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Respiratory Acidosis
Updated: May 10, 2023
Author: Nazir A Lone, MD, MBBS, MPH, FACP, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP

Overview

Practice Essentials
Respiratory acidosis is an acid-base balance disturbance due to alveolar hypoventilation. Production of carbon dioxide
occurs rapidly, and failure of ventilation promptly increases the partial pressure of arterial carbon dioxide (PaCO2).[1] The
normal reference range for PaCO2 is 35-45 mm Hg.[2, 3]

The increase in PaCO2 (ie, hypercapnia) brought on by alveolar hypoventilation decreases the bicarbonate
(HCO3–)/PaCO2 ratio, thereby decreasing the pH. Respiratory acidosis ensues when the removal of carbon dioxide by the
respiratory system is less than the production of carbon dioxide in the tissues.

Lung diseases that cause abnormalities in alveolar gas exchange do not typically result in alveolar hypoventilation. Often
these diseases stimulate ventilation and hypocapnia due to reflex receptors and hypoxia. Hypercapnia typically occurs late
in the disease process with severe pulmonary disease or when respiratory muscles fatigue. (See also Pediatric Respiratory
Acidosis, Metabolic Acidosis, and Pediatric Metabolic Acidosis.)

Acute vs chronic respiratory acidosis

Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO2 is elevated above the upper limit of
the reference range (ie, >45 mm Hg) with an accompanying acidemia (ie, pH < 7.35). In chronic respiratory acidosis, the
PaCO2 is elevated above the upper limit of the reference range, with a normal or near-normal pH secondary to renal
compensation and an elevated serum bicarbonate levels (ie, >30 mEq/L).

Acute respiratory acidosis is present when an abrupt failure of ventilation occurs. This failure in ventilation may result from
depression of the central respiratory center by one or another of the following:

Central nervous system disease or drug-induced respiratory depression

Inability to ventilate adequately, due to a neuromuscular disease or paralysis (eg, myasthenia gravis, amyotrophic
lateral sclerosis [ALS], Guillain-Barré syndrome, muscular dystrophy)

Airway obstruction, usually related to asthma or chronic obstructive pulmonary disease (COPD)

Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in COPD involves
multiple mechanisms, including the following:

Decreased responsiveness to hypoxia and hypercapnia

Increased ventilation-perfusion mismatch leading to increased dead space ventilation

Decreased diaphragmatic function due to fatigue and hyperinflation

Chronic respiratory acidosis also may be secondary to obesity hypoventilation syndrome (OHS—ie, Pickwickian syndrome),
neuromuscular disorders such as ALS, and severe restrictive ventilatory defects such as are observed in interstitial fibrosis
and thoracic skeletal deformities.

Workup in respiratory acidosis

Arterial blood gas (ABG) analysis is necessary in the evaluation of a patient with suspected respiratory acidosis or other
acid-base disorders.[4]

The most common abnormal serum electrolyte finding in chronic respiratory acidosis is the presence of a compensatory
increase in serum bicarbonate concentration.

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A thyrotropin and a free T4 level should be considered in selected patients, since hypothyroidism may cause obesity, leading
to obstructive sleep apnea (OSA) and sleep apnea–related hypoventilation.

Many patients with chronic hypercapnia and respiratory acidosis are also hypoxemic. These patients may have secondary
polycythemia, as demonstrated by elevated hemoglobin and hematocrit values.

In patients without an obvious source of hypoventilation and respiratory acidosis, a drug screen should be performed. The
effects of sedating drugs such as narcotics and benzodiazepines in depressing the central ventilatory drive and causing
respiratory acidosis should be considered. These sedative drugs should be avoided, if possible, in patients with respiratory
acidosis.

Radiography, computed tomography (CT) scanning, and fluoroscopy of the chest may provide helpful information in
determining causes of respiratory acidosis. Radiologic studies (CT scanning and magnetic resonance imaging [MRI]) of the
brain should be considered if a central cause of hypoventilation and respiratory acidosis is suspected.

Pulmonary function test measurements are required for the diagnosis of obstructive lung disease and for assessment of the
severity of disease. Forced expiratory volume in 1 second (FEV1.0) is the most commonly used index of airflow obstruction.

Electromyography (EMG) and measurement of nerve conduction velocity (NCV) are useful in diagnosing neuromuscular
disorders (eg, myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis [ALS]), which can cause
ventilatory muscle weakness.

Measurement of transdiaphragmatic pressure is a useful diagnostic test for documenting respiratory muscle weakness.
However, it is difficult to perform and is usually carried out only in specialized pulmonary function laboratories.

Management of respiratory acidosis

Pharmacologic therapies are generally used as treatment for the underlying disease process. Oxygen therapy is employed
to prevent the sequelae of long-standing hypoxemia.

Therapeutic measures that may be lifesaving in severe hypercapnia and respiratory acidosis include endotracheal intubation
with mechanical ventilation and noninvasive positive pressure ventilation (NIPPV) techniques such as nasal continuous
positive-pressure ventilation (NCPAP) and nasal bilevel ventilation. The latter techniques of NIPPV are preferred treatment
for obesity hypoventilation syndrome (OHS) and neuromuscular disorders, because they help to improve partial pressure of
arterial oxygen (PaO2) and decrease the partial pressure of arterial carbon dioxide (PaCO2).

Noninvasive external negative-pressure ventilation devices are also available for the treatment of selected patients with
chronic respiratory failure.

Rapid correction of the hypercapnia by the application of external noninvasive positive-pressure ventilation or invasive
mechanical ventilation can result in alkalemia. Accordingly, these techniques should be used with caution.

