Respiratory acidosis occurs when the arterial partial pressure of carbon dioxide (Pa CO2) is elevated above the normal range (>44 mm Hg) leading to a blood pH lower than 7.35.  By definition, the diagnosis of respiratory acidosis requires measurement of Pa CO2 and pH. When the diagnosis is made, the underlying cause should be thoroughly investigated.
Respiratory acidosis is not a specific disease. Instead, it is an abnormality that results from an imbalance between production of carbon dioxide by the body and its excretion by the lungs, owing to inadequate minute ventilation. Low 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 and may occur at any age. Acute respiratory acidosis can be life-threatening when a sudden and sharp increase in Pa CO2 is associated with severe hypoxemia and acidemia. In contrast, chronic respiratory acidosis (>24 h) is characterized by a gradual and sustained increase in Pa CO2.
Pa CO2 is directly proportional to carbon dioxide production and inversely proportional to alveolar ventilation. Alveolar ventilation is responsible for carbon dioxide elimination and is calculated when the respiratory rate is multiplied by the difference between the tidal volume and the physiologic dead space. Respiratory acidosis results primarily when alveolar ventilation is decreased or when carbon dioxide production is increased.
Many clinical scenarios contribute to inadequate removal of carbon dioxide 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 carbon dioxide 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 Pa CO2 leads to effective compensatory mechanisms.
In rare instances, increased carbon dioxide production can exceed the patient’s ability to compensate, leading to 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 Pa CO2 rises acutely, other organ systems are affected.
General physiologic and metabolic effects
Carbon dioxide is carried in the blood in 3 forms: dissolved gas, bicarbonate, and protein bound. It diffuses freely across cell membranes, and this diffusion allows it to be efficiently transported from peripheral tissues to the lungs for excretion. When hypercapnia is present, this same property causes excess carbon dioxide to shift intracellularly and decrease intracellular pH.
Carbon dioxide (CO2) normally combines with water (H2 O) to form carbonic acid (H2 CO3), which then dissociates to release hydrogen ion (H+) and bicarbonate (HCO3–), as in the following equation:
CO2 + H2 O ↔ H2 CO3 ↔ H+ + HCO3–
When respiratory acidosis is present, excess carbon dioxide increases H2 CO3 formation, shifting the equilibrium of the equation toward the accumulation of hydrogen ions.
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 carbon dioxide is bound to hemoglobin to form carbaminohemoglobin.
Cellular buffering elevates plasma bicarbonate (HCO3–) only slightly and causes plasma HCO3– to increase by 1 mEq/L for every 10-mm Hg increase in Pa CO2.
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 Pa CO2. 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 Pa CO2. Carbon dioxide is a potent respiratory stimulant, and elevated levels lead to an increase in minute ventilation to excrete increased quantities of carbon dioxide and normalize the pH. However, this effect is attenuated if the carbon dioxide 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.
When a patient develops 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 (PA O2) is equal to the partial pressure of inspired oxygen (PI O2) minus the quantity of alveolar partial pressure of carbon dioxide (PA CO2) divided by the respiratory quotient (RQ), as follows:
PA O2 = PI O2 – (PA CO2/RQ)
The RQ is the ratio of the volume of carbon dioxide expired to the volume of oxygen consumed by an organism. In steady-state conditions, the human body produces carbon dioxide at a rate of approximately 200 mL/min and consumes oxygen at a rate of 250 mL/min; therefore, the RQ is about 0.8. If the RQ is rounded to 1, the alveolar gas equation is reduced as follows:
PA O2 = PI O2 – PA CO2
The PI O2 is equivalent to the difference between the barometric pressure (PB) and the partial pressure of water vapor (PH2 O) multiplied by the fraction of inspired oxygen (FI O2), as follows:
PI O2 = FI O2 (PB – PH2 O)
In view of this equivalence, the alveolar gas equation may be expressed as follows:
PA O2 = FI O2 (PB – PH2 O) – PA CO2
If this equation is rearranged, PA CO2 is seen to be ultimately dependent on the level of inspired oxygen, as follows:
PA CO2 = FI O2 (PB – PH2 O) – PA 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 (FI O2 = 0.21), the sum of PA CO2 and PA O2 adds up to approximately 150 mm Hg, as follows:
PA O2 = 0.21 (760 mm Hg – 47 mm Hg) – PA CO2
PA O2 = 149.7 mm Hg – PA CO2
PA O2 + PA CO2 = 149.7 mm Hg
In the acute setting, Pa CO2 values higher than 80-90 mm Hg while the patient is breathing air are life-threatening because of the associated hypoxemia. When Pa CO2 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 (FI O2 = 0.80). The child has partial airway obstruction or central hypoventilation secondary to narcotic administration. Supplemental oxygen allows an increased Pa CO2 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 scenarios in which Pa CO2 is greater than 150 mm Hg. In the example just given, the alveolar gas equation yields the following results:
PA 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 carbon dioxide 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, the resultant pulmonary vasoconstriction can be severe and life-threatening.
