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RESPIRATORY FAILURE: Early or selective

Causes   Adult onset   Infantile onset Evaluation & Management Exacerbating factors Home ventilation Spirometric abnormalities

Elevated right hemidiaphragm

Adult onset respiratory failure

• Muscle
  • Hereditary
    • Congenital disorders
      • Myopathy: Rod; Centronuclear; Cap
      • Diaphragm defects
    • Cytoplasmic body myopathy
    • Distal myopathy with early respiratory failure
    • Glycogen storage: Acid Maltase; Debrancher
    • LGMD: 2A; 2I
    • Mitochondrial: PEO; Myopathy; Leigh's
    • Myofibrillar myopathy: Desmin ; αB-crystallin
    • Myotonic dystrophy: Central component (Pickwickian syndrome; Hypoventilation)
    • Nemaline rod
    • Congenital fiber type size disproportion: TPM3 mutations
    • Ullrich scleroatonic muscular dystrophy
  • Acquired
    • Acute Quadriplegic Myopathies (Myosin loss)
    • Amyloid myopathy
    • Hydroxychloroquine: Myopathy & Neuropathy
    • Inflammatory Myopathy: Especially Jo-1 myositis; Sarcoid
• Neuromuscular junction
  • Myasthenia Gravis
  • Myasthenic syndrome (LEMS)
  • Myasthenic syndrome with anti-MuSK antibodies
• Nerve
  • ALS
  • Amiodarone toxicity
  • Brachial plexopathy, especially bilateral
  • Churg-Strauss: Asthma & Pulmonary infiltrates
  • CIDP: Multifocal
  • CMT: 1A (Sleep apnea); 2C
  • Diphtheria
  • Guillain-Barré syndrome
  • Hopkins' syndrome (with acute asthma)
  • Krabbe
  • Moebius syndrome
  • Phrenic nerve lesions
    • Direct damage
      • Trauma
      • Post cardiac surgery
      • Neoplasm
      • Radiation
    • Systemic
      • Polio
      • Toxic: n-Hexane (Glue sniffing)
• Spinal
  • Arnold-Chiari Malformation
    • Reduced respiratory drive, or vocal cord paralysis
    • Isolated respiratory failure in adult onset, sporadic type
  • Cervical spondylitic myelopathy
  • Giant cell arteritis of cervical radicular vessels¹
• CNS
  • Congenital central hypoventilation syndrome (CCHS)
  • Depression of ventilatory response to hypoxia and hypercapnia
    
  • Familial lethal sleep apnea

Infantile respiratory failure

• Myopathic
• Congenital myopathies: X-linked myotubular (Centronuclear); Nemaline rod
• Congenital myotonic dystrophy
• Reduced Muscle carnitine uptake (Infantile)
• Diaphragm defects
• Neuromuscular Junction: Congenital myasthenia gravis
• Neuropathic
• Hypomyelinating neuropathies: Congenital
• Arthrogryposis
• Rule out: CNS disorders
  • Congenital central hypoventilation syndrome (CCHS)

Respiratory failure: Evaluation & Management

• Testing
  • Forced vital capacity (FVC): Reliable; May miss some respiratory problems
  • Other testing
    • FVC while supine
    • Formal pulmonary function testis
    • Nocturnal disorders of breathing
• Management
  • Early: Non-invasive nocturnal ventilation, preferably NIPPV
  • Assist cough when needed
  • Avoid early tracheostomy
  • Maintain ideal body weight.
  • Control oral secretions
  • Aggressively treat URI’s.
  • Give Influenza vaccine & Pneumovax.
  • Avoid supplemental O₂ unless addressing hypoventilation fails
• Outcomes in patients with chronic neuromuscular disease,
  • Prolongs life
  • Reduces symptoms
  • Improves quality of life
  • Prevents acute respiratory failure & delays tracheostomy
• End of life
  • Prevent dyspnea and discomfort with O₂
  • Use of narcotics & benzodiazepines
  • Terminal weaning: Not sudden withdrawal of support

Respiratory failure: Exacerbating factors

• Reduced central drive
  • Primary: Myotonic dystrophy
  • Drugs: Sedatives hypnotics
  • Supplemental oxygen
• Physical impediments
  • Obesity: Increased work of chest wall movement
  • Constipation
  • Supine position: Inhibition of diaphragmatic movement
  • Kyphoscoliosis: Reduced chest wall compliance
• Primary lung disease: Obstructive disease
  • FEV₁/FVC ratio reduced
  • Increased airway resistance slows expiration

Restrictive ventilatory defects are characterized by proportional decreases in FVC and FEV₁, leaving the FEV₁/FVC normal or even slightly elevated. Any lesion affecting the lung, chest wall, or respiratory muscles that reduces the ability to take in a normal amount of air but does not affect the conducting airways is classified as a restrictive lung disease.

Obstructive defects are characterized by their involvement of the airways and the resultant reduction in expiratory flow. Spirometric studies of obstructive lung disease generally show a reduced FEV₁, FEV₁/FVC and flow rates with a relatively normal FVC. In severe obstructive lung disease, the FVC may also be reduced.

