eMedicine Specialties > Pulmonology > Acid-Base Disorders

Respiratory Acidosis

Wael El Minaoui, MBBS, Fellow in Pulmonary/Critical Care Medicine, East Tennessee State University
Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University; Chief of Pulmonary Medicine, Medical Director of Respiratory Therapy, Intensive Care Unit, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen Veterans Affairs Medical Center

Updated: Apr 2, 2009

Introduction

Background

Respiratory acidosis is a clinical disturbance due to alveolar hypoventilation. Production of carbon dioxide occurs rapidly, and failure of ventilation promptly increases the partial arterial pressure of carbon dioxide (PaCO₂). The normal reference range for PaCO₂ is 36-44 mm Hg. Alveolar hypoventilation leads to an increased PaCO₂ (ie, hypercapnia). The increase in PaCO₂, in turn, decreases the bicarbonate (HCO₃ ^-)/PaCO₂, decreasing the pH. Hypercapnia and respiratory acidosis ensue when impairment in ventilation occurs and the removal of carbon dioxide by the lungs is less than the production of carbon dioxide in the tissues.

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 value (ie, >30 mm Hg).

Acute respiratory acidosis is present when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by depression of the central respiratory center by cerebral disease or drugs, an inability to ventilate adequately owing to  a neuromuscular disease (eg, myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, muscular dystrophy), or airway obstruction 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 decreased responsiveness to hypoxia and hypercapnia, increased ventilation-perfusion mismatch leading to increased dead space ventilation, and decreased diaphragmatic function due to fatigue and hyperinflation.

Chronic respiratory acidosis also may be secondary to obesity-hypoventilation syndrome (ie, pickwickian syndrome), neuromuscular disorders such as amyotrophic lateral sclerosis, and severe restrictive ventilatory defects as observed in interstitial fibrosis and thoracic deformities.

Lung diseases that primarily cause abnormalities in alveolar gas exchange usually do not cause hypoventilation; however, they tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia. Hypercapnia only occurs if severe disease or respiratory muscle fatigue is present.

Pathophysiology

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 acid accumulation does not occur. 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.^1,2

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, 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 increases the PaCO₂.

In acute respiratory acidosis, the body's compensation occurs in 2 steps. The initial response is cellular buffering that occurs 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 1 mEq/L for each 10-mm Hg rise in PaCO₂.
• Chronic respiratory acidosis: Bicarbonate increases 3.5 mEq/L for each 10-mm Hg rise in PaCO₂.

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

• Acute respiratory acidosis: Change in pH = 0.008 X (40 - PaCO₂)
• Chronic respiratory acidosis: Change in pH = 0.003 X (40 - PaCO₂)

Respiratory acidosis does not have a great effect on 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, but respiratory acidosis rarely causes clinically significant hyperkalemia.

Mortality/Morbidity

The morbidity and mortality of respiratory acidosis depends on the underlying cause of the respiratory acidosis, associated conditions, the patient's compensatory mechanisms, and effectiveness of medical care.

Clinical

History

The clinical manifestations of respiratory acidosis often are 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 usually has minimal symptoms.

Patients may be anxious and may complain of dyspnea. Some patients may have disturbed sleep and daytime hypersomnolence. As the 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

The findings upon physical examination in patients with respiratory acidosis usually are 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 also may be heard.
• Cyanosis may be noted if accompanying hypoxemia is present. Digital clubbing may indicate the presence of a chronic respiratory tract disease or other organ system disorders.
• The patient's mental status may be depressed if he or she has severe elevations of PaCO₂. Patients may have asterixis, myoclonus, and seizures.
• Papilledema may be found during the retina examination. Conjunctival and superficial facial blood vessels also may be dilated.

