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Respiratory Failure and the Indications for Mechanical Ventilation 

Respiratory Failure and the Indications for Mechanical Ventilation
Respiratory Failure and the Indications for Mechanical Ventilation

John W. Kreit

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date: 11 July 2020

Chapters 1 and 2 explained how the respiratory system maintains a normal arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2). Respiratory failure occurs when a disease process significantly interferes with this vital function and causes arterial hypoxemia, hypercapnia, or both. Typically, respiratory failure is divided into three categories, based on the underlying pathophysiology:

  • Ventilation failure

  • Oxygenation failure

  • Oxygenation-ventilation failure

With severe disturbances in gas exchange, mechanical ventilation is often needed to assist the respiratory system and restore the PaCO2, PaO2, or both, to normal.

Respiratory Failure

Ventilation Failure

As defined in this chapter, ventilation failure is caused by a primary decrease in minute ventilation(V˙E) that prevents the respiratory system from maintaining a normal PaCO2. Recall this equation from Chapter 2:


It tells us that, for a given level of CO2 production (V˙PCO2) and dead space ventilation (V˙D), PaCO2 varies inversely with V˙E. As V˙E falls, PaCO2 rises.

As shown in Table 7.1, V˙E can be reduced by any disease that decreases central respiratory drive, interferes with the transmission of neural signals from the brain to the respiratory muscles, or reduces respiratory muscle strength. Inadequate V˙E can also be caused by disorders such as morbid obesity and severe kyphoscoliosis, which reduce chest wall compliance and increase the pressure that must be generated by the respiratory muscles.

Table 7.1 Causes of Ventilation Failure




Reduced respiratory drive

  • Drugs and toxins

  • Metabolic encephalopathy

  • Encephalitis/Meningitis

  • Cerebral or brainstem infarction

  • Intracranial hemorrhage

  • Narcotics, sedatives

  • Liver failure, renal failure

Impaired transmission to the respiratory muscles

  • Spinal cord disease

  • Peripheral neuropathy

  • Disease of the neuromuscular junction

  • Trauma, myelitis, ALS

  • Phrenic nerve injury, Guillain-Barre syndrome

  • Myasthenia gravis, Eaton-Lambert syndrome

Respiratory muscle weakness

  • Myopathy

  • Myositis

  • Endocrine, metabolic, drug-induced

  • Polymyositis, other connective tissue diseases

Chest wall disease

Reduced chest wall compliance

Morbid obesity, severe kyphoscoliosis, large pleural effusions, massive ascites

ALS = amyotrophic lateral sclerosis

Since the diseases that precipitate ventilation failure do not affect the lungs themselves, they do not increase the normal degree of mismatching between ventilation (V˙) and perfusion (Q˙) or affect the normal distribution of V˙/Q˙ ratios.1 This means that the mean alveolar PO2(PA¯O2) calculated from the alveolar gas equation (Chapter 2, Equation 2.4) and the measured PaO2 fall together with the rise in PaCO2, and the difference between them (the A–a gradient) does not change (see Table 7.3).

Table 7.3 Diagnostic Features of Respiratory Failure



A–a Gradient

Ventilation failure


Oxygenation failure

NL or ↓

Oxygenation-ventilation failure

NL = normal

Oxygenation Failure

Oxygenation failure occurs when intrinsic lung disease causes a drop in the PaO2 and arterial hemoglobin saturation (SaO2). As discussed in Chapter 2, this results from the generation of abnormal V˙/Q˙ ratios (including intra-pulmonary shunting), the impairment of gas diffusion, or both. As shown in Table 7.2, oxygenation failure can be caused by any lung disease, regardless of whether it primarily affects the airways, the lung parenchyma, or the pulmonary circulation. Since lung disease does not alter any of the components of the alveolar gas equation, the calculated PA¯O2 is unchanged, and the A–a gradient increases (see Table 7.3). Recall that an abnormal degree of V˙/Q˙ mismatching and diffusion impairment can also cause hypercapnia. In patients with oxygenation failure, an appropriate increase in V˙E mediated by central chemoreceptors maintains a normal PaCO2.