Etiology and Pathophysiology

As noted (see Background), respiratory acidosis may have a variety of different causes, including the following:

COPD – Emphysema, chronic bronchitis, severe asthma[5, 6]

Neuromuscular diseases – ALS, diaphragm dysfunction and paralysis, Guillain-Barré syndrome, myasthenia gravis,
muscular dystrophy, botulism

Chest wall disorders – Severe kyphoscoliosis, status post thoracoplasty, flail chest, and, less commonly, ankylosing
spondylitis, pectus excavatum,[7] or pectus carinatum

Obesity-hypoventilation syndrome

Obstructive sleep apnea (OSA)

Central nervous system (CNS) depression – Drugs (eg, narcotics, barbiturates, benzodiazepines, and other CNS
depressants), neurologic disorders (eg, encephalitis, brainstem disease, and trauma), primary alveolar
hypoventilation, or congenital central alveolar hypoventilation syndrome (Ondine curse)

Other lung and airway diseases – Laryngeal and tracheal stenosis, interstitial lung disease

Lung-protective mechanical ventilation with permissive hypercapnia in the treatment of acute respiratory distress
syndrome (ARDS); these patients typically are heavily sedated and may require paralytic agents

Acute respiratory acidosis may develop rapidly during bronchoscopy-guided percutaneous dilation tracheostomy from
a reduced minute ventilation (aimed at lung-protective ventilation)[8]

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Hypermetabolic states such as sepsis, malignant hyperthermia, thyroid crisis, fever, and overfeeding can elevate
carbon dioxide levels; similarly, administration of bicarbonate to buffer acidosis or citrate-containing anticoagulants
used in dialysis may lead to elevated partial arterial pressure of carbon dioxide (PaCO2) levels; these may result in
the development of acute respiratory acidosis in the critically ill patient[9]

A study by Alfano et al of over 200 patients with coronavirus disease 2019 (COVID-19) found the rate of respiratory acidosis
to be 3.3%. Among the acid-base disturbances in this cohort, metabolic alkalosis had the highest prevalence (33.6%),
followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%), respiratory acidosis, and metabolic acidosis (2.8%). In
addition, 3.6% of patients had other compensated acid-base derangements (3.6%). Overall, about 80% of patients in the
cohort had an acid-base condition.[10]

Metabolism

Metabolism rapidly generates a large quantity of volatile acid (carbon dioxide) and nonvolatile acid. The metabolism of fats
and carbohydrates leads to the formation of a large amount of carbon dioxide. The carbon dioxide combines with water to
form carbonic acid (H2 CO3). The lungs excrete the volatile fraction through ventilation, and normally acid accumulation
does not occur.[11]

A significant alteration in ventilation that affects elimination of carbon dioxide can cause a respiratory acid-base disorder. The
PaCO2 is normally maintained within the range of 35-45 mm Hg.[12, 13]

Alveolar ventilation

Alveolar ventilation is under the control of the central respiratory centers, which are located in the pons and the medulla.
Ventilation is influenced and regulated by chemoreceptors for PaCO2, partial pressure of arterial oxygen (PaO2), and pH
located in the brainstem, as well as by neural impulses from lung-stretch receptors and impulses from the cerebral cortex.
Failure of ventilation quickly results in an increase in the PaCO2.

Physiologic compensation

In acute respiratory acidosis, the body’s compensation occurs in 2 steps. The initial response is cellular buffering that takes
place over minutes to hours. Cellular buffering elevates plasma bicarbonate values, but only slightly (approximately 1 mEq/L
for each 10-mm Hg increase in PaCO2). The second step is renal compensation that occurs over 3-5 days. With renal
compensation, renal excretion of carbonic acid is increased, and bicarbonate reabsorption is increased.

The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:

Acute respiratory acidosis – Bicarbonate increases by 1 mEq/L for each 10-mm Hg rise in PaCO2.The acute change
in bicarbonate is, therefore, relatively modest and is generated by the blood, extracellular fluid, and cellular buffering
system.

Chronic respiratory acidosis – Bicarbonate increases by 3.5 mEq/L for each 10-mm Hg rise in PaCO2. The greater
change in bicarbonate in chronic respiratory acidosis is accomplished by the kidneys. The response begins soon after
the onset of respiratory acidosis but requires 3-5 days to become complete.

The expected change in pH with respiratory acidosis can be estimated with the following equations:

Acute respiratory acidosis – Change in pH = 0.008 × (40 – PaCO2)

Chronic respiratory acidosis – Change in pH = 0.003 × (40 – PaCO2)

Electrolyte levels

Respiratory acidosis does not have a great effect on serum electrolyte levels. Some small effects occur in calcium and
potassium levels. Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels. In
addition, acidemia causes an extracellular shift of potassium.[14] Respiratory acidosis, however, rarely causes clinically
significant hyperkalemia.

Presentation

History
The clinical manifestations of respiratory acidosis are often those of the underlying disorder. Manifestations vary, depending
on the severity of the disorder and on the rate of development of hypercapnia. Mild to moderate hypercapnia that develops
slowly typically has minimal symptoms.

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Patients may be anxious and may complain of dyspnea. Some patients may have disturbed sleep and daytime
hypersomnolence. As the partial arterial pressure of carbon dioxide (PaCO2) increases, the anxiety may progress to
delirium, and patients become progressively more confused, somnolent, and obtunded. This condition is sometimes referred
to as carbon dioxide narcosis.

Physical Examination
Physical examination findings in patients with respiratory acidosis are usually nonspecific and are related to the underlying
illness or the cause of the respiratory acidosis.

