How can respiratory failure be described?

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  Hypoxic respiratory failure

  
  
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  Hypercapnic respiratory failure

  
  
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  Mixed (hypoxic and hypercapnic) respiratory failure

Types of respiratory failure:

What is hypoxic respiratory failure, and what are its causes?

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  It is respiratory failure in the setting of hypoxemia. Not to be confused with tissue hypoxia. Tissue hypoxia can be seen in states of normal blood oxygen content as in the case of carbon monoxide poisoning.

  
  
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  Etiologies:

  
  
  
  
  1. 
     

     Low alveolar oxygen content

     
     
     
     
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       If the inhaled air has low fractional oxygen content, hypoxia can ensue.

       
       
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       If a patient stops or slows ventilation, the alveolar oxygen content will be reduced.

     
     
     
     
  2. 
     

     Decreased diffusing capacity

     
     
     
     
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       The alveolar units involved in gas exchange do not permit such exchange.

       
       
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       Can be seen in cases of alveolar filling processes as in pulmonary edema, and pneumonia, or interstitial processes as in pulmonary fibrosis.

     
     
     
     
  3. 
     

     Ventilated but not perfused lung units—V/Q mismatch

     
     
     
     
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       Example would be pulmonary embolism.

       
       
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       The alveolus has been able to attain high oxygen content; however, sufficient blood does not reach the ventilated alveolus, hence creating a mismatch.

       
       
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       An extreme form of V/Q mismatch is a shunt

     
     
     
     
  4. 
     

     Shunt

     
     
     
     
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       Anatomic and physiologic shunting is possible.

       
       
       
       
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         4a. Anatomic shunts include intracardiac shunting and intrapulmonary shunting

         
         
         
         
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           Atrial septal defect

           
           
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           Ventricular septal defect

           
           
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           Intrapulmonary A-V malformation

         
         

       
       

     
     
     
     
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       4b. Physiologic shunting

       
       
       
       
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         Occurs when the alveolar lumen is filled with fluid, blood, and pus, resulting in hypoxic vasoconstriction and a shunting of blood toward more oxygenated lung units

       
       

     
     

  
  

What is hypercapnic respiratory failure, and what are some of its causes?

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  Respiratory failure associated with decreased ventilation or increased metabolism will lead to a hypercapnic state.

Physiology behind ventilation

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  This can be understood by appreciation of the following equations

  
  
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  PACO₂ = VCO₂ * 0.863/VA

  
  
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  PACO₂ is alveolar CO₂

  
  
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  VA = Ve – Vd; alveolar ventilation (VA) is the difference between the minute ventilation (Ve) and the dead space ventilation (Vd).

  
  
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  Vd: Dead space is the space within the airway that does not participate in gas exchange.

  
  
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  VA is alveolar ventilation (alveolar volume per breath * respiratory rate), which can also be described as minute ventilation – dead space ventilation. The alveolus is the gas exchange unit, while larger airways such as the trachea and bronchi serve as part of the conducting system.

  
  
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  VCO₂ is the metabolic CO₂ product, which, if proportional to the alveolar ventilation (VA), should lead to a PACO₂ in the normal range.

  
  
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  If I take in a breath of 500 cc and 150 cc remains in the conducting airways, then my alveolar ventilation is a product of 350 cc * breaths per minute, while my minute ventilation (Ve) is 500 cc * breaths per minute.

  
  
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  Because CO₂ diffuses readily into the alveolar space, the PACO₂ should be similar to the arterial CO₂ (PaCO₂); hence, the arterial partial pressure of CO₂ is used as an estimation of alveolar CO₂ (PACO₂).

  
  
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  Now looking back at the equation one can see the main determinant in a hypercapnic state is that alveolar ventilation is no longer proportional to the metabolic CO₂ product.

  
  
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  A more simplified equation is PaCO₂ = VCO₂/VA

Reduction in alveolar ventilation (VA) can be caused by:

1. 
   

   Insufficient minute ventilation Ve (Ve = rate * tidal volume)

   
   
2. 
   

   Increase in dead space

   
   
   
   
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     2a. Dead space can be anatomic

     
     
     
     
     1. 
        

        a. Conducting airways

        
        
     2. 
        

        b. Endotracheal tube and tubing

     
     
     
     
   • 
     

     2b. Dead space can be physiologic

     
     
     
     
     1. 
        

        Ventilated but not perfused airways

        
        
     2. 
        

