Hypercapnia, a state of elevated serum carbon dioxide (CO2), can manifest as a broad spectrum of disease, the most severe of which is CO2 narcosis. The delineating feature of CO2 narcosis is a depressed level of consciousness. It is essential to recognize impending or current CO2 narcosis; if left untreated, it can result in coma or death. This article primarily focuses on CO2 narcosis, but it is crucial to appreciate that hypercapnia has multiple end-organ effects that contribute to the patient's deterioration. Many etiologies contribute to hypercapnia; the most commonly encountered is chronic obstructive pulmonary disease (COPD). Treatment is focused on fixing the underlying cause and demands an interprofessional approach to optimize patient outcomes.
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 three groups: decreased minute ventilation, increased physiologic dead space, increased carbon dioxide production.
The first group is anything that 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 functions to control 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 functions to control 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, therefore 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 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, and 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.
The epidemiology of CO2 narcosis is difficult to ascertain due to all the possible disease entities that can contribute to it. Given that most cases of hypercapnia 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 will develop CO2 narcosis. The prevalence of COPD increases as age increases but is more common over the age of 45.
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 levels of glutamate. Patient baseline PaCO2 is important to consider in the development of CO2 narcosis. Normal individuals do not experience alterations in consciousness until PaCO2 greater than75 mmHg. Patients with chronic hypercapnia may not experience alterations in consciousness until PaCO2 exceeds 90 mmHg.
Cerebral autoregulation is a process in which the brain works to maintain 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 pH of the cerebral spinal fluid, causing relaxation or contraction of the smooth muscle. As PaCO2 levels rise, cerebral blood vessels dilate, and as PaCO2 levels drop, cerebral blood vessels constrict. In patients with CO2 narcosis, the smooth muscle will relax, causing dilation of cerebral blood vessels, increasing cerebral blood flow, potentially causing increased intracranial pressure.
Hypercapnia commonly causes respiratory acidosis. CO2 combines with H20 to form H2CO3, which dissociates into H+ and HCO3-. This buffer equation is in constant flux. Giving patients with hypercapnia supplemental bicarbonate will worsen their condition if not adequately ventilating. The supplemental bicarbonate will push the acid/base buffer equation towards increased CO2 production; however, if the patient’s ventilation is inadequate, the equation will move back towards more H+ production, worsening the acidosis. With a respiratory acidosis, the kidneys try to compensate by increasing H+ secretion, raising the HCO3- concentration, assuming the patient has adequate kidney function. In acute respiratory acidosis, the serum HCO3- increases 1 mEq/L for every 10 mmHg elevation in PaCO2. If PaCO2 remains elevated for three to five days despite compensatory mechanisms, it is considered chronic respiratory acidosis. In this state, the serum HCO3- increases from 3.5 to 5 mEq/L for every 10 mmHg elevation in PaCO2.
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 acute respiratory distress syndrome (ARDS) involves the use of low tidal volumes. It is believed low tidal volumes lessen the risk of alveolar overdistention, decreasing the risk of further lung injury. 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, which can result in barotrauma, cardiovascular collapse, or death. One way to prevent auto-PEEP is by decreasing minute ventilation through a reduction of the respiratory rate or tidal volume. In both the strategy for ARDS and obstructive airway disease, an aspect of the 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, as long as the pH remains above 7.2. The data is confounding whether patient outcomes improve by permissive hypercapnia or other concomitant mechanical ventilation goals.
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 patients with COPD, 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 mechanisms such as increased dead space, Haldane effect, and decreased minute ventilation. 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 works by redirecting 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 levels of oxygen. The Haldane effect occurs because CO2 does not bind as tightly to oxyhemoglobin compared to deoxyhemoglobin. The last and smallest component of oxygen-induced hypercapnia was attributed to the original theory of decreased minute ventilation.
