / withdrawal if not a transplant candidate[6] }

MCS pearls for the exam

VA-ECMO is the MCS of choice for PH crisis. It simultaneously unloads the RV (drains the RA), bypasses the high-PVR lung, and delivers oxygenated blood to the systemic circulation — addressing all three limbs of the spiral (RV workload, oxygenation, systemic perfusion).[6] }
'Awake VA-ECMO' as a bridge to transplant. For end-stage PAH patients in crisis who are transplant candidates, elective intubation carries high mortality. Awake (non-intubated) femoral VA-ECMO supports the RV while the patient breathes spontaneously — preserves conditioning, avoids ventilation complications, and is the preferred bridge to lung transplant in expert centres.[3] }
Don't forget LV distension on VA-ECMO. Retrograde arterial flow from femoral VA-ECMO increases LV afterload. If LV function is impaired (or septum already shifted), the LV cannot eject against this — it distends, pulmonary oedema worsens, and LV thrombus can form. Echo monitoring; add LV vent (pigtails, IABP, or Impella) if needed.[9] }

Cardiac tamponade in PH

Pericardial effusion and tamponade in pulmonary hypertension

RECOGNISE THE SETTING — pericardial effusions are COMMON in severe PAH (up to 50% in advanced disease), arising from elevated RA pressure and pericardial lymphatic obstruction. SMALL effusions are usually haemodynamically insignificant; LARGE or rapidly accumulating effusions can cause tamponade
TAMPONADE PHYSIOLOGY IS ATYPICAL IN PH — the high RV pressure partially 'protects' against classical tamponade (equalisation of diastolic pressures still occurs, but the RV is already stiff). Clinical signs: rising RA pressure, falling cardiac output, tachycardia, muffled heart sounds may be absent. Echo: RA collapse (early), RV free-wall collapse (later), plethoric IVC, >1 cm effusion with swing
PERICARDIOCENTESIS — INDICATED for tamponade physiology (echo-confirmed chamber collapse, haemodynamic compromise). PERFORMED under echocardiographic guidance, subxiphoid or apical approach, by experienced operator. Drain slowly — rapid decompression can precipitate acute RV dilatation (the RV, freed from external constraint, suddenly dilates against high PVR)
CAUTION — pericardiocentesis in PH carries higher risk than usual (RV puncture in a dilated RV; bleeding; arrhythmia). Ensure crossmatched blood, continuous monitoring, surgical backup. Leave a drain if effusion is likely to re-accumulate (malignant, uraemic, or ongoing PAH)
AFTER PERICARDIOCENTESIS — reassess RV (echo), continue PH-specific therapy, and address the underlying trigger. Tamponade can be the presenting feature or a complication of PH crisis

[1]

Expanded clinical pearls

High-yield exam pearls — expanded set

The 'five H's that kill the PH RV': Hypoxia, Hypercapnia, Hydrogen ion (acidosis), Hypovolaemia (and hypervolaemia), Hypotension. Each raises PVR or lowers RV perfusion. Memorise these as the cardinal correctables — every PH crisis assessment should screen for and correct all five.[2] }
PA catheter is the diagnostic gold standard in refractory crisis. When vasopressors/inotropes are escalating, a PA catheter quantifies RA pressure, PCWP (pre- vs post-capillary), cardiac index, and PVR (Wood units = [mPAP – PCWP] / CO). Targets: RA pressure 5-10 mmHg, cardiac index >2.0, SvO2 >60%, PVR falling. The PA catheter tells you whether you are winning or losing.[1] }
Background PAH therapy must NEVER be interrupted. This is the single most preventable cause of crisis. On ICU admission: verify and continue sildenafil/tadalafil, bosentan/macitentan/ambrisentan, riociguat, and prostacyclins (inhaled iloprost, SC/IV treprostinil). If NPO, convert to IV/NG equivalent. NEVER stop a chronic prostacyclin infusion — withdrawal precipitates rebound crisis within hours.[3] }
Calcium channel blockers are NOT acute therapy. CCBs (nifedipine, diltiazem, amlodipine) are only useful in the ~10% of idiopathic PAH patients with a positive acute vasodilator challenge at right heart catheterisation, and are DANGEROUS in decompensated PH (negative inotropy → RV failure worsens; hypotension). Do not give CCBs in crisis.[1] }
Pregnancy counselling is a core of PH care. Pregnancy is contraindicated in all WHO Group 1 PAH (maternal mortality 30-50%). Reliable contraception (IUD, implant; oestrogen-containing pills carry VTE risk) is mandatory. If pregnancy occurs: multidisciplinary care, consider termination, planned caesarean under regional anaesthesia (avoid GA), and continue PAH therapy throughout. Postpartum (first 2-6 weeks) is the highest-risk period — volume shifts, autotransfusion, rising PVR.[1] }
Pharmacology of the three PAH pathways (examiner favourite): (1) Prostacyclin pathway — epoprostenol (IV), treprostinil (SC/IV/inhaled/oral), iloprost (inhaled), selexipag (oral IP receptor agonist). (2) Endothelin pathway — bosentan, macitentan, ambrisentan (ERAs). (3) Nitric oxide pathway — sildenafil/tadalafil (PDE5i), riociguat (sGC stimulator). Initial therapy is often combination (e.g., PDE5i + ERA; add prostacyclin if advanced).[1] }
McConnell's sign and the 60/60 sign for acute PE-induced PH crisis. On echo: McConnell's sign = RV free-wall hypokinesia with apical sparing (sensitive for acute PE). 60/60 sign = pulmonary acceleration time <60 ms PLUS tricuspid regurgitant jet velocity <60 mmHg (in the absence of chronic PH). These suggest an acute PE trigger superimposed on (or causing) the crisis.[11] }
TAPSE <17 mm = RV systolic dysfunction. Tricuspid annular plane systolic excursion (TAPSE) is the single most reproducible bedside measure of RV longitudinal systolic function. In PH crisis: serial TAPSE tracks recovery (improving) or deterioration (falling). TAPSE/systolic PV annular velocity (TAPSE/PASP ratio) is an even better RV-pulmonary coupling index.[11] }
Acute kidney injury is both a marker and amplifier of PH crisis. Low cardiac output + venous congestion (high RA pressure) → pre-renal + cardiorenal AKI. Rising creatinine portends poor outcome. Avoid nephrotoxins (NSAIDs, contrast if possible), optimise haemodynamics, and do NOT over-diurese (volume depletion worsens RV preload). CRRT may be needed for volume control in overloaded RV failure.[9] }
Liver function abnormalities are common and prognostic. Congestive hepatopathy (high RA pressure → sinusoidal congestion) → bilirubin rise, AST/ALT 2-5× normal, INR derangement. May mimic acute hepatitis. Improves with RV unloading. A fibrinogen/INR check is part of the PH crisis workup — coagulopathy complicates anticoagulation and ECMO.[9] }
Sepsis in PH is doubly dangerous. Sepsis causes systemic vasodilation (↓ SVR → RV ischaemia) AND sepsis-induced pulmonary microvascular dysfunction (↑ PVR), AND inflammatory myocardial depression (↓ RV contractility). Treat sepsis aggressively (Sepsis Six), but use restrictive fluids (RV hates volume), noradrenaline first-line, and screen for pulmonary source (pneumonia most common).[14] }
Atrial arrhythmia — restore sinus rhythm if possible. In PH, the atrial contribution to RV filling is large (stiff RV). New AF/atrial flutter commonly precipitates crisis. If haemodynamically unstable: synchronised DC cardioversion. If stable: amiodarone (IV load then infusion) for rhythm/rate control. AVOID rate-limiting CCBs (negative inotropy). Dofetilide/ibutilide in expert hands; digoxin for rate. Catheter ablation may be needed for recurrent atrial flutter.[9] }
Portopulmonary PH (Group 1) is a high-risk subtype. Pulmonary arterial hypertension associated with portal hypertension (portopulmonary PH) — decompensates precipitously with volume shifts (TIPS, variceal bleeding, liver failure). Specific: vasopressin and terlipressin (used for variceal bleeding) can spike PVR — use cautiously. Liver transplant is curative only if PVR is controlled pre-operatively.[1] }
The transition from iNO to oral therapy must be planned. iNO cannot be a long-term solution (cost, rebound). Once the crisis is breaking, overlap sildenafil (PO/IV) or inhaled iloprost, then taper iNO in 5-ppm steps over 12-24 h while watching PA pressure/cardiac index. A premature iNO taper causes rebound; a delayed taper wastes cost and delays mobilisation.[3] }
Don't forget venous thromboembolism prophylaxis — but anticoagulate carefully. PH patients are prothrombotic (stasis, low flow, some on prostacyclin lines). Unless actively bleeding, give VTE prophylaxis (LMWH). Many Group 1 PAH patients are on chronic warfarin (target INR ~2). In crisis: continue anticoagulation if possible; balance against bleeding if ECMO is planned. Note: warfarin absorption is unreliable in RV failure (gut congestion) — consider LMWH bridge.[2] }