Causes

Respiratory acidosis may occur due to a variety of etiologies, including the following:

• Chronic obstructive pulmonary disease
  • Emphysema
  • Severe asthma^3,4
  • Chronic bronchitis
• Neuromuscular diseases
  • Amyotrophic lateral sclerosis
  • Diaphragm dysfunction and paralysis
  • Guillain-Barré syndrome
  • Myasthenia gravis
  • Muscular dystrophy
• Chest wall disorders
  • Severe kyphoscoliosis
  • Status post thoracoplasty
  • Flail chest
  • Less commonly, ankylosing spondylitis, pectus excavatum,⁵ or pectus carinatum
• Obesity-hypoventilation syndrome
• Obstructive sleep apnea
• CNS depression
  • Drugs - Narcotics, barbiturates, benzodiazepines, other CNS depressants
  • Neurologic disorders - Encephalitis, brainstem disease, trauma
  • Primary alveolar hypoventilation
• Other lung and airway diseases - Laryngeal and tracheal stenosis

Differential Diagnoses

Other Problems to Be Considered

Amyotrophic lateral sclerosis
Muscular dystrophy
Severe kyphoscoliosis
Guillain-Barré syndrome
Myasthenia gravis

Workup

Laboratory Studies

• Arterial blood gas determination: Acidemia is documented by the presence of a decreased pH (<7.35) shown on arterial blood gas analysis. The presence of an increased PaCO₂ (>45 mm Hg) indicates a respiratory etiology of the acidemia.
• Hypoxemia: This may be present and frequently is associated with pulmonary diseases that can cause respiratory acidosis.
• Serum chemistries: The most common finding in chronic respiratory acidosis is the presence of a compensatory increase in serum bicarbonate concentration.
• Hypothyroidism: Some patients have hypothyroidism as a cause for their obesity (and resulting hypoventilation due to associated obstructive sleep apnea) leading to chronic respiratory acidosis. A thyrotropin and free T4 level should be obtained.
• Complete blood cell count: Many patients with chronic hypercapnia and respiratory acidosis also are hypoxemic. These patients may have secondary polycythemia.
• Drug screens: 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.

Imaging Studies

• Chest radiography
  • 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 hyperinflation and diaphragm flattening secondary to severe obstructive airway disease, infiltrates secondary to pneumonias, elevated diaphragm related to diaphragmatic weakness or paralysis, pneumothorax, and atelectasis.
  • With complicating pulmonary hypertension, the hilar vascular shadows are prominent and the cardiac silhouette may show evidence of right ventricular enlargement.
• CT scanning of the chest: 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 for detecting disease and may reveal abnormalities not observed on chest radiographs.
• CT scanning of the brain: Perform imaging of the brain if a central cause of hypoventilation and respiratory acidosis is suspected. Specific etiologies that may be diagnosed using brain CT scanning include stroke, CNS tumor, and CNS trauma. Pay particular attention to the brainstem for lesions in the pons and medulla.
• MRI of the brain: If a central cause of hypoventilation and respiratory acidosis is suspected and initial findings after brain CT scanning are negative or inconclusive, consider MRI of the brain. The MRI may disclose abnormalities not observed on CT scans, particularly in the brainstem.
• Fluoroscopy: 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. This test is not as useful in bilateral diaphragmatic paralysis compared with unilateral diaphragmatic paralysis.

Other Tests

• Pulmonary function testing
  • These 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) is the most commonly used index of airflow obstruction.
  • The ratio of FEV₁ to forced vital capacity (FVC), ie, FEV₁/FVC, is reduced and is the diagnostic variable in airflow obstruction.
  • Lung volume measurements may document an increase in total lung capacity, functional residual capacity, and residual volume.
  • Measurement of maximal inspiratory and expiratory pressures may be useful in screening for respiratory muscle weakness.
• Electromyography and nerve conduction velocity: Electromyography (EMG) and nerve conduction velocity (NCV) are useful in diagnosing neuromuscular disorders (eg, myasthenia gravis, Guillain-Barré syndrome, amyotrophic lateral sclerosis), which can cause ventilatory muscle weakness. These studies may reveal a neuropathic or a myopathic pattern, depending on the etiology of the diaphragmatic and respiratory muscle dysfunction.
• Measurement of transdiaphragmatic pressure
  • This diagnostic test is useful in documenting respiratory muscle weakness, but it is difficult to perform and usually is performed only in specialized pulmonary function laboratories.
  • 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 2 balloons is the transdiaphragmatic pressure.
  • Patients with diaphragmatic dysfunction and paralysis have a decrease in maximal transdiaphragmatic pressure.

Treatment

Medical Care

The treatment of respiratory acidosis is primarily directed at correcting the underlying disorder. Caution should be exercised when correcting chronic hypercapnia. Rapid correction of the hypercapnia can result in metabolic alkalemia. Alkalinization of the cerebrospinal fluid can result in seizures.

