SPECIAL ARTICLE CME

Rationale of Dead Space Measurement by Volumetric Capnography
Gerardo Tusman, MD,* Fernando Suarez Sipmann, MD, PhD,†‡§ and Stephan H. Bohm, MD
Dead space is the portion of a tidal volume that does not participate in gas exchange because it does not get in contact with blood flowing through the pulmonary capillaries. It is commonly calculated using volumetric capnography, the plot of expired carbon dioxide (CO2) versus tidal volume, which is an easy bedside assessment of the inefficiency of a particular ventilatory setting. Today, Bohr’s original dead space can be calculated in an entirely noninvasive and breath-by-breath manner as the mean alveolar partial pressure of CO2 (Paco2) which can now be determined directly from the capnogram. The value derived from Enghoff’s modification of Bohr’s formula (using Paco2 instead of Paco2) is a global index of the inefficiency of gas exchange rather than a true “dead space” because it is influenced by all causes of ventilation/perfusion mismatching, from real dead space to shunt. Therefore, the results obtained by Bohr’s and Enghoff’s formulas have different physiological meanings and clinicians must be conscious of such differences when interpreting patient data. In this article, we describe the rationale of dead space measurements by volumetric capnography and discuss its main clinical implications and the misconceptions surrounding it. (Anesth Analg 2012;114:866 –74)

ulmonary diseases impair gas exchange by inducing ˙ ˙ a ventilation/perfusion (V/Q) mismatch that may require ventilatory support.1–3 Such treatment aims ˙ ˙ to minimize lung areas of low V/Q and shunt but often at ˙ ˙ the expense of increasing the zones of high V/Q and dead 4,5 space. Thus, the way a mechanical ventilator delivers gas during inspiration determines gas exchange. Given the above scenario, detailed monitoring of ventilation should help in adjusting the ventilator settings to an individual patient’s needs. A simple approach to this monitoring is the breath-wise analysis of carbon dioxide (CO2) kinetics applying the concept of dead space or “wasted” ventilation.6,7 The most popular technique for assessing dead space at the bedside is volumetric capnography (VCap) or the representation of expired CO2 over a tidal breath.7,8 In this article, we describe the rationale of dead space measurement by VCap and discuss its main clinical implications and the misconceptions surrounding it.

P

THE CONCEPT OF DEAD SPACE
A simple depiction of lung physiology is provided by Riley’s 3-compartment model that helps in obtaining a
From the *Department of Anesthesiology, Hospital Privado de Comunidad, Mar del Plata, Argentina; †Department of Surgical Sciences, Section of Anesthesiology & Critical Care, Uppsala University, Uppsala, Sweden; ‡Instituto de Investigacion Sanitaria, Fundacion Jimenez Díaz, IIS-FJD, ´ ´ ´ Madrid, Spain; §CIBERES; and Swisstom AG, Landquart, Switzerland. Accepted for publication December 7, 2011. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.anesthesia-analgesia.org). Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Gerardo Tusman, MD, Department of Anesthesiology, Hospital Privado de Comunidad, Mar del Plata, Argentina. Address e-mail to gtusman@hotmail.com. Copyright © 2012 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e318247f6cc

basic understanding of the problem of dead space ventilation (Fig. 1).9,10 This model groups alveoli according to ˙ ˙ their V/Q ratios ranging from a normally perfused but not ˙ ˙ ventilated unit called “shunt” (unit A with a V/Q of 0) to a normally ventilated but not perfused unit called “dead ˙ ˙ space” (unit C with a V/Q of ). A normally ventilated and ˙ ˙ perfused alveolus called “ideal” unit (unit B with a V/Q of 1) can be found between the above extremes. It is important ˙ ˙ that certain amounts of high V/Q areas (similar to unit C, ˙ ˙ ˙ ˙ but with V/Q 1 but ) and low V/Q areas (similar to ˙ ˙ unit A, but with V/Q 0 but 1) can also be found in mechanically ventilated patients.1,2,4 Gas exchange will depend on the overall quantitative balance of all these different subpopulations of alveoli. Dead space is the portion of ventilation that is not participating in gas exchange because it does not come in contact with the pulmonary capillary blood flow.6,7,11 Therefore, ventilation per unit of time, such as minute ˙ ventilation (Ve), is formed by an effective portion called ˙ “alveolar ventilation” (Va) and an ineffective portion called ˙ dead space ventilation (Vd)6,11:

˙ Ve

˙ Va

˙ Vd

(1)

Because dead space units are not perfused, their gas composition is not much different from inspired gases containing no CO2. This volume of gas free of CO2 is mixed with gases that come from ideal units with CO2, diluting the latter to decrease expired concentrations of CO2. The rationale of dead space analysis is to measure the degree of dilution.6 Dead space can be clinically expressed as an amount of breathing volume per unit of time (Vd), as a fraction of a tidal volume (Vd/Vt), or as an absolute volume value contributing to 1 breath known as the physiological dead space (Vdphys). Vdphys is composed of 2 portions: the dead space of the conducting airways (Vdaw) and the one within the alveolar compartment represented by the lung units C (Vdalv).7,12–14 Table 1 describes the main features of Vdphys and its subcomponents.
April 2012 • Volume 114 • Number 4