Thoracic examination of patients with obstructive lung disease may demonstrate diffuse wheezing, hyperinflation (ie, barrel
chest), decreased breath sounds, hyperresonance on percussion, and prolonged expiration. Rhonchi may also be heard.

Cyanosis may be noted if accompanying hypoxemia is present. Digital clubbing may indicate the presence of a chronic
respiratory disease or other organ system disorders.

The patient’s mental status may be depressed if severe elevations of PaCO2 are present. Patients may have asterixis,
myoclonus, and seizures.

Papilledema may be found during the retinal examination. Conjunctival and superficial facial blood vessels may also be
dilated.

A study by Zorrilla-Riveiro et al of 212 patients indicated that in persons with dyspnea, nasal flaring is a sign of respiratory
acidosis.[15]

Complications
Patients with chronic respiratory acidosis, by definition, have a component of alveolar hypoventilation. Partial arterial
pressure of carbon dioxide (PaCO2) and bicarbonate levels are increased, and obligatory decreases in partial pressure of
arterial oxygen (PaO2) also occur.

Complications are often related to the chronic hypoxemia, which can result in increased erythropoiesis, leading to secondary
polycythemia.

Chronic hypoxia is a cause of pulmonary vasoconstriction. This physiologic response can, in the long term, lead to
pulmonary hypertension, right ventricular failure, and cor pulmonale.

Hypopneas and apneas during sleep lead to impaired sleep quality and cerebral vasodilation, causing morning headaches,
daytime fatigue, and somnolence.

High levels of CO2 can lead to confusion, often referred to as carbon dioxide narcosis. As a late complication of cerebral
vasodilation, patients may have papilledema.[16]

A study by Lun et al indicated that in patients with acute exacerbation of COPD, those with either compensated or
decompensated respiratory acidosis tend to have poorer lung function and a greater risk for future life-threatening events
than do normocapnic patients.[17]

A study by de Miguel-Díez et al indicated that respiratory acidosis is one factor increasing the risk of rehospitalization for
patients within 30 days of initial hospitalization for acute exacerbation of COPD and is also a risk factor for inhospital
mortality in these readmitted patients. Other factors associated with rehospitalization and inhospital mortality included older
age, malnutrition, nonobesity, and treatment with noninvasive ventilation.[18]

Similarly, a study by Fazekas et al indicated that in patients with COPD who survive a first episode of acute hypercapnic
respiratory failure requiring noninvasive ventilation, severe respiratory acidosis predicts decreased long-term survival, as do
chronic respiratory failure and lower body mass index.[19]

In addition, a prospective study by Crisafulli et al indicated that in patients who have been hospitalized for acute
exacerbation of COPD, a modified Medical Research Council dyspnea score of 2 or greater and acute respiratory acidosis
are independent risk factors, if present at admission, for a hospital stay of more than 7 days (odds ratios of 2.24 and 2.75,
respectively).[20]

A study by Al-Azzam et al indicated that in hospitalized patients with COVID-19, an acid-base imbalance increases the
mortality risk. The risk was found to be nearly four-fold in patients with mixed metabolic/respiratory acidosis, and to be two-
fold in those with metabolic acidosis with respiratory compensation, respiratory alkalosis with metabolic compensation, or
respiratory acidosis with no compensation.[21]

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A study by Bar and Aronson indicated that among acid-base abnormalities found in normotensive patients with acute heart
failure, respiratory alkalosis is associated with a greater risk of inhospital mortality than is metabolic acidosis, metabolic
alkalosis, respiratory alkalosis, or mixed acidosis or alkalosis. The adjusted odds ratio for in-hospital mortality for respiratory
alkalosis was greater than 3.[22]

A study by Mochizuki et al indicated that in intensive care unit (ICU) patients, mortality rates from acidemia differ by subtype.
Of over 640,000 ICU patients, 57.8% were found to have acidemia. Metabolic, combined, and respiratory acidemia had
prevalences of 42.9%, 30.3%, and 25.9%, respectively. Combined acidemia had the highest mortality rate (12.7%), followed
by metabolic (11%) and respiratory (5.5%) acidemia. Hospital mortality in respiratory acidemia was best predicted by
PaCO2.[23]

DDx

Diagnostic Considerations
All potential causes of respiratory acidosis should be considered (see Etiology and Pathophysiology). These include lung
disease, neuromuscular diseases, and central neurologic depression. The neuromuscular and skeletal conditions that
should be considered include amyotrophic lateral sclerosis (ALS), muscular dystrophy, severe kyphoscoliosis, Guillain-Barré
syndrome, and myasthenia gravis.

Differential Diagnoses
Asthma

Botulism

Bronchitis

Chronic Obstructive Pulmonary Disease (COPD)

Diaphragm Disorders (Diaphragmatic Dysfunction)

Diaphragmatic Paralysis

Emphysema

Obesity

Opioid Abuse

Sedative, Hypnotic, Anxiolytic Use Disorders

Workup

Workup

Approach Considerations
In patients without an obvious source of hypoventilation and respiratory acidosis, a drug screen should be performed. The
effects of sedating drugs such as narcotics and benzodiazepines in depressing the central ventilatory drive and causing
respiratory acidosis should be considered. These sedative drugs should be avoided, if possible, in patients with respiratory
acidosis.

Radiography, computed tomography (CT) scanning, and fluoroscopy of the chest may provide helpful information in
determining causes of respiratory acidosis. Radiologic studies (CT scanning and magnetic resonance imaging [MRI]) of the
brain should be considered if a central cause of hypoventilation and respiratory acidosis is suspected. Tests for pulmonary
function, nerve function, and transdiaphragmatic pressure (when available), may also be helpful.