        In high-positive end-expiratory pressure (PEEP) states, over-distention of upper zone alveoli will lead to the alveoli being inflated but the high intra-alveolar pressure will limit perfusion.

        
        
     3. 
        

        In certain disease states, obstructing inflammation might develop in the terminal bronchioles, limiting the volume that reaches the alveolus. Example: bronchiolitis.

        
        
     4. 
        

        In certain disease states, a vascular obstruction might lead to ventilated units not being perfused. Example: large PE.

     
     

   
   

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  It must be noted that a substantial increase in PACO₂ will lead to hypoxia, unless the inspired oxygen content is also increased

  
  
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  Alveolar oxygen partial pressure: (FiO₂ * (atmospheric pressure – vapor pressure) – PACO₂/0.8)

  
  
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  If PACO₂ (alveolar CO₂), which is similar to arterial CO₂ (arterial CO₂ can be measured), is high enough, it will prevent the PaO₂ from reaching 60.

  
  
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  Based on the oxygen saturation curve, below a PaO₂ of 60, hemoglobin saturation will drop off dramatically and a “desaturation” less than 88 can be seen.

What are some specific instances of hypoventilation?

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  Examples of sedating drugs: benzodiazepines, narcotics, barbiturates

  
  
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  Examples of CNS-specific conditions: seizures, stroke, herniation, encephalopathies

  
  
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  Examples of general metabolic conditions that result in altered mental status and a subsequent decrease in the respiratory rate as well as depth:

  
  
  
  
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    Severe infections can often lead to altered mental status

    
    
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    CO₂ narcosis as seen in patients with COPD exacerbations

    
    
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    Hepatic encephalopathy

    
    
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    Hypoglycemia

    
    
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    Severe metabolic acidosis

  
  

Supportive Care:

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  With any form of respiratory failure, the goal is to provide supportive measures while actively correcting the underlying etiology. Supplemental oxygen

  
  
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  Positive pressure

  
  
  
  
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    Noninvasive positive pressure ventilation

    
    
    
    
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      Has been shown to reduce the need for intubation, hospital length of stay, and mortality in hypoventilatory states.^1–3

      
      
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      Asthma remains controversial, although some studies suggest a benefit and it is often used in clinical practice.^4–6

      
      
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      Cardiogenic pulmonary edema.⁷

      
      
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      Proven benefit in hypoxic respiratory failure under certain conditions, which include hypercapnia, pulmonary edema, and solid organ transplant.^7–9

      
      
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      Survival benefit and quality-of-life improvement in patients with amyotrophic lateral sclerosis (ALS) without significant bulbar dysfunction.¹⁰ Also shown to improve quality of life and survival in patients with Duchenne muscular dystrophy (DMD).¹¹

    
    
    
    
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    Noninvasive positive pressure ventilation (NIPPV) can be beneficial in the following situations:

    
    
    
    
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      COPD exacerbations

      
      
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      Cardiogenic pulmonary edema

      
      
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      Asthma exacerbations

      
      
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      Solid organ transplant

      
      
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      Chronic hypoventilation syndromes

    
    
    
    
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    Noninvasive ventilation in neuromuscular or chest wall disorders

    
    
    
    
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      Hypoventilation with resultant hypercapnia and hypoxia can be seen in patients with certain chest wall deformities such as kyphosis and scoliosis.¹² Initially hypoventilation is primarily noted in rapid eye movement sleep. Careful attention should be paid to screen for symptoms consistent with nocturnal hypoventilation, and sleep studies should be obtained when indicated.¹³

      
      
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      Neuromuscular disease: Correlation between daytime spirometry and arterial blood gas values with nocturnal hypoventilation has led to the suggestion of obtaining arterial blood gases when FEV₁ drops below 40% and obtaining sleep studies when PaCO₂ rises above 45 especially when present with a base excess above 4.¹⁴

    
    

  
  

What is the difference between bilevel airway pressure ventilation (BPAP) and continuous positive airway pressure ventilation (CPAP)? When are they indicated?

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  BPAP incorporates two set pressures, an inspiratory limb and an expiratory limb; the gradient determines the tidal volume. CPAP consists of a continuous positive pressure, conceptually similar to the expiratory limb.

  
  
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  BPAP is helpful for certain ventilatory and oxygenation disorders, while CPAP is useful only in certain disorders of oxygenation.

  
  
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  BPAP is often described as less comfortable and may not be tolerated as well as CPAP by patients.

  
  
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  CPAP is often used to treat obstructive sleep apnea; in severe cases, BPAP may be necessary.