866

www.anesthesia-analgesia.org

hypovolemia. phase II. respectively. VCap is divided into phases I. PaCO2. FRC functional residual capacity. According to Fowler’s concept. Table 1. Figure 2. and phase III. VT. PETCO2.) patients VDaw VDinst ETT endotracheal tube. VD/VT measured by Bohr’s formula (VDBohr). 10) hypotension. VDaw airway dead space and VDalv alveolar dead space.16 (Fig. and mixed expired partial pressures of CO2. April 2012 • Volume 114 • Number 4 www. PEEP positive end-expiratory pressure. (B) an ideal unit. VDphys is constituted by the sum of airway (VDaw) and alveolar dead space (VDalv or unit C). respectively (Fig. B. respectively. SII and SIII are the lines following the slopes of phase II and III.br (Fig.br. and (C) dead space. end-tidal. Wallingford. PETCO2. and Peco2 are defined as end-tidal. and PECO2 are the arterial. or From ETT to the airwayAny method using Absolute value or Increases with increased body series dead space alveolar interface Fowler’s concept VDaw/VT size. VCap represents the transport of CO2 by convection (Conv) within main airways and by diffusion (Diff) within alveoli. 7) units C Alveolar or parallel From airway-alveolar interface Bohr’s and Fowler’s Absolute value. lung methodologies hypoperfusion.Dead Space Measured by Volumetric Capnography THE TOOL TO MEASURE DEAD SPACE VCaps are generated by specific capnography apparatuses that measure flow and CO2 with mainstream or sidestream sensors placed at the airway opening. and PECO2 are the end-tidal. VDalv/VT Increases with high PEEP and/ or VDalv/VTalv dead space until the alveolar-capillary or VT. pulmonary membrane of units C together (Eq. which is then integrated to obtain volume. Paco2. A.15. the pure alveolar gas. II. Petco2. of gadget calculation of VDaw space size of VT applied.anesthesia-analgesia. a tidal volume is divided into an airway dead space (VDaw) and an alveolar tidal volume (VTalv). not to time but to expiratory flow. mean alveolar. respectively. and mixed expired partial pressures of CO2. mainstream important in pediatric sensors. Riley’s model of the lungs and volumetric capnography (VCap). The slopes of phases II and III contain important physiological information mainly related to the distribution of ventilation within the lungs7. The black dot in phase II is the inflection point of the whole VCap that marks the airway-alveolar interface (Aw-alv). and mixed expired partial pressures of CO2. and III. or the portion of tidal volume free of CO2. The main difference between VCap and time-based capnography is that CO2 raw data are related point by point.org 867 . Dead Space Components Abbreviation Name Physiological dead VDphys space VDalv Limits Measurement Clinical presentation Factors that change it From ETT to the alveolarBohr’s formula Absolute value or VD/VT It is affected by factors that capillary membrane of change both VDalv and VDaw (Eq. PACO2. The area under the curve in gray is the VTCO2. 2B). Dead space values are commonly normalized by tidal volume (VT) to allow comparison among patients with different VT size: VDaw/VT airway dead space to tidal volume ratio and VDalv/VTalv alveolar dead space to alveolar tidal volume ratio. Decreases with adequate treatment of the above conditions Airway. which are delimited by the airway-alveolar interface (dotted line). VCap is the breath-wise tidal elimination of CO2 by measuring the area under the curve or Vtco2. anatomical. PEEP. VCap (top) is collected by proper sensors placed at the airway’s opening. Using volume instead of time has the advantage of being able to directly derive volume-based variables such as dead space or the amount of CO2 eliminated per tidal breath. Very connectors. CT). the NICO (Philips Respironics. 2A). Decreases with inspiratory pause Instrumental or Its clinical effect depends on Any gadget between ETT and Water displacement Included in the apparatus dead the size of gadget and the the Y piece (humidifiers. VCap is the plot of expired carbon dioxide (CO2) on the y-axis versus the expired volume on the x-axis. During inspiration. mean alveolar. 2A). physiological dead space (VDphys) is filled with air containing no CO2 shown as white area. etc. PACO2. Adaptation of Riley’s 3-compartment model of the lungs with (A) representing shunt. representing the CO2 coming from lung units with different rates of ventilation and perfusion. Volumetric capnography (VCap) and derived variables. The most frequently used clinical VCap device is the COSMO2 Plus and its newest version. Figure 2 shows the main features of VCaps. It is important to address here the difference in the slope of phase III Figure 1. The capnogram is divided into 3 phases: phase I. and FRC. VDphys physiological dead space. mean alveolar.

