### Function

Ventilation is the manner by which air enters the lungs. There are two equations needed to calculate the volume that enters the lungs and the volume that reaches the alveoli. The volume that enters the lung per minute is known as minute ventilation (VE). The equation states VE equals tidal volume (VT) multiplied by respiratory rate (RR). This equation demonstrates that the total volume entering the lung is not equivalent to the total volume of gas reaching the alveoli because it does not factor in the gas in the anatomical dead space resting in the conductive airway. Thus, to know the volume of gas that reaches the alveoli per unit time we use the alveolar ventilation equation which states; alveolar ventilation (VA) equals VT minus physiologic dead space (VD) multiplied by RR. From this equation, clinicians can determine that the total volume gas inspired is not being fully utilized in the gas exchange due to the constant anatomical dead space.[4][5][6]

### Mechanism

The Bohr equation can be used to calculate the amount of dead space in a lung. Understanding the equation will simplify the concept of dead space greatly. The equation states VD is equal to VT multiplied by the partial pressure of arterial carbon dioxide (PaCO2) minus partial pressure of expired carbon dioxide (PeCO2) divided by PaCO2.

Breaking down this equation, there is the tidal volume which is the normal amount of inspired and expired gas equivalent to 500 mL. This inspired air is assumed to contain a relatively zero amount of carbon dioxide. The second half of the equation is representative of the fractional amount of dead space. Simply translating to the amount of carbon dioxide (CO2) exchanged for oxygen (O2). The exchange of gases through the respiratory membrane is so rapid that we can assume the arterial CO2 partial pressure is equal to that in the alveoli. The exchanged CO2 will now become PeCO2. PeCO2 will always have a smaller value than arterial CO2 due to the mixture and dilution of CO2 gases with the 150 mL of anatomical dead space sitting in the conductive airway that is assumed to be free of CO2. Thus, by subtracting PeCO2 from PaCO2 and dividing by the PaCO2 one has you have determined a fractional equivalent of the lung is not contributing to gas exchange. Multiply that value by the normal amount of air inspired (VT) you achieve a value for physiologic dead space.

### Pathophysiology

Until now, clinicians have assumed the patient is a healthy individual with properly functioning alveoli. In disease states where alveoli have lost function, there will be a decrease in gas exchange and an increase in alveolar dead space. This can be seen most rapidly with sudden decreases in perfused to ventilated alveoli. This is usually seen in an abrupt decrease in cardiac output, hypotension, or pulmonary embolism, due to fat, air, or amniotic fluid. While obstruction can cause decreased perfusion in PE, the greatest decrease in pulmonary blood flow is due to vasoconstriction caused by locally released vasoactive substances. In these situations, a lack of gas exchange at the alveolar level results in a decrease of PaCO2 gas being exchange by the remaining healthy alveoli and ultimately a lower PeCO2. Looking back at the equation, a lower PeCO2 will result in an increase in the physiologic dead space value for that individual. When an area of the lung is properly ventilated, but poorly perfused, there is an increase in physiologic dead space.[7][8]

### Clinical Significance

Clinically, disease states and environmental factors, such as smoking, all play a major role in the increase of dead space. Increases in dead space can be seen in lung disease states including emphysema, pneumonia, and acute respiratory distress syndrome (ARDS). Emphysema results in the enlargement of air spaces and decreases in the diffusing capacity of the alveolar membrane due to the destruction of alveolar walls. In ARDS there is endothelial damage leading to an increase in the alveolar-capillary permeability, thereby leading to leakage of protein-rich fluid into the alveolar. This results in the formation of intra-alveolar hyaline membranes, which decrease the exchange of CO2 and O2 in the lung contributing to a larger dead space. Studies looking at the causes of death in this disease have shown an increase in dead space in the non-survivors versus survivors. The strongest association of an increased volume of dead space with mortality risk is seen in patients with ARDS.[9]

