Carbon Dioxide Narcosis

Etiology

Overall, the driving mechanism of CO₂ narcosis is acute hypercapnia. The etiology can be extensive, but it can be helpful to divide the potential causes into 3 groups: decreased minute ventilation, increased physiologic dead space, and increased carbon dioxide production.[1] 

The first group causes decreased minute ventilation (respiratory rate x tidal volume). The central respiratory center in the medulla takes feedback from multiple inputs and integrates them into a respiratory drive, which controls our minute ventilation. Anything that affects the central respiratory center can affect the minute ventilation. Notable etiologies include overdose of sedative medications (narcotics, benzodiazepines, tricyclic antidepressants, etc), stroke, and hypothermia. Although the medulla controls the respiratory drive, many peripheral nerves and respiratory muscles are needed to perform respirations. Decreased respiratory neuromuscular function can decrease minute ventilation. Notable etiologies include Guillain-Barre, myasthenia gravis, amyotrophic lateral sclerosis, myositis, multiple sclerosis, phrenic nerve injury, tetanus, botulism, organophosphates, and ciguatera. Deformity of the thoracic cage can impact tidal volumes, decreasing minute ventilation.

The second group is anything that increases physiologic dead space (part of the lung that does not participate in gas exchange); this is ventilation without perfusion. This condition can be due to pulmonary capillary compression (positive pressure ventilation) or the destruction of pulmonary capillaries (pulmonary vasculitides, COPD, asthma, interstitial lung disease). A large pulmonary embolism can also cause significant dead space. The third group is anything that increases CO₂ production. It is more likely that this group only partially contributes to hypercapnia, which is not commonly the primary cause but can occur in conditions that increase metabolic rate, sepsis, thyrotoxicosis, or fever. Environmental exposure to areas rich in carbon dioxide, such as volcanoes or geothermal activity, puts patients at risk for carbon dioxide poisoning. Another unique situation to consider is oxygen-induced hypercapnia, which presents in some patients with COPD when given supplemental oxygen.

Epidemiology

The epidemiology of CO₂ narcosis is difficult to ascertain due to all the possible contributing disease entities. Given that most hypercapnia cases result from lung diseases that increase dead space, one can make a generalized estimation. Approximately 5% of the US population is affected by COPD, and it appears to be more prevalent in women than men. Of this 5%, not all patients with COPD develop CO₂ narcosis. The prevalence of COPD increases as age increases but is more common over the age of 45.[2][3][4]

Pathophysiology

The current belief is that hypercapnia changes neurotransmitter levels involved with consciousness. There is a hypothesis that there are increased levels of glutamine and gamma-aminobutyric acid (GABA) and decreased glutamate levels.[5][6][7] Patient baseline PaCO₂ is important to consider in the development of CO₂ narcosis. Normal individuals do not experience alterations in consciousness until PaCO₂ is greater than 75 mmHg. Patients with chronic hypercapnia may not experience alterations in consciousness until PaCO₂ exceeds 90 mmHg.[8]

Cerebral autoregulation is a process in which the brain maintains a constant and steady supply of nutrients and oxygen despite changes in cerebral perfusion pressure. CO₂ plays a fundamental role in the regulation of cerebral blood flow. The belief is that changes in PaCO₂ drive changes in the cerebral spinal fluid's pH, causing smooth muscle relaxation or contraction. As PaCO₂ levels rise, cerebral blood vessels dilate; as PaCO₂ levels drop, cerebral blood vessels constrict.[9] In patients with CO₂ narcosis, the smooth muscle relaxes, causing dilation of cerebral blood vessels, increasing cerebral blood flow, and potentially causing increased intracranial pressure.

Hypercapnia commonly causes respiratory acidosis. CO₂ combines with H20 to form H2CO3, dissociating into H+ and HCO^3-. This buffer equation is in constant flux. Giving patients with hypercapnia supplemental bicarbonate worsens their condition if they are not adequately ventilating. The supplemental bicarbonate pushes the acid/base buffer equation towards increased CO2 production; however, if the patient’s ventilation is inadequate, the equation moves back towards more H+ production, worsening the acidosis. With respiratory acidosis, the kidneys try to compensate by increasing H+ secretion, raising the HCO^3- concentration, assuming the patient has adequate kidney function. In acute respiratory acidosis, the serum HCO^3- increases 1 mEq/L for every 10 mmHg elevation in PaCO₂. If PaCO₂ remains elevated for 3 to 5 days despite compensatory mechanisms, it is considered chronic respiratory acidosis. In this state, the serum HCO^3- increases from 3.5 to 5 mEq/L for every 10 mmHg elevation in PaCO2.[10][11][12][13]