6 Because this technique is time-consuming. In the past. meaning that a heterogeneous lung is represented by a broad spectrum of Paco2 values. http://links. The shallower alveolar slope of time-based capnography may lead to the erroneous assumptions of a relative equivalence of the Paco2 and Petco2 values. fast CO2 sensors and pneumotachographs placed at the airway opening allow VCap to be determined on a breath-by-breath basis. VCap contains all of the information needed to calculate dead space on a breath-by-breath basis. before reliable Paco2-dependent calculations such as the one for dead space can be conducted. 868 www. it is imperative to first agree on a standardized method to measure mean Paco2. To avoid errors in dead space calculation because of these factors. bothersome. Later. Because of the exponential passive nature of the expiratory flow.16 The recently validated noninvasive determination of Paco2 from VCap marks a turning point in the monitoring of VdBohr because where K is a constant and Vco2 is the amount of CO2 delivered to the lungs by the pulmonary circulation. as seen in Figure 3.lww. one intuitive solution is to use the mean Paco2 for a respiratory cycle. Fortunately.org ANESTHESIA & ANALGESIA .19 (Fig. Paco2 can be determined from VCap as the value located at the midpoint on the slope of phase III within Vtalv.17.26 confirmed that the mean Paco2 will correspond to the midpoint of phase III in volumebased but not in time-based capnography. 3). which depends on the balance between pulmonary perfusion and Va.SPECIAL ARTICLE between time-based and volume-based capnography.7. Two factors should be considered when measuring Paco2: (1) Any single lung unit has its own Paco2 depend˙ ˙ ing on its individual V/Q ratio.com/AA/A363). for more details see Online Supplement. By definition.19 This implies that reliable and physiologically meaningful breath-by-breath dead space values can be obtained noninvasively using standard VCap. the precise moment during a breath at which a sample of alveolar CO2 is taken is crucial for the determination of representative dead space values. Thus.23 DuBois et al. the 2 key constituents of Bohr’s formula.20 –22 Therefore. 2B). and prone to handling errors. Currently. is expressed as Vdphys. fractions or partial pressures of CO2 can be used interchangeably: VdBohr or Vd/Vt (Paco2 Peco2)/Paco2 (6) VdBohr constitutes the Vd/Vt ratio representing the dilution of the CO2 concentration by “dead air” stemming from both the main airways and from ventilated but not perfused alveoli. which is calculated as: Vdphys VdBohr Vt (7) VdBohr was originally obtained noninvasively using a Douglas bag.25 Fletcher and Jonson7 extended the above concept by suggesting that mean Paco2 could theoretically be measured as the Pco2 value found at the midpoint of phase III of VCap.lww. mean Paco2 can only be determined from expiratory gases because Pico2 is zero. dead space must be calculated by considering both gas from Riley’s units C and the gas within the conducting airways.24. it resolves a key limitation of the past.20. this measurement of Paco2 has been the cause of intense debates. A brief explanation of our systematic analysis of VCap17 can be found in the Online Supplement (see Supplemental Digital Content 1.24 showed similar mean Paco2 values for inspiration and expiration despite the fluctuation of CO2 during the respiratory cycle (Fig. which in VCap is represented by the alveolar tidal volume (Vtalv). The absolute volume of dead space. Below. Paco2 must be measured within the alveolar compartment. The calculated values differ depending on whether the alveolar sample is obtained at end-inspiration or at end-expiration.com/AA/A363).18: Feco2 ˙ Vt Faco2 ˙ Va Fico2 ˙ Vd (2) Va in Equation 1 can also be expressed as the difference between Vt and Vd: Feco2 ˙ Vt ˙ Faco2(Vt ˙ Vd) Fico2 ˙ Vd (3) A simple rearrangement delivers: Vd/Vt (Faco2 Feco2)/(Faco2 Fico2) (4) Because inspired gases usually do not contain CO2 (Fico2 0).7. The Measurement of PACO2 Paco2 is the mean value of CO2 within the alveolar compartment. http://links. Therefore. it has never reached broad clinical acceptance and has therefore rarely been applied systematically in mechanically ventilated patients. VCap separates the volume of gas that belongs to main airways from the one located within the alveolar compartment (Fig. This is what Christian Bohr proposed in 1891 using a formula based on the principle of conservation of mass of CO2. Because the CO2 sensor is placed at the airway opening. mean Paco2 has been shown to be represented most reliably by an alveolar sample taken shortly after mid-expiration time. we describe how Paco2 and Peco2. 2B. Experimental and theoretical studies showed that in normal lungs at rest.anesthesia-analgesia. which is then to be eliminated by Va. and (2) Paco2 changes cyclically with the respiratory cycle. then the Bohr’s formula can be simplified as: Vd/Vt (Faco2 Feco2)/Faco2 (5) In Bohr’s equation.8.6 Bohr’s dead space (VdBohr)11 was thus calculated in the following way6. these tidal swings in alveolar Pco2 are in the order of 2 to 3 mm Hg and 4 to 5 mm Hg during exercise. however. Breen et al. The classic alveolar air equation describes such relationship as: Paco2 K ˙ Vco2/Va (8) THE CALCULATION OF DEAD SPACE Following the above reasoning. can be determined from VCap.12 Thus. VCap shows a steeper alveolar slope than the corresponding time-based capnogram because most of the volume is exhaled early during expiration.