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 by 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 carbon dioxide gas can be administered to preoperative neonates with hypoplastic left heart syndrome and low systemic cardiac output associated with high arterial saturations (> 85%). Pa CO2 is maintained above 40 mm Hg, and the patient is mechanically ventilated, sedated, and paralyzed to prevent a compensatory tachypnea.
Inspired 3% carbon dioxide improved cerebral oxygenation measured by near-infrared spectroscopy and mean arterial pressure in preoperative neonates with single ventricles.  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.
The clinical manifestations of acute hypercapnia are primarily neurologic. Acute elevations of Pa CO2 above 60 mm Hg cause confusion and headache. A Pa CO2 higher than 70 mm Hg produces a hypercapnic encephalopathy or carbon dioxide 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 Pa CO2 was 269 mm Hg) did not have long-term adverse neurologic or developmental effects. 
Acute elevations in Pa CO2 increase intracranial pressure by increasing cerebral blood flow (CBF) and cerebral blood volume secondary to vasodilatation. With a Pa CO2 of 40-80 mm Hg, CBF increases by 1-2 mL per 100 g of brain per minute for each 1-mm Hg increase in Pa CO2. A Pa CO2 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, carbon dioxide 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 carbon dioxide by the lungs). If the CSF acidosis persists for several hours, HCO3– levels in the CSF gradually increase to normalize the pH. In general, the response of the cerebral circulation to Pa CO2 increases during development from the neonatal period to adulthood.
Causes of respiratory acidosis related to central nervous system (CNS) respiratory drive suppression include the following:
Infection (eg, encephalitis, meningitis, or respiratory syncytial virus infection)
Toxins, overdose (eg, of narcotics or alcohol)
Seizures - Postictal state
Spinal causes (eg, trauma to C3-C5 or impairment of phrenic nerve function)
Nerve-related causes include the following:
Spinal muscular atrophy
Phrenic nerve trauma
Neuromuscular junction–related causes include the following:
Muscle causes (eg, muscular dystrophy)
Airway-related causes include the following:
Loss of CNS control (eg, from brain injury, toxin or overdose, trauma, angioedema, tonsillar adenoid hypertrophy, thermal or chemical burn, foreign body, pharyngeal abscess, epiglottitis, or paralyzed vocal cords)
Congenital lesions (eg, subglottic stenosis, laryngomalacia, craniofacial abnormalities, tracheal rings, or vascular slings)
Neoplasm, mediastinal mass
Acute lung injury–related causes include the following:
Chronic lung disease–related causes include the following:
Chronic obstructive pulmonary disease
Causes related to chest wall restriction and reduced respiratory compliance include the following:
Causes related to increased carbon dioxide production causes the following:
The effects of respiratory acidosis vary according to the severity, the duration, the underlying disease, and the associated arterial saturation. Hypercapnic neurologic changes are reversible with no residual effect. The most important consideration may be the degree to which hypercarbia or the underlying disease adversely affects arterial oxygenation.
The prognosis depends on the underlying etiology. Respiratory acidosis can be an acute and transient event with no long-term sequelae if it is not associated with hypoxemia (eg, seizure and treatment-associated hypoventilation). Respiratory acidosis may be associated with a chronic disease that has associated morbidity (eg, asthma or Duchenne muscular dystrophy). It may also be the sign of an irreversible progressive disease that leads to death (eg, idiopathic pulmonary hypertension).
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