Expanded red flags

Critical triggers and deterioration red flags

Sudden withdrawal of prostacyclin infusion → rebound fatal PH crisis within hours. Secure lines, never run dry, have backup pump.[3] }
New atrial fibrillation in known PH → loss of atrial kick can collapse RV output. Cardiovert if unstable.[9] }
Aggressive fluid bolus >500 mL → RV dilatation → septal shift → cardiogenic shock. Restrictive strategy.[9] }
Propofol induction for intubation → profound vasodilation → cardiovascular collapse. Use ketamine; have noradrenaline running.[10] }
Phenylephrine or metaraminol for hypotension → disproportionate PVR rise. Use noradrenaline.[7] }
High PEEP (>10) in ventilated PH patient → raised intrathoracic pressure → RV afterload spike. Lowest PEEP for oxygenation.[11] }
Systemic vasodilators (GTN, SNP) for 'afterload reduction' → catastrophic hypotension → RV ischaemia. CONTRAINDICATED.[9] }
Calcium channel blockers in decompensated PH → negative inotropy → RV failure worsens. AVOID in crisis.[1] }
Untreated hypoxia (SpO2 <90%) or acidosis (pH <7.2) → pulmonary vasoconstriction → spiral worsens. Correct immediately.[2] }
Pregnancy in severe PH → 30-50% maternal mortality. Contraception mandatory; multidisciplinary care if pregnant.[1] }
Pericardial effusion with chamber collapse on echo → tamponade — pericardiocentesis under echo guidance; drain slowly.[9] }
Rising lactate despite two vasopressors + inotrope → refractory cardiogenic shock — call ECMO team / transplant centre early.[6] }

Key trials and evidence

SUPER-1 — Sildenafil for PAH (Galie 2005)

Design: RCT, 278 patients with PAH, 12 weeks. Sildenafil 20/40/80 mg TDS vs placebo. Result: Improved 6-minute walk distance (+45-50 m), improved haemodynamics (lower mPAP, PVR), improved functional class. Effect maintained at 1 year. Significance: Established sildenafil (PDE5i) as first-line oral therapy for PAH. Basis for IV sildenafil use in PH crisis (pulmonary-selective vasodilation, oral step-down).[4] }

EARLY — Bosentan in mildly symptomatic PAH (Galie 2008)

Design: RCT, 185 patients with WHO Class II PAH. Bosentan (ERA) vs placebo, 6 months. Result: Reduced PVR by 22.6%, improved exercise capacity, delayed clinical worsening. Significance: Established EARLY initiation of endothelin receptor antagonists in mild PAH — underscored that PAH is a progressive disease and earlier therapy reduces events.[13] }

Hoeper 2019 — Intensive care, RV support and lung transplantation in PH

Scope: Authoritative review defining the ICU management of decompensated PH, RV support strategies, and the role of mechanical support / lung transplantation. Key messages: (1) PH crisis mortality remains 20-50% in ICU. (2) Standardised bundle — fix triggers, maintain SVR (noradrenaline), lower PVR (inhaled vasodilators), support RV (milrinone), avoid volume overload. (3) VA-ECMO (preferably awake) as bridge to transplant in refractory cases. (4) Lung transplant remains the definitive therapy for end-stage PAH. Significance: The reference framework cited in ESC/ERS and contemporary ICU guidelines for PH crisis.[3] }

CRASH report — Price 2017

Design: National UK survey of acute physicians managing PH crisis. Identified the commonest dilemmas: fluid resuscitation, choice of vasopressor, inhaled vasodilator availability, and inter-hospital transfer. Findings: Wide practice variation; only a minority of hospitals had iNO available; fluid over-resuscitation was common; missed background PAH therapy was a recurrent precipitant. Significance: Catalysed standardised pathways and the message 'do no harm — give noradrenaline, give inhaled vasodilator, withhold fluids, restart PAH drugs, ask the PH team'.[2] }

Hussain 2017 — Vasoconstrictor effects on human pulmonary arteries

Design: Ex-vivo human pulmonary artery ring tension study comparing noradrenaline, phenylephrine, vasopressin, metaraminol. Findings: Noradrenaline and metaraminol produced less pulmonary vasoconstriction than phenylephrine at equi-effective systemic doses; vasopressin had minimal effect on pulmonary arterial tone. Significance: Provides the mechanistic rationale for preferring noradrenaline (and vasopressin) over phenylephrine in PH crisis — minimise the pulmonary vasoconstrictive 'cost' of restoring SVR.[7] }

Sarkar 2015 — Vasopressin in severe PH (animal model)

Design: Porcine model of severe pulmonary hypertension. Compared vasopressin vs noradrenaline on PVR:SVR ratio. Findings: Vasopressin lowered the PVR:SVR ratio (relatively more systemic than pulmonary vasoconstriction) — favourable for RV. Noradrenaline raised both, vasopressin preferentially raised SVR. Significance: Mechanistic support for vasopressin as a useful adjunct in PH crisis shock — particularly when PVR is rising or noradrenaline dose is escalating.[8] }

Arrigo 2024 — RV failure from acutely increased RV afterload (ESC position)

Scope: European Society of Cardiology position paper on acute RV failure from sudden afterload rise (PE, ARDS, PH crisis, post-cardiotomy). Key messages: (1) Acute RV failure is under-recognised and carries >50% mortality. (2) The RV is 'afterload-intolerant'. (3) Management bundle: reverse the trigger, optimise preload (cautious — usually already overloaded), reduce RV afterload (inhaled vasodilators, correct hypoxia/acidosis), support contractility (milrinone, dobutamine, levosimendan), maintain SVR (noradrenaline), and MCS (VA-ECMO) for refractory cases. Significance: Contemporary authoritative framework directly applicable to PH crisis.[9] }

References

[1]Humbert M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Eur Heart J, 2022.PMID 36017548
[2]Price LC, et al. The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension Thorax, 2017.PMID 28904006
[3]Hoeper MM, et al. Intensive care, right ventricular support and lung transplantation in patients with pulmonary hypertension Eur Respir J, 2019.PMID 30545979
[4]Galie N, et al. Sildenafil citrate therapy for pulmonary arterial hypertension N Engl J Med, 2005.PMID 16291984
[5]Hoeper MM, et al. Long-term effects of intravenous iloprost in patients with idiopathic pulmonary arterial hypertension deteriorating on non-parenteral therapy BMC Pulm Med, 2011.PMID 22133492
[6]Hoeper MM, et al. Extracorporeal Life Support in Pulmonary Hypertension: Practical Aspects Semin Respir Crit Care Med, 2023.PMID 37709284
[7]Hussain A, et al. The differential effects of systemic vasoconstrictors on human pulmonary artery tension Eur J Cardiothorac Surg, 2017.PMID 28164217
[8]Sarkar J, et al. Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock Shock, 2015.PMID 25565637
[9]Arrigo M, et al. Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale): a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology Eur Heart J Acute Cardiovasc Care, 2024.PMID 38135288
[10]Price LC, et al. Perioperative management of patients with pulmonary hypertension undergoing non-cardiothoracic, non-obstetric surgery: a systematic review and expert consensus statement Br J Anaesth, 2021.PMID 33612249
[11]Aubry A, Vieillard-Baron A. [Cor pulmonale] Rev Mal Respir, 2020.PMID 32088063
[12]Pavsic N, et al. The association between myocardial ischemia and myocardial dysfunction in adult patients with systemic right ventricle - A single centre multimodality study Int J Cardiol, 2023.PMID 37087053
[13]Galie N, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial Lancet, 2008.PMID 18572079
[14]Bernier ML, et al. Spectrum of Current Management of Pediatric Pulmonary Hypertensive Crisis Crit Care Explor, 2019.PMID 32166278