30 (Fig. Point c is the highest PCO2 found at the end of expiration. is located at the end of inspiration at different depths within the lungs. because of airway asymmetry. Once Vdphys and Vdaw have been obtained sequentially by Bohr’s equation and Fowler’s concept.30 Because Petco2 is the value at the very top end of this slope. alveolar gas is sampled and PACO2 can be measured directly in capnograms at the middle point of phase III (modified from DuBois et al. To create a feasible approximation of dead space. Whereas Paco2 is the average value for all ventilated alveoli.35– 40 All of them use Fowler’s original concept to determine the position of the airwayalveolar interface.19 The Calculation of VDaw and VDalv A complete dead space analysis requires a separation of Vdphys into the airway and alveolar components. best done following Fowler’s concept. has on the CO2 residing within the lungs. it becomes obvious that using Petco2 in Bohr’s formula will systematically overestimate Vdphys in sicker lungs. its value is higher than the value of Paco2 located at the middle of such slope (Figs. they have more time to equilibrate with the higher CO2 values of the incoming blood. these interfaces move mouthward and reach the gas sensor at different times.0001). P 0.12 Fowler described a concept based on the analysis of expired gases (irrespective of the tracer gas used)28 representing the mechanisms of gas transport within lungs. it does not measure any CO2 in the inspired fresh gas (PICO2 0).19. Wolff et al. in the past clinicians have replaced the lacking Paco2 in Bohr’s equation by the surrogates Petco2 or arterial Pco2 (Paco2). These rather theoretical ideas about the true mean value of Paco2 in VCap have recently been confirmed and validated in an experimental model of lung injury for a ˙ ˙ broad range of V/Q conditions. During expiration. a volume normally free of CO2.7.39 and Tang et al. Using Petco2 instead of Paco2 in Bohr’s formula will increase the calculated value for Vdphys. Peco2 is influenced not only by Vdalv but also by Vdaw and therefore. These data show that mean Paco2 can be calculated with accuracy ˙ ˙ even under conditions of high V/Q dispersion and irrespective of the resultant deformations of the shape of the capnogram.96. thereby causing the typical wide spread in gas concentrations of phase II. Changes in the partial pressure of CO2 within the alveolar compartment during the respiratory cycle are represented by the dotted line.17. lead to erroneous values for Vdphys. 2B).31 According to theoretical and experimental calculations. because these lung units have a longer expiratory time constant than the remainder of the alveoli.10.41 Most approaches are based in a geometric calculation and their performances are affected by changes in the shape of VCap as observed in pulmonary diseases.6 Peco2 is measured using VCap as: Peco2 Feco2 barometric pressure (9) This measurement has been validated comparing it against reference values derived either from indirect calorimetry27 or from MIGET.39 and our group17 have published methodologies that show a more stable and robust measurement of Vdaw even in deformed capnograms. however. which.Dead Space Measured by Volumetric Capnography Figure 3. Black dots represent the mean PACO2 during both inspiration and expiration.19 A strong correlation between mean Paco2 as measured by VCap and the one calculated by the alveolar air equation (Equation 8) using Vco2 values obtained from the multiple inert gas technique (MIGET) algorithms was found (r 0.org 869 .20).19 Additionally. Point a represents the reinhalation of CO2 at the beginning of inspiration coming from the airways and from instrumental dead spaces. Pearson correlation between Vco2 from capnograms and MIGET was also good (r 0.12 The limitations of these methodologies were highlighted by Wolff et al.25. P 0.anesthesia-analgesia. thereby increasing the CO2 concentration within these units. Petco2 represents only those alveoli with the highest Pco2 resulting from ventilatory inhomogeneities within the lungs as witnessed by the positive sloping of phase III. which is the result of the dilution by the CO2-free inhaled tidal volume. this mean interface is found at the midpoint of phase II.99. either by convection within the main airways or by diffusion within the wide cross-sectional areas of the lung periphery29. especially under pathological lung conditions. This is April 2012 • Volume 114 • Number 4 www.29. As the CO2 sensor is placed at the airway opening. it is used in Bohr’s equation to calculate Vdphys. Only in those healthy patients with flat slopes of phase III will the Measurement of PECO2 Peco2 is determined by the dilution effect that the inspired Vt.0001). Alveolar CO2 during the respiratory cycle and its relationship with volumetric capnography.42 Both of these substitutes. Point b is the lowest PCO2 found at the end of inspiration. the next step is to calculate Vdalv as follow: Vdalv Vdphys Vdaw (10) How PACO2 Has Been Approximated in the Past The direct measurement of Paco2 by VCap has not been validated until very recently. A limit or stationary interface between these 2 mechanisms of CO2 transport is found in each bronchiole.31–34 Several techniques to measure Vdaw by means of VCap have been published.43 From the above explanation. Thus. 2B and 3).9. Once the gas in the airway dead space has been washed out during expiration. capnograms represent the way CO2 travels. The mean value of these many individual interfaces defines the so-called airway-alveolar interface that allows the differentiation between main airway and the alveolar compartment.12.

Type of measurement Physiological factors having an influence on parameter Noninvasive.45 The VdB-E equation not only measures the real Vdalv but also includes all other causes of venous admixture because it considers arterial blood. Table 2. Using Bohr’s true dead space as a reference. Subsequently. asthma.10 proposed the concept of ideal lungs where Paco2 was considered identical with Paco2 assuming that all lung ˙ ˙ units have a perfect V/Q matching. the clinical implications. end-tidal. Riley and Cournand9.anesthesia-analgesia. however. and mean alveolar partial pressures of carbon dioxide. continuous. PEEP positive end-expiratory pressure. PaCO2. the main drawback of this concept of an ideal lung is that even perfectly healthy lungs are never ideal but always show certain amounts of anatomical shunt and dead space. breath by breath Alveolar overdistension by excessive PEEP and/ or VT. Using Paco2 instead of Paco2 in Bohr’s formula also overestimates the true value of Vdphys. Although these differences seem to be nothing more than simple semantic problems.6 As we already stated above. respectively.org ANESTHESIA & ANALGESIA . PACO2. VT tidal volume.18 This effect is easy to understand in Figure 1: if pulmonary artery blood with its high Pco2 bypasses the lungs via shunt pathways. However. discontinuous provides information only when arterial blood samples are obtained Idem Bohr’s approach plus all causes of shunt and low ˙ ˙ V/Q: atelectasis. 870 www. VdB-E or Vd/Vt (Paco2 Peco2)/Paco2 (11) Any increase in the Bohr-Enghoff value (VdB-E) beyond normal reflects the degree by which a patient’s lung deviates from the assumed ideal condition. mean alveolar. PaCO2.46 called this fictitious type of Vdalv shunt dead space or why Fletcher and Jonson7 Should Values Derived from Enghoff’s Formula Be Called Dead Space? We believe the main source of misconception is the use of the term dead space for the variables derived from Enghoff’s modification of Bohr’s original formula. COPD. use of Petco2 in Bohr’s formula deliver dead space values similar to those where Paco2 is used. Paco2 will exceed that of Paco2. pulmonary embolism. and PACO2 are the arterial. Such deviation has long been thought to be attributable to dead space only. COPD chronic obstructive pulmonary disease. it must not be called dead space (Table 2). By definition. VDaw airway dead space and VDalv alveolar dead space. only Bohr’s formula is measuring true dead space (units C) because it is viewing the dilution of CO2 from only the alveolar side of the alveolar-capillary membrane. Figure 4 shows how venous admixture increases dead space if Enghoff’s approach is used. COMMON MISCONCEPTIONS ABOUT DEAD SPACE Having introduced the rationale for a meaningful dead space analysis. pneumonia.7. etc. V/Q ventilation/perfusion ratio. hypovolemia. Enghoff ingeniously modified Bohr’s equation applying this concept by rewriting the formula as44: used the term apparent dead space. PETCO2. pulmonary hypotension ˙ ˙ VDBohr VD/VT measured by Bohr’s formula. Wagner47 highlighted the effect that low ˙ ˙ V/Q areas have on Paco2. These facts support the idea that VdB-E must be consid˙ ˙ ered an index of global V/Q mismatching rather than a dead space. Following the same line of reasoning.SPECIAL ARTICLE Figure 4. which in turn leads to an overestimation of dead space.4. Graphical representation of the approaches of Bohr and Enghoff. because VdB-E includes information from both the blood and the alveolar gas side. of the differences between VdBohr and VdB-E may be enormous (see below).1. This was the reason why Suter et al. and PECO2 the arterial. endtidal. Differences Between the Approaches of Bohr and Enghoff Formula Origin of PACO2 ˙ ˙ Type of V/Q analyzed Bohr’s approach VDBohr (PACO2 PECO2)/PACO2 Mean PACO2 as the average PCO2 coming from all lung units ˙ ˙ V/Q of (units C) ˙ ˙ High V/Q 1 but Enghoff’s approach VDB-E (PaCO2 PECO2)/PaCO2 PaCO2 replaces PACO2 following Riley’s concept of an ideal lung ˙ ˙ V/Q of (units C) ˙ ˙ High V/Q 1 but ˙ ˙ V/Q of 0 (unit A) ˙ ˙ Low V/Q 1 but 0 Invasive. and mixed expired partial pressures of carbon dioxide. PETCO2. we discuss below the main misconceptions and misunderstandings around the topic. respectively.