There is a hypothesis that in certain circumstances, high levels of PaCO₂ can be protective; this refers to a mechanical ventilation strategy called permissive hypercapnia, in which hypercapnia is tolerated to achieve other goals while on the mechanical ventilator. This strategy is useful in patients with acute respiratory distress syndrome (ARDS), COPD, and asthma. The ventilator strategy in patients with ARDS involves using low tidal volumes. It is believed low tidal volumes lessen the risk of alveolar overdistention, decreasing the risk of further lung injury.[14][15] Patients with COPD or asthma undergoing mechanical ventilation are at risk for dynamic auto-inflation or auto-PEEP. This condition occurs when there is incomplete exhalation on the ventilator, and air progressively accumulates in the lungs with each breath, potentially resulting in barotrauma, cardiovascular collapse, or death. One way to prevent auto-PEEP is by decreasing minute ventilation by reducing the respiratory rate or tidal volume.[16][17][18] In both the strategy for ARDS and obstructive airway disease, minute ventilation requires reduction to prevent adverse effects of mechanical ventilation. As a consequence of these strategies, the patient may develop hypercapnia, which is considered acceptable if the pH remains above 7.2. The data confounds whether patient outcomes improve by permissive hypercapnia or other concomitant mechanical ventilation goals.[19]

Oxygen-induced hypercapnia can develop in some patients with COPD. Formerly, the belief was that these patients depended on a hypoxemic respiratory drive due to a blunted sensitivity to CO₂. According to this previous theory, when giving supplemental oxygen to COPD patients, they would develop hypercapnia due to a loss of their hypoxemic respiratory drive with a resultant decrease in alveolar ventilation. However, recent studies support that oxygen-induced hypercapnia in select COPD patients is due to increased dead space, Haldane effect, and decreased minute ventilation.[20][21][22][23][24][25][26] In these studies, the largest component of acute hypercapnia was due to increased dead space ventilation (increased V/Q mismatch). This mismatch is believed to be due to a loss of hypoxic pulmonary vasoconstriction. Normally, this compensatory mechanism redirects blood to areas of good perfusion to maximize the exchange of oxygen and CO₂ between alveoli and capillaries. Blunting this compensatory mechanism causes a redirection of blood flow from areas of good perfusion to poor perfusion. The second-largest component of acute hypercapnia was due to the Haldane effect. In this mechanism, hemoglobin has a decreased affinity for CO₂, which appears as a rightward shift on the CO₂-hemoglobin dissociation curve that occurs with increased oxygen levels. The Haldane effect occurs because CO₂ does not bind as tightly to oxyhemoglobin as deoxyhemoglobin. The last and smallest component of oxygen-induced hypercapnia was attributed to the original theory of decreased minute ventilation.

History and Physical

The initial patient encounter should always begin with evaluating the airway, breathing, and circulation. Once these have been secured and addressed, continue with the history and physical exam. A neurologic exam and Glasgow coma scale (GCS) are necessary. The severity of the patient's presentation varies depending on the PaCO₂ accumulation in the blood. Initially, with mild hypercapnia, the patient may only present with non-specific headache, mild dyspnea, tachypnea, or somnolence. As higher levels of CO₂ accumulate, patients can become delirious, confused, bradypnea and can ultimately progress to coma once the patient develops a depressed level of consciousness, known as CO₂ narcosis. Acute hypercapnia initially increases the respiratory drive (tachypnea) but, over time, reduces the respiratory drive (bradypnea).[27] When evaluating the skin, it can have a variable appearance, depending on the patient’s respiratory drive. If the patient retains their respiratory drive, their skin color appears normal because they still receive adequate oxygen. However, if the patient’s respiratory drive decreases as a result of their hypercapnia, they may become hypoxic with a resultant cyanotic appearance of the skin.

