SPECIAL ARTICLE

CME

Rationale of Dead Space Measurement by Volumetric CapnographyGerardo 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)

Pulmonary 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 space.4,5 Thus, the way a mechanical ventilator delivers gas during

inspiration determines gas exchange.Given the above scenario, detailed monitoring of ventila-tion should help in adjusting the ventilator settings to an individual

patient’s needs. A simple approach to this moni-toring 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 impli-cations and the misconceptions surrounding it.

THE CONCEPT OF DEAD SPACEA 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 Investigacio´n Sanitaria, Fundacio´n Jime´nez 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 Anesthe-siology, Hospital Privado de Comunidad, Mar del Plata, Argentina. Address e-mail to gtusman@hotmail.com.

Copyright © 2012 International Anesthesia Research SocietyDOI: 10.1213/ANE.0b013e318247f6cc

basic understanding of the problem of dead space ventila-tion (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 ₃). 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

˙ ₃1 but §₃) and low V

˙/Q

˙ areas (similar to unit A, but with V

˙/Q

˙ ₃0 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 (V˙E), is formed by an effective portion called “alveolar ventilation” (V ˙A) and an ineffective portion called dead space ventilation (V˙D)6,11:

˙ ˙ ˙VE ₃ VA VD (1)

Because dead space units are not perfused, their gas compo-sition is not much different from inspired gases containing no CO 2. 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 (V D), as a fraction of a tidal volume (VD/VT), or as an absolute volume value contributing to 1 breath known as the physiological deadspace (VDphys). VDphys is composed of 2 portions: the dead space of the conducting airways (VDaw) and the one withinthe alveolar compartment represented by the lung units C (VDalv).

7,12–14 Table 1 describes the main features of VDphys and its subcomponent.THE TOOL TO MEASURE DEAD SPACEVCaps are generated by specific capnography appara-tuses that measure flow and CO2 with mainstream or sidestream sensors placed at

the airway opening. The most frequently used clinical VCap device is the COSMO2 Plus and its newest version, the NICO (Philips

Respironics, Wallingford, CT). The main difference be-tween VCap and time-based capnography is that CO2 raw data are related point by point, not to time but to expiratory flow, which is then integrated to obtain volume. 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.

Figure 2 shows the main features of VCaps. VCap is the breath-wise tidal elimination of CO2 by measuring the areaunder the curve or VTCO2,br (Fig. 2A). PETCO2, PACO2, and PE₃CO2 are defined as end-tidal, mean alveolar, and mixedexpired partial pressures of CO2, respectively (Fig. 2B). The capnogram is divided into 3 phases: phase I, or theportion of tidal volume free of CO2; phase II, representing the CO2 coming from lung units with different rates of ventilation and perfusion; and phase III, the pure alveolar gas. The slopes of phases II and III contain important physiological information mainly related to the distribution of ventilation within the lungs7,15,16 (Fig. 2A). It is impor-tant to address here the difference in the slope of phase III

Figure 1. Riley’s model of the lungs and volumetric capnography (VCap). Adaptation of Riley’s 3-compartment model of the lungs with(A) representing shunt, (B) an ideal unit, and (C) dead space. During inspiration, physiological dead space (VDphys) is filled with air con-taining no CO2 shown as white area. VDphys is constituted by the sumof airway (VDaw) and alveolar dead space (VDalv or unit C), which are delimited by the airway-alveolar interface (dotted line). VCap (top) is

collected by proper sensors placed at the airway’s opening. PETCO2, PACO2, and PE₃CO2 are the end-tidal, mean alveolar, and mixed

expired partial pressures of CO2, respectivel

Figure 2. Volumetric capnography (VCap) and derived variables. VCap is the plot of expired carbon dioxide (CO2) on the y-axis versus the expired volume on the x-axis. A, VCap is divided into phases I, II,and III. SII and SIII are the lines following the slopes of phase II and III, respectively. The area under the curve in gray is the V TCO2,br. B, VCap represents the transport of CO2 by convection (Conv) withinmain airways and by diffusion (Diff) within alveoli. The black dot in phase II is the inflection point of the whole VCap that marks the airway-alveolar interface (Aw-alv). According to Fowler’s concept, a tidal volume is divided into an airway dead space (VDaw) and analveolar tidal volume (VTalv). PaCO2, PACO2, PETCO2, and PE₃CO2 are the arterial, mean alveolar, end-tidal, and mixed expired partial pres-sures of CO2, respectively.