[1]

WHO PH classification

Group	Cause	Examples	Key features
1 (PAH)	Pulmonary arterial disease	Idiopathic, heritable (BMPR2), CTD (scleroderma), portal HTN, congenital heart disease, drugs	Pre-capillary, elevated PVR, responsive to PAH-specific therapy
2 (Left heart)	Post-capillary	HFrEF, HFpEF, valvular (mitral), congenital	Elevated PCWP (>15), treat underlying heart disease
3 (Lung disease)	Hypoxia-driven	COPD, ILD, OSA, chronic high altitude	Treat underlying lung disease, oxygen
4 (CTEPH)	Chronic thromboembolic	Organised thrombi in pulmonary arteries	Potentially curable: pulmonary endarterectomy
5 (Multifactorial)	Various	Sarcoidosis, haematological, metabolic, renal	Treat underlying cause

[1]

Management of acute pulmonary hypertensive crisis

RECOGNISE — known PH patient with: hypotension (SBP <90), rising lactate, RV dysfunction on echo (dilated RV, septal shift, reduced TAPSE), rising CVP, falling cardiac output
IDENTIFY AND CORRECT PRECIPITANTS — (a) Hypoxia (SpO2 <90 → pulmonary vasoconstriction). (b) Acidosis (pH <7.3 → pulmonary vasoconstriction). (c) Hypercapnia (PaCO2 >45 → pulmonary vasoconstriction). (d) Arrhythmia (AF — common in PH, worsens RV filling). (e) Volume overload (excess fluids → RV dilatation). (f) Sepsis/infection. (g) Pulmonary embolism. (h) Non-adherence to PH medications (sildenafil, bosentan)
MAINTAIN SYSTEMIC BP — noradrenaline (alpha vasoconstriction → systemic BP ↑ → coronary perfusion to RV). Target: MAP ≥65. Avoid: pure alpha agonists (phenylephrine — may worsen PVR). Vasopressin: variable effect (may reduce PVR — some evidence)
REDUCE PVR — (a) Inhaled NO (5-20 ppm — selective pulmonary vasodilation, no systemic hypotension). (b) Inhaled epoprostenol (10-50 ng/kg/min — alternative to NO). (c) IV sildenafil (10-20 mg TDS — PDE5 inhibitor — reduces PVR). (d) IV riociguat (soluble guanylate cyclase stimulator). (e) Correct hypoxia/acidosis/hypercapnia (reduces hypoxic pulmonary vasoconstriction)
SUPPORT RV — (a) Milrinone (PDE3 inhibitor — inotropy + pulmonary vasodilation — PREFERRED). (b) Dobutamine (beta-1 — inotropy — may cause hypotension). (c) Levosimendan (calcium sensitiser — inotropy — less arrhythmia). (d) Target: cardiac index >2.0 L/min/m², mixed venous saturation >60%
AVOID EXCESS FLUIDS — volume loading >500 mL → RV dilatation → septal shift → LV compression → worse output. If hypovolaemic: cautious 250 mL bolus (assess response). If overloaded: diurese (frusemide)
MECHANICAL SUPPORT (refractory) — VA-ECMO (bridge to recovery, transplant, or decision). Reduces RV load (bypasses pulmonary circulation), supports systemic perfusion
TREAT UNDERLYING PH — restart/optimize PAH-specific therapy (sildenafil, bosentan, macitentan, riociguat, prostacyclins). Consider: lung transplant evaluation (if end-stage)

[1]

Exam practice

SAQ — Pulmonary hypertensive crisis with right ventricular failure

10 minutes · 10 marks

[1]

SAQ — Escalation of therapy in refractory pulmonary hypertension

10 minutes · 10 marks

[1]

Clinical pearls [1]