CO₂ narcosis is classically considered in patients with a history of sedative use or chronic lung diseases that increase dead space, such as COPD. However, there is a wide range of etiologies that can contribute to CO₂ narcosis. Identifying a risk factor or underlying disorder can help with its identification. Perhaps the patient is known to be a drug user or smokes tobacco. In the latter, be on the lookout for clubbing or wheezing. When evaluating the patient, look at the patient's body habitus. Evaluate for thoracic cage abnormalities or obesity. Inquire about a known history of neuromuscular disorders. If the patient just had surgery with anesthesia, consider that the patient was in a state of hypoventilation. An important point is that the patient does not need to be hypoxemic to be hypercapnic. If the patient is on supplemental oxygen and has an acceptable oxygen saturation due to hypoventilation, the patient may retain CO₂. This situation can exist in COPD. Patients may be compensated with increased breathing work, allowing them to have an acceptable PaO₂, but due to the tachypnea, there is less time for exhalation, contributing to the hypercapnia. When the patient develops sufficient hypercapnia, the respiratory drive can decrease with subsequent hypoventilation and a decreased level of consciousness. Additionally, giving a hypoxic patient supplemental oxygen in COPD or another hypoventilation state can worsen the hypercapnia.[20][21]

Evaluation

The labs and studies obtained help build a complete picture of why the patient has CO₂ narcosis. A complete blood count can be informative for the chronically hypoxic patient, as it can detect polycythemia. Serum chemistry can reveal an elevated bicarbonate level, reflecting the patient's body trying to compensate for the acidosis from chronic hypercapnia. ABG analysis is critical in the evaluation of CO₂ narcosis. A PaCO₂ greater than 45 mmHg is considered hypercapnia. The accompanying pH indicates whether the patient's hypercapnia is acute or chronic. Acute hypercapnia typically has a pH of less than 7.35. Chronic hypercapnia has near-normal pH. A toxicology screen, including opiates and benzodiazepines, helps determine a possible cause. Thyroid function tests may reveal findings consistent with hypothyroidism. A chest X-ray should be performed on these patients to evaluate for hyperinflation, flattened diaphragms, thoracic cage abnormalities, or diaphragm abnormalities. CT imaging of the neck or brain should not be done routinely, only in select patients with a high degree of suspicion for a stroke, tumor, or traumatic dissection.[8]

Treatment / Management

As stated above, the initial patient encounter should always begin with evaluating the airway, breathing, and circulation. After addressing and securing these, the rest of the treatment can proceed. Therapy aims to determine the underlying cause and correct the hypercapnia. If the patient is having a COPD exacerbation, treat the patient with bronchodilators and steroids. In patients with suspected overdose, consider antidotes for reversal of sedative medications such as naloxone for opiate overdose. If the patient has significant pneumonia, including antibiotics in the treatment is necessary. If the patient has developed anaphylaxis that has threatened their airway, they need to be intubated and started on therapies, including H1 and H2 blockers, corticosteroids, and epinephrine. If the patient already has a depressed level of consciousness, with poor respiratory effort or impending respiratory failure, they need to be intubated, followed by mechanical ventilation. Non-invasive ventilation is inappropriate for patients with CO₂ narcosis due to the high risk of aspiration of gastric contents. These patients require admission to the ICU for close monitoring. A repeat ABG analysis is needed to monitor for improvement of PaCO₂ while undergoing mechanical ventilation. If the patient has a new-onset acute hypercapnia, the goal is to correct the normocapnia. If the patient has acute or chronic hypercapnia, the goal is to go back to the patient's baseline levels.[8] In rare cases where the individual has been exposed to high levels of carbon dioxide, the first step is to remove the individual from the environment and treat it accordingly, as stated above.

Differential Diagnosis

Patients who present with a depressed level of consciousness have a broad differential, and many etiologies need to be considered, such as toxins, sedative drugs, metabolic derangements, infections, and supratentorial or infratentorial abnormalities.[28] The clinician can differentiate CO₂ narcosis by both a depressed level of consciousness and hypercapnia. The diagnosis of CO₂ narcosis and ruling out other disease processes depends on the clinical presentation, lab findings, and imaging.

Prognosis

The prognosis of CO₂ narcosis depends on many factors, including the patient's age, comorbidities, underlying etiology, presenting symptoms, the severity of symptoms, and response to therapy.

Complications

A complication that can occur when managing a patient with CO₂ narcosis is overcorrecting the chronic hypercapnia in a patient with underlying COPD. Overcorrecting can result in alkalemia, reduce respiratory drive, and possibly induce seizures.[29] Mechanically ventilated patients can develop barotrauma, volutrauma, oxygen toxicity, ventilator-associated pneumonia, or auto-PEEP.[29][30]