Hypercapnia PDF

exchange.scholarrx.com /brick/hypercapnia Hypercapnia 15-19 minutes NK is a 56-year-old male with chronic obstructive pulmonary disease (COPD) due to long-term heavy smoking. He uses supplemental oxygen at home. He now comes to the emergency department with worsening dyspnea. The initial evaluatio...

exchange.scholarrx.com /brick/hypercapnia Hypercapnia 15-19 minutes NK is a 56-year-old male with chronic obstructive pulmonary disease (COPD) due to long-term heavy smoking. He uses supplemental oxygen at home. He now comes to the emergency department with worsening dyspnea. The initial evaluation suggests a COPD exacerbation. He is treated with bronchodilators and supplemental oxygen. With administered oxygen, his oxygen saturation increases from 89% to 95%. However, his estimated partial pressure of arterial carbon dioxide (PaCO2) as measured by capnography rises from 45 mm Hg to 70 mm Hg. NK now appears confused. What explains the change in his lab values and clinical condition after treatment? Consider your answer as you read, and we’ll revisit NK at the end of the brick. Go to Conclusion Hypercapnia (sometimes called hypercarbia) is an elevation of the partial pressure of carbon dioxide in the blood (PaCO2). It is usually defined as an elevation in PaCO2 to more than 42 to 45 mm Hg. This elevation is concerning because: CO2 is the main stimulus for the respiratory drive in most people. Hypercapnia is often a marker for severe pulmonary disease (due to failed ventilation) or for central nervous system (CNS) disorders (due to depression of the respiratory centers in the brain), most famously in opioid overdose. Hypercapnia often causes respiratory acidosis, which is a cause of acidemia (low pH) if the CO2 elevation is sufficiently severe or acute. The acidemia can cause abnormal cardiac and nerve conduction. Patients with severe hypercapnia may require intubation and ventilation, and the PaCO2 is followed closely in patients in the intensive care unit (ICU). Patients with hypercapnia often have histories of pulmonary disease (eg, chronic obstructive pulmonary disease [COPD]) but may also have disorders that disrupt their CNS drive to breathe (eg, opioid or barbiturate overdoses, head trauma, or other CNS disease). These patients are often quite short of breath. Sometimes this occurs because they also have hypoxemia as part of their lung disease. However, even without hypoxemia, an elevated PaCO2 is an extremely noxious stimulus to the CNS respiratory centers, and even mild elevations will provoke a feeling of dyspnea. It will also trigger hyperventilation to correct the hypercapnia. Other symptoms may include flushing with palmar erythema (due to vasodilation) and encephalopathy with asterixis or decreased mental state, even coma. However, some patients may not have symptoms. Unlike with hypoxemia, the body can safely tolerate mild degrees of hypercapnia, and even severe hypercapnia if it is chronic, as we’ll see next. Why do patients with hypercapnia often have dyspnea? Carbon dioxide is a potent central nervous system stimulus and conveys the sense of shortness of breath as part of the increased drive to breathe in patients with hypercapnia. The body compensates for hypercapnia with both hyperventilatory and metabolic responses. Increasing PaCO2 can stimulate the central chemoreceptors in the brain’s medulla as well as the peripheral receptors in the aortic arch and carotid arteries (Figure 1). Figure 1 Credit: ScholarRx These receptors then stimulate the respiratory center in the CNS and cause a higher respiratory rate and increased tidal volume. The result is increased minute ventilation, which drops the PaCO2 back toward normal. If the increased respiratory rate cannot keep up with the buildup of CO2, hypercapnia results. Why would this happen? Possibilities include the following: Over time, the body becomes habituated to the sensation of hypercapnia, such that it fails to stimulate the respiratory drive as much. This blunted response of the brain respiratory centers is more marked in patients taking CNS depressants, like opioids. These patients may have asymptomatic, high values of PaCO2. The respiratory muscles can become fatigued, especially in patients who are chronically ill or malnourished, and this compensatory ventilation is less effective. This also occurs in rapidly breathing patients having an acute exacerbation of COPD or asthma. They can tire out, leading to a rise in PaCO2. Patients with emphysema tend to take fast, shallow breaths. Each breath must completely fill the anatomic dead space before it can reach the alveoli. So each shallow breath has the volume of the anatomic dead space subtracted from it, making these shallower breaths less efficient and reducing the expected rise in minute ventilation. What might prevent the normal hyperventilatory response to hypercapnia? Blunting of the brain respiratory center response (eg, by opiates), respiratory muscle weakness, and shallow breathing seen in emphysema can prevent the normal hyperventilatory response to hypercapnia. In hypercapnia, excess acid leads to respiratory acidosis because CO2 reacts with water to form carbonic acid (H2CO3), which then dissociates into bicarbonate (HCO3–) and hydrogen (H+) ions. As in any acid-base disturbance, the body compensates for the acidosis to try to keep the pH as normal as possible. In this case, the kidney provides the main compensation, retaining filtered bicarbonate to correct the low blood pH back toward normal. Many of the symptomatic consequences