Pulmonary · Topic 1 of 28

Acute Respiratory Failure

Pulmonary · acute respiratory failure

Acute Respiratory Failure

Hypoxemic failure (PaO₂ < 60) or hypercapnic failure (PaCO₂ > 50 with pH < 7.35) — the A–a gradient tells you which mechanism.

Key numbers

Hypoxemic failure: PaO₂ below 60 mmHgPaO₂ < 60 mmHg

Hypercapnic failure: PaCO₂ > 50 mmHgPaCO₂ > 50 · pH < 7.35

Normal A–a gradient < age/4 + 4A–a < age/4 + 4

01 · Defined byHypoxemic failure: PaO₂ below 60 mmHg

Acute hypoxemic (type 1) respiratory failure = severe hypoxemia — PaO₂ below 60 mmHg (SpO₂ below about 88–90%, P/F below 300) — from airspace filling or collapse that oxygen alone often cannot fix.

02 · Defined byHypercapnic failure: PaCO₂ > 50 mmHg

Acute hypercapnic (type 2, ventilatory) failure = respiratory acidosis on the ABG, e.g. PaCO₂ above 50 mmHg with pH below 7.35, because minute ventilation cannot clear CO₂.

03 · CalculateNormal A–a gradient < age/4 + 4

A–a gradient = PAO₂ − PaO₂, with PAO₂ = FiO₂ × (760 − 47) − PaCO₂/0.8 (about 150 − PaCO₂/0.8 on room air); normal is under age/4 + 4, typically below 20 mmHg.

What it is

Core idea

Normal A–a: hypoventilation; wide A–a: lung disease must knowHypoxemia with a normal A–a gradient = hypoventilation or low inspired oxygen (altitude); a widened gradient = V/Q mismatch, shunt or diffusion impairment inside the lung.

Shunt hypoxemia does not respond to oxygenLow V/Q (COPD, asthma), diffusion impairment and hypoventilation all improve with supplemental oxygen; right-to-left shunt (flooded or collapsed alveoli, intracardiac shunt) does not.

Causes & risk factors

Why it happens

Hypercapnic causes: COPD, asthma, overdose, neuromuscularCommon causes of hypercapnic failure: COPD exacerbation, severe asthma, obstructive sleep apnea and obesity hypoventilation, opioid or benzodiazepine overdose, and neuromuscular disease (Guillain–Barré, myasthenia gravis, botulism).

Hypoxemic causes: edema, ARDS, pneumonia, PECommon causes of hypoxemic failure: cardiogenic pulmonary edema or fluid overload, ARDS, pneumonia, alveolar hemorrhage, atelectasis, pulmonary embolism, pneumothorax and aspiration.

Presentation

What you'll see

Neuromuscular weakness: falling vital capacityIn neuromuscular weakness failure may come without distress: vital capacity below 10–15 mL/kg or a negative inspiratory force weaker than 15 cmH₂O predicts imminent ventilatory failure; in Guillain–Barré, intubate when VC < 15 mL/kg.

Fatigue signs: RR over 30, paradoxical breathingA respiratory rate above 28–30/min cannot be sustained for long; accessory muscle use, paradoxical abdominal motion, falling tidal volume and confusion signal a tiring patient near arrest.

Do right now

In this order

First moves

Get an ABG, chest x-ray and ECG

→

Hypoxemic: oxygen, then high-flow, then ventilate

→

Hypercapnic: treat the cause, BiPAP early

Why each step

Get an ABG, chest x-ray and ECGStart oxygen while evaluating: order an ABG (oxygenation and ventilation), chest x-ray and ECG, with continuous pulse oximetry; a BNP and point-of-care ultrasound help separate heart failure and pneumothorax.

Hypoxemic: oxygen, then high-flow, then ventilateTreat hypoxemic failure with oxygen (non-rebreather or high-flow nasal cannula) while fixing the cause; if SpO₂ stays below 90% despite noninvasive support, intubate and ventilate.

Hypercapnic: treat the cause, BiPAP earlyTreat hypercapnic failure by reversing the cause (bronchodilators, naloxone for opioid overdose) and supporting ventilation — NIPPV is the preferred first support in COPD with acute-on-chronic failure.

The rules

Know these

Chronic CO₂ retainers: judge by pHPatients with chronic ventilatory failure may live with a PaCO₂ of 60–90 mmHg and a near-normal pH; in them, the degree of acidemia, not the PaCO₂, marks acute decompensation.

Avoid excess oxygen in CO₂ retainersGive oxygen cautiously to patients with COPD or chronic hypoventilation: overcorrecting hypoxemia can worsen hypercapnia (see the oxygen therapy topic for SpO₂ targets).

Hypoxemic or hypercapnic failure?

Commonly confused

Defining blood gas	PaO₂ < 60 mmHg (SpO₂ < 90%)
A–a gradient	Widened
Mechanism	V/Q mismatch, shunt, diffusion limit
Typical causes	Pulmonary edema, ARDS, pneumonia, PE, atelectasis
First support	Oxygen, high-flow nasal cannula

More detail

Reference

Show 6 reference facts

Severe acute acidemia (pH < 7.2) causes pulmonary vasoconstriction, systemic vasodilation, reduced contractility, hyperkalemia, hypotension and arrhythmias; acute hypercapnia also dilates cerebral vessels and raises intracranial pressure.

Physiologic dead space is normally 30–40% of tidal volume, about 50% in intubated patients and over 70% in massive PE, severe emphysema or status asthmaticus — the more dead space, the poorer CO₂ clearance.

Increased CO₂ production (fever, sepsis, burns, hyperthyroidism) causes hypercapnia only when the patient cannot raise ventilation; in total apnea PaCO₂ rises 3–6 mmHg per minute.

Diffusion impairment rarely causes hypoxemia alone; it appears with high cardiac output (exercise) or low barometric pressure (altitude) and, like low V/Q, widens the A–a gradient but responds to oxygen.

Perioperative respiratory failure is usually atelectasis: prevent and treat it with good analgesia, upright positioning and early mobilization; incentive spirometry alone is ineffective.

The A–a gradient widens with age and with higher FiO₂; another bedside estimate of the normal upper limit is the FiO₂ percentage (under 21 on room air, under 30 on 30% oxygen).

Pearl

A normal A–a gradient means the lungs are fine and the pump is failing — hypoventilation; a wide gradient means the lung itself is sick.

Sources · Merck Manual Professional — Acute Hypoxemic Respiratory Failure (AHRF), Including ARDS · Merck Manual Professional — Hypoxia in Hospitalized Patients · Merck Manual Professional — Ventilatory Failure · Merck Manual Professional — Measurement of Gas Exchange · Merck Manual Professional — Table: Equations for Calculating Alveolar Oxygen Pressure and A–a Gradient · Merck Manual Professional — Guillain-Barré Syndrome (GBS) · Merck Manual Professional — Other Types of Respiratory Failure · Lawn ND et al. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol 2001;58:893–898 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).