Home ventilation: Types

• Mechanisms
  • Patient initiates breath
  • Machine senses negative pressure
  • Air delivered until set pressure is reached
  • End inspiration pressure drops to set (positive) level
  • Typical settings
    • IPAP: 12 to 20 cm H₂O
    • EPAP: 3 to 4 cm H₂O
• Advantages
  • 1st step: When hypoventilation in only nocturnal
  • Can deliver breaths without patient triggering: For sleep apnea
  • Simple to operate
  • Inexpensive
  • Semi-portable
• Disadvantages
  • Can't deliver large volumes: No cough assist
  • Most unit have no battery

• Mechanisms
  • Patient initiates breath
  • Machine senses negative pressure
  • Air delivered until set volume is reached
  • No compenstaion for air leakage: Set for large volumes (10 to 15 cc/kg)
• Advantages
  • Battery back-up
  • Back-up alarms
  • Better for full time respiratory support
  • Adjustable flow rates
  • Can increase voice volume & cough
• Disadvantages
  • Expensive
  • Units may be heavy: But can be place on power wheelchair

MYOSIN-LOSS (Acute Quadriplegic; Critical Illness) MYOPATHIES²

• General Syndrome
  • Rapidly Evolving Myopathy with Myosin-Deficient Fibers
• Clinical features
  • History
    • Progressive proximal > distal weakness over days to weeks
    • Unexplained, persistent weakness after respiratory support or neuromuscular paralysis
  • Epidemiology
    • Age: Mean 6th decade
    • Sex: Males & Females involved
  • Weakness
    • Diffuse: Proximal > Distal; Neck flexors
    • Symmetric
    • Respiratory failure (80%)
    • Severe cases: Face & occasional EOM
    • Mild cases: Monophasic; May have Proximal arm weakness
  • Often associated with some rhabdomyolysis
  • Sensory: Normal, or Mild distal loss
  • Tendon reflexes: Reduced
  • Prognosis
    • Slow improvement in weakness (months) when steroids tapered
    • High mortality (30% to 50%) from associated disorders
• Associated factors
  • Corticosteroids (80%): Especially higher doses
  • Transplant: Lung; Liver
  • Systemic disease
    • Sepsis
    • Myasthenia gravis
    • Dialysis
    • Severe "critical" illness
  • Post-Paralysis Paralysis
    • History
      • Paralytic treatment for Status asthmaticus or other disorders
      • Treatment with NMJ blocking agents
        • Non-depolarizing agents; e.g. Vecuronium; ?Corticosteroids
        • Treatment > 1 week
    • Inability to wean from respirator
    • Persistent weakness
• Laboratory
  • Serum CK: Elevated or Normal
    • High in 1st 2 weeks in status asthmaticus patients
    • Normal in all after 2 weeks
  • Electrodiagnostic
    • NCV
      • CMAP: Small
      • Normal: Nerve conduction velocity; Distal Latencies; Sensory potentials
    • EMG
      • Often normal, or mild non-specific changes
      • Irritative changes
        • Occur early in course: Some patients
        • Fibrillations
        • Positive sharp waves
      • Myopathic changes
        • Occur in some patients: Later in course
        • Action potentials: Low amplitude, Short duration
    • Repetitive nerve stimulation
      • Occasional decrement early: 1st week after discontinuation of paralytic agent
      • Normal late
    • Muscle fibers may be electrically inexcitable
  • Muscle Pathology
    • Myosin loss in muscle fibers on ATPase stain (ATPase, pH 9.4 & 4.3)
      • ATPase
        • pH 9.4: Fibers with staining intensity less than type 1
        • pH 4.3: Fibers with reduced staining intensity at pH 9.4 also show reduced staining at pH 4.3
      • Some biopsies show loss diffuse loss within muscle fibers
      • Others show focal regions of myosin loss within fibers
      • Myosin loss present in scattered muscle fibers throughout musle biopsy: Not focal or diffuse regions
      • Quantitation³
        • Normal myosin/actin ratio in muscle: 1.31 to 1.57
        • Critical illness myopathy myosin/actin ratio is low: 0.37
      • Differential diagnosis
        • Dermatomyositis in focal regions of muscle fiber damage
        • HIV with nemaline rods
        • Muscle fiber necrosis
    • Atrophic muscle fibers
      • Basophilic, atrophic type II muscle fibers (60%)
      • All fibers atrophic (30%)
      • Enlarged nuclei in atrophic muscle fibers
    • Degeneration & Regeneration of muscle fibers: Occasional; Early
• Weakness: Pathophysiology
  • Muscle membrane inexcitability
    • Animal (rat) model
      • Denervate hindlimb + High dose dexamethasone
      • Loss of myosin with preservation of actin
    • Increased glucocorticoid receptors in muscle membrane
    • Muscle membrane changes
      • Depolarization
      • Reduced Membrane impedance 2° to Increased Cl^- conductance
      • Reduced Na⁺ current amplitudes
        • Reduced number of Na⁺ channels
        • Reduced Na⁺ channel conductance or voltage-dependent gating
  • Myosin loss
    • ? via Calpain pathway
    • ? Related to Increased general muscle catabolism
    • Protein degradation pathways possibly involved⁴
      • TGF-β/MAPK
      • Atrogin-1/proteasome
• Also see: Critical illness polyneuropathy

CONGENITAL DEFECTS OF THE DIAPHRAGM

• Frequently unilateral
  

• Frequent neonatal death
  

Cough & Neuromuscular Disorders

• HSN + Cough & GE reflux
• CMT 1B
• Autonomic disorders
  • Holmes-Adie syndrome
  • Acute pandysautonomia
  • Vagal mononeuropathy

Hoarse voice & Neuromuscular Disorders

• HSN + Cough & GE reflux
• HMSN 2C
• HMSN 4A
• HMN 7