Laboratory Tests

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Arterial blood gas (ABG) analysis is necessary in the evaluation of a patient with suspected respiratory acidosis or other
acid-base disorders.[4] The bicarbonate level reported on the blood gas analysis is calculated from the Henderson-
Hasselbalch equation. Thus, a measured serum bicarbonate level must also be obtained. Other tests that may be helpful
include serum electrolytes and biochemistries, thyroid studies, a complete blood count (CBC), and drug and toxicology
screens.

Acidemia is documented by the presence of a decreased pH (< 7.35) on ABG analysis. The presence of an increased partial
pressure of arterial carbon dioxide (PaCO2) (>45 mm Hg) indicates a respiratory etiology of the acidemia. Hypoxemia may
be present and is frequently associated with pulmonary diseases that cause respiratory acidosis.

The most common abnormal serum electrolyte finding in chronic respiratory acidosis is the presence of a compensatory
increase in serum bicarbonate concentration.

Some patients with hypothyroidism hypoventilate. In addition, hypothyroidism may cause obesity, leading to obstructive
sleep apnea (OSA) and sleep apnea–related hypoventilation. Obesity hypoventilation syndrome (OHS) also leads to chronic
respiratory acidosis. A thyrotropin and a free T4 level should, therefore, be considered in selected patients.

Many patients with chronic hypercapnia and respiratory acidosis are also hypoxemic. These patients may have secondary
polycythemia, as demonstrated by elevated hemoglobin and hematocrit values.

Drug and toxicology screens should be performed in patients presenting with unexplained hypercapnia and respiratory
acidosis. Screening for specific drugs, including opiates, barbiturates, and benzodiazepines, should be performed.

A study by Sadot et al found alveolar hypoventilation to be frequent among children undergoing flexible bronchoscopy. The
investigators stated, therefore, that during the procedure children, especially those susceptible to complications from
respiratory acidosis or who are expected to need a large amount of sedation, should be monitored for a rise in
transcutaneous carbon dioxide, an indicator of alveolar hypoventilation. The study included 95 children.[24]

Plain Radiography and Fluoroscopy

Chest radiography should be performed to help rule out pulmonary disease as a cause of hypercapnia and respiratory
acidosis. Findings on chest radiographs that may help determine an etiology of respiratory acidosis include the following:

Hyperinflation and diaphragmatic flattening due to severe obstructive airway disease

Infiltrates secondary to pneumonias

Elevated diaphragm related to diaphragmatic weakness or paralysis

Pneumothorax

Atelectasis

Thoracic skeletal deformities

If complicating pulmonary hypertension is present, the hilar vascular shadows may be prominent and the cardiac silhouette
may show evidence of right ventricular enlargement.

A fluoroscopic “sniff test,” in which paradoxical elevation of the paralyzed diaphragm is observed with inspiration, can
confirm diaphragmatic paralysis, even in the presence of a normal appearance on chest radiographs. However, this test is
not as useful in bilateral diaphragmatic paralysis as it is in unilateral diaphragmatic paralysis.

CT and MRI
A CT scan of the chest may be obtained if the results of chest radiography are inconclusive or if a pulmonary disorder
remains high on the differential diagnosis. CT scanning is more sensitive than plain radiography for detecting pulmonary
diseases and may reveal abnormalities not observed on chest radiographs.

Specific etiologies that may be diagnosed by using brain CT scanning include stroke, central nervous system (CNS) tumor,
and CNS trauma. Pay particular attention to the brainstem for lesions in the pons and medulla.

If a central cause of hypoventilation and respiratory acidosis is suspected and after initial findings brain CT imaging is
negative or inconclusive, a MRI of the brain should be perfromed. MRI may disclose abnormalities not observed on CT
scans, particularly in the brainstem.

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Pulmonary Function Testing

Pulmonary function test measurements are required for the diagnosis of obstructive lung disease and for assessment of the
severity of disease. Forced expiratory volume in 1 second (FEV1.0) is the most commonly used index of airflow obstruction.
The ratio of FEV1.0 to forced vital capacity (FVC) (ie, FEV1.0/FVC), is reduced and is the diagnostic variable in airflow
obstruction.

Lung volume measurements may document an increase in total lung capacity (TLC), functional residual capacity (FRC), and
residual volume (RV) in obstructive airway diseases. TLC is decreased in restrictive lung diseases. Measurement of maximal
inspiratory and expiratory pressures may be useful in screening for respiratory muscle weakness.

EMG and Nerve Conduction Velocity

Electromyography (EMG) and measurement of nerve conduction velocity (NCV) are useful in diagnosing neuromuscular
disorders (eg, myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis [ALS]), which can cause
ventilatory muscle weakness. These studies may reveal a neuropathic pattern or a myopathic pattern, depending on the
etiology of the diaphragmatic and respiratory muscle dysfunction. Some centers can perform phrenic nerve conduction
studies and diaphragmatic EMG in the workup of diaphragmatic dysfunction.

Measurement of Transdiaphragmatic Pressure

Measurement of transdiaphragmatic pressure is a useful diagnostic test for documenting respiratory muscle weakness.
However, it is difficult to perform, and it is usually performed only in specialized pulmonary function laboratories.

The test is performed by placing an esophageal catheter with an esophageal balloon and a gastric balloon. The difference
between the pressures measured at the 2 balloons is the transdiaphragmatic pressure. Patients with diaphragmatic
dysfunction and paralysis have a decrease in maximal transdiaphragmatic pressure.