High-yield PH crisis points for CICM/FFICM exam

RV failure is the MAIN cause of death in PH crisis. RV pumps against high PVR → afterload too high → RV dilates → septum shifts LEFT → compresses LV → LV cannot fill → low cardiac output → cardiogenic shock → death. The vicious cycle: high PVR → RV failure → low output → ischaemia → more RV failure. MUST break the cycle by reducing PVR + supporting RV.[2] }
AVOID excess volume loading (>500 mL). In most shock states: give fluids to increase preload → increase cardiac output (Frank-Starling). BUT in PH crisis: RV is on the FLAT part of Starling curve (dilated, failing — volume doesn't increase output). MORE volume → MORE RV dilatation → MORE septal shift → LESS LV filling → LESS output → WORSE. CAREFUL fluids: 250 mL bolus, assess, don't repeat if no improvement.[2] }
Noradrenaline is FIRST-LINE vasopressor. Alpha vasoconstriction → systemic BP ↑ → coronary perfusion to RV (RV ischaemia is a major problem in PH crisis — RV needs oxygen but low output → ischaemia). Noradrenaline: slightly increases PVR (alpha on pulmonary vessels) but SYSTEMIC effect dominates (net benefit — RV perfusion preserved). Avoid: phenylephrine (pure alpha — may significantly worsen PVR).[3] }
Inhaled NO — selective pulmonary vasodilation. NO gas inhaled → reaches ventilated alveoli → diffuses to pulmonary vessels → vasodilation → reduces PVR. RAPIDLY metabolised by haemoglobin (no systemic effect — no systemic hypotension). Dose: 5-20 ppm (titrate). Response: improved cardiac output, lower PVR, better oxygenation. CAUTION: methaemoglobinaemia (monitor), rebound PH on withdrawal (taper slowly — never abrupt). COST: very expensive ($150-300/hour).[5] }
Hypoxia, acidosis, hypercapnia — pulmonary vasoconstrictors. These are POTENT pulmonary vasoconstrictors (hypoxic pulmonary vasoconstriction — normal physiological response but DANGEROUS in PH). In PH crisis: MUST correct immediately. Hypoxia: 100% FiO2 (pulmonary vasodilator — oxygen relaxes pulmonary vessels). Acidosis: correct (bicarbonate if pH <7.2 — acidosis constricts). Hypercapnia: ventilate (if intubated — increase rate, but avoid high intrathoracic pressure — see below).[2] }
Mechanical ventilation — carefully adjusted. If intubating: (1) Use LOW tidal volumes (4-6 mL/kg — high intrathoracic pressure compresses RV). (2) Low PEEP (≤5 — high PEEP increases intrathoracic pressure → reduces venous return → worsens RV output). (3) Low respiratory rate (allow long expiration — reduce intrathoracic pressure). (4) Permissive hypercapnia (if pH >7.2 — accept high CO2 to avoid high pressures). (5) Ketamine induction (maintains BP — avoid propofol/fentanyl — hypotension in PH is dangerous).[3] }
Arrhythmia — common precipitant (especially AF). PH patients: dilated RV → atrial stretch → atrial fibrillation (AF). AF → loss of atrial kick (important for RV filling in stiff RV) → reduced preload → reduced cardiac output → crisis. MANAGEMENT: (a) RATE CONTROL: amiodarone (IV — rate + rhythm), digoxin (IV — rate). Avoid: calcium channel blockers (negative inotropy — worsen RV failure), beta-blockers (negative inotropy — caution). (b) RHYTHM CONTROL: cardioversion (if haemodynamically unstable — synchronised DC shock).[3] }
Milrinone — PREFERRED inotrope for PH crisis. PDE3 inhibitor → increases cAMP → increases contractility (inotropy) + vasodilation (both systemic and pulmonary). ADVANTAGES: (a) Improves RV contractility (support failing RV). (b) REDUCES PVR (pulmonary vasodilation — reduces RV afterload). (c) Less tachycardia than dobutamine. DISADVANTAGES: (a) Systemic hypotension (vasodilation — may need noradrenaline concurrently). (b) Long half-life (2-3h — not rapidly titratable). DOSE: 0.125-0.75 mcg/kg/min.[4] }
Sildenafil (PDE5 inhibitor) — oral/IV for PH. PDE5 inhibitor → increases cGMP → pulmonary vasodilation → reduces PVR. DOSE: 10-20 mg IV TDS (or 20 mg PO TDS). RESPONSE: lower PVR, improved cardiac output, improved 6-minute walk distance (chronic). ADVANTAGE: oral available (transition from IV). CAUTION: systemic hypotension (less than milrinone). Do NOT combine with nitrates (severe hypotension).[4] }
Echo assessment in PH crisis — ESSENTIAL. (1) RV SIZE: dilated (RV/LV ratio >1 — normal <0.6). (2) SEPTAL MOTION: D-shaped LV (septum pushed into LV during diastole — from RV volume/pressure overload). (3) TAPSE (tricuspid annular plane systolic excursion): <17 mm = RV systolic dysfunction. (4) TRICUSPID REGURGITATION: velocity >2.8 m/s = elevated pulmonary pressure. (5) PERICARDIAL EFFUSION: common in PH (from RV failure). (6) IVC: dilated, non-collapsing = high RA pressure. SERIAL echo: track response to therapy (RV shrinking? septum returning to normal?).[2] }
Pulmonary embolism — common in PH. PH → venous stasis + RV dysfunction → DVT/PE risk. PE → acute increase in PVR → PH crisis. ALWAYS: DVT prophylaxis (LMWH — enoxaparin 40 mg daily — unless contraindicated). If PH crisis + suspected PE: CT pulmonary angiography (if stable enough), or empiric anticoagulation (LMWH — if unstable). THROMBOLYSIS: only if massive PE with shock (controversial in PH — bleeding risk).[2] }
Pregnancy is CONTRAINDICATED in severe PH. Pregnancy → volume overload (50% increase blood volume) + increased cardiac output + hypercoagulable → PH crisis → maternal mortality 30-50%. CONTRACEPTION: essential (effective methods — IUD, implant). If pregnant: early termination recommended (if severe PH). If continuing: multidisciplinary care (PH specialist + obstetrics + anaesthetics), planned delivery (caesarean), PAH-specific therapy throughout.[1] }
Lung transplant — definitive for end-stage PH. INDICATIONS: (1) Refractory PH despite maximal therapy (sildenafil, bosentan, prostacyclins). (2) Recurrent PH crises. (3) Declining functional capacity (NYHA IV). (4) Cardiac index <2.0, RA pressure >15, PVR >5 Wood units despite therapy. TYPES: bilateral lung transplant (preferred for PH — more room for new lungs) or heart-lung transplant (if severe RV failure — irreversible). OUTCOMES: 1-year survival 80-90%, 5-year survival 50-60%. BRIDGE: VA-ECMO (if crisis → stabilise until transplant).[6] }
CICM exam: distinguish pre-capillary from post-capillary PH. PRE-CAPILLARY (Groups 1, 3, 4, 5): PCWP ≤15 mmHg (no left heart obstruction — problem is in PULMONARY vessels). Treat: pulmonary vasodilators (NO, sildenafil, prostacyclins). POST-CAPILLARY (Group 2): PCWP >15 mmHg (left heart disease — problem is UPSTREAM). Treat: LEFT HEART (diurese, afterload reduce, treat valve). DON'T give pulmonary vasodilators to post-capillary PH (may worsen pulmonary oedema — more blood flows to lungs but can't exit through left heart).[1] }

Red flags

Prognosis

PH crisis outcomes (Price 2019)

Pregnancy with PH: maternal mortality 30-50% (contraindicated).

[1]

Triggers and precipitants

Common precipitants of acute PH decompensation

Trigger	Mechanism of decompensation	Key management point
Hypoxia / hypercapnia / acidosis	Hypoxic pulmonary vasoconstriction + acidosis directly constrict pulmonary arterioles → PVR rises sharply	Correct immediately: 100% FiO2, ventilate to normocapnia, bicarbonate if pH <7.2[2] }
Arrhythmia (new AF/flutter)	Loss of atrial kick → loss of ~25-30% RV preload → RV output collapses; atrial stretch from dilated RA is the substrate	Urgent rhythm/rate control — synchronised cardioversion if unstable; amiodarone; AVOID CCB/beta-blocker monotherapy[9] }
Sepsis / systemic infection	Sepsis-induced myocardial depression + vasodilation (low systemic BP → RV ischaemia) + pulmonary neutrophil activation ↑ PVR + iNOS downregulation	Early antibiotics, source control, careful vasopressor support (noradrenaline); restrictive fluids[14] }
Acute pulmonary embolism	Acute obstruction of pulmonary vasculature → sudden PVR spike on already-compromised RV	Empiric anticoagulation if unstable; CTPA if stable; thrombolysis for massive PE with shock (weigh bleeding)[11] }
Withdrawal of PH-specific therapy	Sudden cessation of PDE5i/ERA/prostacyclin → rebound pulmonary vasoconstriction; missed doses are a leading avoidable cause of crisis	NEVER interrupt background PAH therapy — confirm and restart sildenafil, bosentan, prostacyclin immediately on admission; NG/IV route if NPO[3] }
Pregnancy	50% increase in blood volume + ↑ cardiac output + hypercoagulability + labour-related surges → RV cannot adapt → crisis; maternal mortality 30-50%	Contraception mandatory; if pregnant: multidisciplinary PH-OB-anaesthesia clinic, planned caesarean, epidural (avoid GA), continue PAH therapy[1] }
Volume overload / aggressive fluid resuscitation	RV on flat Starling curve → dilates further → septal shift → LV compression → output falls	Cautious 250 mL boluses with reassessment; diurese if overloaded; target RA pressure 5-10 mmHg[9] }
Perioperative / procedural	Anaesthetic vasodilation + positive-pressure ventilation + withdrawal of PAH drugs intra-op	Highest-risk period: continue PAH therapy peri-op, avoid hypotension, plan post-op ICU admission[10] }
Anaemia / blood loss	Reduced oxygen-carrying capacity → worsens RV ischaemia; tachycardia ↑ RV demand	Transuse to keep Hb ≥90-100 g/L in decompensated PH (RV oxygen supply/demand is critical)[12] }
High-altitude exposure / air travel	Hypobaric hypoxia → hypoxic pulmonary vasoconstriction	Supplemental oxygen for all flights; avoid altitude in uncontrolled PH

Identifying the trigger — a systematic approach

BEDSIDE — exclude immediate killers: Airway/breathing (hypoxia? SpO2, ABG — acidosis/hypercapnia?), Circulation (arrhythmia? 12-lead + rhythm strip — new AF/VT?), Disability (sepsis? temperature, lactate, cultures)
DRUG HISTORY — the single most common avoidable trigger: Confirm the patient has received their usual sildenafil/tadalafil, bosentan/macitentan, riociguat, and prostacyclin (inhaled iloprost, SC/IV treprostinil). A missed dose or stopped infusion can precipitate crisis within hours. Check adherence, supply, and whether any were withheld (e.g., for procedures)
INFECTION SCREEN — pneumonia (most common infection trigger), line infection, UTI, bacteraemia. Send cultures, CXR, procalcitonin, lactate. Treat early and broadly
EXCLUDE PE — D-dimer (low utility in PH), CTPA if haemodynamically stable; bedside echo (acute RV dilatation with McConnell sign suggests PE). Empiric LMWH if suspicion high
ECHO — compare to prior: worsening RV dilatation, new septal shift, change in TAPSE, new pericardial effusion, new TR jet velocity
VOLUME STATUS — clinical (JVP, oedema, hepatomegaly), echo (IVC, RA size), and if available PA catheter (RA pressure, PCWP, cardiac index, PVR). A common error is over-resuscitating the failing RV