Table 7.2 Causes of Oxygenation Failure



Obstructive lung diseases

  • Emphysema

  • Chronic bronchitis

  • Asthma

  • Bronchiectasis

Restrictive lung diseases

  • Idiopathic pulmonary fibrosis

  • Sarcoidosis

  • Pneumoconioses

Airspace filling diseases

  • ARDS

  • Cardiogenic edema

  • Pneumonia

Pulmonary vascular diseases

  • Pulmonary arterial hypertension

  • Pulmonary embolism

ARDS = acute respiratory distress syndrome

Oxygenation-Ventilation Failure

It will probably come as no surprise that this type of respiratory failure combines the features of both oxygenation and ventilation failure. Its pathophysiology is largely the same as pure oxygenation failure. The difference is that the underlying lung disease causes such a profound abnormality in lung compliance or resistance that the respiratory system either cannot maintain a normal V˙E or it cannot increase V˙E to compensate for hypercapnia caused by V˙/Q˙ mismatching or diffusion impairment. As shown in Table 7.3, patients with oxygenation-ventilation failure have a reduced PaO2, an elevated PaCO2, and an increased A–a gradient. In theory, any of the diseases listed in Table 7.2 can lead to oxygenation-ventilation failure, but the most common causes are the acute respiratory distress syndrome (ARDS), cardiogenic pulmonary edema, chronic obstructive pulmonary disease (COPD), and severe acute asthma.

Acute, Chronic, and Acute-on-Chronic Hypercapnia

Hypercapnia in patients with either ventilation failure or oxygenation-ventilation failure can occur quickly over a period of minutes to hours, or develop gradually over weeks, months, or years. Chronic hypercapnia leads to renal compensation, which increases the serum bicarbonate concentration and returns the arterial pH toward normal. That’s why the terms “acute” and “chronic” also imply differences in clinical manifestations and in the urgency of therapy. Patients with chronic, compensated hypercapnia may also develop an acute decompensation that worsens respiratory acidosis. This is referred to as “acute-on-chronic” hypercapnia.

Indications for Mechanical Ventilation

There are four indications for intubation and mechanical ventilation:

  • Acute or acute-on-chronic hypercapnia

  • Oxygenation failure with refractory hypoxemia

  • Inability to protect the lower airway

  • Upper airway obstruction

Acute or Acute-on-Chronic Hypercapnia

Hypercapnia itself is rarely dangerous. It’s the accompanying acidemia (low arterial pH) that may cause major morbidity or even death. So it’s the patient with acute or acute-on-chronic ventilation or oxygenation-ventilation failure that often needs mechanical ventilation, not the patient with chronic, compensated respiratory acidosis from, say, long-standing COPD or morbid obesity.

As a rule of thumb, patients with hypercapnia-induced acidemia should be intubated when their arterial pH falls below about 7.20. Recognize, though, that this is a very general guideline, and that clinical judgment must always prevail. For example, earlier intubation is usually advisable in patients whose hypercapnia and arterial pH are steadily worsening despite aggressive therapy.

In many cases, in fact, patients with respiratory distress are intubated before any change in PaCO2 or pH has occurred. That’s because early intubation for impending hypercapnia is much safer than waiting until the onset of respiratory muscle fatigue, which can precipitate acute, severe, and life-threatening acidemia. On the other hand, a patient with a pH < 7.20 may not require intubation if the cause can be rapidly corrected (e.g., narcotic-induced ventilation failure). Also keep in mind that the decision to intubate a patient is often made in the absence of blood gas measurements. For instance, an unresponsive patient who is taking very slow and shallow breaths should be immediately intubated and ventilated without waiting to confirm the presence of severe hypercapnia and acidemia.

Refractory Hypoxemia

In most patients, oxygenation failure can be adequately treated simply by providing oxygen through a nasal cannula or face mask. Intubation and mechanical ventilation are needed only when the PaO2 and SaO2 remain critically low despite high-flow supplemental oxygen. This is referred to as “refractory hypoxemia” and typically occurs in patients with ARDS, cardiogenic edema, and other diseases that cause extensive alveolar filling. Here, my use of the term “critically low” is intentionally vague. Although a PaO2 > 60 mmHg and an SaO2 > 90% are reasonable goals, there’s no generally accepted PaO2 or SaO2 that mandates intubation, and decisions must be made on a case-by-case basis.