Table 1. Dead Space ComponentsAbbreviation Name Limits Measurement Clinical presentation

VDphys Physiological dead From ETT to the alveolar- Bohr’s formula Absolute value or VD/VT

space capillary membrane of (Eq. 7)units C

VDalv Alveolar or parallel From airway-alveolar interface Bohr’s and Fowler’s Absolute value, VDalv/VT

dead space until the alveolar-capillary methodologies or VDalv/VTalv

membrane of units C together (Eq. 10)

VDaw Airway, anatomical, or From ETT to the airway- Any method using Absolute value orseries dead space alveolar interface Fowler’s concept VDaw/VT

VDinst Instrumental or Any gadget between ETT and Water displacement Included in the

apparatus dead the Y piece (humidifiers, of gadget calculation of VDaw

space connectors, mainstreamsensors, etc.)

Factors that change it

It is affected by factors that change both VDalv and VDaw

Increases with high PEEP and/ or VT, hypovolemia, lung hypoperfusion, pulmonary hypotension. Decreases with adequate treatment of the above conditions

Increases with increased body size, VT, PEEP, and FRC. Decreases with inspiratory pauseIts clinical effect depends on the size of gadget and the size of VT applied. Very important in pediatric patients

ETT ₃ endotracheal tube; PEEP ₃ positive end-expiratory pressure; FRC ₃ functional residual capacity; VD/VT measured by Bohr’s formula (VDBohr); VDphys ₃ physiological dead space; VDaw ₃ airway dead space and VDalv ₃ alveolar dead space. Dead space values are commonly normalized by tidal volume (VT) to allow comparison among patients with different VT size: VDaw/VT ₃ airway dead space to tidal volume ratio and VDalv/VTalv ₃ alveolar dead space to alveolar tidal volume ratio.

April 2012 • Volume 114 • Number 4 www.anesthesia-analgesia.org

SPECIAL ARTICLEbetween time-based and volume-based capnography. Be-cause of the exponential passive nature of the expiratory flow, VCap shows a steeper alveolar slope than the corre-sponding time-based capnogram because most of the vol-ume is exhaled early during expiration. The shallower alveolar slope of time-based capnography may lead to the erroneous assumptions of a relative equivalence of the PACO2 and PETCO2 values.

VCap separates the volume of gas that belongs to main airways from the one located within the alveolar compart-ment (Fig. 2B).7,12

Thus, VCap contains all of the information needed to calculate dead space on a breath-by-breath basis. A brief explanation of our systematic analysis of VCap17 can be found in the Online Supplement (see Supplemental Digital Content 1, http://links.lww.com/AA/A363).

THE CALCULATION OF DEAD SPACEFollowing the above reasoning, dead space must be calcu-lated by considering both gas from Riley’s units C and the gas within the conducting airways. This is what Christian Bohr proposed in 1891 using a formula based on the principle of conservation of mass of CO2.

6 Bohr’s dead

space (VDBohr)11 was thus calculated in the following way6,18:

˙ ˙ ˙

FE₃CO2 → VT ₃ FACO2 → VA FICO2 → VD (2)VA in Equation 1 can also be expressed as the difference between VT and VD:

˙ ˙ ˙ ˙FE₃CO2 → VT ₃ FACO2(VT VD) FICO2 → VD (3)

A simple rearrangement delivers:

VD/VT ₃ (FACO2 FE₃CO2)/(FACO2 FICO2) (4)

Because inspired gases usually do not contain CO2 (FICO2 ₃ 0), then the Bohr’s formula can be simplified as:

VD/VT ₃ (FACO2 FE₃CO2)/FACO2 (5)

In Bohr’s equation, fractions or partial pressures of CO2 can be used interchangeably:

VDBohr or VD/VT ₃ (PACO2 PE₃CO2)/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. The absolute volume of dead space, however, is expressed as VDphys, which is calculated as:

VDphys ₃ VDBohr → VT (7)

VDBohr was originally obtained noninvasively using a Douglas bag.6 Because this technique is time-consuming, bothersome, and prone to handling errors, it has never reached broad clinical acceptance and has therefore rarely been applied systematically in mechanically ventilated patients. Currently, fast CO2 sensors and pneumotacho-graphs placed at the airway opening allow VCap to be determined on a breath-by-breath basis.7,8,16 The recently validated noninvasive determination of PACO2 from VCap marks a turning point in the monitoring of VDBohr because

it resolves a key limitation of the past.19 This implies that reliable and physiologically meaningful breath-by-breath dead space values can be obtained noninvasively using standard VCap.

