9.3 Respiratory Failure & Sleep-Disordered Breathing

Respiratory failure occurs when the respiratory system fails to maintain adequate gas exchange, resulting in defective arterial oxygenation, defective carbon dioxide elimination, or both. In the MRCP(UK) Part 1 exam, candidates must master arterial blood gas (ABG) interpretation, distinguish physiological mechanisms of hypoxaemia, apply Berlin criteria for ARDS, know precise indications and settings for Non-Invasive Ventilation (NIV), and recall diagnostic criteria and legal driving requirements in sleep-disordered breathing.

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1. Type 1 Respiratory Failure (Hypoxaemic)

Type 1 respiratory failure is defined by arterial hypoxaemia with a PaO2 < 8.0 kPa (60 mmHg) breathing room air, accompanied by a normal or low PaCO2 (<6.0 kPa / 45 mmHg). Hyperventilation driven by hypoxaemic peripheral chemoreceptor stimulation typically causes hypocapnia and respiratory alkalosis.

Pathophysiological Mechanisms

1. Ventilation-Perfusion (V/Q) Mismatch: The most common physiological mechanism. Regions of lung receive inadequate ventilation relative to their perfusion (low V/Q ratio). Seen in pulmonary embolism, pneumonia, pulmonary oedema, asthma, and chronic obstructive pulmonary disease. Hypoxaemia caused by V/Q mismatch corrects readily with modest supplemental oxygen.
2. Right-to-Left Shunt (Intrapulmonary or Intracardiac): Deoxygenated blood bypasses ventilated alveolar spaces entirely and enters the arterial circulation unchanged (V/Q = 0). Examples include alveolar flooding (severe pneumonia, ARDS, acute pulmonary oedema), complete lobar atelectasis, pulmonary arteriovenous malformations (Osler-Weber-Rendu syndrome), or cyanotic congenital heart disease (Eisenmenger syndrome). True shunt hypoxaemia is refractory to supplemental oxygen therapy because non-ventilated lung units cannot oxygenate incoming blood regardless of alveolar FiO2.
3. Diffusion Impairment: Destruction or thickening of the alveolar-capillary membrane impairs oxygen transit time across the blood-gas barrier. Exemplified by idiopathic pulmonary fibrosis, fibrotic sarcoidosis, and systemic sclerosis-associated interstitial lung disease. At rest, transit time is sufficient, but hypoxaemia worsens significantly during exercise as pulmonary capillary transit time drops.
4. Alveolar Hypoventilation at High Altitude: Reduced inspired oxygen fraction ($P_iO_2$) due to low barometric pressure, with normal alveolar-arterial (A-a) oxygen gradient.

Acute Respiratory Distress Syndrome (ARDS): The Berlin Definition

ARDS is a catastrophic form of acute non-cardiogenic diffuse alveolar injury characterized by increased alveolar-capillary membrane permeability, leakage of protein-rich fluid into the alveoli, surfactant loss, and extensive microvascular thrombosis.

The Berlin Definition of ARDS

Oxygen Delivery Strategies in Type 1 Failure

• High-Flow Nasal Oxygen (HFNO): Delivers heated, fully humidified gas mixtures at flow rates up to 60 L/min with accurate FiO2 (0.21–1.0). Physiological advantages include washout of anatomical dead space (nasopharyngeal reservoir), reduction in work of breathing, and delivery of a modest positive airway pressure (~2–5 cmH2O).
• Continuous Positive Airway Pressure (CPAP): Delivers constant positive pressure throughout inspiration and expiration. It recruits collapsed alveoli, increases Functional Residual Capacity (FRC), decreases intrapulmonary shunt, and drives fluid out of alveolar spaces into the interstitial lymphatic bed. First-line non-invasive therapy for acute cardiogenic pulmonary oedema.

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2. Type 2 Respiratory Failure (Hypercapnic)

Type 2 respiratory failure is characterized by hypoxaemia (PaO2 < 8.0 kPa) accompanied by hypercapnia (PaCO2 > 6.0 kPa / 45 mmHg), representing failure of alveolar ventilation ("pump failure").