by removing the effects of venous admixture from Enghoff’s formula.0375 and 0. What we are trying to convey is the simple fact that true dead space can only be determined by April 2012 • Volume 114 • Number 4 www.12 Fowler’s concept determines Vdaw. The corresponding BlandAltman plot showed a mean bias of 0.6. First. Thus. The answer to this key question can be found in the definition of Paco2. making it impossible to differ˙ ˙ entiate high V/Q from pure dead space areas.anesthesia-analgesia.org 871 .0425 (Fig. http://links.19 Conceptually but also practically. CLINICAL IMPLICATIONS OF THE APPROACHES OF BOHR AND ENGHOFF Table 2 shows the main differences between the formulas of Bohr and Enghoff that are of clinical relevance. Vdphys becomes similar to the one obtained by Bohr’s original equation. using phase III of the capnograms. it seems legitimate to assume that dead space ˙ ˙ and high V/Q are the same thing. data from MIGET calculations showed that the ˙ ˙ zones of dead space and high V/Q develop even in healthy patients undergoing anesthesia or mechanical ventilation.31. Because Fletcher and others used the ideal Paco2 in their dead space calculations. however. using the Bohr-Enghoff formula. we have reanalyzed part of our data from an animal model of acute lung injury and details of this analysis are given in the Online Supplement. Following this reasoning. they overestimated Vdphys because of the inadvertent addition of a fictitious Vdalv from other sources. It was postulated that this effect is caused by the intermediate solubility of CO2 in blood. the calculation of Va suffers from the same problem as dead space whenever the concept of ideal lung is included in the formula.7. In other words. provided the latter was corrected for shunt effects using the formula described by Kuwabara and Duncalf49 as follow: PvCO2 Vd/Vt PvCO2 1 PaCO2 Qs/Qt PECO2 Does Bohr’s Original Formula Measure VDalv or VDphys? Until the end of the 19th century. measures Vdphys based on the dilution effect of inspired gases on CO2 of the entire tidal breath. The intention of this report is to highlight these important differences but not to judge whether Bohr’s equation is better than Enghoff’s or vice versa. we now know that VdBohr measures Vdphys accurately and that VdB-E underestimates Va because of the addition of a shunt-related apparent or fictitious Vdalv. alveolar gas could be clearly differentiated from the one within the Vdaw.0025 and limits of agreement between 0. Second. 2B). Consequently. it would not be plausible to confuse Vdaw with VdBohr neither from a theoretical nor from a clinical point of view. we understand that these pioneers erroneously thought that VdBohr underestimated Vdphys.33 Bohr’s formula.0001) between VdBohr and the corrected VdB-E.Dead Space Measured by Volumetric Capnography Does Bohr’s Formula Measure Only Dead Space? Alveoli with an excess of ventilation relative to perfusion ˙ ˙ (high V/Q areas) generate a Vdalv-like effect and will contribute to the calculation of Vdalv performed by VCap.11: ˙ Va ˙ Ve ˙ Vd (13) Fletcher proposed that Va should be measured by Enghoff’s approach and not by Bohr’s original equation because he postulated that VdBohr underestimated Vdphys. Correcting our experimental data this way revealed a Pearson correlation of r2 0.18. 5). making use of phase II and thus detects the gas interface that marks the limit between conducting and gas-exchanging airways (Fig.com/AA/A363. we found in 70 anesthetized patients with healthy lungs that Vdalv constituted PvCO2 PvCO2 1 PaCO2 Qs/Qt (12) where Pvco2 is the partial pressure of CO2 in mixed venous blood and Qs/Qt the right-to-left shunt.lww.11 As has been pointed out above. Therefore. similar to many other researchers.6. Va is a real volume that can be adjusted on the ventilator whereas the fictitious volume is not.18 From the ˙ ˙ physiological point of view. the question arises what VdBohr really is.12.11 Hence he concluded. Issues Related to the Calculation of VA The opposing twin concept of dead space is the effective part of ventilation within the alveolar compartment that is in close contact with the capillary blood (Va). The following facts support this point of view. VdBohr comprises a true Vdalv component and Vdphys is not underestimated by this formula. no matter which one of ˙ ˙ these V/Q mismatches prevails. VdBohr was considered neither representative of Vdaw nor of Vdphys. that VdBohr had limited clinical value because it was not adequately representing the Vdalv component. These results confirm that. Today. Therefore. approximately one-third of the Vdphys (personal unpublished data). Ever since the work of Haldane and Priestley48 in the first years of the next century. it must be highlighted that the rationales behind the methodologies of both Fowler and Bohr have been clearly described and that the physiological meaning of Vdaw and VdBohr have been clearly differentiated from one another. We hypothesized that Vphys obtained by Bohr’s formula would be the same as the one obtained using Enghoff’s approach. both V/Q mismatches have a similar diminishing effect on CO2 clearance and can thus be considered part of the same problem.19 Thus. to provide even stronger support for this point of view. we firmly believe that VdBohr encompasses a well-defined airway as well as an alveolar component provided that the mean Paco2 is used to calculate it.4 Using VCap and Bohr’s formula. The formula to calculate Va is a direct derivative of Equation (1)6.93 (P 0. for clinical purposes. Third. Fletcher found that VdBohr was always higher than Vdaw but lower than Vdphys. the concept of alveolar dead space was ignored and VdBohr was thought to be related only to the anatomical dead space measured in cadavers.14. Therefore.