Below, we describe how PACO2 and PE₃CO2, the 2 key constituents of Bohr’s formula, can be determined from VCap.

The Measurement of PACO2

PACO2 is the mean value of CO2 within the alveolar compartment, which depends on the balance between pulmonary perfusion and VA. The classic alveolar air equation describes such relationship as:

˙

PACO2 ₃ K → VCO2/VA (8)where K is a constant and VCO2 is the amount of CO2 delivered to the lungs by the pulmonary circulation, which is then to be eliminated by VA.

By definition, PACO2 must be measured within the alveolar compartment, which in VCap is represented bythe alveolar tidal volume (VTalv). Thus, PACO2 can be determined from VCap as the value located at the midpoint on the slope of phase III within VTalv.

17,19

(Fig. 2B; for more details see Online Supplement, http://links.lww.com/AA/A363).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, meaning that a heteroge-neous lung is represented by a broad spectrum of PACO2 values; and (2) PACO2 changes cyclically

with the respira-tory cycle. Experimental and theoretical studies showed that in normal lungs at rest, these tidal swings in alveolar PCO2

are in the order of 2 to 3 mm Hg and 4 to 5 mm Hg during exercise.20 –22 Therefore, 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, as seen in Figure 3. The calculated values differ depending on whether the alveolar sample is obtained at end-inspiration or at end-expiration.

To avoid errors in dead space calculation because of these factors, one intuitive solution is to use the mean PACO2 for a respiratory cycle. Therefore, before reliable PACO2-dependent calculations such as the one for dead space can be conducted, it is imperative to first agree on a standardized method to measure mean PACO2.

In the past, this measurement of PACO2 has been the cause of intense debates.23 DuBois et al.20,24 showed similar mean PACO2 values for inspiration and expiration despite the fluctuation of CO2 during the respiratory cycle (Fig. 3). Because the CO2 sensor is placed at the airway opening, mean PACO2 can only be determined from expiratory gases because PICO2 is zero. Fortunately, mean PACO2 has been shown to be represented most reliably by an alveolar sample taken shortly after mid-expiration time.24,25 Fletcher and Jonson7

extended the above concept by sug-gesting that mean PACO2 could theoretically be measured as the PCO2 value found at the midpoint of phase III of VCap. Later, Breen et al.26 confirmed that the mean PACO2 will correspond to the midpoint of phase III in volume-based but not in time-based capnography.

868 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA

Dead Space Measured by Volumetric Capnography

Figure 3. Alveolar CO2 during the respiratory cycle and its relation-ship with volumetric capnography. Changes in the partial pressure of CO2 within the alveolar compartment during the respiratory cycle are represented by the dotted line. Point a represents the reinhalation of CO2 at the beginning of inspiration coming from the airways and from instrumental dead spaces. Point b is the lowest PCO2 found at the end of inspiration, which is the result of the dilution by the CO2-free inhaled tidal volume. Point c is the highest PCO2 found at the end of expiration. Black dots represent the mean PACO2 during both inspi-ration and expiration. As the CO2 sensor is placed at the airway opening, it does not measure any CO2 in the inspired fresh gas (PICO2 ₃ 0). Once the gas in the airway dead space has been washed out during expiration, alveolar gas is sampled and P ACO2 can be measured directly in capnograms at the middle point of phase III (modified from DuBois et al.20).

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.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 ₃ 0.99, P § 0.0001). Pearson correlation between VCO2 from capnograms and MIGET was also good (r ₃ 0.96, P § 0.0001). These data show that mean PACO2 can be calculated with accuracy even under conditions of high V

˙/Q

˙

dispersion and irre-spective of the resultant deformations of the shape of the capnogram.

Measurement of PE₃CO2

PE₃CO2 is determined by the dilution effect that the inspired VT, a volume normally free of CO2, has on the CO2 residingwithin the lungs. PE₃CO2 is influenced not only by VDalv but also by VDaw and therefore, it is used in Bohr’s equation tocalculate VDphys.