Other Tests
Capnography, or end-tidal carbon dioxide monitoring

Capnography is a noninvasive bedside diagnostic tool for measurement of the partial pressure of carbon dioxide in exhaled
breath, especially in the operating room, endoscopy suite settings, and the emergency department (ED) setting. A meta-
analysis of 13 randomized, controlled trials showed that with capnography monitoring, employed in combination with visual
assessment and pulse oximetry, there was a reduction in respiratory compromise during procedural sedation and analgesia
administered for ambulatory surgery, in comparison with the use of visual assessment and pulse oximetry alone.[25]

Treatment

Approach Considerations
Treatment of respiratory acidosis is primarily directed at the underlying disorder or pathophysiologic process. Caution should
be exercised in the correction of chronic hypercapnia: too-rapid correction of the hypercapnia can result in metabolic
alkalemia. Alkalization of the cerebrospinal fluid (CSF) can result in seizures.

The criteria for admission to the intensive care unit (ICU) vary from institution to institution but may include patient confusion,
lethargy, respiratory muscle fatigue, and a low pH (< 7.25). All patients who require tracheal intubation and mechanical
ventilation must be admitted to the ICU. Most acute care facilities require that all patients being treated acutely with
noninvasive positive-pressure ventilation (NIPPV) be admitted to the ICU.

Consider consultation with pulmonologists and neurologists for assistance with the evaluation and treatment of respiratory
acidosis. Results from the history, physical examination, and available laboratory studies should guide the selection of the
subspecialty consultants.

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Pharmacologic Therapy
Pharmacologic therapies are generally used as treatment for the underlying disease process.

Bronchodilators

Bronchodilators such as beta agonists (eg, albuterol and salmeterol), anticholinergic agents (eg, ipratropium bromide and
tiotropium), and methylxanthines (eg, theophylline) are helpful in treating patients with obstructive airway disease and severe
bronchospasm. Theophylline may improve diaphragm muscle contractility and may stimulate the respiratory center.

Respiratory stimulants

Respiratory stimulants have been used but have limited efficacy in respiratory acidosis caused by disease.

Medroxyprogesterone increases central respiratory drive and may be effective in treating obesity-hypoventilation syndrome
(OHS). Medroxyprogesterone has also been shown to stimulate ventilation is some patients with COPD and alveolar
hypoventilation. This medication does not improve apnea frequency or sleepiness symptoms in patients with sleep apnea.

There is an increased risk of thromboembolism with progestational agents. Many experts do not recommend the use of
medroxyprogesterone as a means to increase alveolar ventilation.

Acetazolamide is a diuretic that increases bicarbonate excretion and induces a metabolic acidosis, which subsequently
stimulates ventilation. However, acetazolamide must be used with caution in this setting. Inducing a metabolic acidosis in a
patient with a respiratory acidosis could result in a severely low pH. If the patient's respiratory system cannot compensate for
the metabolic acidosis it induces, the patient may suffer hyperkalemia and potentially a life-threatening cardiac arrhythmia.

Theophylline increases diaphragm muscle strength and stimulates the central ventilatory drive. In addition, theophylline is a
bronchodilator.

Drug antagonists
Drug therapy aimed at reversing the effects of certain sedative drugs may be helpful in the event of an accidental or
intentional overdosage. Naloxone may be used to reverse the effects of narcotics. Flumazenil may be used to reverse the
effects of benzodiazepines. However, care must be taken in reversing the effects of benzodiazepines because patients may
have seizures if benzodiazepine reversal is accomplished too vigorously.

Bicarbonate

Infusion of sodium bicarbonate is rarely indicated. This measure may be considered after cardiopulmonary arrest with an
extremely low pH (< 7.0-7.1). In most other situations, sodium bicarbonate has no role in the treatment of respiratory
acidosis.

Oxygen Therapy
Because many patients with hypercapnia are also hypoxemic, oxygen therapy may be indicated. Oxygen therapy is
employed to prevent the sequelae of long-standing hypoxemia. Patients with COPD who meet the criteria for oxygen therapy
have been shown to have decreased mortality when treated with continuous oxygen therapy. Oxygen therapy has also been
shown to reduce pulmonary hypertension in some patients.

Oxygen therapy should be used with caution because it may worsen hypercapnia in some situations. For example, patients
with COPD may experience exacerbation of hypercapnia during oxygen therapy. This observation is thought by many to be
primarily a consequence of ventilation-perfusion mismatching, in opposition to the commonly accepted concept of a
reduction in hypoxic ventilatory drive. The exact pathophysiology, however, remains controversial.

Hypercapnia is best avoided by titrating oxygen delivery to maintain oxygen saturation in the low 90% range and partial
arterial pressure of oxygen (PaO2) in the range of 60-65 mm Hg.

Ventilatory Support
Therapeutic measures that may be lifesaving in severe hypercapnia and respiratory acidosis include endotracheal intubation
with mechanical ventilation and noninvasive positive pressure ventilation (NIPPV) techniques such as nasal continuous
positive-pressure ventilation (NCPAP) and nasal bilevel ventilation. The latter techniques of NIPPV are preferred treatment
for OHS and neuromuscular disorders, because they help to improve PaO2 and decrease the partial pressure of arterial
carbon dioxide (PaCO2).
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Noninvasive external negative-pressure ventilation devices are also available for the treatment of selected patients with
chronic respiratory failure.

Rapid correction of the hypercapnia by the application of external noninvasive positive-pressure ventilation or invasive
mechanical ventilation can result in alkalemia. Accordingly, these techniques should be used with caution.

A study comparing noninvasive techniques with invasive ventilation in myasthenic crisis found that patients who underwent
noninvasive ventilation had better outcomes than patients who underwent invasive ventilation.[26]

A 4-year retrospective study reported that NIPPV was highly beneficial in the treatment of COPD with hypercapnia (type II)
respiratory failure.[27] NIPPV led to a decreased length of stay and a reduced cost of hospitalization.

