Hypoventilation Syndromes Workup

Updated: Jul 22, 2021
  • Author: Jazeela Fayyaz, DO; Chief Editor: Guy W Soo Hoo, MD, MPH  more...
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Approach Considerations

A diagnosis of lung disease should not be assumed in patients with hypoventilation, because other organ system dysfunction may be the primary cause of the condition. Central and peripheral neurologic disorders and muscular disorders should be considered.

The effects of sedating drugs such as narcotics and benzodiazepines in causing or worsening hypoventilation should always be considered. In patients without an obvious source of hypoventilation, a drug screen should be performed.

Although the differential diagnosis for hypoventilation syndromes is broad, a thorough history, physical examination, and laboratory evaluation should be helpful in limiting it.

Serum chemistries

The most common finding in chronic hypoventilation after chemistry analysis is the presence of a compensatory increase in the serum bicarbonate (HCO3) concentration secondary to respiratory acidosis. A bicarbonate level of greater than 27 mmol/L can be used as a screening tool for obesity hypoventilation and hypercapnia. A bicarbonate level of less than 27 mmol/L has a high negative predictive value for excluding obesity hypoventilation syndrome when suspicion is not high. [11] Patients also occasionally may have hypercalcemia and hyperkalemia.

Complete blood cell count

Many patients with chronic hypoventilation also are hypoxemic. These patients also may have secondary polycythemia, and a complete blood cell (CBC) count may reveal an elevated hematocrit level.

Thyroid function studies

Hypothyroidism is a potential cause of obesity. Obesity, in turn, can contribute to hypoventilation and OSA. Thyroid function should be evaluated in all patients with alveolar hypoventilation who are suspected of having central etiology or OSA.

Arterial blood gas analysis

Alveolar hypoventilation can be documented by the presence of hypercapnia or elevated PaCO2 (>45 mm Hg). In addition, PaO2 should be evaluated because hypoxemia may be present and frequently is associated with alveolar hypoventilation.

HCO3 and pH should be evaluated to determine the presence of acute or chronic acidosis and the degree of compensation.

Transdiaphragmatic pressure

Measurement of transdiaphragmatic pressure is useful in documenting respiratory muscle weakness. This test is performed by placing an esophageal catheter with an esophageal balloon and a gastric balloon. The difference between the pressures measured at the two balloons is the transdiaphragmatic pressure, which is decreased in patients with diaphragmatic dysfunction and paralysis.


Chest Radiography

Perform a chest radiograph to rule out pulmonary disease as a cause of hypoventilation. Findings on chest radiographs that may help to determine the etiology of a hypoventilation syndrome include hyperinflation of lung volumes, diaphragm flattening, and elevation of the hemidiaphragms.

Hyperinflation of lung volumes and diaphragm flattening occur secondary to severe obstructive airway disease. With complicating pulmonary hypertension, the hilar vascular shadows are prominent secondary to pulmonary artery enlargement, and the cardiac silhouette may become prominent secondary to right ventricular enlargement.

Elevation of the hemidiaphragms may be related to diaphragm weakness or paralysis or to atelectasis.

Evidence of bony thoracic abnormalities, such as severe kyphoscoliosis, also may be present. Patients with mild kyphosis of scoliosis generally do not develop hypercapnia.


The fluoroscopic "sniff test" (in which paradoxical elevation of the paralyzed diaphragm is seen during inspiratory effort against a closed glottis) can confirm chest radiographic findings regarding unilateral diaphragmatic paralysis. This test is less useful in the diagnosis of bilateral diaphragmatic paralysis.


CT Scanning and MRI

Chest CT scanning

Computed tomography (CT) scanning of the chest may be performed for the same reasons as chest radiography. However, a CT scan is more sensitive for detecting disease and may reveal abnormalities not seen on a chest radiograph, having greater sensitivity, for example, in detecting emphysema, diaphragm abnormalities, and skeletal thoracic abnormalities.

Brain CT scanning

Perform imaging of the brain if a central cause of hypoventilation is suspected. Specific etiologies that may be diagnosed by brain CT scan include cerebrovascular accident and CNS tumor or trauma. Pay particular attention to the brainstem for lesions in the pons and medulla.