• 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.
• Bronchodilators such as beta-agonists (eg, albuterol, salmeterol), anticholinergic agents (eg, ipratropium bromide, tiotropium), and methylxanthines (eg, theophylline) are helpful in treating patients with obstructive lung disease and severe bronchospasm. Theophylline may improve diaphragm muscle contractility and may stimulate the respiratory center.
• Treatment also should be aimed at assisting or increasing ventilation. Therapeutics that may be life saving include endotracheal intubation with mechanical ventilation and noninvasive positive-pressure ventilation (NIPPV) techniques such as nasal continuous positive-pressure ventilation and nasal bilevel ventilation. The later techniques are preferred treatment for obesity-hypoventilation syndrome and neuromuscular disorders because they help improve PaO₂ and decrease PaCO₂. A study comparing noninvasive techniques with invasive ventilation in myasthenic crisis found that patients had better outcomes with noninvasive ventilation compared with patients who had invasive ventilation.⁶
• A 4-year retrospective study reported that NIPPV is highly beneficial in the treatment of COPD with hypercapnia (type II) respiratory failure. NIPPV led to decreased length of stay and cost of hospitalization.⁷
• Noninvasive, external, negative-pressure ventilation devices are available for the treatment of selected patients with chronic respiratory failure.
• Drug therapy aimed at reversing the effects of certain sedative drugs may be helpful in the event of an overdosage. Naloxone (Narcan) may be used to reverse the effects of narcotics. Flumazenil (Romazicon) may be used to reverse the effects of benzodiazepines. Care must be used when reversing the effects of benzodiazepines. Patients may have seizures if benzodiazepine reversal is accomplished too vigorously.
• Oxygen therapy may be indicated because many patients with hypercapnia also are hypoxemic. Oxygen therapy is indicated 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 oxygen.
  • Oxygen therapy has been shown to reduce pulmonary hypertension.
  • Oxygen therapy should be used with caution because it may worsen hypercapnia in some situations. Patients with COPD may develop worsening of hypercapnia following oxygen therapy. This observation is thought by many to be primarily a consequence of ventilation-perfusion mismatching. This is opposed to the commonly accepted concept of a reduction in hypoxic ventilatory drive. The exact pathophysiology remains controversial.
  • Hypercapnia is best avoided by titration of oxygen delivery to maintain oxygen saturations in the low 90% range and a PaO₂ of 60-65 mm Hg.
• Respiratory stimulants have been used but have limited efficacy in respiratory acidosis caused by disease.
  • Medroxyprogesterone increases the central respiratory drive and is effective in treating obesity-hypoventilation syndrome.
  • Acetazolamide is a diuretic that increases bicarbonate excretion and causes a metabolic acidosis. The metabolic acidosis subsequently stimulates ventilation.
  • Theophylline increases diaphragm muscle strength and stimulates the central ventilatory drive.

Surgical Care

• In severe kyphoscoliosis, spine fusion is sometimes indicated for angles greater than 40°.
• Patients with obesity-hypoventilation syndrome might benefit from weight reduction surgery. Bariatric surgical techniques, including vertical banded gastroplasty, adjustable gastric banding, and roux-en-Y gastric bypass, can be offered to these patients. Roux-en-Y gastric bypass is gaining more acceptance because it is performed laparoscopically and because it has better short- and long-term outcomes.
• According to the US National Institutes of Health consensus statement  guidelines, surgery should be recommended to patients with a body mass index greater than 35 kg/m² and an obesity-related comorbid condition (including obesity-hypoventilation syndrome) or patients with a body mass index greater than 40 kg/m².
• Diaphragmatic pacing can be performed for the treatment for primary alveolar hypoventilation. One study reported that diaphragmatic pacing is an effective treatment of congenital central alveolar hypoventilation syndrome (Ondine curse). This is performed through bilateral axillary thoracotomy.⁸

Consultations

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.

Medication

No drugs are used to specifically treat respiratory acidosis. Medical therapies are directed at the underlying disease or disorder causing hypoventilation and, therefore, respiratory acidosis.

Bronchodilators

These agents decrease muscle tone in both small and large airways in the lungs, increasing ventilation. This category includes beta-adrenergics, methylxanthines, and anticholinergics.

Albuterol (Proventil Ventolin)

Beta-agonist for bronchospasm that is refractory to epinephrine. Relaxes bronchial smooth muscle by its action on beta2-receptors, with little effect on cardiac muscle contractility.