Based on a literature review, Fielding-Singh et al recommended that in refractory respiratory acidosis resulting from ARDS,
patients be treated with “initial modest liberalization of tidal volumes, followed by neuromuscular blockade and prone
positioning.”[28]

A study by Nentwich et al indicated that in patients with hypercapnia and concomitant renal failure, respiratory acidosis can
be decreased and ventilation requirements reduced through the use of low-flow extracorporeal CO2 removal in combination
with renal replacement therapy.[29]

Investigational therapy

Extracorporeal carbon dioxide removal (ECCO2 R) is a newer technique for removing carbon dioxide via venovenous
bypass without affecting oxygenation. ECCO2 R is being evaluated in the treatment of respiratory acidosis as a complication
of the low tidal volume lung-protective ventilation with permissive hypercapnia. However, this technique has been associated
with serious complications and requires more investigation.[30]

Medication

Medication Summary
No drugs are used specifically to treat respiratory acidosis. Medical therapies are directed at the underlying disease or
disorder causing hypoventilation and, therefore, respiratory acidosis. The drugs for these various conditions are included in
this review.

Beta2 Agonists

Class Summary
Beta2 agonists, by decreasing muscle tone in both small and large airways in the lungs, increase ventilation. Beta2 agonists
activate the beta2 -adrenergic receptors on the surface of smooth muscle cells of the bronchial airways, thereby increasing
intracellular cyclic adenosine monophosphate (cAMP). This interaction results in smooth muscle relaxation.

The short-acting beta2 agonists (albuterol, levalbuterol, metaproterenol, and pirbuterol) are used for the treatment or
prevention of bronchospasm. These medications are typically delivered to the bronchial smooth muscles through inhalation
of aerosolized or nebulized preparations of these medications. Oral preparations of albuterol and metaproterenol are
available but are less effective and more prone to complications.

The long-acting beta2 agonists (arformoterol, formoterol, indacaterol, and salmeterol) are typically used in patients with more
persistent symptoms. The bronchodilating effects of these drugs last more than 12 hours. Each requires twice-daily dosing,
except for indacaterol, which is administered once daily.

Albuterol (Proventil HFA, Ventolin HFA, AccuNeb, ProAir HFA)

Albuterol is a beta agonist for bronchospasm that is refractory to epinephrine. This agent relaxes bronchial smooth muscle
through its action on beta2 receptors; it has little effect on cardiac muscle contractility.

Salmeterol (Serevent Diskus)

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By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or
bronchiectasis, salmeterol can relieve bronchospasms. It also may facilitate expectoration. The long-acting bronchodilating
effect of salmeterol lasts for more than 12 hours. This agent is used on a fixed schedule, in addition to regular use of
anticholinergic agents. When salmeterol is administered at higher or more frequent doses than recommended, the incidence
of adverse effects is higher.

Metaproterenol
Metaproterenol is a beta2-adrenergic agonist that relaxes bronchial smooth muscle, with little effect on heart rate.

Levalbuterol (Xopenex, Xopenex HFA)

Levalbuterol acts on beta2 receptors, causing relaxation of bronchial smooth muscle, with little effect on heart rate.

Pirbuterol (Maxair)
Pirbuterol is a beta2-adrenergic agonist with a structure similar to that of albuterol. Binding to beta2-adrenergic receptors
causes relaxation of bronchial smooth muscle.

Formoterol (Foradil, Perforomist)

Formoterol acts on beta2 receptors, with little effect on the cardiovascular system. It is long acting and relaxes the smooth
muscles of the bronchioles, with little effect on heart rate.

Indacaterol (Arcapta Neohaler)

Indacaterol acts on beta2 receptors, with little effect on the cardiovascular system. It is long acting and relaxes the smooth
muscles of the bronchioles, with little effect on heart rate.

Arformoterol (Brovana)
Arformoterol acts on beta2 receptors, with little effect on the cardiovascular system. It is long acting and relaxes the smooth
muscles of the bronchioles, with little effect on heart rate.

Anticholinergics, Respiratory

Class Summary
The anticholinergic medications compete with acetylcholine for postganglionic muscarinic receptors, thereby inhibiting
cholinergically mediated bronchomotor tone and resulting in bronchodilatation. These agents effectively block vagally
mediated reflex arcs that cause bronchoconstriction. When inhaled, these medications are poorly absorbed systemically and
are, therefore, relatively safe.

Compared with beta2-adrenergic agents, the inhaled short-acting anticholinergic medication ipratropium has equivalent-to-
superior bronchodilator activity in stable chronic obstructive pulmonary disease (COPD) patients. When ipratropium is used
in combination with beta2-adrenergic agonists, a synergistic effect on bronchodilatation occurs. This medication has a
slower onset of action than the beta2-adrenergic agents and is, therefore, less suitable for use on an as-needed basis.

Ipratropium (Atrovent HFA)

Ipratropium is an anticholinergic bronchodilator that is chemically related to atropine. It inhibits serous and seromucous
gland secretions.

Tiotropium (Spiriva)
Tiotropium is a quaternary ammonium compound that elicits anticholinergic and antimuscarinic effects with inhibitory effects
on M3 receptors on airway smooth muscles, leading to bronchodilation. This agent is available in a capsule form that

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contains a dry powder for oral inhalation via the HandiHaler inhalation device. Tiotropium helps patients by dilating narrowed
airways and keeping them open for 24 hours. It is given once daily.