[1]

Right ventricular failure pathophysiology — the vicious spiral

The decompensation spiral: how RV failure becomes irreversible

TRIGGER raises PVR (hypoxia, acidosis, PE, sepsis, arrhythmia) → pulmonary artery pressure rises acutely
RV cannot eject against high afterload → RV end-systolic and end-diastolic volume INCREASE → RV dilates. The normal RV is a thin-walled, low-pressure, volume-tolerant chamber that CANNOT acutely generate high pressures (unlike the LV)
RV wall stress rises (Laplace: T = P × r / 2h) → RV oxygen demand rises sharply at the same time that coronary perfusion is falling. RV myocardium becomes ischaemic — RV infarction patterns (ST elevation in V4R) can develop[12] }
RV ISCHAEMIA — uniquely vulnerable: the RV receives coronary perfusion in BOTH systole and diastole (low-pressure chamber normally), but as RV pressure rises, systolic perfusion is lost; falling systemic BP (from low output) reduces diastolic perfusion. Supply-demand mismatch → RV dysfunction worsens → lower output → worse perfusion — a true vicious cycle[12] }
SEPTAL SHIFT — RV dilatation pushes the interventricular septum LEFTWARD into the LV cavity (paradoxical/D-shaped septum on echo). This is the central mechanical lesion of PH crisis
LV COMPRESSION — the septum compresses the LV during diastole → LV cannot fill adequately → LV preload falls → LV stroke volume falls (despite a normal LV). LV end-diastolic volume may be tiny
LOW CARDIAC OUTPUT → systemic hypotension → coronary hypoperfusion (both LV and RV) → worsening biventricular ischaemia → further RV failure. The patient is now in cardiogenic shock
TRICUSPID REGURGITITATION WORSENS — RV annular dilatation from RV enlargement → functional TR → further reduction in forward RV output → worsening venous congestion
VENOUS CONGESTION & ENDO-ORGAN FAILURE — high RA pressure → congested liver (ischemic hepatitis), kidneys (pre-renal + congestive nephropathy → AKI), gut (ileus, malabsorption). This is the clinical face of irreversible RV failure
DEATH if the spiral is not broken by reducing PVR + restoring RV perfusion + mechanical support (VA-ECMO)

RV–LV interdependence — the concept examiners love

The RV and LV share the interventricular septum and pericardial space. They are not independent pumps — what happens in one directly constrains the other. This is RV–LV interdependence (ventricular coupling). In PH crisis, the failing RV IMPRISIONS the LV via septal shift and pericardial constraint.[11] }
Why the normal RV cannot cope with acute afterload. The RV is crescent-shaped, thin-walled (3-5 mm), and adapted to ejecting into a low-resistance circuit (normal PVR ~1-2 Wood units). It has little contractile reserve against acute pressure. The LV, by contrast, is conical, thick-walled, and pressure-adapted. When PVR rises suddenly, the RV decompensates at an afterload the LV would tolerate easily.[11] }
RV coronary perfusion is bivascular and phase-dependent. The RV free wall is supplied by the right coronary artery (RCA) branches. Normally perfused in BOTH systole and diastole (because RV pressure is low). As RV systolic pressure rises toward systemic, systolic perfusion is LOST. Combined with falling systemic diastolic pressure (shock), RV ischaemia develops. This is why maintaining systemic BP with noradrenaline is RV-protective — it preserves coronary driving pressure.[12] }
The 'suicide RV'. Once the spiral is established (high PVR → RV failure → low output → ischaemia → more RV failure), it becomes self-sustaining and the RV is said to be 'committed to failure' — only mechanical unloading (VA-ECMO) or dramatic PVR reduction can break it. Recognise and intervene EARLY before this point.[3] }

ICU management — drug-by-drug

Vasopressors in PH crisis — effect on systemic vs pulmonary vasculature

Agent	Systemic effect	Pulmonary effect	Role in PH crisis
Noradrenaline (FIRST-LINE)	α1 vasoconstriction → ↑ SVR, ↑ MAP	Mild α1 on pulmonary vessels → slight ↑ PVR, but NET beneficial (systemic effect dominates)	FIRST-LINE: restores systemic BP → restores RV coronary perfusion. Titrate to MAP ≥65[3] }
Adrenaline	α + β → ↑ SVR + inotropy + chronotropy	Modest ↑ PVR, ↑ RV O2 demand (tachycardia, arrhythmia)	Second-line if noradrenaline inadequate; adds inotropy. Caution: lactate rise, arrhythmia
Vasopressin	V1 → ↑ SVR (peripheral)	Pulmonary vasculature relatively INSPARIED; may REDUCE PVR:PVR ratio (favourable)	USEFUL ADD-ON: can reduce PVR relative to SVR. Consider in refractory shock with rising PVR[8] }
Phenylephrine (AVOID)	Pure α1 → ↑ SVR	Significant ↑ PVR (no β2 offset) → WORSENS RV afterload	AVOID — pure afterload rise on RV can precipitate or worsen crisis[7] }
Metaraminol	α1 (some β1) → ↑ SVR	Variable ↑ PVR	CAUTION — common peri-induction agent but can spike PVR; use only short-term, transition to noradrenaline

Inotropes in PH crisis — supporting the failing RV

Agent	Mechanism	RV effect	PVR effect	Cautions
Milrinone (PREFERRED)	PDE3 inhibitor → ↑ cAMP	↑ RV contractility	↓ PVR (pulmonary vasodilation)	Systemic hypotension (often need noradrenaline concurrently); long half-life (2-3 h); thrombocytopenia; cannot rapidly titrate off[3] }
Dobutamine	β1 agonist → ↑ cAMP	↑ RV (and LV) contractility	Mild ↓ PVR (β2) at low doses	Tachycardia, arrhythmia, hypotension at higher doses; ↑ myocardial O2 demand; less pulmonary-selective than milrinone
Levosimendan	Cardiac myofilament Ca²⁺ sensitizer (no cAMP)	↑ contractility without ↑ O2 demand	↓ PVR	Cost, limited availability; QT prolongation; less tachyarrhythmia than dobutamine — consider if tachyarrhythmia limits catecholamines
Digoxin	Na-K ATPase inhibition → ↑ intracellular Ca²⁺	Modest inotropy	None	Mainly for RATE CONTROL of AF, not primary inotrope in crisis; narrow therapeutic window

Pulmonary vasodilators — selective vs non-selective

Agent	Route	Selectivity	Onset/dose	Key advantages	Key cautions
Inhaled nitric oxide (iNO)	Inhaled gas	HIGHLY SELECTIVE pulmonary (inhaled → ventilated alveoli only; bound by Hb systemically → no systemic vasodilation)	5-20 ppm; onset seconds	Gold standard for selective pulmonary vasodilation; rapid; no systemic hypotension	Methaemoglobinaemia; rebound PH on withdrawal (taper slowly); cost ($150-300/h); NO2 toxicity at high dose; V/Q matching improved (only ventilated units vasodilate)
Inhaled epoprostenol (PGI2)	Nebulised	SELECTIVE pulmonary	10-50 ng/kg/min; nebulised continuously	Cheaper than iNO; equipotent; avoids methaemoglobinaemia	Requires continuous nebuliser; abrupt interruption causes rebound; systemic leak possible at high doses
Inhaled iloprost (PGI2 analogue)	Nebulised 6-9×/day	SELECTIVE pulmonary	2.5-5 mcg/inhaled dose	Oral/inhaled chronic formulation available; useful for step-down from iNO	Frequent dosing; cough; reversible with cessation
IV epoprostenol / treprostinil	Continuous IV	NON-SELECTIVE (pulmonary AND systemic)	Eoprostenol 1-12 ng/kg/min; titrate slowly	Potent background therapy for Group 1 PAH	Systemic hypotension (dangerous in crisis); central line sepsis risk; cannot abruptly stop; prostacyclin withdrawal can precipitate crisis
Sildenafil (PDE5i)	IV or oral	Pulmonary-selective (lung PDE5-rich)	10-20 mg IV TDS; 20 mg PO TDS	Oral available; smooth step-down from iNO; well-tolerated	Systemic hypotension (mild); NEVER with nitrates (profound hypotension); onset slower than inhaled
Riociguat (sGC stimulator)	Oral	Pulmonary	1-2.5 mg TDS	Alternative cGMP pathway	Hypotension; not combined with PDE5i (both ↑ cGMP — additive hypotension)
SYSTEMIC vasodilators — GTN, SNP, hydralazine	IV	NON-SELECTIVE (systemic > pulmonary)	—	None in crisis	DANGEROUS — systemic hypotension → RV ischaemia → worsening crisis. CONTRAINDICATED in acute decompensated PH

