Anatomy, Anatomic Dead Space

Structure and Function

Dead space of the respiratory system refers to the volume of inspired air in a given breath in which oxygen (O₂) and carbon dioxide (CO₂) gases are not exchanged across the alveolar membrane in the respiratory tract.[1] This is comprised of 2 segments: the anatomic dead space (parts of the airway that are not alveolar exchange membranes) and the alveolar dead space (alveoli that are ventilated but not perfused with pulmonary capillary blood flow).[4] See Figure. Anatomical Dead Space Diagram.

Anatomic dead space refers to the volume of air in the respiratory tract segments that conduct air to the alveoli and respiratory bronchioles but do not participate in gas exchange. These segments of the respiratory tract include the upper airways, trachea, bronchi, and terminal bronchioles. On the other hand, alveolar dead space refers to the volume of air in the alveoli that is ventilated but not perfused; thus, gas exchange does not occur.[5][6] See Figure. Anatomic Dead Space.

Physiologic dead space (VD-Phys) is the sum of the anatomic (VD-Ana) and alveolar (VD-Alv) dead space. Thus:

VD-Phys = VD-Ana + VD-Alv (L)

Dead space ventilation (VD) is then calculated by multiplying VD-Phys by the respiratory rate (RR):

VD = VD-Phys x RR (L/min)

Total ventilation (VE) is, therefore, the sum of alveolar ventilation (Valv) and VD:

VE = Valv + VD (L/min)

Enghoff's equation compiles these variables with PaCO₂, tidal volume (TV), and expired CO₂ (PECO₂). It is then implied that V/VT represents the portion of a tidal volume that does not participate in gas exchange [7]:

V/VT = (PaCO₂ - PECO₂)/PaCO₂q

Dead space is of particular significance in the concepts of ventilation (V) and perfusion (Q) in the lung, as reflected in the V/Q ratio. Alveoli with no perfusion have a V/Q of infinity (Q=0), whereas alveoli with no ventilation have a V/Q of 0 (V=0). Therefore, in situations (ie, V/Q =infinity) in which the alveoli are ventilated but not perfused, gas exchange cannot occur, such as when pulmonary embolism increases alveolar dead space.

Although initially counterintuitive, multiple functions of the non-gas-exchanging upper airway, including the anatomical dead space, are important to normal respiratory function. Carbon dioxide is retained, resulting in bicarbonate-buffered blood and interstitium. Inspired air is raised or lowered to body temperature, increasing the affinity of hemoglobin for O₂ and improving O₂ uptake.[8] Particulate matter is trapped in the mucus that lines the conducting airways, allowing its removal by mucociliary transport and thereby serving as a first-line barrier against foreign matter. Finally, inspired air is humidified in the upper airways, which is important for its temperature regulation and gas exchange functions.[9]

Alveolar dead space is typically negligible in a healthy adult. Anatomic (and therefore physiological) dead space is typically estimated at 2 mL/kg body weight and comprises 1/3 of the TV in healthy adults; it is even higher in pediatric patients.[10] Effectively, 1/3 of a TV of inhaled air is rebreathed due to dead space. At the end of expiration, the dead space contains a gas mixture that is high in CO₂ and low in O₂ relative to ambient air. The composition of end-expiratory dead volume air is 5 to 6% carbon dioxide and 15 to 16% oxygen. In comparison, ambient air comprises 0.04% carbon dioxide and 21% oxygen.

Physiologic Variants

Numerous physiologic factors can influence the anatomic dead space, owing to variations in its function with posture and sleep, and to the anatomy of the upper airway itself and the associated bony and soft-tissue structures.

Respiratory Cycle

Inhalation increases bronchial diameter and length, effectively increasing the anatomic dead space. Likewise, exhalation decreases the amount of anatomic dead space by "deflating" the bronchial tree.

Positioning

Dead space decreases in the supine position and increases in the sitting position. In the upright position, a mismatch between ventilation (V) and perfusion (Q) can occur, in which the apices of the lungs are not as well ventilated as perfused (due to gravity's greater effect on blood than air), resulting in wasted ventilation and an increase in dead-space volume.[11]

Sleep

Anatomic dead space is believed to decrease during sleep and to be the primary physiologic cause of the observed decreases in tidal volume, minute ventilation, and respiratory rate.[12][13]

Maxilla

Variation can also occur in patients with maxillary defects or those who have undergone maxillectomy procedures. These patients have an increased anatomic dead space due to communication between the nasal and oral cavities, ultimately affecting respiratory function.

Surgical Considerations

In patients with disease-free lungs who are undergoing general anesthesia for procedures non-affective of the thoracic cavity or diaphragm, dead space and compliance of the lungs have enabled physicians to tailor patients' PEEP to optimal levels, with the reasoning that the point of minimum dead space with maximum compliance represents the point at which the maximum amount of alveoli are opened for ventilation. Increasing VD, however, may indicate that alveoli are overdistending due to overly aggressive ventilation parameters. Lung recruitment maneuvers, in addition to PEEP during mechanical ventilation, have been shown to significantly increase functional residual capacity, compliance, and PaO2, with a decrease in dead space, compared with PEEP alone.[14][15][16]

Clinical Significance

Dead space can be affected by various clinical scenarios, both by lung and airway pathology that alter the anatomical dead space and by healthcare interventions that alter physiology, such as mechanical ventilation.