Xanthine Derivatives

Class Summary
Xanthine derivatives such as theophylline inhibit phosphodiesterase, resulting in an increase in cAMP. The increase in cAMP
causes relaxation of bronchial smooth muscle. Theophylline is dosed orally. Its analogue, aminophylline, can be given
intravenously (IV). In addition, theophylline may improve diaphragmatic muscle contractility and stimulate the central
nervous system (CNS) respiratory center.

Theophylline (Theo-24, Elixophyllin)

Theophylline potentiates exogenous catecholamines by stimulating endogenous catecholamine release and diaphragmatic
muscular relaxation, which, in turn, stimulates bronchodilation. The popularity of this agent has decreased because of its
narrow therapeutic range and its toxicities. Theophylline's therapeutic range is relatively narrow, between 8-15 mg/dL.
Unfortunately, bronchodilation may require near-toxic levels (>20 mg/dL). The clinical efficacy of this agent is controversial,
especially in the acute setting.

Corticosteroids

Class Summary
Inflammation plays a significant role in the pathogenesis of asthma. Although the inflammatory pathway mediators differ,
inflammation is also important in the pathogenesis of COPD. Accordingly, glucocorticosteroids are used to temper the
inflammation in these diseases.

The inhaled glucocorticoids (budesonide, fluticasone, and mometasone) have a direct route to the airways. They are only
minimally absorbed systemically and thus have fewer adverse side effects than systemic glucocorticoids do. Inhaled
glucocorticoids improve airflow in asthmatic patients by reducing inflammation and, in the long-term, preventing airway
remodeling. These medications are less effective in COPD patients. They may slow the rate of progression in patients with
COPD.

The systemic glucocorticoids (methylprednisolone, prednisone, and prednisolone) are highly efficacious in the treatment of
acute exacerbations of asthma. They are also widely accepted and recommended in the treatment of COPD exacerbations.
For long-term use of these medications, the adverse effect profile must be weighed against the potential benefits.

Budesonide inhaled (Pulmicort Flexhaler, Pulmicort Respules)

Budesonide reduces inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the production
of cytokines and other mediators involved in bronchospasm. This agent is available as Pulmicort Flexhaler powder for
inhalation (90 µg/actuation and 180 µg/actuation; each actuation delivers 80 µg and 160 µg, respectively) or Pulmicort
Respules.

Fluticasone inhaled (Flovent Diskus, Flovent HFA)

Fluticasone may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It
also has vasoconstrictive activity.

Mometasone (Asmanex Twisthaler)

Mometasone reduces inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the
production of cytokines and other mediators involved in bronchospasm.

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Methylprednisolone (A-Methapred, Medrol, Solu-Medrol)

Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes (PMNs) and
reversing increased capillary permeability.

Prednisone
The immunosuppressant prednisone is a first-line therapy administered for the treatment of autoimmune disorders. It may
decrease inflammation by reversing increased capillary permeability and suppressing PMN activity and CD4 counts.

Prednisolone (Pediapred, Flo-Pred, Orapred)

Prednisolone may reduce inflammation by reversing increased capillary permeability and suppressing PMN activity and CD4
counts.

Benzodiazepine Toxicity Antidotes

Class Summary
Benzodiazepine antagonists are used in reversing the CNS-depressing effects of benzodiazepine overdoses. However,
these agents’ ability to reverse the benzodiazepine-induced respiratory depression is less predictable. Care must be taken in
reversing the effects of benzodiazepines because patients may have seizures if benzodiazepine reversal is accomplished
too vigorously.

Flumazenil (Romazicon)
Flumazenil reverses the effects of benzodiazepines in an overdose by selectively antagonizing the gamma-aminobutyric
acid (GABA)–benzodiazepine receptor complex. If an overdosed patient has not responded after 5 minutes of administration
of flumazenil to a cumulative dose of 5 mg, the cause of the sedation is unlikely to be a benzodiazepine.

Flumazenil is a short-acting agent, with a half-life of 0.7-1.3 hours; however, because most benzodiazepines have longer
half-lives, multiple doses should be administered so that patients do not relapse into a sedative state.

Opioid Antagonists

Class Summary
Opioid abuse, toxicity, and overdose are potential etiologies of hypoventilation and respiratory acidosis. Opioid antagonists
can be used to reverse the effects of opiates and to improve ventilation.

Naloxone
Naloxone is a pure opioid antagonist that prevents or reverses opioid effects (eg, hypotension, respiratory depression, and
sedation), possibly by displacing opiates from their receptors. This agent is used to reverse opioid intoxication.

Naltrexone (Vivitrol, ReVia)

Naltrexone is an opioid antagonist that prevents or reverses opioid effects (eg, hypotension, respiratory depression, and
sedation), possibly by displacing opiates from their receptors. It shows a higher affinity for mu receptors. This agent may be
used to reverse opioid intoxication.

Questions & Answers

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Overview

What is respiratory acidosis?

How are acute and chronic respiratory acidosis defined?

What causes failure in ventilation in acute respiratory acidosis?

What are possible etiologies of chronic respiratory acidosis?

Which lab analysis is necessary to evaluate suspected respiratory acidosis?

What is the most common serum electrolyte finding in chronic respiratory acidosis?

What is the role of thyrotropin and a free T4 level measurement in the workup of respiratory acidosis?

What other conditions may be present in patients with respiratory acidosis?

When is a drug screen indicated in the workup of respiratory acidosis?

What is the role of imaging studies in the workup of respiratory acidosis?

What is the role of pulmonary function testing in the workup of respiratory acidosis?

What is the role of electromyography (EMG) and measurement of nerve conduction velocity (NCV) in the workup of
respiratory acidosis?

What is the role of transdiaphragmatic pressure measurement in the workup of respiratory acidosis?

What are the treatment options for respiratory acidosis?

