Hypercarbia

Etiology

There are several causes of hypercarbia worth mentioning.

First, hypoventilation resulting in inadequate carbon dioxide removal from the body. Hypoventilation can be further subdivided by cause: inadequate respiratory drive from the central nervous system (CNS) depression, respiratory muscle insufficiency, or ventilation-perfusion mismatch—though these are not mutually exclusive.[3][4]

Second, excess carbon dioxide (CO2) production with inadequate respiratory compensation. CO2 is an end product of metabolism in humans. It has many biological and physiological effects, beyond just serving as the waste product of metabolism.[5] In critically ill patients, there can be excess production from numerous causes, including fever, metabolic acidosis, sepsis, thyroid disease, and others. Any of these can overwhelm the body’s ability to compensate. Increased CO2 production is especially dangerous in patients with underlying lung or CNS disorders. Diets high in carbohydrates for patients with lung impairment can sometimes cause hypercarbia as well.[6]

Third, exogenous carbon dioxide exposure. CO2 is often used for insufflation for various surgical procedures. While generally well-tolerated, this can cause hypercarbia and resultant circulatory complications.[7] Patients exposed to CO2-enriched environments, such as an enclosed space with limited circulation, are also at risk for hypercarbia.

Fourth, chronic hypercarbia in a setting of lung disease. This is often a slow onset failure of ventilation, allowing time for renal compensation. On blood gas analysis, the pH will often be in the normal range, with elevation in CO2 above the normal range and elevated bicarbonate.[8]

Epidemiology

As a general acid-base disturbance, the exact incidence of hypercarbia is not routinely tracked. It is typically used to evaluate and monitor an underlying disease process.

Pathophysiology

Carbon dioxide is produced intracellularly during aerobic respiration, a process that uses glucose (C6H1206) and oxygen (O2) to create adenosine triphosphate (ATP). ATP provides energy to drive many intracellular processes. CO2 is a waste product of its production.

• C6H1206 + 6O2 —> 6CO2 + 6H2O + Heat

Intracellularly produced CO2 is absorbed into the bloodstream, where it is neutralized using a bicarbonate-carbon dioxide buffer system to maintain physiologic pH. Homeostasis of the bicarbonate-carbon dioxide buffer system is dependent on pulmonary excretion of CO2 and renal excretion of hydrogen ions.

• CO2 + H2O <—> H2CO3 <—> HCO3- + H+

Once carbon dioxide in the bloodstream reaches the pulmonary capillaries, it is exchanged for oxygen across the alveolar-capillary membrane.[3] This process occurs via concentration gradient mediated diffusion. CO2 is then expelled from the body during exhalation.

The concentration of CO2 in the bloodstream determines the speed with which it is removed from the body by controlling the respiratory drive.[9][10] Increased CO2 in the blood crosses the blood-brain barrier, resulting in a decrease in the pH of cerebrospinal fluid. The lower pH is detected by central chemoreceptors and causes an increase in minute ventilation (MV).[9]

• MV = respiratory rate x tidal volume

Physiologic derangements in the following can produce pathological hypercarbia:

• Metabolic processes that increase CO2 production
• Renal dysfunction resulting in an imbalance in the bicarbonate-carbon dioxide buffer system
• Impairment of gas exchange across the alveolar-capillary membrane
• Depression of centrally mediated respiratory centers
• Exogenous exposure to an elevated level of CO2 during surgical procedures

History and Physical

Presentation of hypercarbia can be acute or chronic, with a range in severity and symptoms depending on the underlying process. Most often, patients with acutely developing hypercarbia will complain of dyspnea, fatigue, and confusion that can progress to somnolence. Other potential symptoms can include headache, flushed skin, and nausea. For chronic hypercarbia, patients will often note dyspnea on exertion, but also fatigue, irritability, and headache. If possible, a full medical history should be obtained, including past medical history, social history, and medication list.

Physical exam findings can also be variable. Reduced respiratory rate, shallow breathing, use of accessory muscles of respiration, altered level of consciousness, fever, diaphoresis, or wheezing may be present. Hypercarbia is often accompanied by hypoxia, and some of the signs and symptoms will overlap. For patients with low oxygen saturation noted on pulse oximetry, hypercarbia should be considered.[11]

Patients with drug overdose may have signs of illicit drug use or cardiac murmur. For patients with chronic lung disease, wheezing, or rhonchi may be present. It is important to assess patients for the use of chronic oxygen therapy, as excess supplemental oxygen delivery (to saturations more than 94%) can cause oxygen-induced hypercarbia.[12]

Evaluation

To establish the diagnosis of hypercarbia, blood gas analysis is essential. While a venous blood gas can provide information about the pH and an estimate of CO2 retention, the CO2 content in venous blood is naturally higher than arterial blood as it has not passed through the lungs. Arterial blood gas analysis is the preferred technique for diagnosing hypercarbia, with any partial pressure of CO2 (PaCO2) level greater than 45 mmHg qualifying. The next step in evaluation is to refer to the pH from the same sample. If it is within a normal range, there is either a mixed acid-base disorder, or the hypercarbia is chronic. If the pH is less than 7.35, there is respiratory acidosis.[1]

Further evaluation should be driven by history and physical exam findings. A basic metabolic panel is useful to assess for metabolic derangements and better characterize the serum bicarbonate. A urine drug screen is useful if an overdose is suspected. Work up for sepsis and fever should include complete blood count, chest imaging, and blood and sputum cultures. Thyroid function is important to assess as different disease states can contribute to hypercarbia (increased production in thyrotoxicosis, decreased clearance in myxedema coma).[13] Head imaging is also critical in evaluation, as an acute stroke can cause CNS depression and subsequent hypoventilation.