Dosing

Adult

2-4 mg per dose PO divided tid/qid; not to exceed 32 mg/d
MDI: 1-2 puffs q4-6h; not to exceed 12 inhalations per d
Nebulizer: Dilute 0.5 mL (2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS; administer 2.5-5 mg q4-6h diluted in 2-5 mL sterile saline or water via nebulizer

Pediatric

<2 years: Not established
2-5 years: 0.1-0.2 mg/kg/dose PO divided tid; not to exceed 12 mg/d
5-12 years: 2 mg/dose PO divided tid/qid; not to exceed 24 mg/d
>12 years: Administer as in adults
MDI
<12 years: 1-2 inhalations qid with tube spacer
>12 years: Administer as in adults
Nebulizer
<5 years: Dilute 0.25-0.5 mL (1.25-2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS and administer q4-6h in equally divided doses
>5 years: Administer as in adults

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders

Metaproterenol (Alupent, Metaprel)

Beta2-adrenergic agonist that relaxes bronchial smooth muscle with little effect on heart rate.

Dosing

Adult

0.3 mL of 5% solution diluted in 2.5 mL of 0.45% or 0.9% NS nebulized over 5-15 min q4h

Pediatric

0.1-0.2 mL of 5% solution diluted in 3 mL of 0.45% or 0.9% NS over 5-15 min q4h

Interactions

Decreases effect of beta-receptor blockers; increases toxicity of MAOIs, TCAs, and sympathomimetics

Contraindications

Documented hypersensitivity; arrhythmia associated with tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypertension, cardiovascular disease, congestive heart failure, hyperthyroidism, diabetes, and seizures; not recommended for breastfeeding mothers; adverse reactions include tachycardia, headache, nervousness, dizziness, tremor, gastrointestinal upset, hypertension, paradoxical bronchospasm, and cough

Ipratropium (Atrovent)

Anticholinergic bronchodilator chemically related to atropine.

Dosing

Adult

MDI: 2-4 puffs q4-6h
Nebulizer: 250 mcg diluted with 2.5 mL NS q4-6h

Pediatric

MDI: 1-2 puffs tid; not to exceed 6 puffs per d
Nebulizer: 250 mcg diluted with NS tid

Interactions

Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol may increase effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction

Theophylline (Aminophyllin, Theo-24, Theolair, Theo-Dur, Slo-bid)

Potentiates exogenous catecholamines. Stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. Popularity has decreased because of narrow therapeutic range and frequent toxicity.
Therapeutic range is 10-20 mg/dL, but bronchodilation may require near-toxic (>20 mg/dL) levels. Clinical efficacy is controversial, especially in the acute setting.

Dosing

Adult

Initial: 10 mg/kg/d PO divided q8-12h; 5.6 mg/kg loading dose IV over 20 min (based on aminophylline), followed by maintenance infusion of 0.1-1.1 mg/kg/h
Maintenance: 10 mg/kg/d PO qd or divided bid; adjust dose in increments of 25% to maintain serum theophylline level of 5-15 mcg/mL; not to exceed 800 mg/d

Pediatric

<6 weeks: Not established
6 weeks to 6 months: 0.5 mg/kg/h loading dose IV in first 12 h (based on aminophylline), followed by maintenance infusion of 12 mg/kg/d; may administer continuous infusion by dividing total daily dose by 24 h
6 months to 1 year: 0.6-0.7 mg/kg/h loading dose IV in first 12 h, followed by maintenance infusion of 15 mg/kg/d; may administer as continuous infusion, as above
>1 year: Administer as in adults

Interactions

Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon

Contraindications

Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients diagnosed with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance

Tiotropium (Spiriva)

A quaternary ammonium compound. Elicits anticholinergic/antimuscarinic effects with inhibitory effects on M3 receptors on airway smooth muscles, leading to bronchodilation. Available in cap form containing a dry powder for oral inhalation via HandiHaler inhalation device. Helps patients with COPD by dilating narrowed airways and keeping them open for 24 h.

