Respiratory Acidosis Treatment & Management

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
Pharmacologic Therapy
Pharmacologic therapies are generally used as treatment of 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 (PaO
2
) 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
improve PaO
2
and decrease the partial pressure of arterial carbon dioxide (PaCO
2
).
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.
[10]

A 4-year retrospective study reported that NIPPV was highly beneficial in the treatment of COPD with
hypercapnia (type II) respiratory failure.
[11]
NIPPV led to a decreased length of stay and a reduced cost of
hospitalization.
Investigational therapy
Extracorporeal carbon dioxide removal (ECCO
2
R) is a newer technique for removing carbon dioxide via
venovenous bypass without affecting oxygenation. ECCO
2
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
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
Beta
2
agonists, by decreasing muscle tone in both small and large airways in the lungs, increase ventilation.
Beta
2
agonists activate the beta
2
-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 beta
2
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 beta
2
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.
View full drug information
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.
View full drug information
Salmeterol (Serevent Diskus)

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.
View full drug information
Metaproterenol

Metaproterenol is a beta2-adrenergic agonist that relaxes bronchial smooth muscle, with little effect on heart
rate.
View full drug information
Levalbuterol (Xopenex, Xopenex HFA)

Levalbuterol acts on beta2 receptors, causing relaxation of bronchial smooth muscle, with little effect on heart
rate.
View full drug information
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.
View full drug information
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.
View full drug information
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.
View full drug information
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 beta
2
-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 beta
2
-adrenergic agonists, a synergistic effect on
bronchodilatation occurs. This medication has a slower onset of action than the beta
2
-adrenergic agents and is,
therefore, less suitable for use on an as-needed basis.
View full drug information
Ipratropium (Atrovent HFA)

Ipratropium is an anticholinergic bronchodilator that is chemically related to atropine. It inhibits serous and
seromucous gland secretions.
View full drug information
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 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.
View full drug information
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.
View full drug information
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 g/actuation and 180 g/actuation; each actuation delivers 80 g and 160
g, respectively) or Pulmicort Respules.
View full drug information
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.
View full drug information
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.
View full drug information
Methylprednisolone (A-Methapred, Medrol, Solu-Medrol)

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