6 PE₃CO2 is measured using VCap as:

PE₃CO2 ₃ FE₃CO2 → barometric pressure (9)

This measurement has been validated comparing it against reference values derived either from indirect calo-rimetry27 or from MIGET.19

The Calculation of VDaw and VDalv

A complete dead space analysis requires a separation of VDphys into the airway and alveolar components. This is

best done following Fowler’s concept.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. Thus, capnograms represent the way CO2 travels, either by

convection within the main airways or by diffusion within the wide cross-sectional areas of the lung periphery29,30 (Fig. 2B). A limit or

station-ary interface between these 2 mechanisms of CO2 transport is found in each bronchiole, which, because of airway asymmetry, is located at the end of inspiration at different depths within the lungs. During expiration, these interfaces move mouthward and reach the gas sensor at different times, thereby causing the typical wide spread in gas concentrations of phase II. The mean value of these many individual interfaces defines the so-called airway-alveolar interface that allows the differentiation between main air-way and the alveolar compartment.12,17,31 According to theoretical and experimental calculations, this mean inter-face is found at the midpoint of

phase II.31–34

Several techniques to measure VDaw by means of VCap have been published.7,19,25,35– 40 All of them use Fowler’s original concept

to determine the position of the airway-alveolar interface.12 The limitations of these methodologies were highlighted by Wolff et al.39

and Tang et al.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. Wolff et al.39 and our group17 have published methodologies that show a more stable and

robust measurement of VDaw even in deformed capnograms.

Once VDphys and VDaw have been obtained sequentially by Bohr’s equation and Fowler’s concept, the next step is tocalculate VDalv as follow:

VDalv ₃ VDphys VDaw (10)

How PACO2 Has Been Approximated in the PastThe direct measurement of PACO2 by VCap has not been validated until very recently. To create a feasible approxi-mation of dead space, in the past clinicians have replaced the lacking PACO2 in Bohr’s equation by the surrogates PETCO2 or arterial PCO2 (PaCO2).

9,10,42

Both of these substi-tutes, however, lead to erroneous values for VDphys, espe-cially under pathological lung conditions.

Using PETCO2 instead of PACO2 in Bohr’s formula will increase the calculated value for VDphys. Whereas PACO2 is the average value for all ventilated alveoli, PETCO2 repre-sents only those alveoli with the highest PCO2 resulting from ventilatory inhomogeneities within the lungs as wit-nessed by the positive sloping of phase III.29,30 Because PETCO2 is the value at the very top end of this slope, its value is higher than the value of PACO2 located at the middle of such slope (Figs. 2B and 3).19 Additionally, because these lung units have a longer expiratory time constant than the remainder of the alveoli, they have more time to equilibrate with the higher CO2 values of the incoming blood, thereby increasing the CO2 concentration within these units.43 From the above explanation, it be-comes obvious that using PETCO2 in Bohr’s formula will systematically overestimate VDphys in sicker lungs. Only in those healthy patients with flat slopes

of phase III will the

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Figure 4. Graphical representation of the ap-proaches of Bohr and Enghoff. VDaw ₃ airway dead space and VDalv ₃ alveolar dead

space. PaCO2, PETCO2, and PACO2 are the arterial, end-tidal, and mean alveolar partial pressures of carbon dioxide, respectively

SPECIAL ARTICLE

Table 2. Differences Between the Approaches of Bohr and EnghoffTable 2. Differences Between the Approaches of Bohr and Enghoff

Bohr’s approach Enghoff’s approach

Formula VDBohr ₃ (PACO2 ₃ PE₃CO2)/PACO2 VDB-E ₃ (PaCO2 ₃ PE₃CO2)/PaCO2

Origin of PACO2 Mean PACO2 as the average PCO2 coming from all PaCO2 replaces PACO2 following Riley’s concept of anlung units ideal lung

˙ ˙ ˙ ˙ ˙ ˙Type of V/Q analyzed V/Q of ₃ (units C) V/Q of ₃ (units C)

˙ ˙ ˙ ˙High V/Q ₃1 but §₃ High V/Q ₃1 but §₃

˙ ˙V/Q of 0 (unit A)

˙ ˙Low V/Q §1 but ₃0

Type of measurement Noninvasive, continuous, breath by breath Invasive, discontinuous provides information only whenarterial blood samples are obtained