Brain MRI

If a central cause of hypoventilation is suspected and the initial brain CT scan is negative or inconclusive, consider a magnetic resonance imaging (MRI) scan of the brain. MRI may disclose abnormalities that are not seen on CT scanning. Pay particular attention to the brainstem, as with the CT scan mentioned above.



Echocardiography is indicated to evaluate patients with hypoventilation syndromes for evidence of pulmonary hypertension and right ventricular enlargement. It also is useful to determine the presence of other potential complicating factors, such as left ventricular dysfunction and valvular dysfunction. [12]

On 2-dimensional (2D) echocardiography, patients with pulmonary artery hypertension have increased thickness of the right ventricle. As pulmonary hypertension becomes severe, a paradoxical bulging of the interventricular septum into the left ventricle occurs during systole. Later, the right ventricle dilates, becomes hypokinetic, and the septum develops diastolic flattening.

Doppler echocardiography is the most reliable method of estimating pulmonary artery pressure (PAP). Patients with pulmonary artery hypertension may have functional tricuspid valve regurgitation. The maximum tricuspid regurgitant (TR) jet velocity is recorded, and the PAP is calculated using a modified Bernoulli equation: PAP systolic = (4 x TR jet velocity squared) + RAP. RAP is right atrial pressure, estimated from the size of the inferior vena cava (IVC) and respiratory variation in flow in the IVC.


Pulmonary Function Testing

These measurements are required for the diagnosis of obstructive and restrictive lung diseases and for assessment of the severity of disease.

The ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) is reduced in airflow obstruction and is the diagnostic variable. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines obstructive lung disease as an FEV1/FVC ratio of less than 0.70. Others recommend that obstructive lung disease be diagnosed if the FEV1/FVC ratio is below the lower limits of normal. Note that the FEV1/FVC ratio decreases with age; this helps avoid overdiagnosis of obstructive lung disease in elderly patients. [13]

FEV1 is used to evaluate the degree of airflow obstruction. Generally, when the FEV1 drops to less than 30% (very severe COPD), patients may have hypercapnia. Lung volume measurements may document an increase in total lung capacity, functional residual capacity, and residual volume in obstructive pulmonary disease.

Lung volume measurements are also helpful in the diagnosis of restrictive ventilatory defects. When lung volumes are reduced without a reduction in the diffusing capacity for carbon monoxide, this indicates extrathoracic restriction. Obesity and thoracic cage disorders such as severe kyphoscoliosis may cause this.

Measurement of maximal inspiratory and expiratory pressures may be useful in screening for respiratory muscle weakness and neuromuscular disorders.


ECG, EMG, and Nerve Conduction Velocity


Electrocardiography (ECG) may show signs of right heart strain, right ventricular hypertrophy, and right atrial enlargement. [2]

Electromyography and nerve conduction velocity

Electromyography (EMG) and nerve conduction velocity study are useful in diagnosing neuromuscular disorders, such as myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis, that may be the cause of ventilatory muscle weakness. These studies may reveal a neuropathic or myopathic pattern, depending on the etiology.



Polysomnography should be performed in all patients with OHS because the majority of these individuals also have OSA. Polysomnography involves monitoring of multiple physiologic variables to include respiratory effort, airflow, oxygen saturation, sleep stages, body position, limb movements, and electrocardiogram. [14]

Sleep stages and arousals are monitored by electroencephalogram, to determine brain wave activity; electro-oculogram, to determine eye movement; and submental electromyogram, to detect muscle tone. The electro-oculogram and electromyogram facilitate the determination of the REM sleep stage, which is associated with decreased muscle tone and increased frequency of obstructive apneas.

Respiratory effort is recorded using devices to measure abdominal and chest wall movement. These devices include strain gauges, impedance devices, electromyographic bands, and an esophageal balloon with respiratory inductive plethysmography.

From the collected data, sleep stage distribution, arousals, apneas, and hypopneas can be quantitated and central and obstructive apneas can be differentiated. The apnea index and apnea-plus-hypopnea index (AHI) can be calculated by dividing the total number of apneas or apneas plus hypopneas by the total sleep time. The AHI also is known as the respiratory disturbance index. An AHI is considered abnormal at 5 per hour, and an AHI of 5-15 represents mild OSA.