Though less useful in an acute setting, pulmonary function testing can be used to assess for obstructive lung disease or pick up on a subtle decline from a neuromuscular disease like amyotrophic lateral sclerosis. If the clinical picture is appropriate, polysomnography could be obtained to evaluate for sleep-disordered breathing such as obesity hypoventilation syndrome.

Treatment / Management

As hypercarbia is most often the result of hypoventilation, the primary method for treatment is to augment ventilation. This can be started while the investigative workup is still in process. For a breathing patient, the first-line option is non-invasive positive pressure ventilation. In most hospital settings, this is usually delivered by a full face mask with bilevel positive airway pressure settings. If effective ventilation is delivered, there should be some improvement in CO2 in a span of minutes to hours.

If non-invasive ventilation fails to improve the hypercarbia, the patient is not breathing, or there is a contraindication to the use of non-invasive ventilation, then intubation and mechanical ventilation are the next steps. After this general treatment with supplemental ventilation, closer scrutiny can be given to correcting the underlying cause. Patient-specific treatment will vary depending on the particular cause for the hypoventilation: bronchospasm from exacerbation of obstructive lung disease, illicit drug or medication toxicity, neuromuscular compromise, or other disease processes. As the hypercarbia is corrected, the patient will often become more alert and wean from ventilatory support.

Mechanical ventilation usually leads to the correction of hypercarbia in a matter of hours for cases not driven by intrinsic pulmonary pathology. For cases driven by significant lung diseases such as asthma exacerbation, severe pneumonia, or acute respiratory distress syndrome (ARDS), it may take days to gradually correct the CO2 level. In some cases, complete normalization of CO2 is not the goal immediately or at all. An important concept in treating ARDS is permissive hypercarbia. To avoid overdistention and ventilator-induced lung injury, a lung-protective ventilation strategy is employed. Tidal volumes are limited to 6-8 mL/kg of ideal body weight, which can slightly compromise ventilation. The resultant respiratory acidosis is typically well-tolerated, so long as the pH is greater than 7.25. There is not a specific cut-off for the CO2 level.[14](B3)

Permissive hypercarbia is also allowed for severe asthma exacerbation, though for a different reason. Due to bronchospasm, full exhalation is not possible with higher respiratory rates, which can lead to progressive air-trapping with worsening respiratory and hemodynamic consequences. Therefore, while treating the exacerbation with bronchodilators and steroids, a lower respiratory rate is set on the ventilator, which will lead to an increase in CO2, but enhance airflow dynamics.[15]

For patients with severe hypercarbia that fail or cannot tolerate the above interventions, there is a treatment modality known as extracorporeal carbon dioxide removal (ECCO2R). It is an emerging form of life support, characterized by carbon dioxide removal directly from the blood. It is not widely available at all centers.[16]

As hypercarbia can cause respiratory acidosis, many providers are tempted to correct this by giving alkali or basic therapy. However, while this may briefly improve pH, it is ultimately counterproductive and will worsen hypercarbia. Bicarbonate (HCO3-) is the base most often given, but after binding with a hydrogen ion (H+), it breaks down to water and CO2, which worsens the acidosis.[17](B3)

Differential Diagnosis

The differential diagnosis of hypercarbia varies over a wide range of acute and chronic conditions. It includes, but is not limited to the following:

• Chronic obstructive pulmonary disease
• Acute obstructive pulmonary disease
• Chronic restrictive lung disease
• Acute restrictive lung disease
• Chronic renal failure
• Acute renal failure
• Exogenous drug administration
• Interstitial lung disease
• Pulmonary edema
• Acute respiratory distress syndrome
• Sepsis
• High carbohydrate diet
• Injury to the central nervous system
• Exogenous exposure to CO2 during laparoscopy, thoracoscopy, or endoscopy
• Malignancy
• Neuromuscular disorders
• Obstructive or central sleep apnea
• Thyrotoxicosis or myxedema coma

Prognosis

The prognosis of hypercarbia varies and depends heavily on the underlying etiology. For acute hypercarbia, if a reversible underlying cause is quickly diagnosed and treated, the prognosis is fair. For patients with chronic obstructive pulmonary disease (COPD) and chronic hypercarbia, there is higher associated mortality compared to patients with COPD without chronic hypercarbia.[2]

Complications

The deleterious effects of hypercarbia on the body are numerous and include the following:

• Unconsciousness/coma
• Confusion/depression/paranoia
• Panic attacks
• Arrhythmias
• Cardiovascular collapse