  
  
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  CPAP is also used to temporize cardiogenic pulmonary edema while an intervention such as diuresis or dialysis is implemented.

When can BPAP help a neurologist?

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  Conditions associated with hypercapnia are listed below:

  
  
  
  
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    Neuromuscular disease with nocturnal or daytime hypoventilation

    
    
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    Severe sleep apnea

    
    
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    COPD exacerbation, asthma

  
  

When can CPAP help a neurologist?

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  Certain conditions associated with isolated hypoxia

  
  
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  Remember CPAP provides only PEEP while BPAP provides an inspiratory and expiratory pressure.

  
  
  
  
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    Obstructive sleep apnea

    
    
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    Pulmonary edema (neurogenic, cardiogenic)

  
  

What are some complications of noninvasive ventilation?

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  Aspiration with subsequent worsening of respiratory failure

  
  
  
  
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    Air insufflation of the stomach with emesis and aspiration of gastric contents

    
    
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    Patients who are on NIPPV should not be obtunded and should have the capacity to remove the mask if needed (during emesis).

  
  
  
  
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  Skin breakdown around a tight-fitting mask

Invasive ventilation

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  Conventional mechanical ventilation via either an endotracheal tube or a tracheostomy tube.

  
  
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  A detailed discussion on the modes of invasive ventilation is outside the scope of this text.

What are some examples of neurological conditions that can cause respiratory failure?

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  Amyotrophic lateral sclerosis (ALS)

  
  
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  Guillain-Barré syndrome (GBS)

  
  
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  Chronic inflammatory demyelinating polyneuropathy (CIPD)

  
  
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  Duchenne muscular dystrophy (DMD)

  
  
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  Multiple sclerosis (MS)

  
  
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  Myasthenia gravis (MG)

  
  
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  Lambert-Eaton myasthenic syndrome (LEMS)

  
  
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  Poliomyelitis

  
  
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  Botulism

  
  
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  Organophosphate poisoning

  
  
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  Ciguatera poisoning

  
  
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  Tetrodotoxin (Puffer fish) poisoning

  
  
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  Mitochondrial myopathies

  
  
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  Spino-bulbar muscular atrophy (Kennedy syndrome)

  
  
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  Polymyositis/Dermatomyositis

What is the pathogenesis of respiratory failure associated with neuromuscular disease?

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  Bulbar dysfunction leading to aspiration with resultant pneumonia, bronchitis, and pneumonitis. Repeated insults will eventually damage the muco-ciliary apparatus leading to bronchiectasis, further compromising the lungs.

  
  
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  Respiratory muscle weakness will lead to hypoventilation and a muted cough reflex.

  
  
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  After either bulbar dysfunction and/or respiratory muscle failure, a progression of aspiration, inability to clear secretions, and hypoventilation will ensue.

What can I do to slow down respiratory deterioration?

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  Limit impact of bulbar dysfunction

  
  
  
  
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    Percutaneous tube feeding if dysphagia

    
    
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    Aspiration precautions at all times

  
  
  
  
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  Overcome respiratory muscle weakness

  
  
  
  
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    Cough assist device

    
    
    
    
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      Consider use when peak expiratory flow <270 L/min.¹⁶

      
      
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      Consider use when maximal expiratory pressures <60 cmH₂O.¹⁷

    
    
    
    
  • 
    

    Manually assisted cough

    
    
    
    
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      Not as good as mechanical devices.¹⁸

    
    
    
    
  • 
    

    Intrapulmonary percussive ventilation

    
    
    
    
    • 
      

      It can be used as an adjunct for mucous clearance in neuromuscular disease. Suggested by a small case series and a study looking at weight of expectorated sputum.^19,20

    
    

  
  

Are there early indicators that herald the onset of respiratory failure?

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  A retrospective study in ICU patients with Guillain-Barré syndrome has identified several features: vital capacity less than 20 mL/kg, maximal inspiratory pressure less than 30 cm H₂O, maximal expiratory pressure less than 40 cmH₂O, and the presence of bulbar dysfunction leading to aspiration. This is the inspiration for the often-mentioned 20/30/40 rule.¹⁵

What are some examples of neuromuscular disease that cause a more rapid decline?

Guillain-Barré syndrome²¹

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  Classically described as ascending paralysis.

  
  
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  Part of a spectrum of disorders involving autoantibodies directed against peripheral nerves.

  
  
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  Antibody targets could include myelin or axon components.