Pathophysiological Categories & Etiologies

1. Depressed Central Respiratory Drive:
   • Drug-induced respiratory depression (opioids, benzodiazepines, barbiturates, general anaesthetics)
   • Brainstem lesions (infarction, hemorrhage, trauma, encephalitis)
   • Central sleep apnoea and severe obesity hypoventilation syndrome
2. Neuromuscular Respiratory Muscle Weakness (Pump Failure):
   • Motor neurone disease (amyotrophic lateral sclerosis)
   • Guillain-Barré syndrome
   • Myasthenia gravis crisis (myasthenic crisis)
   • Cervical spinal cord injury (above C3–C5 involving phrenic innervation)
   • Severe electrolyte depletion (profound hypophosphataemia, hypokalaemia, hypomagnesaemia)
   • Clinical Clue: Paradoxical abdominal motion (inward movement of abdomen on inspiration), marked orthopnoea, and a drop in Forced Vital Capacity (FVC) >20% from sitting to supine position.
3. Thoracic Cage & Chest Wall Deformities:
   • Severe kyphoscoliosis, ankylosing spondylitis with thoracic rigidity, thoracoplasty, flail chest, massive morbid obesity (chest wall loading).
4. Increased Mechanical Workload & Severe Airflow Limitation:
   • Acute exacerbation of chronic obstructive pulmonary disease (AECOPD)
   • Life-threatening acute severe asthma (exhaustion)
   • End-stage cystic fibrosis and severe non-CF bronchiectasis
5. Obesity Hypoventilation Syndrome (OHS / Pickwickian Syndrome):
   • Triad of BMI >=30 kg/m², daytime hypercapnia (PaCO2 >6.0 kPa), and sleep-disordered breathing, in the absence of alternative causes of hypoventilation.

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3. Non-Invasive Ventilation (NIV / BiPAP)

Non-Invasive Ventilation using Bilevel Positive Airway Pressure (BiPAP) delivers two distinct levels of positive airway pressure: Inspiratory Positive Airway Pressure (IPAP), which augments tidal volume to blow off CO2 and reduce the work of breathing, and Expiratory Positive Airway Pressure (EPAP), which splints open airways, maintains functional residual capacity, and enhances alveolar oxygenation.

Primary Indication in COPD

According to BTS and NICE guidelines, NIV is indicated in patients with an acute exacerbation of COPD presenting with acute hypercapnic respiratory failure and uncompensated respiratory acidosis: $\text{Arterial pH } 7.25 \text{ to } 7.35 \quad \text{and} \quad \text{PaCO}_2 > 6.0\text{ kPa}$ persisting despite optimal initial medical therapy for at least 60 minutes (controlled oxygen via 24–28% Venturi mask to maintain SaO2 88–92%, nebulised salbutamol and ipratropium, oral prednisolone 30 mg or IV hydrocortisone, and empirical antibiotics if sputum purulence is present).

The pH < 7.25 Threshold: If the arterial pH is <7.25, NIV should still be initiated without delay, but the patient must be managed in a high-dependency (HDU) or intensive care (ICU) environment with immediate preparation for invasive endotracheal intubation and mechanical ventilation should NIV fail.

Contraindications to NIV

• Facial trauma, burns, extensive facial deformity, or recent facial/upper gastrointestinal surgery
• Fixed upper airway obstruction
• Severe encephalopathy, coma, or inability to protect the airway (except when NIV is explicitly designated as the ceiling of care in COPD)
• Active vomiting or severe gastrointestinal bleeding (high risk of fatal pulmonary aspiration)
• Undrained tension pneumothorax or massive hemothorax
• Severe hemodynamic instability (uncontrolled cardiogenic or septic shock)

Initial Settings & Monitoring Protocol

• Starting Pressures: IPAP 10–12 cmH2O; EPAP 4–5 cmH2O.
• Titration: Rapidly titrate IPAP upwards in increments of 2–3 cmH2O every 15–30 minutes up to 16–20 cmH2O to achieve a target tidal volume of 6–8 mL/kg predicted body weight and clinical resolution of tachypnoea.
• Repeat Arterial Blood Gas: Mandatory at 1 hour after initiating NIV, and again at 4 hours. Successful response is demonstrated by a rising pH, falling PaCO2, reduction in respiratory rate, and clinical stabilization.

