eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Critical Care

Acidosis, Respiratory

Author: Margaret A Priestley, MD, Assistant Professor of Clinical Anesthesiology and Critical Care, University of Pennsylvania School of Medicine; Clinical Director, Pediatric Intensive Care Unit, The Children's Hospital of Philadelphia
Coauthor(s): Ronald Litman, DO, Associate Professor of Anesthesiology and Pediatrics, University of Pennsylvania School of Medicine
Contributor Information and Disclosures

Updated: Jan 5, 2009

Introduction

Background

Respiratory acidosis occurs when the arterial partial pressure of carbon dioxide (PaCO₂) is elevated above the normal range (>44 mm Hg) leading to a blood pH less than 7.35.¹ Respiratory acidosis is not a specific disease. Instead, it is an abnormality that results from an imbalance between carbon dioxide (CO₂) production by the body and excretion by the lungs, providing adequate minute ventilation. A deficiency of minute ventilation can occur anywhere along the continuum of the respiratory system, from central initiation of ventilation to appropriate gas exchange at the capillary alveolar interface.

Respiratory acidosis may result from an acute or chronic process. Acute respiratory acidosis can be life threatening when a sudden and sharp increase in PaCO₂ is associated with severe hypoxemia and acidemia (see Equation 2 in Pathophysiology). In contrast, chronic respiratory acidosis (>24 h) is characterized by a gradual and sustained increase in PaCO₂.

By definition, the diagnosis of respiratory acidosis requires measurement of the arterial PaCO₂ and pH. When the diagnosis is made, the cause should be thoroughly investigated.

Pathophysiology

PaCO₂ is directly proportional to CO₂ production and inversely proportional to alveolar ventilation. Alveolar ventilation is responsible for CO₂ elimination and is calculated when the respiratory frequency is multiplied by the difference between the tidal volume and the physiologic dead space. Respiratory acidosis results primarily when alveolar ventilation is decreased or if CO₂ production is increased.

Many clinical scenarios contribute to inadequate removal of CO₂ from the blood. A few examples include depressed central respiratory drive, acute paralysis of the respiratory muscles, acute parenchymal lung and airway diseases, and increased dead space or wasted ventilation. If breathing ceases, arterial CO₂ increases further at a rate of 3-6 mm Hg/min. In other cases, hypercarbia gradually develops as it does in a progressive neuromuscular disease, in worsening scoliosis leading to restrictive lung disease, or in chronic pulmonary diseases. In this scenario, persistently elevated PaCO₂ leads to effective compensatory mechanisms.

In rare instances, increased CO₂ production can exceed the patient's ability to compensate, leading to a respiratory acidosis. This situation occurs during hypermetabolic states, such as extensive burn injury, malignant hyperthermia, or fever when the patient is unable to increase minute ventilation. When PaCO₂ accumulates acutely, other organ systems are affected.

General physiologic and metabolic effects

CO₂ is carried in the blood in 3 forms: dissolved gas, bicarbonate, and protein bound. It diffuses freely across cell membranes, and this diffusion allows for its efficient transport from peripheral tissues to the lungs for excretion. When hypercapnia is present, this same property causes excess CO₂ to shift intracellularly and decrease intracellular pH. CO₂ normally combines with water (H₂ O) to form carbonic acid (H₂ CO₃), which then dissociates to release hydrogen ion [H⁺] and bicarbonate (HCO₃ ^-) (Equation 1). When a respiratory acidosis is present, excess CO₂ increases H₂ CO₃ formation, shifting the equilibrium of the equation toward the accumulation of hydrogen ions.

Equation 1: CO₂ + H₂ O ↔ H₂ CO₃ ↔ H⁺ + HCO₃ ^-

The body has several compensatory systems to minimize the decrease in pH. Intracellular proteins and inorganic phosphates are initially the most effective buffers. The most important blood buffer is hemoglobin. Deoxygenated hemoglobin readily accepts hydrogen ions to prevent substantial changes in pH, and approximately 10% of CO₂ is bound to hemoglobin to form carbaminohemoglobin.

Cellular buffering elevates plasma bicarbonate (HCO₃ ^-) only slightly and causes plasma HCO₃ ^- to increase 1 mEq/L for every 10-mm Hg increase in PaCO₂.