The initial patient encounter should always begin with an evaluation of the airway, breathing, and circulation. Once all of 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 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, and 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). When evaluating the skin, it can have a variable appearance, depending on the patient’s respiratory drive. If the patient still retains their respiratory drive, the skin color will appear normal because they are still getting adequate oxygen delivery. 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 always 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 to note is that the patient does not need to be hypoxemic to be hypercapnic. If the patient is on supplemental oxygen, and they have an acceptable oxygen saturation, due to hypoventilation, the patient may be retaining CO2. This situation can exist in COPD. Patients may be compensating with increased work of breathing, allowing them to have an acceptable PaO2, but as a consequence of 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 the setting of COPD or another hypoventilation state can worsen the hypercapnia.
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. Determining whether the patient's hypercapnia is acute or chronic depends on the accompanying pH. 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.
As stated above, the initial patient encounter should always begin with an evaluation of the airway, breathing, and circulation. After addressing and securing these, the rest of the treatment can proceed. The goal in therapy is 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, it is necessary to include antibiotics in the treatment. 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 new-onset acute hypercapnia, the goal is a correction to normocapnia. If the patient has acute on chronic hypercapnia, the goal is back to the patient's baseline levels.  In the rare case that the individual had environmental exposure to high levels of carbon dioxide, the first step is to remove the individual from the environment and then treat accordingly, as stated above.
Patients that 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. 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 is dependent upon the clinical presentation, lab findings, and imaging.
The prognosis of CO2 narcosis is dependent upon many factors, including the patient's age, comorbidities, underlying etiology, presenting symptoms, the severity of symptoms, and response to therapy.
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, reducing respiratory drive, and possibly induce seizures. Mechanically ventilated patients can develop barotrauma, volutrauma, oxygen toxicity, ventilator-associated pneumonia, or auto-PEEP.
Identifying which patients may develop this as a complication of their underlying disease process is paramount. Early recognition of hypercapnia can help prevent further deterioration of the patient's condition into CO2 narcosis. Prodromal symptoms to recognize before CO2 narcosis develops can include increased confusion, and increased work of breathing. After identification, treatment should be sought immediately. A modifiable risk factor is tobacco abuse. Encourage patients to stop abusing tobacco and provide information regarding nicotine replacement therapy and other cessation treatment.
Caring for a patient that develops CO2 narcosis can be challenging and requires an interprofessional approach to optimize patient outcome. The etiology of CO2 narcosis can be broad, and depending on the cause can produce different challenges for the care of the patient. Each member of the team plays an integral role in patient care, but involvement is largely a function of the underlying cause of hypercapnia. These patients are in the intensive care unit (ICU) and require continuous monitoring by nurses. The patient has multiple needs during their care. Chiefly, their condition needs to be addressed ideally by a pulmonologist or an intensivist. Their tools to treat the patient include various modalities such as medications and ventilator management. Nurses play an essential role in these patients by constantly monitoring them, administering medications, and informing the clinicians of any changes in the patient's condition. Nutritionists are also vital to patient care to develop a diet tailored to the patient's needs. This requirement is especially crucial for the patient on a ventilator. Additionally, pharmacists must assist with medication optimization as well as patient education regarding the proper use of their medications. Poor medication compliance and adherence may have contributed to the patient's condition. After the patient has returned to their baseline, some patients may benefit by speaking to case management regarding living and social environments. Many patients that develop CO2 narcosis have an acute exacerbation of an underlying chronic disease state, such as COPD. These patients may become frustrated and become distressed by their chronic disease. Speaking to a psychologist after the condition resolves may improve the patient's outlook on the future and frame of mind. This is why an interprofessional team approach is needed to address these patients, so they can achieve improved outcomes. [Level 5]
While no trial has taken place examining the role of an interprofessional team in the care of CO2 narcosis, data obtained from other sources such as the National Emphysema Treatment Trial (NETT) can be useful and loosely applied as many patients with CO2 narcosis, have a chronic underlying lung disease. [Level 1]
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