Lung Disease

Chronic obstructive pulmonary disease (COPD) destroys alveolar tissue, leading to air trapping and reduced diffusion surface area, thereby increasing dead-space volume.[17][18] Acute respiratory distress syndrome (ARDS) disrupts the pulmonary microvasculature, potentially increasing dead space. However, it is unclear whether these portions of the lung are sufficiently ventilated to be considered dead space. VDphys/VT measured by Enghoff's equation increases in ARDS; however, because the ratio reflects V/Q changes, which occur in pulmonary shunting mechanisms (perfusion without ventilation). Elevated dead-space fractions have been observed in critical care cohorts of patients with ARDS to be associated with an increased likelihood of death, both in the early and intermediate stages of the disease.[2][19]

Pulmonary Embolism

Clinical trials have demonstrated that, in patients with suspected pulmonary embolism, dead-space and capnography measurements, along with the biochemical test D-dimer, can be used to exclude the diagnosis. The clinical diagnosis of pulmonary embolism when not critically unwell is difficult because common signs such as shortness of breath, chest pain, and mild hypoxia may be caused by various clinical entities. Furthermore, computed tomography pulmonary angiography is a relatively expensive diagnostic imaging modality and therefore requires appropriate clinical triage. In this setting, volumetric capnography was a sensitive but not specific test for pulmonary embolism, with a sensitivity of 98.4% (95% confidence interval [CI], 91.6%-100.0%).[20] Furthermore, capnography can be used to monitor thrombolysis treatment for pulmonary embolism by tracking changes in dead-space measurements.[21] Dead space and capnography can thus prove to be useful tools, minimizing unnecessary tests by ruling out pulmonary embolism with simple capnography measurements.

Mechanical Ventilation

When patients require mechanical ventilation, the tubing from the ventilator to the endotracheal tube increases dead space volume by increasing the length of the conduit between inhaled air and the alveolar gas-exchange region. In other words, the tubing of mechanical ventilators obviously does not participate in gas exchange, and minimizing this space is important when considering the optimal care of mechanically ventilated patients, particularly during critical illness.[22]

Positive end-expiratory pressure (PEEP) is commonly used in the ventilation of critically ill patients with respiratory failure, such as in ARDS. The ventilation modality increases the anatomic dead space by expanding the conducting airways.[23] Excessive PEEP can overdistend alveoli, leading to lung barotrauma and increased dead space volume.

Furthermore, in patients who have been mechanically ventilated during a critical care illness, the dead-space-to-tidal-volume ratio (Vd/Vt) is clinically useful for extubation decisions in both adult and pediatric populations. In adults, a study demonstrated that a low Vd/Vt ratio was strongly predictive of extubation failure, with an area under the ROC curve of 0.94 (95% CI, 0.86-0.98; p < 0.0001).[24] Similarly, in the pediatric population, a Vd/Vt ratio of <0.50 was significantly associated with successful intubation.[25] However, another large prospective study found that although no single value reliably predicted extubation success, a high Vd/Vt was predictive of the need for a high level of respiratory support post-extubation among critically ill pediatric patients.[10]

Specifically, within the pediatric population who are mechanically ventilated, studies have shown that preterm infants have higher anatomical dead space volumes compared to neonates born at term. The median anatomical dead space volume was 3.7 ml/kg in infants born prematurely and 2.4 ml/kg in infants born at term.[26] This is clinically important because it likely affects the work of breathing and the efficacy of low-volume mechanical ventilation in infants with a proportionally larger fraction of their tidal volume occupied by anatomic dead space.

Anesthesia

Bronchodilation induced by inhalational anesthetic agents, particularly isoflurane, increases dead-space volume.[27] Estimating the dead space can be of significant value in clinical situations for diagnostic, prognostic, and therapeutic purposes. Dead space is an integral component of volume capnography, which measures expired CO₂ and dead space (VDphys/VT) on a breath-by-breath basis to support efficient monitoring of patient ventilation. Even though the VDphys/VT ratio measured by Enghoff's equation is adversely affected by pulmonary shunting in ARDS, VDphys/VT is a significant predictor of mortality during early-phase acute respiratory distress syndrome (ARDS), and increases in the VDphys/VT ratio correlated with poorer patient outcomes. Measurement of this dead space provides a quantifiable indicator of overall lung function that physicians can assess throughout the hospital course of ARDS patients. PEEP, an integral component of ARDS ventilation management, can be titrated to a patient's specific needs based on capnography and dead-space monitoring. Still, this finding has not been consistently demonstrated across studies.

High-flow nasal oxygen

Clearance of the anatomic dead space is believed to play a significant role in the use of nasal high-flow cannulas. It is believed that increased nasal airflow allows dead space to be cleared more rapidly, thereby decreasing the fraction of dead space that is rebreathed and increasing alveolar ventilation.[28] A recent study demonstrated that administering nasal high-flow oxygen cleared expired air, thereby reducing physiologic dead space, and that this effect extended below the soft palate.[29] This may reduce the amount of reinhaled air, improve alveolar ventilation, and reduce respiratory rate.