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4. Sleep-Disordered Breathing & OSAHS

Sleep-disordered breathing encompasses obstructive sleep apnoea-hypopnoea syndrome (OSAHS), central sleep apnoea (CSA), and obesity hypoventilation syndrome.

Obstructive Sleep Apnoea-Hypopnoea Syndrome (OSAHS)

OSAHS is characterized by repetitive collapse and occlusion of the upper pharyngeal airway during sleep, resulting in transient cessation of airflow (apnoea; airflow reduction >=90% for >=10 seconds) or partial reduction (hypopnoea; airflow reduction >=30% for >=10 seconds accompanied by >=3% oxygen desaturation or electroencephalographic arousal).

Risk Factors & Etiology

• Male sex (2–3 times higher prevalence)
• Obesity (BMI >30 kg/m²; fat deposition in parapharyngeal soft tissues narrows the pharyngeal lumen)
• Increased collar/neck circumference: >43 cm (17 inches) in men; >40 cm (16 inches) in women
• Craniofacial abnormalities: Retrognathia, micrognathia, maxillary hypoplasia, macroglossia (e.g., Down syndrome, acromegaly), tonsillar hypertrophy
• Systemic disorders: Hypothyroidism, acromegaly, polycystic ovary syndrome (PCOS)
• Exogenous agents: Evening alcohol consumption and sedative medications (relax upper airway dilator muscles)

Clinical Features & Epworth Sleepiness Scale (ESS)

• Nocturnal Symptoms: Habitual loud snoring, witnessed apnoeic pauses, choking/gasping arousals, restless unrefreshing sleep, nocturia.
• Daytime Symptoms: Excessive daytime somnolence, morning frontal headaches, cognitive impairment, poor concentration, irritability, personality changes, impotence/loss of libido.
• Epworth Sleepiness Scale (ESS): Validated 8-item self-administered questionnaire evaluating the likelihood of dozing in routine daytime situations (scored 0 to 24). A score >10 indicates abnormal, excessive daytime sleepiness.

Diagnostic Polysomnography & AHI Severity

Definitive diagnosis requires overnight respiratory polygraphy or full in-laboratory polysomnography (recording EEG, EOG, EMG, airflow, thoracic-abdominal effort, and pulse oximetry):

• Apnoea-Hypopnoea Index (AHI): The average number of apnoeas and hypopnoeas recorded per hour of sleep:
  • Normal: AHI < 5 events/hour
  • Mild OSAHS: AHI 5 to 14 events/hour
  • Moderate OSAHS: AHI 15 to 29 events/hour
  • Severe OSAHS: AHI >= 30 events/hour

Treatment Modalities

1. Continuous Positive Airway Pressure (CPAP): Gold-standard, first-line treatment for moderate to severe OSAHS (AHI >=15), and for mild OSAHS with refractory daytime symptoms. CPAP acts as a pneumatic splint, preventing pharyngeal collapse.
2. Mandibular Advancement Splints (MAS): Customized intraoral dental appliances that advance the mandible and tongue base. Indicated in mild-to-moderate OSAHS or patients unable to tolerate CPAP.
3. Lifestyle Modifications: Supervised weight loss (bariatric surgery if BMI >=35–40 kg/m²), complete cessation of evening alcohol and sedatives, and positional therapy (sleep position trainers to avoid supine sleep).

UK DVLA Driving Regulations (Critical Exam Knowledge)

Under UK Driver and Vehicle Licensing Agency (DVLA) regulations:

• Any patient diagnosed with OSAHS who suffers from excessive daytime sleepiness that impairs or is likely to impair safe driving must immediately cease driving and must notify the DVLA.
• Failure to notify the DVLA is a criminal offence.
• Driving may resume once satisfactory symptom control has been established (typically verified by objective CPAP compliance data downloads showing usage >4 hours per night on >=70% of nights) and formal confirmation is received from the DVLA.
• Professional/vocational drivers (Group 2 license holders: lorries and buses) are subject to stricter compliance standards and mandatory annual specialist clinical reviews.