Renal compensation for sustained hypercapnia begins in 6-12 hours, but 3-5 days pass before maximal compensation occurs. The kidneys increase excretion of hydrogen ions (predominantly in the form of ammonium [NH₄ ⁺]) and chloride while retaining HCO₃ ^- and sodium (Na⁺). This process increases the plasma HCO₃ ^- concentration by approximately 3.5-4 mEq/L for every 10-mm Hg increase in PaCO₂. As a result, additional NaHCO₃ ^- is available to buffer free hydrogen ions. Because neonates and infants have a relatively large amount of hemoglobin and interstitial fluid for their body weight, their increase in plasma HCO₃ ^- concentrations and decrease in plasma hydrogen ion concentrations are greater than those of older children.

Chemoreceptors in the brainstem and in the carotid body rapidly detect changes in PaCO₂. CO₂ is a potent respiratory stimulant and elevated levels lead to an increase in minute ventilation to excrete increased quantities of CO₂ and normalize the pH. However, this effect is attenuated if the CO₂ level remains elevated for more than several hours. In general, acute respiratory acidemia causes no change or only a slight increase in extracellular potassium and phosphate levels.

Respiratory effects

When a patient develops a respiratory acidosis while breathing air, the alveolar gas equation predicts that hypoxemia will develop. The alveolar gas equation (Equation 2) states that the alveolar partial pressure of oxygen (P_A O₂) is equal to the partial pressure of inspired oxygen (P_i O₂) minus the quantity of alveolar partial pressure of CO₂ (P_A CO₂) divided by the respiratory quotient (RQ), as follows:

Equation 2: P_A O₂ = P_i O₂ - (P_A CO₂/RQ)

The RQ is the ratio of the volume of CO₂ expired to the volume of O₂ consumed by an organism (see nutrition effects on RQ below). In steady-state conditions, the human body produces CO₂ at a rate of approximately 200 mL/min and consumes O₂ at a rate of 250 mL/min; therefore, RQ = 0.8. If RQ is rounded to 1, the equation reduces to the following (Equation 3):

Equation 3: P_A O₂ = P_i O₂ - P_A CO₂

The P_i O₂ is the difference between the barometric pressure (PB) and the partial pressure of water vapor (PH₂ O) multiplied by the fraction of inspired oxygen (F_i O₂), as shown below (Equation 4):

Equation 4: P_i O₂ = F_i O₂ (PB - PH₂ O)

If the equation is rearranged, P_A CO₂ is ultimately dependent on the level of inspired O₂ (Equation 5):

Equation 5: P_A CO₂ = F_i O₂ (PB - PH₂ O) - P_A O₂

Because PB at sea level is 760 mm Hg and PH₂ O in the atmosphere is 47 mm Hg, when a person is breathing air (F_i O₂ = 0.21), the sum of P_A CO₂ and P_A O₂ adds up to approximately 150 mm Hg, as follows (Equations 6 and 7):

Equation 6: P_A O₂ = 0.21 (760 mm Hg - 47 mm Hg) - P_A CO₂

Equation 7: P_A O₂ + P_A CO₂ = 149.7 mm Hg

In the acute setting, PaCO₂ values higher than 80-90 mm Hg while the patient is breathing air are life threatening because of the associated hypoxemia. When the PaCO₂ exceeds 100 mm Hg, an iatrogenic or an acute on chronic condition is present. Hypoventilation can lead to clinically significant hypercarbia without hypoxemia only if a patient is breathing supplemental oxygen.

Consider the case of a child in the pediatric ICU who is breathing supplemental oxygen given by a mask (F_i O₂ = 0.80). The child has partial airway obstruction or central hypoventilation secondary to narcotic administration. Supplemental oxygen allows for an increased PaCO₂ given the principle of the alveolar gas equation without arterial desaturation. The profound acidemia associated with the hypercapnia can lead to bradycardia, the first sign of the problem. Some have used the term supercarbia to describe when the PaCO₂ is greater than 150 mm Hg. In this case, P_A O₂ = [0.80 (760 mm Hg - 47 mm Hg)] - 150 mm Hg = 420 mm Hg.