If clinicians misinterpret such a scenario as PEEP-induced lung “overdistension.e. for example. Currently.SPECIAL ARTICLE Figure 5. it can easily be applied at the bedside. Although this technique may not be as precise and detailed as the investigational “gold standard” of MIGET.53 to adjust PEEP. Enghoff’s approach has important clinical applications: it has been used to diagnose pulmonary embolism. Conflicts of Interest: Gerardo Tusman is the inventor and applicant of patent EP 04007355. Name: Fernando Suarez Sipmann. to avoid misunderstanding using dead space as a descriptor of the output of Enghoff’s formula is no longer justified. we encourage caution and a critical reappraisal of some of these results. MD. DISCLOSURES Name: Gerardo Tusman. Bohr’s formula cannot detect what is happening at the capillary side of the alveolar-capillary membrane. Following both approaches separately provides the clinician with useful complementary information when monitoring mechanically ventilated patients at the bedside. MD. Data were obtained in an experimental model of acute lung injury (n 12 pigs. both. Relationship between VDBohr and VDB-E corrected for shunt fraction of a tidal volume (VD/VT) measured by Bohr’s formula (VDBohr) versus the one calculated by the Enghoff approach but corrected for the effect of shunt using the formula described by Kuwabara and Duncalf49 (VDB-Ecorr). Contribution: This author helped prepare the manuscript.50 Enghoff’s approach includes a similar but less specific calculation. Thus.56 demonstrated that Vd/Vt obtained by Enghoff’s approach seems to be a predictor of mortality in acute respiratory distress syndrome patients. Contrarily.. i. wasted ventilation and ˙ ˙ wasted perfusion (shunt plus low V/Q areas).54 to detect lung collapse. Therefore.52 to guide the weaning process and to predict tracheal extubation.56 Despite these ample publications. PhD.55 or to predict survival in acute respiratory distress syndrome patients. 144 data points).anesthesia-analgesia. For example. (A) Pearson correlation and (B) Bland-Altman plot showing the mean bias and limit of agreement between variables. CONCLUSIONS ˙ ˙ VCap is clinically useful to monitor the V/Q relationship in mechanically ventilated patients.org ANESTHESIA & ANALGESIA . Contribution: This author helped prepare the manuscript. Nuckton et al. and tables. Enghoff’s approach has a notable clinical advantage because it provides a good idea of the global state of gas exchange from using just one single arterial blood sample.51. figures. it is obvious why Enghoff’s approach is clinically useful because it provides a good ˙ ˙ global estimate of a lung’s state of V/Q. Enghoff’s approach uses an arterial blood sample and delivers an index of global ˙ ˙ V/Q matching considering both. This is the case. It will detect an excess of ventilation caused by large Vt and/or too much positive end-expiratory pressure (PEEP) or at a fixed ventilatory setting a respective deficit in lung perfusion caused by hypovolemia. the novel direct determination of Paco2 by VCap allows the calculation of wasted ventilation (true dead ˙ ˙ space together with areas of high V/Q) using Bohr’s equation on a breath-by-breath basis. Was mortality really related to dead space or was it more related to the amount of shunt? What would happen if we determined true dead space using Bohr’s equation? Can a link between overdistension and mortality be established? In future studies. Therefore. or embolism. We think it is time to call these important physiological variables by their appropriate names. Bohr’s approach is useful to determine the balance between effective and wasted ventilation. This answer is.” they might want to decrease the level of PEEP while in fact more PEEP is needed to overcome the atelectatic and shunting state. in atelectatic lungs where the fictitious Vdalv is ˙ ˙ increased by high shunt and low V/Q.3: non-invasive method and apparatus for optimizing the respiration of atelectatic lungs. 872 www. Bohr’s formula. Conflicts of Interest: This author has no conflicts of interest to declare. all of these questions need to be addressed by appropriate methodologies considering that the clinical role of VCap in monitoring lung function is grossly enriched if both Bohr’s and Enghoff’s approaches are used synergistically. depending on the clinical problem or disease to be addressed. On the one hand. However. the question of which formula we must use at the bedside deserves an answer. pulmonary hypotension. it can give a false-positive diagnosis of an increment in dead space or type C units.