  
  
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  Antecedent symptoms usually consistent with respiratory or gastrointestinal infection.

  
  
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  Weakness usually begins in the lower extremities and progresses superiorly in a symmetric manner.

  
  
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  Sensory and autonomic dysfunction can also be present.

  
  
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  Progression to involve bulbar muscles or respiratory muscles can lead to respiratory failure.

  
  
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  Disease severity can vary from mild dysfunction, to quadriplegia requiring mechanical ventilation.

  
  
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  Acute motor axonal neuropathy (AMAN) is the pure motor neuron form. It can progress rapidly to respiratory failure and also require a longer duration to recover function.²²

  
  
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  Predictors of impending respiratory failure have been previously mentioned. Notably vital capacity (VC) <20 mL/kg, negative inspiratory force of less than 30 cmH₂O and expiratory force less than 40 cmH₂O.¹⁵

  
  
• 
  

  The Erasmus GBS respiratory insufficiency score has been able to predict an increased need for mechanical ventilation based on the following parameters: medical research council sum score, time from symptoms to presentation for hospital admission, and presence or absence of bulbar/facial weakness at hospital admission.²³

  
  
• 
  

  Full recovery of motor function expected in 60% at 1 year. Approximately 5% will die within the first year of diagnosis. Dependence on mechanical ventilation indicates a 20% mortality within the first year.^24–26

Myasthenia gravis²⁷

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  Antibodies directed against nicotinic motor endplate receptors.

  
  
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  Crisis with profound weakness leading to respiratory can be potentiated by certain drugs, which include phenytoin and aminoglycosides among others.²⁸

  
  
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  Another seemingly benign drug that has been shown to precipitate respiratory failure in these patients is magnesium sulfate.²⁹

  
  
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  Ocular manifestations often noted at presentation. Approximately 80% of these patients will proceed to have generalized MG. In approximately 50% of patients presenting with ocular symptoms, generalized symptoms were noted within 6 months, while 20% developed generalized myasthenia within the first month. Most patients will experience an episode of maximum weakness within the first year of onset of MG.³⁰

Botulism

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  Initial symptoms are often related to cranial nerve dysfunction; this can be followed by symmetric descending weakness, which can precipitate respiratory failure by involvement of the diaphragm or upper airway.³¹

  
  
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  Severity of disease can vary; low-dose toxin exposure resulting in limited symptoms restricts gastrointestinal dysfunction; however, higher doses can precipitate death from respiratory failure.³²

  
  
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  Can progress to respiratory failure.

  
  
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  Pathogenesis involves endocytosis of toxins, which leads to loss of function of that specific presynaptic terminal.^33–35

  
  
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  Peripheral cholinergic nervous system and neuromuscular junctions are affected.³⁶

  
  
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  Appropriate diagnosis requires a high index of suspicion based on clinical history.

  
  
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  Etiologies that inevitably will be considered include GBS, MG, and ciguatera toxin.

Management

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  Detailed discussion of therapy should be reserved for a separate chapter.

  
  
• 
  

  Supportive care is essential in all forms of neuromuscular respiratory failure.

  
  
• 
  

  IVIG and plasmapheresis are the mainstay of therapy for MG and GBS. A role for corticosteroids is also present in MG.

Summary for neuromuscular disorders

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  Anticipate respiratory problems associated with a poor cough reflex and hypoventilation.

  
  
• 
  

  Screen for subtle signs of nocturnal hypoventilation during each clinic visit. Obtain spirometry with arterial blood gas evaluation to augment screening of nocturnal hypoventilation.

  
  
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  Obtain annual evaluation for nocturnal hypoventilation with polysomnography.

  
  
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  In the absence of other signs of daytime respiratory failure, NIF, MEP, and vital capacity can be used to determine need for daytime ventilator support.

  
  
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  Consider noninvasive ventilation if appropriate

  
  
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  In the event of bulbar dysfunction with aspiration, invasive ventilation is the mode of choice.

  
  
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  Invasive ventilation with nonemergent tracheostomy tube placement; if prolonged, mechanical ventilation is expected. Placement of a tracheostomy tube will itself lead to a host of problems. These should be discussed in detail with the patient and care giver.

  
  
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  For patients with progressive disease, palliative care and hospice consultation should be discussed.

  
  
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  For all patients with progressive neuromuscular disease, goals of care including tube feeding and mechanical ventilation should be discussed early in the disease process and should not be delayed until respiratory failure is imminent.