Hypercapnia is associated with increased pulmonary vascular resistance. However, the absolute CO₂ level does not have the greatest effect on pulmonary vascular tone; rather, decreased serum pH most likely mediates the effect. When hypercapnia is combined with acidemia and hypoxemia, resultant pulmonary vasoconstriction can be severe and life threatening.

Cardiovascular effects

Acute respiratory acidosis increases epinephrine and norepinephrine release. Several studies have shown that acute moderate hypercapnia produces a hyperdynamic state defined by tachycardia, high cardiac output, and reduced systemic vascular resistance. In experimental models, cardiac contractility decreases with acute respiratory acidosis. Some have proposed that the rapid development of intracellular acidosis interferes with the interaction between calcium and myofilaments. This adverse effect of acute moderate hypercapnia on myocardial contractility has not been seen in adult human studies. With severe acidemia at a serum pH of less than 7.20, the catecholamine response is blunted, and this change may contribute to a state of decreased cardiac output.

Supraventricular arrhythmias are increased in the presence of a severe respiratory acidosis, but these problems are most likely caused by concomitant hypoxemia, electrolyte shifts, and increased catecholamines rather than a direct hypercapnia-induced cardiac irritability. Cardiovascular symptoms of respiratory acidosis are often difficult to discern because of the concomitant effects of hypoxemia and metabolic acidosis.

Inhaled CO₂ gas can be administered to preoperative neonates with hypoplastic left heart syndrome and low systemic cardiac output associated with high arterial saturations (>85%). PaCO₂ is maintained above 40 mm Hg, and the patient is mechanically ventilated, sedated, and paralyzed to prevent a compensatory tachypnea. Inspired 3% CO ₂ improved cerebral oxygenation measured by near-infrared spectroscopy and mean arterial pressure in preoperative neonates with single ventricles.² Experimental evidence also suggests that hypercarbia may have some beneficial effects at assisting the mechanical recovery of hypoxic injured myocytes; however, further human clinical correlation is still needed.

CNS effects

The clinical manifestations of acute hypercapnia are primarily neurologic. Acute elevations of PaCO₂ greater than 60 mm Hg cause confusion and headache. PaCO₂ more than 70 mm Hg produces a hypercapnic encephalopathy or CO₂ narcosis manifesting as drowsiness, depressed consciousness, or coma. However, the neurologic changes associated with hypercarbia are reversible. In one report, children without hypoxemia but with severe respiratory acidosis (lowest pH was 6.76, and highest PaCO₂ was 269 mm Hg) did not have long-term adverse neurologic or developmental effects.³

Acute elevations in PaCO₂ increase intracranial pressure by increasing cerebral blood flow (CBF) and cerebral blood volume secondary to vasodilatation. With a PaCO₂ of 40-80 mm Hg, CBF increases 1-2 mL per 100 g of brain per minute for each 1-mm Hg increase in PaCO₂. A PaCO₂ of 80 mm Hg or more produced a maximal increase in CBF in anesthetized animals. During sustained hypercapnia, CBF returns to baseline after about 36 hours as brain extracellular pH is corrected.

In acute hypercapnia, CO₂ rapidly diffuses across the blood-brain barrier, which leads to accumulation of hydrogen ions in the cerebrospinal fluid (CSF). This change in pH is rapidly detected by the brainstem, causing rapid compensation (ie, increased elimination of CO₂ by the lungs). If the CSF acidosis persists for several hours, CSF HCO₃ ^- levels gradually increase to normalize the pH. In general, the response of the cerebral circulation to PaCO₂ increases during development from the neonatal period to adulthood.

Frequency

See Background.

Mortality/Morbidity

The effects of respiratory acidosis vary according to the severity, the duration, the underlying disease, and the associated arterial saturation. The most important consideration may be the degree to which hypercarbia or the underlying disease adversely affects arterial oxygenation.

Race

No racial distribution is known.

Age

Respiratory acidosis can occur at any age.