MD.36:588 –99 2.12:148 –9 April 2012 • Volume 114 • Number 4 www. Menaldo E. Rodríguez-Nieto MJ. Palm PE. Components of the respiratory dead space and their variation with pressure breathing and with bronchoactive drugs. Langley F. Quintal M. Causes of high physiological dead space in critically ill patients. Gomez DM.and diffusion-dependent ventilation misdistribution in normal subjects. Wolff G. J Physiol 1952.47:847–52 43. Mascia L. Convection. N Engl J Med 1975. Measurement of continuous distributions of ventilation-perfusion ratios: theory. Ventilation-perfusion relationships following experimental pulmonary contusion. Conflicts of Interest: Stephan H. Tusman G. Br J Anaesth 1985. Skand Arch Physiol 1891. J Appl Physiol 1968. Contribution of continuing gas exchange to phase III exhaled PCO2 and PO2 profiles.125:90 –117 24. Colloques Inst Natl Sante Recherche Med 1975. This manuscript was handled by: Steven L. Breen PH. Areta M. J Physiol 1928. Bowes CL. Appl Cardiopul Pathophysiol 1989.98:828 –34 42. Ventilation-perfusion relationships during anaesthesia. Deadspace. Fractal nature of regional ventilation distribution.37:870 – 4 20. J Appl Physiol 2005. Thorax 1994. Cournand A. Ohlsson J. Assessing dead space: a meaningful variable? Minerva Anestesiol 2006.10:335– 48 15. Effect of breathing pattern on gas mixing in a model of asymmetrical alveolar ducts. Brunner JX. J Appl Physiol 1983. Douglas CG. Isserles SA. Contribution: This author helped prepare the manuscript. Comparison of end-tidal PCO2 and average alveolar expired PCO2 during positive end-expiratory pressure. Gronlund J. Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of the lungs: theory. Engel LA. Bohm is the inventor and applicant of patent EP 04007355. Rosboch G. Am J Physiol 1948. Am J Respir Crit Care Med 2007.72:521– 8 19. Horsfield K. Cunningham DJC.22:275–94 33. Harrison BA. J Appl Physiol 2000. Engel LA. Baker AB. nitrogen or helium.103: 895–902 4.org 873 . Paiva M. Volumen inefficax. Br J Anaesth 1981. Turner MJ.154:405–16 13. Suarez Sipmann F.4:77–101 11.Dead Space Measured by Volumetric Capnography Name: Stephan H. Uber die Lungeatmung.5:341–7 36. Climente C. invasive and non-invasive. Fowler WS. Respir Physiol 1985. DuBois AB. Clin Sci (Lond) 1982. Batchinsky AI.292:284 –9 47. Uppsala Lakareforen Forh 1938.anesthesia-analgesia. Prakash O. Jonson B. Kallet RH.47:431– 45 22.175:160 – 6 ¨ 6. Cournand A. Fletcher R. Garcia O. Weibel W. Bowes CL. ¨ Model fitting of volumetric capnograms improves calculations of airway dead space and slope of phase III. The respiratory dead space measured by single breath analysis of oxygen. Shafer. On the fluctuation in the composition of the alveolar air during the respiratory cycle in muscular exercise.62:541–7 39. Bohm SH. Effect of pulmonary perfusion on the slopes of single-breath test of CO2. Cook KM.50:462–7 28.51: ´ 209 –14 37. Breen PH. Glenny RW. Jordan BS. Ranieri VM.62:257–72 23. Bemerkungen zur Frage des schadlichen Raumes. Scandurra A. Hedenstierna G.62:2467–76 44.33:41– 8 29. Corno E. Anatomical and series dead space volume: concept and measurement in clinical praxis. Terragni PP. J Appl Physiol 1985. Bohm SH.52:491– 8 38. Bertschmann W. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Skinner SC. J Appl Physiol 2007. Olsson SG.44:191– ¨ ¨ 218 45. J Appl Physiol 1957. Weiss WB. Cumming G. J Appl Physiol 1951. Ventilatory consequences of unilateral pulmonary artery occlusion. Cancelada DA.57:245–9 12. Muchenberger R. Saltzman HA. Richardson JD. Tealdi A. Clinical studies of gas exchange during ventilatory support: a method using the Siemens-Elema CO2 analyzer. Matthay MA. Dubois AB. Clara F. Briscoe WA.65:389 – 411 26.59:838 – 46 30.72:2029 –35 9. Respiratory dead space. Alveolar CO2 and O2 during breath holding. The carbon dioxide stimulus to breathing in severe exercise. J Appl Physiol 1951. Anesth Analg 1996. Cancio LC. Cumming G. Guyatt AR. Sandhagen B. Gattinoni L.51:723–7 16. Hedenstierna G. Isenberg MD. Cumming G. Optimum end-expiratory airway pressure in patients with acute pulmonary failure. Wagner P. J Clin Monit Comput 2009.8:102–10 14. Slutsky AS. Suarez Sipmann F.23:197–206 18. Mazumdar B. Engel LA. Can J Anaesth 2004. The concept of deadspace with special reference to the single breath test for carbon dioxide. Br J Anaesth 2007. expiration and inspiration. A physico-mathematical study of lung function in normal subjects and in patients with obstructive pulmonary diseases. Pappenheimer IR. J Appl Physiol 1987. Tusman G. Bartels J. Computation of the boundary conditions for diffusion in the human lung.5:1–12 25. Hlastala MP. Nicolas RL. Duroux P. Validation of Bohr dead space measured by volumetric capnography. Melot C. Makowska M. MD. J Appl Physiol 1949. McKinney S. Suter PM. Paiva M. Suarez Sipmann F. Folkow B. REFERENCES 1. Daniel BM. Herrman P. McCarthy G.49:1251– 8 3. J Appl Physiol 1990.58:18 –26 41. J Physiol 1954. J Physiol 1913. Bohr C. Aitken RS. Intensive Care Med 2011.1:825– 47 10. Even P.5:585–95 34. Fletcher R. Wagner PD. J Appl Physiol 1985. Davini O. Accuracy of physiologic dead space measurements in patients with ARDS using volumetric capnography: comparison with the metabolic monitor method. carbon dioxide. Tang Y.82:368 –73 27. Fenn WO. Bannister RG.4:535– 48 21. Alveolar gas mixing efficiency in the human lung. Ventilation-perfusion relationship in acute respiratory failure. Crawford ABH. Tusman G. Lindhard J. Riley RL.2:236 – 8 7. Clack-Kennedy AE. The respiratory dead space. J Appl Physiol 1955. Systematic errors and susceptibility to noise of four methods for calculating anatomical dead space from the CO2 expirogram. II. Roizen MF. On the average composition of the alveolar air and its variations during the respiratory cycle. Turchetto E. Lung function studies. Alveolar CO2 during the respiratory cycle. 99:650 –5 17. Severinghaus JW.3: non-invasive method and apparatus for optimizing the respiration of atelectatic lungs.53:77– 88 8. Horsfield K. Gandini G. Enghoff H. Alveolar ¨ ´ recruitment improves ventilatory efficiency of the lungs during anesthesia. Br J Anaesth 1975. Br J Anaesth 1980. Ideal alveolar air and the analysis of ventilation-perfusion relationships in the lungs. Simple computer measurement of pulmonary VCO2 per breath. Verbank S. Model analysis of intra-acinar gas exchange. Riley RL.2:299 –307 40. J Appl Physiol 1992. Fairley HB. Med Thorac 1965. Dick EJ. The effect of anaesthesia and intermittent positive pressure ventilation with different frequencies on the anatomical and alveolar deadspace. Alveolar deadspace as an index of distribution of blood flow in pulmonary capillaries.50:85–91 5. J Clin Invest 1954. Model simulations of gas mixing and ventilation distribution in the human lung.54:609 –18 35. Severinghaus JW.24:384 –90 32. Krogh A. Hedenstierna G. Swenson ER. Paiva M. Bates DV. Borges JB. Stupfel M. Paiva M. Hedenstierna G. Crit Care 2008. Britt AG. J Appl Physiol 1953. Thorax 1995. Functional consequences of airway morphology. Altemeier WA.69:2269 –79 31. West JB. Respir Care 2005. Hatch T. Fletcher R. Nordstroem L. Jonson B. Comput Biomed Res 1972. Tusman G. Forster RE. Bohm SH. Cumming G. Bohm. Suarez Sipmann F. Plit R.88:1551–7 46. J Appl Physiol 1974. Gas mixing within acinus of the lung.