Which ventilation techniques are used in the treatment of respiratory acidosis?

What is the role of alveolar ventilation in the pathogenesis of respiratory acidosis?

What causes of respiratory acidosis?

What role does metabolism play in the pathogenesis of respiratory acidosis?

What is the physiologic compensation response to acute respiratory acidosis?

What is the change in serum bicarbonate concentration estimated in respiratory acidosis?

How is the change in pH estimated in respiratory acidosis?

What is the role of electrolytes in the pathogenesis of respiratory acidosis?

Presentation

What are the signs and symptoms of respiratory acidosis?

What are the physical findings suggestive of respiratory acidosis?

What are possible complications of in respiratory acidosis?

What is the progression of chronic hypoxia in respiratory acidosis?

What are the effects of hypopneas and apneas in respiratory acidosis?

What is the effect of high levels of carbon dioxide in respiratory acidosis?

Which risks are increased in patients with chronic obstructive pulmonary disease (COPD) and respiratory acidosis?

DDX

What should be considered in the differential diagnosis of respiratory acidosis?

What are the differential diagnoses for Respiratory Acidosis?

Workup

Which tests may be helpful in the diagnosis of respiratory acidosis?

What is the role of arterial blood gas (ABG) analysis in the workup of respiratory acidosis?

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Which serum electrolyte finding suggests chronic respiratory acidosis?

What is the role of thyroid function tests in the workup of respiratory acidosis?

When are drug and toxicology screens indicated in the workup of respiratory acidosis?

Which patients are at increased risk of developing respiratory acidosis while undergoing flexible bronchoscopy?

What is the role of chest radiography in the workup of respiratory acidosis?

What is the role of a fluoroscopic "sniff test" in the workup of respiratory acidosis?

What is the role of CT scanning in the workup of respiratory acidosis?

Which respiratory acidosis etiologies may be diagnosed with brain CT scanning?

What is the role of MRI in the workup of respiratory acidosis?

What is the role of pulmonary test measurements in the workup of respiratory acidosis?

What is the role of electromyography (EMG) and measurement of nerve conduction velocity (NCV) in the workup of
respiratory acidosis?

What is the role of transdiaphragmatic pressure measurement in the workup of respiratory acidosis, and how effective is
capnography in end-tidal carbon dioxide monitoring?

Treatment

What is the focus of respiratory acidosis?

When is inpatient care indicated for respiratory acidosis?

When should specialist consultations be considered in the evaluation and treatment of respiratory acidosis?

What is the role of bronchodilators in the treatment of respiratory acidosis?

What is the role of respiratory stimulants in the treatment of respiratory acidosis?

What is the role of drug antagonists in the treatment of respiratory acidosis?

What is the role of sodium bicarbonate in the treatment of respiratory acidosis?

What is the role of oxygen therapy in the treatment of respiratory acidosis?

What is the role of ventilation in the treatment of respiratory acidosis?

What is the role of extracorporeal carbon dioxide removal (ECCO2 R) in the treatment of respiratory acidosis?

Medications

Which drugs are used to treat respiratory acidosis?

Which medications in the drug class Beta2 Agonists are used in the treatment of Respiratory Acidosis?

Which medications in the drug class Anticholinergics, Respiratory are used in the treatment of Respiratory Acidosis?

Which medications in the drug class Xanthine Derivatives are used in the treatment of Respiratory Acidosis?

Which medications in the drug class Corticosteroids are used in the treatment of Respiratory Acidosis?

Which medications in the drug class Benzodiazepine Toxicity Antidotes are used in the treatment of Respiratory Acidosis?

Which medications in the drug class Opioid Antagonists are used in the treatment of Respiratory Acidosis?

Contributor Information and Disclosures

Author

Nazir A Lone, MD, MBBS, MPH, FACP, FCCP Physician in Pulmonary and Critical Care Medicine, Peconic Bay Medical
Center, Northwell Health

Nazir A Lone, MD, MBBS, MPH, FACP, FCCP is a member of the following medical societies: American Association for
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Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Physicians,
International Association for the Study of Lung Cancer, Medical Society of the State of New York, Society of Critical Care
Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Nancy W Bethuel, MD Resident Physician, Department of Internal Medicine, Basset Medical Center

Nancy W Bethuel, MD is a member of the following medical societies: American College of Physicians, American Medical
Association

Disclosure: Nothing to disclose.

Laurel Whitney MD Candidate, Columbia University College of Physicians and Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor
and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai
Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians,
American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen
College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American
Thoracic Society

Disclosure: Nothing to disclose.

Thomas M Roy, MD Chief, Division of Pulmonary Disease and Critical Care Medicine, Quillen Mountain Home Veterans
Affairs Medical Center; Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, Fellowship
Program Director, James H Quillen College of Medicine, East Tennessee State University

Thomas M Roy, MD is a member of the following medical societies: American College of Chest Physicians, American
College of Physicians, American Medical Association, American Thoracic Society, Southern Medical Association, Wilderness
Medical Society

Disclosure: Nothing to disclose.

Acknowledgements

Wael El Minaoui, MBBS Fellow in Pulmonary/Critical Care Medicine, East Tennessee State University, James H Quillen
College of Medicine

Disclosure: Nothing to disclose.

Jackie A Hayes, MD, FCCP Clinical Assistant Professor of Medicine, University of Texas Health Science Center at San
Antonio; Chief, Pulmonary and Critical Care Medicine, Department of Medicine, Brooke Army Medical Center

Jackie A Hayes, MD, FCCP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest
Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Oleh Wasyl Hnatiuk, MD Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army
Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences

Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American
College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

https://emedicine.medscape.com/article/301574-print 15/17
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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy;
Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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