of hypercapnia (eg, cardiac conduction disturbances) are due to the acidemia, not to the high PaCO2 per se. So, this renal compensation (especially prominent in patients with chronic hypercapnia) is one reason why some patients with marked elevations of PaCO2 may be asymptomatic. Most cases of hypercapnia are from reduced excretion of CO2 by the lungs. Increased production of CO2 (from, eg, exercise, stress, infection) can contribute to the PaCO2 elevation but rarely cause hypercapnia on its own. The two main reasons for decreased CO2 excretion by the lungs are: Reduced minute ventilation (most common) Ventilation/perfusion (V̇ /Q̇ ) mismatching, including increased pathologic dead space Some causes of hypercapnia are a decrease in the volume of air moving in and out of the respiratory system per unit time. The equation for minute ventilation is: VE = RR × VT where VE represents minute ventilation; RR, respiratory rate; and VT, tidal volume. This means that when either the respiratory rate or tidal volume is reduced, minute ventilation initially drops. Often, if one drops (eg, the rate), a compensatory increase occurs in the other (eg, the tidal volume increases). However, when this compensation fails, minute ventilation can be persistently reduced. The partial pressure of alveolar carbon dioxide (PACO2), then increases because it cannot be excreted during ventilation. Because the PACO2 is equal to the PaCO2 (CO2 is very soluble and easily diffusible across the alveolar-capillary membrane), the PaCO2 also rises, causing hypercapnia. Decreased Respiratory Rate. This is mostly due to inhibition of the CNS respiratory centers. Causes include: Head trauma Drug intoxications (eg, opioids, alcohol, other sedatives) Brain herniation or increased cerebral pressure Note that most pulmonary diseases instead raise the respiratory rate because they cause hypoxemia. However, sometimes, COPD, severe asthma, or pneumonia can present with reduced respiratory rate. Decreased Tidal Volume. Tidal volume can drop due to CNS depression because head trauma, intoxication, brain herniation, and so on can decrease the strength of respiratory muscle contraction. However, the most common cause of reduced tidal volume is an upper or lower respiratory tract problem or disease: Airway obstruction due to trauma, edema in burns and anaphylaxis, airway secretions, bronchoconstriction in COPD and asthma, and excess neck mass in sleep apnea Respiratory muscle fatigue from increased work of breathing in acute COPD and asthma exacerbation, acute respiratory distress syndrome (ARDS), and increased metabolic demand in sepsis or critical illness Shallow breathing due to weakness of respiratory muscles in myasthenia gravis, botulism, Guillain-Barré syndrome, phrenic nerve palsy, or neuromuscular blocker toxicity Shallow breathing from chest wall deformities such as kyphoscoliosis, pectus excavatum, rib fracture, and ankylosing spondylitis restricting chest wall expansion (however, these are mostly chronic disorders, so they are usually better compensated) Effective gas exchange requires well-matched lung perfusion (Q̇ ) and ventilation (V̇ ). Decreases in V̇ or Q̇ , leading to V̇ /Q̇ mismatch, most often cause hypoxemia, but in some cases can also cause hypercapnia. Underventilation of Multiple Lung Segments. The most common type of V̇ /Q̇ mismatch causing hypercapnia is characterized by underventilation of multiple lung segments. An example, due to mucus plugging, is shown in Figure 2. Figure 2 Credit: ©ScholarRx Note that the blood going to the left atrium is now a mixture of blood coming from normally ventilated alveoli (A) and those with poor ventilation (B). The result can be hypoxemia and/or hypercapnia. Hypercapnia due to V̇ /Q̇ mismatch with reduced ventilation can occur in many pulmonary diseases, either by loss of alveoli (eg, in bronchitis/COPD) or by fluid entering the alveoli (eg, in pneumonia, cardiogenic pulmonary edema, ARDS, cystic fibrosis). Oxygen Therapy. Interestingly, hypercapnia due to V̇ /Q̇ mismatch can also be caused by aggressive oxygen treatment of COPD. In COPD, pulmonary arterioles are normally constricted to try to shunt blood away from poorly ventilated areas of the lung (hypoxic pulmonary vasoconstriction), minimizing V̇ /Q̇ mismatch. Oxygen therapy can reverse this compensation, creating mismatched areas of ventilation and perfusion (now with reduced perfusion to some areas) and causing reduced gas exchange and hypercapnia. The administered oxygen may also cause hypercapnia by suppressing the CNS respiratory drive. This is why oxygen therapy in patients with COPD should be done judiciously, with monitoring of the PaCO2. Increased Pathologic Dead Space. A less common cause of hypercapnia with V̇ /Q̇ mismatching occurs with increased pathologic dead space, where lung segments are ventilated but not perfused. What happens when pathologic dead space increases? Gas exchange drops, and the CO2 starts to build up in the alveolus and the blood, causing hypercapnia. The most common way in which pathologic dead space causes hypercapnia occurs in emphysema, one of the types of COPD. Here, perfusion is reduced by both external compression of the pulmonary capillaries by overinflated alveoli and by destruction of the capillaries as part of the disease process (Figure 3). Figure 3 Credit: ©ScholarRx Note that COPD can cause hypercapnia both by reducing ventilation due to obstruction of the alveoli in bronchitis and by reducing perfusion because of destruction of capillaries in emphysema, and this