[1]

Vasoactive drug selection — exam-grade reasoning

Why noradrenaline over phenylephrine. Both raise SVR. But phenylephrine is a PURE α1 agonist with no β2 — it constricts the pulmonary bed disproportionately and removes the favourable β2 pulmonary vasodilation that noradrenaline's modest β activity provides. In ex-vivo human pulmonary artery rings, phenylephrine produces greater pulmonary vasoconstriction than noradrenaline at equi-systemic doses. Net: phenylephrine raises PVR more per unit SVR gained — harmful.[7] }
Vasopressin — the dark horse. Pulmonary vasculature expresses little V1 receptor activity, so vasopressin raises SVR without proportionally raising PVR — the PVR:SVR ratio FALLS. In animal models of severe PH, vasopressin improved RV perfusion without worsening PVR. Use as an add-on when noradrenaline alone is insufficient or PVR is rising.[8] }
The milrinone + noradrenaline 'combo' is the workhorse. Milrinone lowers PVR and supports RV inotropy but causes systemic hypotension; noradrenaline restores SVR. Together they achieve the therapeutic goal: low PVR + adequate systemic BP + supported RV. This combination is the most frequently used vasoactive strategy in PH crisis.[3] }
SYSTEMIC vasodilators are CONTRAINDICATED. Glyceryl trinitrate, sodium nitroprusside, hydralazine, and high-dose dobutamine alone all lower SVR → systemic hypotension → RV ischaemia → spiral worsens. They may 'open' the pulmonary bed slightly but the systemic cost is catastrophic. The exception is when used as part of a deliberately balanced strategy WITH a vasopressor backing SVR — but this is advanced, not routine.[9] }
Inhaled vs IV prostacyclin. Inhaled epoprostenol/iloprost vasodilates only ventilated alveoli (improves V/Q matching) with no systemic spillover. IV prostacyclin vasodilates the entire pulmonary tree AND the systemic tree → hypotension. In crisis, prefer INHALED (or iNO) for selective pulmonary vasodilation. Reserve IV prostacyclin for patients already established on it chronically — and NEVER stop it abruptly (withdrawal crisis).[5] }
The iNO withdrawal trap. Abrupt cessation of iNO causes rebound pulmonary hypertension that can be WORSE than baseline and fatal. ALWAYS taper iNO slowly (e.g., reduce by 5 ppm every few hours) while transitioning to an oral agent (sildenafil) or inhaled prostacyclin. Plan the exit before you start iNO.[3] }

Mechanical ventilation in PH crisis

Ventilation strategy to protect the RV (lung-protective AND RV-protective)

AVOID INTUBATION if possible. Non-invasive ventilation may avoid the haemodynamic collapse that accompanies intubation in PH (anaesthetic vasodilation + loss of sympathetic tone + positive pressure → RV failure). Use NIV/HHF if the patient can protect their airway and oxygenation/ventilation failure is reversible
IF INTUBATING — anticipate cardiovascular collapse. Have noradrenaline, milrinone, and inhaled NO RUNNING BEFORE induction. Use a haemodynamically neutral induction: ketamine (maintains SVR, sympathetic preservation) or etomidate. AVOID propofol (profound vasodilation). AVOID high-dose opiates as sole agent. Full-stomach precautions; RSI with minimal apnoea
LUNG-PROTECTIVE + RV-PROTECTIVE settings: (a) Low tidal volumes 4-6 mL/kg PBW. (b) Lowest PEEP that maintains oxygenation (≤5-8 cmH2O — high PEEP raises intrathoracic pressure → compresses pulmonary vessels → raises transpulmonary pressure → raises RV afterload). (c) Plateau pressure <30 cmH2O. (d) Allow permissive hypercapnia if pH >7.2 (avoid hypercapnia that causes pulmonary vasoconstriction, but do not chase normocapnia at the cost of high pressures). (e) Lowest mean airway pressure possible
MINIMISE INTRATHORACIC PRESSURE — this is the cardinal rule. High intrathoracic pressure: (i) reduces venous return (preload falls), (ii) raises PVR (compresses alveolar vessels), (iii) reduces RV coronary perfusion. Use short inspiratory time, long expiratory time, low rate if possible
CORRECT THE GAS EXCHANGE FIRST — 100% FiO2 (pulmonary vasodilator), normalise pH, target SpO2 >92% and PaCO2 35-40 (or permissive up to 55 if pH >7.2)
AVOID DYNAMIC HYPERINFLATION / AUTO-PEEP — in COPD-Group 3 PH especially, trapped gas raises intrathoracic pressure catastrophically. Slow rate, long expiratory time
EXTUBATE EARLY — once the trigger is corrected and PVR-controlled, wean to spontaneous breathing/NIV as soon as possible. Positive-pressure ventilation is haemodynamically hostile to the PH RV

[1]

Mechanical circulatory support (MCS)

Mechanical support options for refractory PH crisis

Modality	Mechanism	Indication	Limitations
VA-ECMO (preferred MCS)	Drains RA → oxygenates → returns to femoral artery; bypasses RV AND lung → unloads RV, supports systemic perfusion, restores coronary perfusion	Refractory cardiogenic shock from RV failure despite maximal medical therapy; bridge to transplant / recovery / decision	Bleeding, stroke, infection, limb ischaemia (femoral), LV distension (afterload from retrograde flow) — may need LV vent; can worsen pulmonary congestion if LV failing
Pulmonary artery pulsatility / RV assist device (RVAD)	Surgically or percutaneously (TandemHeart, ProtekDuo) unloads RA/RV directly → drains RA, returns to PA	RV failure without severe lung disease (need native lung gas exchange); bridge in selected centres	Requires functional lungs; not suitable if hypoxia is the driver; cannulation expertise needed
V-AV ECMO	Adds venous return to support both RV (VA) and oxygenation (VV)	Combined RV failure + severe hypoxaemia	Complexity, more cannulae, higher anticoagulation burden
IABP (intra-aortic balloon pump)	↓ LV afterload, ↑ coronary perfusion	Largely UNHELPFUL for primary RV failure — no direct RV support. Only if concomitant LV failure	Not first-line for PH crisis

[1]

VA-ECMO in PH crisis — when and how

INDICATION — PH crisis with refractory cardiogenic shock (rising lactate despite inotropes/vasopressors, MAP <65 on two pressors, cardiac index <1.8) despite: (a) maximal vasoactive therapy (noradrenaline + milrinone ± vasopressin), (b) inhaled pulmonary vasodilator (iNO or epoprostenol), (c) corrected triggers, (d) lung-protective ventilation
GOAL — unload the RV (rest), restore systemic perfusion and coronary perfusion, break the ischaemia spiral, allow time for reversibility or bridge to lung transplant
CANNULATION — femoro-femoral VA-ECMO is fastest; central cannulation if post-cardiotomy or for transplant bridge. Consider LV venting if LV distension (septal shift means LV is small — assess by echo; some need IABP or pigtail vent)
ANTICOAGULATION — unfractionated heparin to ACT 1.5× baseline (balance bleeding vs clotting; PH patients often on background anticoagulation)
MANAGE THE LUNG — on VA-ECMO, continue lung-protective ventilation (rest settings), keep iNO/pulmonary vasodilators running (to lower PVR for when ECMO is weaned), avoid high PEEP
DE-ESCALATION — as the trigger reverses (infection treated, PE anticoagulated, PAH therapy restarted), taper vasoactives, then trial off VA-ECMO by reducing flows while monitoring RV function (echo) and lactate. Wean iNO last (after ECMO decannulation)
DESTINATION — recovery (rare in fixed PAH), lung transplant (bridge to transplant in decompensated end-stage PAH — awake VA-ECMO preferred), or palliation / withdrawal if not a transplant candidate[6] }