Clinicians use the understanding of dead space to manage mechanically ventilated patients. Even in a healthy patient, ventilation via an endotracheal tube will increase the dead space volume because the breathing circuit does not participate in gas exchange. During mechanical ventilation, capnography is used; this records the volume of expired CO2, a value used to determine the physiologic dead space in patients. Adjustments in ventilation rates and the use of positive end-expiratory pressure (PEEP) are used to decrease dead space. Although multiple studies have failed to show this expected effect consistently, it is still widely used in cases of ARDS. Proper use of mechanical ventilation, as well as PEEP, is important considering both have been implicated in causing lung injury. Also, the use of high-flow nasal cannula has been shown to decrease dead space in patients with acute and chronic respiratory diseases. This is largely due to decreasing rebreathing in the existing anatomic dead space. Understanding dead space and being able to calculate it is a vital tool for physicians dealing with ventilated, critically ill patients.

###### Details

Editor:

William Gossman

Updated:

7/4/2023 12:28:23 AM

### References

[1]

Coppola S, Froio S, Marino A, Brioni M, Cesana BM, Cressoni M, Gattinoni L, Chiumello D. Respiratory Mechanics, Lung Recruitability, and Gas Exchange in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome. Critical care medicine. 2019 Jun:47(6):792-799. doi: 10.1097/CCM.0000000000003715. Epub     [PubMed PMID: 30908313]

[2]

Huang B, De Vore D, Chirinos C, Wolf J, Low D, Willard-Grace R, Tsao S, Garvey C, Donesky D, Su G, Thom DH. Strategies for recruitment and retention of underrepresented populations with chronic obstructive pulmonary disease for a clinical trial. BMC medical research methodology. 2019 Feb 21:19(1):39. doi: 10.1186/s12874-019-0679-y. Epub 2019 Feb 21     [PubMed PMID: 30791871]

[3]

Kiefmann M, Tank S, Tritt MO, Keller P, Heckel K, Schulte-Uentrop L, Olotu C, Schrepfer S, Goetz AE, Kiefmann R. Dead space ventilation promotes alveolar hypocapnia reducing surfactant secretion by altering mitochondrial function. Thorax. 2019 Mar:74(3):219-228. doi: 10.1136/thoraxjnl-2018-211864. Epub 2019 Jan 12     [PubMed PMID: 30636196]

[4]

Plantier L, Delclaux C. Increased physiological dead space at exercise is a marker of mild pulmonary or cardiovascular disease in dyspneic subjects. European clinical respiratory journal. 2018:5(1):1492842. doi: 10.1080/20018525.2018.1492842. Epub 2018 Jul 5     [PubMed PMID: 30627360]

[5]

Ferluga M, Lucangelo U, Blanch L. Dead space in acute respiratory distress syndrome. Annals of translational medicine. 2018 Oct:6(19):388. doi: 10.21037/atm.2018.09.46. Epub     [PubMed PMID: 30460262]

[6]

Frat JP, Coudroy R, Thille AW. Non-invasive ventilation or high-flow oxygen therapy: When to choose one over the other? Respirology (Carlton, Vic.). 2019 Aug:24(8):724-731. doi: 10.1111/resp.13435. Epub 2018 Nov 8     [PubMed PMID: 30406954]

[7]

Quinn M, St Lucia K, Rizzo A. Anatomy, Anatomic Dead Space. StatPearls. 2024 Jan:():     [PubMed PMID: 28723045]

[8]

Godinas L, Sattler C, Lau EM, Jaïs X, Taniguchi Y, Jevnikar M, Weatherald J, Sitbon O, Savale L, Montani D, Simonneau G, Humbert M, Laveneziana P, Garcia G. Dead-space ventilation is linked to exercise capacity and survival in distal chronic thromboembolic pulmonary hypertension. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2017 Nov:36(11):1234-1242. doi: 10.1016/j.healun.2017.05.024. Epub 2017 May 22     [PubMed PMID: 28666570]

[9]

Gogniat E, Ducrey M, Dianti J, Madorno M, Roux N, Midley A, Raffo J, Giannasi S, San Roman E, Suarez-Sipmann F, Tusman G. Dead space analysis at different levels of positive end-expiratory pressure in acute respiratory distress syndrome patients. Journal of critical care. 2018 Jun:45():231-238. doi: 10.1016/j.jcrc.2018.01.005. Epub     [PubMed PMID: 29754942]