Clinical

History

The following questions should be assessed:

• Does the patient have a history of headaches? With chronic hypercapnia, headaches typically occur at nighttime or when the patient awakens in the morning.
• Does the patient have disturbed sleep patterns? Chronic hypercapnia can disturb sleep patterns, leading to a reversed sleep-wake cycle.
• Is the patient irritable or anxious or is he or she having trouble concentrating?
• Does the patient have a possible or known exposure to sedatives (eg, narcotics, benzodiazepines, tricyclic antidepressants)? Is the patient recovering from a procedure in which general anesthesia was used?
• Does the patient have symptoms of neuromuscular weakness or paralysis?
  • Bulbar dysfunction suggesting myasthenia gravis
  • Proximal or distal weakness suggesting a myopathy or Guillain-Barré syndrome
  • Apnea associated with a traumatic injury suggesting an injury to the cervical spinal cord
• Does the patient have a long-standing pulmonary disease, such as bronchopulmonary dysplasia, CF, asthma, or emphysema?
• Does the patient have an acute change in mental status (eg, signs of stroke, postictal state)?
  • Is the change in mental status associated with a fever, which may suggest encephalitis or meningitis?
  • Does the patient have signs of increased intracranial pressure (eg, headaches, visual changes, emesis)?
• Does the patient have a potential for an anaphylactic reaction?
• Does the patient have a potential traumatic mechanism leading to brain injury?

Physical

• Neurologic findings
  • Early signs include anxiety, disorientation, confusion, and lethargy.
  • Somnolence or coma occurs when PaCO₂ is greater than 70 mm Hg.
  • Tremor, myoclonus, or asterixis are occasionally seen.
  • Brisk deep tendon reflexes are seen in mild-to-moderate respiratory acidosis.
  • Depressed deep tendon reflexes are seen in severe respiratory acidosis.
  • Papilledema or blurring of the optic disc may be present.
• Cardiovascular findings
  • Tachycardia
  • Bounding arterial pulses
  • Hypotension (severe respiratory acidosis or acidemia and hypoxemia)
• Skin findings
  • Warm, flushed, or mottled
  • Diaphoretic
• Respiratory findings
  • Acute hypercapnia is seen in association with increase work of breathing
  • Tachypnea, dyspnea, or deep labored breaths may be observed.
  • Accessory muscle use and nasal flaring are usually present.
  • With CNS or peripheral nervous system disease, respiratory distress may not be present.
  • Decreased aeration, crackles, wheezes, or other signs of airway disease may be observed.
  • Clubbing is a sign of chronic respiratory disease.

Causes

• CNS respiratory drive suppression causes include the following:
  • Trauma
  • Infection (eg, encephalitis, meningitis, respiratory syncytial virus)
  • Neoplasm
  • Stroke
  • Hypoxia
  • Toxins, overdose (eg, narcotics, alcohol)
  • Seizures - Postictal state
• Spinal causes include trauma (C-spine C3-C5, phrenic nerve function).
• Nerve causes include the following:
  • Spinal muscular atrophy
  • Guillain-Barré syndrome
  • Poliomyelitis
  • Phrenic nerve trauma
• Neuromuscular junction causes include the following:
  • Myasthenia gravis
  • Botulism
  • Neuromuscular blockade
• Muscle causes include muscular dystrophies.
• Airway causes include the following:
  • Loss of CNS control
    • Brain injury
    • Toxin, overdose
  • Trauma
  • Angioedema
  • Tonsillar adenoid hypertrophy
  • Thermal or chemical burn
  • Foreign Body
  • Pharyngeal abscess
  • Epiglottitis
  • Paralyzed vocal cords
  • Congenital lesions
    • Subglottic stenosis
    • Laryngomalacia
    • Craniofacial abnormalities
    • Tracheal rings
    • Vascular slings
  • Laryngotracheobronchitis (croup)
  • Neoplasm, mediastinal mass
  • Bronchiolitis
  • Asthma
• Acute lung injury causes include the following:
  • Pneumonia
  • Pulmonary edema
  • Lung contusion
  • Bronchiolitis
• Chronic lung disease causes include the following:
  • Bronchopulmonary dysplasia
  • CF
  • Chronic bronchitis
  • Chronic obstructive pulmonary disease
• Chest wall restriction and reduced respiratory compliance causes include the following:
  • Flail chest
  • Pneumothorax
  • Pleural effusions
  • Kyphoscoliosis
  • Abdominal distension
• Increased CO ₂ production causes include the following:
  • Malignant hyperthermia
  • Extensive burns
  • Overfeeding

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