MCS pearls for the exam

VA-ECMO is the MCS of choice for PH crisis. It simultaneously unloads the RV (drains the RA), bypasses the high-PVR lung, and delivers oxygenated blood to the systemic circulation — addressing all three limbs of the spiral (RV workload, oxygenation, systemic perfusion).[6] }
'Awake VA-ECMO' as a bridge to transplant. For end-stage PAH patients in crisis who are transplant candidates, elective intubation carries high mortality. Awake (non-intubated) femoral VA-ECMO supports the RV while the patient breathes spontaneously — preserves conditioning, avoids ventilation complications, and is the preferred bridge to lung transplant in expert centres.[3] }
Don't forget LV distension on VA-ECMO. Retrograde arterial flow from femoral VA-ECMO increases LV afterload. If LV function is impaired (or septum already shifted), the LV cannot eject against this — it distends, pulmonary oedema worsens, and LV thrombus can form. Echo monitoring; add LV vent (pigtails, IABP, or Impella) if needed.[9] }

Cardiac tamponade in PH

Pericardial effusion and tamponade in pulmonary hypertension

RECOGNISE THE SETTING — pericardial effusions are COMMON in severe PAH (up to 50% in advanced disease), arising from elevated RA pressure and pericardial lymphatic obstruction. SMALL effusions are usually haemodynamically insignificant; LARGE or rapidly accumulating effusions can cause tamponade
TAMPONADE PHYSIOLOGY IS ATYPICAL IN PH — the high RV pressure partially 'protects' against classical tamponade (equalisation of diastolic pressures still occurs, but the RV is already stiff). Clinical signs: rising RA pressure, falling cardiac output, tachycardia, muffled heart sounds may be absent. Echo: RA collapse (early), RV free-wall collapse (later), plethoric IVC, >1 cm effusion with swing
PERICARDIOCENTESIS — INDICATED for tamponade physiology (echo-confirmed chamber collapse, haemodynamic compromise). PERFORMED under echocardiographic guidance, subxiphoid or apical approach, by experienced operator. Drain slowly — rapid decompression can precipitate acute RV dilatation (the RV, freed from external constraint, suddenly dilates against high PVR)
CAUTION — pericardiocentesis in PH carries higher risk than usual (RV puncture in a dilated RV; bleeding; arrhythmia). Ensure crossmatched blood, continuous monitoring, surgical backup. Leave a drain if effusion is likely to re-accumulate (malignant, uraemic, or ongoing PAH)
AFTER PERICARDIOCENTESIS — reassess RV (echo), continue PH-specific therapy, and address the underlying trigger. Tamponade can be the presenting feature or a complication of PH crisis

[1]

Expanded clinical pearls

High-yield exam pearls — expanded set

The 'five H's that kill the PH RV': Hypoxia, Hypercapnia, Hydrogen ion (acidosis), Hypovolaemia (and hypervolaemia), Hypotension. Each raises PVR or lowers RV perfusion. Memorise these as the cardinal correctables — every PH crisis assessment should screen for and correct all five.[2] }
PA catheter is the diagnostic gold standard in refractory crisis. When vasopressors/inotropes are escalating, a PA catheter quantifies RA pressure, PCWP (pre- vs post-capillary), cardiac index, and PVR (Wood units = [mPAP – PCWP] / CO). Targets: RA pressure 5-10 mmHg, cardiac index >2.0, SvO2 >60%, PVR falling. The PA catheter tells you whether you are winning or losing.[1] }
Background PAH therapy must NEVER be interrupted. This is the single most preventable cause of crisis. On ICU admission: verify and continue sildenafil/tadalafil, bosentan/macitentan/ambrisentan, riociguat, and prostacyclins (inhaled iloprost, SC/IV treprostinil). If NPO, convert to IV/NG equivalent. NEVER stop a chronic prostacyclin infusion — withdrawal precipitates rebound crisis within hours.[3] }
Calcium channel blockers are NOT acute therapy. CCBs (nifedipine, diltiazem, amlodipine) are only useful in the ~10% of idiopathic PAH patients with a positive acute vasodilator challenge at right heart catheterisation, and are DANGEROUS in decompensated PH (negative inotropy → RV failure worsens; hypotension). Do not give CCBs in crisis.[1] }
Pregnancy counselling is a core of PH care. Pregnancy is contraindicated in all WHO Group 1 PAH (maternal mortality 30-50%). Reliable contraception (IUD, implant; oestrogen-containing pills carry VTE risk) is mandatory. If pregnancy occurs: multidisciplinary care, consider termination, planned caesarean under regional anaesthesia (avoid GA), and continue PAH therapy throughout. Postpartum (first 2-6 weeks) is the highest-risk period — volume shifts, autotransfusion, rising PVR.[1] }
Pharmacology of the three PAH pathways (examiner favourite): (1) Prostacyclin pathway — epoprostenol (IV), treprostinil (SC/IV/inhaled/oral), iloprost (inhaled), selexipag (oral IP receptor agonist). (2) Endothelin pathway — bosentan, macitentan, ambrisentan (ERAs). (3) Nitric oxide pathway — sildenafil/tadalafil (PDE5i), riociguat (sGC stimulator). Initial therapy is often combination (e.g., PDE5i + ERA; add prostacyclin if advanced).[1] }
McConnell's sign and the 60/60 sign for acute PE-induced PH crisis. On echo: McConnell's sign = RV free-wall hypokinesia with apical sparing (sensitive for acute PE). 60/60 sign = pulmonary acceleration time <60 ms PLUS tricuspid regurgitant jet velocity <60 mmHg (in the absence of chronic PH). These suggest an acute PE trigger superimposed on (or causing) the crisis.[11] }
TAPSE <17 mm = RV systolic dysfunction. Tricuspid annular plane systolic excursion (TAPSE) is the single most reproducible bedside measure of RV longitudinal systolic function. In PH crisis: serial TAPSE tracks recovery (improving) or deterioration (falling). TAPSE/systolic PV annular velocity (TAPSE/PASP ratio) is an even better RV-pulmonary coupling index.[11] }
Acute kidney injury is both a marker and amplifier of PH crisis. Low cardiac output + venous congestion (high RA pressure) → pre-renal + cardiorenal AKI. Rising creatinine portends poor outcome. Avoid nephrotoxins (NSAIDs, contrast if possible), optimise haemodynamics, and do NOT over-diurese (volume depletion worsens RV preload). CRRT may be needed for volume control in overloaded RV failure.[9] }
Liver function abnormalities are common and prognostic. Congestive hepatopathy (high RA pressure → sinusoidal congestion) → bilirubin rise, AST/ALT 2-5× normal, INR derangement. May mimic acute hepatitis. Improves with RV unloading. A fibrinogen/INR check is part of the PH crisis workup — coagulopathy complicates anticoagulation and ECMO.[9] }
Sepsis in PH is doubly dangerous. Sepsis causes systemic vasodilation (↓ SVR → RV ischaemia) AND sepsis-induced pulmonary microvascular dysfunction (↑ PVR), AND inflammatory myocardial depression (↓ RV contractility). Treat sepsis aggressively (Sepsis Six), but use restrictive fluids (RV hates volume), noradrenaline first-line, and screen for pulmonary source (pneumonia most common).[14] }
Atrial arrhythmia — restore sinus rhythm if possible. In PH, the atrial contribution to RV filling is large (stiff RV). New AF/atrial flutter commonly precipitates crisis. If haemodynamically unstable: synchronised DC cardioversion. If stable: amiodarone (IV load then infusion) for rhythm/rate control. AVOID rate-limiting CCBs (negative inotropy). Dofetilide/ibutilide in expert hands; digoxin for rate. Catheter ablation may be needed for recurrent atrial flutter.[9] }
Portopulmonary PH (Group 1) is a high-risk subtype. Pulmonary arterial hypertension associated with portal hypertension (portopulmonary PH) — decompensates precipitously with volume shifts (TIPS, variceal bleeding, liver failure). Specific: vasopressin and terlipressin (used for variceal bleeding) can spike PVR — use cautiously. Liver transplant is curative only if PVR is controlled pre-operatively.[1] }
The transition from iNO to oral therapy must be planned. iNO cannot be a long-term solution (cost, rebound). Once the crisis is breaking, overlap sildenafil (PO/IV) or inhaled iloprost, then taper iNO in 5-ppm steps over 12-24 h while watching PA pressure/cardiac index. A premature iNO taper causes rebound; a delayed taper wastes cost and delays mobilisation.[3] }
Don't forget venous thromboembolism prophylaxis — but anticoagulate carefully. PH patients are prothrombotic (stasis, low flow, some on prostacyclin lines). Unless actively bleeding, give VTE prophylaxis (LMWH). Many Group 1 PAH patients are on chronic warfarin (target INR ~2). In crisis: continue anticoagulation if possible; balance against bleeding if ECMO is planned. Note: warfarin absorption is unreliable in RV failure (gut congestion) — consider LMWH bridge.[2] }