Physiological factors having an Alveolar overdistension by excessive PEEP and/ Idem Bohr’s approach plus all causes of shunt and low

influence on parameter or VT, pulmonary embolism, hypovolemia, ˙ ˙V/Q: atelectasis, pneumonia, COPD, asthma, etc.

pulmonary hypotension

VDBohr ₃ VD/VT measured by Bohr’s formula; VT ₃ tidal volume; PEEP ₃ positive end-expiratory pressure; V˙/Q

˙ ₃ ventilation/perfusion ratio; PaCO2, PETCO2,

PACO2, and PE₃CO2 ₃ the arterial, end-tidal, mean alveolar, and mixed expired partial pressures of carbon dioxide, respectively; COPD ₃ chronic obstructive pulmonary disease.

used the term apparent dead space. Following the same line of reasoning, 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.

COMMON MISCONCEPTIONS ABOUT DEAD SPACEHaving introduced the rationale for a meaningful dead space analysis, we discuss below the main misconceptions and misunderstandings around the topic.

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 Eng-hoff’s modification of Bohr’s original formula. By defini-tion, 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.6 As we already stated above, because VDB-E includes infor-mation from both the blood and the alveolar gas side, it must not be called dead space (Table 2). Although these differences seem to be nothing more than simple semantic problems, the clinical implications, however, of the differ-

ences between VDBohr and VDB-E may be enormous (see below).

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. It was postulated that this effect is caused by the intermediate solubility of CO 2 in blood,

making it impossible to differ-entiate high V˙/Q

˙ from pure dead space areas.14,18 From the physiological point of view, both V

˙/Q

˙

mismatches have a similar diminishing effect on CO2 clearance and can thus be considered part of the same problem. Therefore, for

clinical purposes, it seems legitimate to assume that dead space and high V˙/Q

˙ are the same thing, no matter which one of these V

˙/Q

˙

mismatches prevails.

Does Bohr’s Original Formula MeasureVDalv or VDphys?Until the end of the 19th century, the concept of alveolardead space was ignored and VDBohr was thought to be related only to the anatomical dead space measured incadavers. Ever since the work of Haldane and Priestley48 in the first years of the next century, alveolar gas could be clearly differentiated from the one within the VDaw. Con-sequently, using the Bohr-Enghoff formula, Fletcher foundthat VDBohr was always higher than VDaw but lower than VDphys.

11 Hence he concluded, similar to many otherresearchers, that VDBohr had limited clinical value because it was not adequately representing the VDalv component. In other words, VDBohr was considered neither representativeof VDaw nor of VDphys.

Therefore, the question arises what VDBohr really is. The answer to this key question can be found in the definition of PACO2. Because Fletcher and others used the ideal PACO2 in their dead space calculations, they overestimated VDphys because of the inadvertent addition of a fictitious VDalv from other sources. Today, we understand that these pioneers erroneously thought that VDBohr

underestimated VDphys. Following this reasoning, we firmly believe thatVDBohr encompasses a well-defined airway as well as an alveolar component provided that the mean PACO2 is usedto calculate it. The following facts support this point of view.

First, it must be highlighted that the rationales behind the methodologies of both Fowler and Bohr have been clearly described and that the physiological meaning ofVDaw and VDBohr have been clearly differentiated from one another.6,12 Fowler’s concept determines VDaw, making use

of phase II and thus detects the gas interface that marks the limit between conducting and gas-exchanging airways (Fig. 2B). 12,31,33

Bohr’s formula, however, measures VDphys based on the dilution effect of inspired gases on CO2 of the entire tidal breath, using phase

III of the capnograms.6,19 Thus, it would not be plausible to confuse VDaw with VDBohr neither from a theoretical nor from a clinical point of view.