Dosing

Adult

Inhale contents of 1 cap (18 mcg) via HandiHaler device qd

Pediatric

Not established

Interactions

Coadministration with other anticholinergic-containing drugs (eg, ipratropium) may increase toxicity risk

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

For maintenance treatment only; not effective for acute (rescue) therapy of bronchospasm; discontinue use and consider other treatments if immediate hypersensitivity reactions (including angioedema) or paradoxical bronchospasm occur; caution with narrow-angle glaucoma, prostatic hyperplasia, or bladder neck obstruction; commonly causes dry mouth; may cause constipation, increased heart rate, blurred vision, glaucoma, and urinary difficulty or retention; monitor patients with moderate-to-severe renal impairment

Benzodiazepine antagonists

Used in reversing the CNS-depressant effects of benzodiazepine overdose. Ability to reverse the benzodiazepine-induced respiratory depression is less predictable.

Flumazenil (Romazicon)

Reverses effects of benzodiazepines in an overdose by selectively antagonizing the GABA/benzodiazepine receptor complex. If overdosed patient has not responded after 5 min of administering a cumulative dose of 5 mg, cause of sedation likely not benzodiazepines. Short acting, with a half-life of 0.7-1.3 h. However, because most benzodiazepines have longer half-lives, multiple doses should be administered so that patients do not relapse into sedative state.

Dosing

Adult

0.2 mg IV initially over 30 seconds, repeat at 1-min intervals with 0.5 mg over 30 seconds until satisfactory response is attained or 3 mg is administered; may require additional titration to a total 5 mg

Pediatric

0.01 mg/kg IV initially over 15 seconds, repeat at 1-min intervals with 0.005-0.01 mg/kg; not to exceed 0.2 mg per dose

Interactions

Caution in cases of mixed-drug overdose; toxic effects due to other drugs taken in overdose (eg, TCAs) may occur with reversal of benzodiazepine effects

Contraindications

Documented hypersensitivity; serious cyclic antidepressant overdosage; patients administered a benzodiazepine for control of potentially life-threatening condition (eg, intracranial pressure, status epilepticus)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for resedation (at least 2 h), respiratory depression, seizures, or other benzodiazepine residual effects; caution in drug or alcohol dependence, head injury, hepatic disease, and panic disorder; patients on benzodiazepines for prolonged periods may experience seizures

Opioid antagonists

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

Naloxone (Narcan)

Pure opioid antagonist. Prevents or reverses opioid effects (eg, hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors. Used to reverse opioid intoxication.

Dosing

Adult

0.4-2 mg IV/IM/SC q2-3min prn; use increments of 0.1-0.2 mg in patients who are opioid dependent; may need to repeat dose q20-60min; if no response observed after administering 10 mg, question the diagnosis

Pediatric

0.1 mg/kg IV/IM/SC, repeat q2-3min prn

Interactions

Decreases analgesic effects of narcotics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease; may precipitate withdrawal symptoms in patients who are addicted to opiates

Follow-up

Further Inpatient Care

• ICU admission
  • The criteria for admission to the ICU vary from institution to institution but may include confusion, lethargy, respiratory muscle fatigue, and a low pH.
  • All patients who require tracheal intubation and mechanical ventilation require ICU admission.
  • Most acute care facilities require that all patients being treated acutely with NIPPV also be admitted to the ICU.

Further Outpatient Care

• Oxygen therapy
  • Oxygen therapy should be continued in the outpatient setting in patients who meet the specific criteria for long-term oxygen therapy.
  • The specific criteria for long-term oxygen therapy include a PaO₂ of less than 55 mm Hg or a PaO₂ of less than 59 mm Hg with evidence of polycythemia or cor pulmonale.
  • Patients should be reevaluated 1-3 months after initiating therapy to reassess their ongoing need for continuing long-term oxygen therapy.
• Noninvasive ventilation: Noninvasive ventilation can be continued in the outpatient setting. Nasal bilevel positive-pressure ventilation can be used long-term to treat patients with neuromuscular disorders, COPD with hypercapnia, primary alveolar hypoventilation, and obesity-hypoventilation syndrome.
• Noninvasive ventilation augments the benefits of pulmonary rehabilitation in COPD patients with chronic hypercapnic respiratory failure because it improves several measures of health-related quality of life, functional status, and gas exchange.⁹

Deterrence/Prevention

• Smoking cessation is an important aspect in the long-term treatment, especially in COPD patients.
• Weight loss is very helpful, especially in patients with obesity-hypoventilation syndrome. It improves daytime symptoms and the PCO₂. In patients with obstructive sleep apnea, weight loss decreases the number of apneas and hypopneas.