Expanded red flags

Critical triggers and deterioration red flags

Sudden withdrawal of prostacyclin infusion → rebound fatal PH crisis within hours. Secure lines, never run dry, have backup pump.[3] }
New atrial fibrillation in known PH → loss of atrial kick can collapse RV output. Cardiovert if unstable.[9] }
Aggressive fluid bolus >500 mL → RV dilatation → septal shift → cardiogenic shock. Restrictive strategy.[9] }
Propofol induction for intubation → profound vasodilation → cardiovascular collapse. Use ketamine; have noradrenaline running.[10] }
Phenylephrine or metaraminol for hypotension → disproportionate PVR rise. Use noradrenaline.[7] }
High PEEP (>10) in ventilated PH patient → raised intrathoracic pressure → RV afterload spike. Lowest PEEP for oxygenation.[11] }
Systemic vasodilators (GTN, SNP) for 'afterload reduction' → catastrophic hypotension → RV ischaemia. CONTRAINDICATED.[9] }
Calcium channel blockers in decompensated PH → negative inotropy → RV failure worsens. AVOID in crisis.[1] }
Untreated hypoxia (SpO2 <90%) or acidosis (pH <7.2) → pulmonary vasoconstriction → spiral worsens. Correct immediately.[2] }
Pregnancy in severe PH → 30-50% maternal mortality. Contraception mandatory; multidisciplinary care if pregnant.[1] }
Pericardial effusion with chamber collapse on echo → tamponade — pericardiocentesis under echo guidance; drain slowly.[9] }
Rising lactate despite two vasopressors + inotrope → refractory cardiogenic shock — call ECMO team / transplant centre early.[6] }

Key trials and evidence

SUPER-1 — Sildenafil for PAH (Galie 2005)

EARLY — Bosentan in mildly symptomatic PAH (Galie 2008)

Hoeper 2019 — Intensive care, RV support and lung transplantation in PH

CRASH report — Price 2017

Hussain 2017 — Vasoconstrictor effects on human pulmonary arteries

Sarkar 2015 — Vasopressin in severe PH (animal model)

Arrigo 2024 — RV failure from acutely increased RV afterload (ESC position)

References

[1]Humbert M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Eur Heart J, 2022.PMID 36017548
[2]Price LC, et al. The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension Thorax, 2017.PMID 28904006
[3]Hoeper MM, et al. Intensive care, right ventricular support and lung transplantation in patients with pulmonary hypertension Eur Respir J, 2019.PMID 30545979
[4]Galie N, et al. Sildenafil citrate therapy for pulmonary arterial hypertension N Engl J Med, 2005.PMID 16291984
[5]Hoeper MM, et al. Long-term effects of intravenous iloprost in patients with idiopathic pulmonary arterial hypertension deteriorating on non-parenteral therapy BMC Pulm Med, 2011.PMID 22133492
[6]Hoeper MM, et al. Extracorporeal Life Support in Pulmonary Hypertension: Practical Aspects Semin Respir Crit Care Med, 2023.PMID 37709284
[7]Hussain A, et al. The differential effects of systemic vasoconstrictors on human pulmonary artery tension Eur J Cardiothorac Surg, 2017.PMID 28164217
[8]Sarkar J, et al. Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock Shock, 2015.PMID 25565637
[9]Arrigo M, et al. Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale): a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology Eur Heart J Acute Cardiovasc Care, 2024.PMID 38135288
[10]Price LC, et al. Perioperative management of patients with pulmonary hypertension undergoing non-cardiothoracic, non-obstetric surgery: a systematic review and expert consensus statement Br J Anaesth, 2021.PMID 33612249
[11]Aubry A, Vieillard-Baron A. [Cor pulmonale] Rev Mal Respir, 2020.PMID 32088063
[12]Pavsic N, et al. The association between myocardial ischemia and myocardial dysfunction in adult patients with systemic right ventricle - A single centre multimodality study Int J Cardiol, 2023.PMID 37087053
[13]Galie N, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial Lancet, 2008.PMID 18572079
[14]Bernier ML, et al. Spectrum of Current Management of Pediatric Pulmonary Hypertensive Crisis Crit Care Explor, 2019.PMID 32166278

Your progress

Exam practice

SAQ — Pulmonary hypertensive crisis with right ventricular failure

SAQ — Escalation of therapy in refractory pulmonary hypertension

Clinical pearls [1]

Red flags

Prognosis

PH crisis outcomes (Price 2019)

Triggers and precipitants

Right ventricular failure pathophysiology — the vicious spiral

ICU management — drug-by-drug

Mechanical ventilation in PH crisis

Mechanical circulatory support (MCS)

Cardiac tamponade in PH

Expanded clinical pearls

Expanded red flags

Key trials and evidence

SUPER-1 — Sildenafil for PAH (Galie 2005)

EARLY — Bosentan in mildly symptomatic PAH (Galie 2008)

Hoeper 2019 — Intensive care, RV support and lung transplantation in PH

CRASH report — Price 2017

Hussain 2017 — Vasoconstrictor effects on human pulmonary arteries

Sarkar 2015 — Vasopressin in severe PH (animal model)

Arrigo 2024 — RV failure from acutely increased RV afterload (ESC position)

References

Your progress

Exam practice

SAQ — Pulmonary hypertensive crisis with right ventricular failure

SAQ — Escalation of therapy in refractory pulmonary hypertension

Clinical pearls [1]

Red flags

Prognosis

PH crisis outcomes (Price 2019)

Triggers and precipitants

Right ventricular failure pathophysiology — the vicious spiral

ICU management — drug-by-drug

Mechanical ventilation in PH crisis

Mechanical circulatory support (MCS)

Cardiac tamponade in PH

Expanded clinical pearls

Expanded red flags

Key trials and evidence

SUPER-1 — Sildenafil for PAH (Galie 2005)

EARLY — Bosentan in mildly symptomatic PAH (Galie 2008)

Hoeper 2019 — Intensive care, RV support and lung transplantation in PH

CRASH report — Price 2017

Hussain 2017 — Vasoconstrictor effects on human pulmonary arteries

Sarkar 2015 — Vasopressin in severe PH (animal model)

Arrigo 2024 — RV failure from acutely increased RV afterload (ESC position)

References