So why is mechanical ventilation beneficial to patients with refractory hypoxemia? After all, their PaCO2 is usually normal or low, so they don’t need assistance with ventilation. The main advantage is that endotracheal intubation allows us to go from an open to a closed system of oxygen delivery. Patients receiving supplemental oxygen via a face mask always inhale a variable volume of room air. This causes the fractional concentration of inspired oxygen (FIO2) to be less than the concentration of O2 flowing to the patient (FO2). Following intubation, though, the cuff of the endotracheal tube prevents room air from entering. This means that an FIO2 of 1.0, or any other concentration, can be reliably delivered, and this is usually accompanied by a significant improvement in PaO2 and SaO2.

The other benefit of mechanical ventilation is that it allows the use of positive end-expiratory pressure. As discussed in several previous chapters, by maintaining positive (supra-atmospheric) pressure in the airways and alveoli throughout expiration, PEEP prevents alveoli that were opened or “recruited” during mechanical inflation from collapsing during expiration. This reduces the volume of blood passing through unventilated alveoli (intra-pulmonary shunt) and improves oxygenation.

Inability to Protect the Lower Airway

Normally, several very effective mechanisms prevent saliva, food, and liquids from entering the trachea. During spontaneous breathing, the true and false vocal folds are abducted (separated), the entrance to the trachea (glottis) is open, and air passes freely in and out of the tracheobronchial tree. If saliva or another substance enters the larynx, reflexes mediated via the vagus nerve immediately adduct (bring together) the vocal folds and close the glottis. If aspiration does occur, irritant receptors in the larynx and trachea trigger a powerful cough response that forces the material back up through the glottis. When we swallow, there are two barriers to aspiration. First, the vocal folds adduct and close the glottis. (That’s why we can’t breathe and swallow at the same time). Second, the larynx is pulled upward toward the base of the tongue, which pushes the epiglottis downward like a protective cover over the laryngeal inlet.

Endotracheal intubation is commonly performed when a patient is believed to have lost these vital protective reflexes. But there are two big problems. Problem #1: How do you know when patients are unable to “protect their airway”? Usually, this is based on the assumption that the patient’s mental status predicts the effectiveness of their protective reflexes. Although this makes sense and a general correlation is supported by some observational studies, the actual relationship between the level of consciousness and the presence of airway protective reflexes is simply unknown. In other words, we don’t know what proportion of comatose, obtunded, or lethargic patients cannot protect themselves from aspiration. Compounding this problem is the fact that bedside assessments are unreliable. In particular, most studies have shown a poor correlation between the presence or absence of a gag reflex and protective laryngeal reflexes.

Why is this so important? Isn’t it just better to intubate a patient with altered mental status and make sure that their airway is protected? Well, this brings us to Problem #2. I want you to consider what happens to normal protective reflexes when a patient is intubated. The patient is now unable to close the glottis, elevate the larynx, or cough. In other words, all protective reflexes have been eliminated. In fact, saliva can (and does) freely flow into the trachea between the endotracheal tube and the vocal folds. But doesn’t the cuff of the endotracheal tube still protect the lower airway? It protects against acute, large-volume (massive) aspiration, but saliva and other substances eventually pass around the cuff and enter the tracheobronchial tree. In fact, this is the pathogenesis of ventilator-associated pneumonia.

So, as you can see, intubating a patient to “protect” their lower airway is sometimes the wrong thing to do, because it prevents intact laryngeal reflexes from functioning. We just don’t know when it’s the wrong thing to do. Based on everything I’ve told you, I intubate patients for airway protection under two circumstances. The first is when a condition that is not quickly reversible causes the patient to be completely unresponsive or responsive only to painful stimuli. The second is when a patient who is having or is likely to have large-volume emesis (e.g., gastric outlet or small bowel obstruction, upper GI bleeding) has even a modest decline in his or her level of consciousness.

Upper Airway Obstruction

This is the most obvious but least common indication for intubation and mechanical ventilation. When narrowing of the pharynx or larynx prevents adequate ventilation, it must be bypassed with an artificial airway. This can usually be accomplished with an endotracheal tube, but tracheostomy may be needed when there is marked anatomical distortion or complete airway obstruction.


1 This will only be true if impaired ventilation does not lead to lung atelectasis.