Complications

• Patients with chronic respiratory acidosis, by definition, have a component of alveolar hypoventilation. The patients have increased PaCO₂ and bicarbonate levels. They also have obligatory decreases in PaO₂. Complications are often related to the chronic hypoxemia.
• Chronic hypoxemia can result in increased erythropoiesis leading to polycythemia.
• Chronic hypoxia is a well-known cause of pulmonary vasoconstriction. This physiologic response can, in the long term, lead to pulmonary hypertension, right ventricular failure, and cor pulmonale.
• The hypopneas and apneas during sleep lead to impaired sleep quality and cerebral vasodilation, causing morning headaches, daytime fatigue, and somnolence.
• High levels of PaCO₂ can lead to confusion, often referred to as carbon dioxide narcosis. As a late complication of cerebral vasodilation, patients may have papilledema.¹⁰

Prognosis

• The prognosis for patients with respiratory acidosis varies and depends on the severity of the underlying pathophysiologic process.

Patient Education

• For excellent patient education resources, see eMedicine's Lung and Airway Center and patient education article Chronic Obstructive Pulmonary Disease (COPD).

Miscellaneous

Medicolegal Pitfalls

• All potential causes of respiratory acidosis should be considered. These include lung disease, neuromuscular diseases, and central neurologic depression.
• The effects of sedating drugs such as narcotics and benzodiazepines in depressing the central ventilatory drive and causing respiratory acidosis should also be considered. These sedative drugs should be avoided in patients with respiratory acidosis. In patients without an obvious source of hypoventilation and respiratory acidosis, a drug screen should be performed.
• Oxygen therapy should be used cautiously in patients with COPD and respiratory acidosis because higher fractions of inspired oxygen can worsen hypoventilation.

References

1. Ehrsam RE, Heigenhauser GJ, Jones NL. Effect of respiratory acidosis on metabolism in exercise. J Appl Physiol. Jul 1982;53(1):63-9. [Medline].

2. Kazmaier S, Weyland A, Buhre W, et al. Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease. Anesthesiology. Oct 1998;89(4):831-7. [Medline].

3. Adnet F, Plaisance P, Borron SW, Levy A, Payen D. Prolonged severe hypercapnia complicating near fatal asthma in a 35-year-old woman. Intensive Care Med. Dec 1998;24(12):1335-8. [Medline].

4. Cham GW, Tan WP, Earnest A, Soh CH. Clinical predictors of acute respiratory acidosis during exacerbation of asthma and chronic obstructive pulmonary disease. Eur J Emerg Med. Sep 2002;9(3):225-32. [Medline].

5. Theerthakarai R, El-Halees W, Javadpoor S, Khan MA. Severe pectus excavatum associated with cor pulmonale and chronic respiratory acidosis in a young woman. Chest. Jun 2001;119(6):1957-61. [Medline].

6. Wu JY, Kuo PH, Fan PC, Wu HD, Shih FY, Yang PC. The Role of Non-invasive Ventilation and Factors Predicting Extubation Outcome in Myasthenic Crisis. Neurocrit Care. 2009;10(1):35-42. [Medline].

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Keywords

respiratory acidosis, hypoventilation, hypercapnia, alveolar hypoventilation, impaired ventilation, central respiratory depression, myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barre syndrome, muscular dystrophy, asthma, airway obstruction, chronic obstructive pulmonary disease, COPD, increased ventilation-perfusion mismatch, decreased diaphragm function, diaphragm dysfunction, obesity hypoventilation syndrome, obesity-hypoventilation syndrome, pickwickian syndrome, respiratory muscle fatigue, emphysema, chronic bronchitis, bronchitis, amyotrophic lateral sclerosis, diaphragm paralysis, kyphoscoliosis

Contributor Information and Disclosures

Author

Wael El Minaoui, MBBS, Fellow in Pulmonary/Critical Care Medicine, East Tennessee State University
Disclosure: Nothing to disclose.

Coauthor(s)

Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University; Chief of Pulmonary Medicine, Medical Director of Respiratory Therapy, Intensive Care Unit, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen Veterans Affairs Medical Center
Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Gregg T Anders, DO, Medical Director, Great Plains Regional Medical Command , Brook Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio
Gregg T Anders, DO 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.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Jackie A. Hayes, MD, FCCP, to the development and writing of this article.

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