Am Rev Respir Dis 1986. Alonso JA. Effect of anatomic shunt on physiological dead space o ratio: a new equation. The regulation of the lung-ventilation. Tripp DS.SPECIAL ARTICLE 48. Diagnosis accuracy of a bedside D-dimer assay and alveolar dead space measurement for rapid exclusion of pulmonary embolism: a multicenter study. The dead space to tidal volume ratio in the diagnosis of pulmonary embolism. Kline JA. Thys F.285: 761– 8 52. Tusman G. Craig DM. Haldane JS. Bohm SH. Chest 2004.32:225– 66 49. Tusman G. Reissmann H. Plewa MC. Michelson EA. Verschuren F. Kallet RH. Meliones JN. Portelli DC. Compliance and dead space fraction indicate an optimal level of positive end-expiratory pressure after recruitment in anesthetized patients. Anesth Analg 2008.346:1281– 6 874 www. N Engl J Med 2002. Pittet JF. Priestley JG. Deadspace to tidal volume ratio predicts successful extubation in infants and children. Nuckton TJ. Bohm SH.106:175– 81 56. Roeseler J. Anesthesiology 1969. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. Gentile MA. Hedenstierna G. Coffeng R. Matthay MA. Monitoring dead space during recruitment and PEEP titration in an experimental model. Crit Care Med 2000. Israel EG. Suarez Sipmann F. Daniel BM. Intensive Care Med 2006.28:2034 – 40 54. Reynaert M.133:679 – 85 51. Listro G. Hubble CL. Rutkowski T.32:1863–71 55.org ANESTHESIA & ANALGESIA . Zech F. Meschino G.anesthesia-analgesia. J Physiol 1905. Cheifetz IM. Scandurra A. Maisch S. Burki NK.125:841–50 53. Fuellekrug B. Weismann D. Reissmann H.31:575–7 50. Eisner MD. Duncalf D. O’Neil BJ. Kuwabara S. JAMA 2001. Pech T. Volumetric capnography as a screening test for pulmonary embolism in the emergency department.