Second, 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.4 Using VCap and Bohr’s formula, we found in 70 anesthe-tized patients with

healthy lungs that VDalv constituted

approximately one-third of the VDphys (personal unpub-lished data).Third, to provide even stronger support for this point of view, 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, http://links.lww.com/AA/A363. We hypothesized thatVphys obtained by Bohr’s formula would be the same as the one obtained using Enghoff’s approach, provided thelatter was corrected for shunt effects using the formula described by Kuwabara and Duncalf49 as follow:

PvCO2 PvCO2 PaCO2

PE₃CO2

VD/VT ₃ ₃ 1 Qs/Qt ↨

₃PvCO2 PaCO2

↨PvCO2

1 Qs/Qt(12)

where Pv₃CO2 is the partial pressure of CO2 in mixed venous blood and Qs/Qt the right-to-left shunt.Correcting our experimental data this way revealed a Pearson correlation of r2 ₃ 0.93 (P § 0.0001) between VDBohr and the corrected

VDB-E. The corresponding Bland-Altman plot showed a mean bias of 0.0025 and limits of agreement between ₃0.0375 and 0.0425 (Fig. 5).

These results confirm that, by removing the effects of venous admixture from Enghoff’s formula, VDphys becomes similar to the one obtained by Bohr’s original equation.Thus, VDBohr comprises a true VDalv component and VDphys is not underestimated by this formula.

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 formula to calculate VA is a direct derivative of Equation (1)6,11:

˙ ˙ ˙VA ₃ VE VD (13)

Fletcher proposed that VA should be measured by Eng-hoff’s approach and not by Bohr’s original equation because he postulated that VDBohr underestimated VDphys.

7,11 As hasbeen pointed out above, we now know that VDBohr mea-sures VDphys accurately and that VDB-E underestimates VA

because of the addition of a shunt-related apparent or fictitious VDalv.18,19 Conceptually but also practically, VA is a real volume that

can be adjusted on the ventilator whereas the fictitious volume is not. Therefore, the calcu-lation of V A suffers from the same problem as dead space whenever the concept of ideal lung is included in the formula.

CLINICAL IMPLICATIONS OF THE APPROACHES OF BOHR AND ENGHOFFTable 2 shows the main differences between the formulas of Bohr and Enghoff that are of clinical relevance. The inten-tion 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. What we are trying to convey is the simple fact that true dead space can only be determined by

SPECIAL ARTICLE

.

Figure 5. 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). (A) Pearson correlation and (B) Bland-Altman plot showing the mean bias and limit of agreement between variables. Data were obtained in an experimental model of acute lung injury (n ₃ 12 pigs, 144 data points).

Bohr’s formula. However, 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

˙. Therefore, the question of which formula we must use at the bedside deserves an answer. This answer is, both,

depending on the clinical problem or disease to be addressed.

On the one hand, Bohr’s approach is useful to determine the balance between effective and wasted ventilation. 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, pulmonary hypotension, or embo-lism.50 Enghoff’s approach includes a similar but less specific calculation, i.e., it can give a false-positive diagnosis of an increment in dead space or type C units. This is the

case, for example, in atelectatic lungs where the fictitious VDalv is increased by high shunt and low V/Q.˙˙

If clinicians misinter-pret such a scenario as PEEP-induced lung “overdistension,” they might want to decrease the level of PEEP while in fact more PEEP is needed to overcome the atelectatic and shunting state.

Bohr’s formula cannot detect what is happening at the capillary side of the alveolar-capillary membrane. Eng-hoff’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. Thus, Enghoff’s approach has important clinical applications: it has been used to diagnose pulmonary embolism,51,52 to guide

the weaning process and to predict tracheal extuba-tion,53 to adjust PEEP,54 to detect lung collapse,55 or to predict survival in acute

respiratory distress syndrome patients.56 Despite these ample publications, we encourage caution and a critical reappraisal of some of

these results. For example, Nuckton et al.56 demonstrated that VD/VT obtained by Enghoff’s approach seems to be a predictor of mortality in acute respiratory distress syndrome patients. 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, 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.

CONCLUSIONS

VCap is clinically useful to monitor the V˙/Q

˙ relationship in mechanically ventilated patients. Although this tech-nique may not be as

precise and detailed as the investi-gational “gold standard” of MIGET, it can easily be applied at the bedside.

Currently, 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. Contrarily, Enghoff’s approach uses an arterial blood

sample and delivers an index of global V/Q˙˙

matching considering both, wasted ventilation and wasted perfusion (shunt plus low

V˙/Q

˙ areas). Therefore, to avoid misunderstanding using dead space as a descriptor of the output of Enghoff’s formula is no longer

justified.Following both approaches separately provides the cli-nician with useful complementary information when moni-toring

mechanically ventilated patients at the bedside. We think it is time to call these important physiological vari-ables by their appropriate names.