makes patients with COPD susceptible to hypercapnia. Also note that a major cause of increased dead space, pulmonary emboli (PE), does not commonly cause hypercapnia. The hypoxia caused by a PE stimulates a strong hyperventilation response, keeping the PaCO2 normal or decreased in most cases. Why does emphysema cause increased dead space? Emphysema causes increased dead space because capillaries are destroyed or compressed by enlarged alveoli, decreasing perfusion. An increased PaCO2 level has multiple consequences. In some cases, it’s not clear whether the main culprit is the elevated CO2 or the secondary drop in blood pH (respiratory acidosis). Both may contribute. Acute elevations in PaCO2 will usually depress a patient’s level of consciousness when it exceeds 75 to 80 mm Hg. Severe acute hypercapnia can even lead to coma, cardiac or respiratory arrest, and death. It’s a common reason to intubate patients in emergency departments. In contrast, patients with chronic hypercapnia (eg, COPD) can usually tolerate higher PaCO2 values without CNS changes. These patients will have elevated serum bicarbonate levels and more normal blood pH due to the renal compensation discussed earlier. This suggests that the pH is at least partially responsible for the CNS effects. The effects of elevated CO2 on the brain are not well understood but may involve altered levels of CNS neurotransmitters like glutamine and -aminobutyric acid (GABA). Hypercapnia also causes vasodilation, with an increase in intracranial pressure. This is not usually severe enough to cause direct damage to the brain. Patients with acute hypercapnia can have arrhythmias or hypotension. These are thought to be due more to the acidosis than to the high PaCO2. Why are patients with chronic hypercapnia less likely to develop CNS effects than patients with acute hypercapnia? Chronic hypercapnia leads to more compensations, including renal retention of bicarbonate with normalization of the pH, so it is less likely to cause CNS effects. Because hypercapnia can be a fatal event or predict respiratory failure, effective detection of acute reversible causes is key. Hypercapnia should be looked for in any patient with respiratory complaints, especially if severe or progressive. It should also be evaluated for in patients with mental status changes of unknown cause. Hypercapnia can be diagnosed using arterial or venous blood gas testing (the PACO2 and PaCO2 values are quite close) or capnography. Capnography uses a device attached to an endotracheal tube, nasal cannula, or face mask to measure inspired and expired CO2 in real time. This can indirectly estimate the blood partial pressure of carbon dioxide without the need to draw blood, thus avoiding the discomfort of venipuncture. What advantages does capnography offer over blood gas testing in diagnosing hypercapnia? Capnography monitors CO2 in real time and does not require drawing blood. Management of hypercapnia relies on first identifying and addressing the underlying cause to prevent future episodes or slow its progression in chronic patients. Most critical is reversing acutely correctable causes, for example, in patients with hypercapnia due to substance overdose, an antidote like naloxone (opioid overdose) or flumazenil (benzodiazepines). All emergency department patients with an unknown cause of hypercapnia (and or decreased respiratory rate) should be given naloxone while the evaluation is initiated. Patients taking opioids should be given naloxone for home use and instructed on when to use it. For patients with persistent hypercapnia (with or without hypoxia), mechanical ventilation is sometimes needed. We can start with noninvasive ventilation. Continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) devices are both used to increase tidal volumes. These modalities are particularly useful in those with respiratory failure due to cardiogenic pulmonary edema (ie, heart failure), which can sometimes lead to hypercapnia due to V̇ /Q̇ mismatch. BiPAP is sometimes used for severe exacerbations of COPD. Here, the increased airway pressures lead to increased tidal volumes and minute ventilation, with a consequent drop in the respiratory rate, decreasing the work of breathing. Invasive ventilation (eg, endotracheal intubation) is required in sicker patients with hypercapnia. The PaCO2 measurement is not used by itself in the decision to intubate but is used together with the PaO2 and overall patient symptoms, signs, and observed course. Specific numerical criteria for when to intubate do not exist— this is a judgment call requiring integration of all available data. What drugs can be useful in the management of patients with hypercapnia due to substance overdose? Naloxone and flumazenil are antidotes to opioids and benzodiazepines, respectively. Thinking back to NK, what explains his changed clinical condition after treatment? While oxygen and bronchodilators were appropriate to treat his dyspnea and hypoxemia, oxygen does run a risk. It can suppress the central drive to hyperventilate as well as cause increasing V̇ /Q̇ mismatch by reversing the usual hypoxic vasoconstriction that shunts blood away from poorly ventilated areas of the lung. Together, this can lead to reduced air exchange and a rising PaCO2, even with improvement in the PaO2. To avoid complications of hypercapnia, the emergency department staff reduced the administered oxygen to keep adequate oxygen saturation without causing PaCO2 to rise. After 3 hours of treatment, NK was back to baseline and ready to go home.