# Rationale of Dead Space Measurement by Volumetric Capnography

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 (CO_{2}) 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 CO_{2} (PACO_{2}) which can now be determined directly from the capnogram. The value derived from Enghoff's modification of Bohr's formula (using PaCO_{2} instead of PACO_{2}) 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.

Published ahead of print March 1, 2012 Supplemental Digital Content is available in the text.

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 Investigación Sanitaria, Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain; ^{§}CIBERES; and ^{‖}Swisstom AG, Landquart, Switzerland.

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.

Accepted December 7, 2011

Published ahead of print March 1, 2012

Pulmonary diseases impair gas exchange by inducing a ventilation/perfusion (V[Combining Dot Above]/Q[Combining Dot Above]) mismatch that may require ventilatory support.^{1}^{–}^{3} Such treatment aims to minimize lung areas of low V[Combining Dot Above]/Q[Combining Dot Above] and shunt but often at the expense of increasing the zones of high V[Combining Dot Above]/Q[Combining Dot Above] 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 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 (CO_{2}) 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 CO_{2} 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.

## THE CONCEPT OF DEAD SPACE

A simple depiction of lung physiology is provided by Riley's 3-compartment model that helps in obtaining a basic understanding of the problem of dead space ventilation (Fig. 1).^{9},^{10} This model groups alveoli according to their V[Combining Dot Above]/Q[Combining Dot Above] ratios ranging from a normally perfused but not ventilated unit called “shunt” (unit A with a V[Combining Dot Above]/Q[Combining Dot Above] of 0) to a normally ventilated but not perfused unit called “dead space” (unit C with a V[Combining Dot Above]/Q[Combining Dot Above] of ∞). A normally ventilated and perfused alveolus called “ideal” unit (unit B with a V[Combining Dot Above]/Q[Combining Dot Above] of 1) can be found between the above extremes. It is important that certain amounts of high V[Combining Dot Above]/Q[Combining Dot Above] areas (similar to unit C, but with V[Combining Dot Above]/Q[Combining Dot Above] >1 but <∞) and low V[Combining Dot Above]/Q[Combining Dot Above] areas (similar to unit A, but with V[Combining Dot Above]/Q[Combining Dot Above] >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 (V[Combining Dot Above]E), is formed by an effective portion called “alveolar ventilation” (V[Combining Dot Above]A) and an ineffective portion called dead space ventilation (V[Combining Dot Above]D)^{6},^{11}:

Because dead space units are not perfused, their gas composition is not much different from inspired gases containing no CO_{2}. This volume of gas free of CO_{2} is mixed with gases that come from ideal units with CO_{2}, diluting the latter to decrease expired concentrations of CO_{2}. 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 (VD_{phys}). VD_{phys} is composed of 2 portions: the dead space of the conducting airways (VD_{aw}) and the one within the alveolar compartment represented by the lung units C (VD_{alv}).^{7},^{12}^{–}^{14}Table 1 describes the main features of VD_{phys} and its subcomponents.

## THE TOOL TO MEASURE DEAD SPACE

VCaps are generated by specific capnography apparatuses that measure flow and CO_{2} with mainstream or sidestream sensors placed at the airway opening. The most frequently used clinical VCap device is the COSMO_{2} Plus and its newest version, the NICO (Philips Respironics, Wallingford, CT). The main difference between VCap and time-based capnography is that CO_{2} 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 CO_{2} eliminated per tidal breath.

Figure 2 shows the main features of VCaps. VCap is the breath-wise tidal elimination of CO_{2} by measuring the area under the curve or VTCO_{2,br} (Fig. 2A). PETCO_{2}, PACO_{2}, and PēCO_{2} are defined as end-tidal, mean alveolar, and mixed expired partial pressures of CO_{2}, respectively (Fig. 2B).

The capnogram is divided into 3 phases: phase I, or the portion of tidal volume free of CO_{2}; phase II, representing the CO_{2} 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 lungs^{7},^{15},^{16} (Fig. 2A). It is important to address here the difference in the slope of phase III between time-based and volume-based capnography. Because of the exponential passive nature of the expiratory flow, VCap shows a steeper alveolar slope than the corresponding time-based capnogram because most of the volume 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 PACO_{2} and PETCO_{2} values.

VCap separates the volume of gas that belongs to main airways from the one located within the alveolar compartment (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 VCap^{17} can be found in the Online Supplement (see Supplemental Digital Content 1, http://links.lww.com/AA/A363).

## THE CALCULATION OF DEAD SPACE

Following the above reasoning, dead space must be calculated 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 CO_{2}.^{6} Bohr's dead space (VD_{Bohr})^{11} was thus calculated in the following way^{6},^{18}:

VA in Equation 1 can also be expressed as the difference between VT and VD:

A simple rearrangement delivers:

Because inspired gases usually do not contain CO_{2} (FICO_{2} = 0), then the Bohr's formula can be simplified as:

In Bohr's equation, fractions or partial pressures of CO_{2} can be used interchangeably:

VD_{Bohr} constitutes the VD/VT ratio representing the dilution of the CO_{2} 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 VD_{phys}, which is calculated as:

VD_{Bohr} 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 CO_{2} sensors and pneumotachographs 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 PACO_{2} from VCap marks a turning point in the monitoring of VD_{Bohr} 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 PACO_{2} and PēCO_{2}, the 2 key constituents of Bohr's formula, can be determined from VCap.

### The Measurement of PACO_{2}

PACO_{2} is the mean value of CO_{2} within the alveolar compartment, which depends on the balance between pulmonary perfusion and VA. The classic alveolar air equation describes such relationship as:

where *K* is a constant and VCO_{2} is the amount of CO_{2} delivered to the lungs by the pulmonary circulation, which is then to be eliminated by VA.

By definition, PACO_{2} must be measured within the alveolar compartment, which in VCap is represented by the alveolar tidal volume (VT_{alv}). Thus, PACO_{2} can be determined from VCap as the value located at the midpoint on the slope of phase III within VT_{alv}.^{17},^{19} (Fig. 2B; for more details see Online Supplement, http://links.lww.com/AA/A363).

Two factors should be considered when measuring PACO_{2}: (1) Any single lung unit has its own PACO_{2} depending on its individual V[Combining Dot Above]/Q[Combining Dot Above] ratio, meaning that a heterogeneous lung is represented by a broad spectrum of PACO_{2} values; and (2) PACO_{2} changes cyclically with the respiratory cycle. Experimental and theoretical studies showed that in normal lungs at rest, these tidal swings in alveolar PCO_{2} 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 CO_{2} 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 PACO_{2} for a respiratory cycle. Therefore, before reliable PACO_{2}-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 PACO_{2}.

In the past, this measurement of PACO_{2} has been the cause of intense debates.^{23} DuBois et al.^{20},^{24} showed similar mean PACO_{2} values for inspiration and expiration despite the fluctuation of CO_{2} during the respiratory cycle (Fig. 3). Because the CO_{2} sensor is placed at the airway opening, mean PACO_{2} can only be determined from expiratory gases because PICO_{2} is zero. Fortunately, mean PACO_{2} has been shown to be represented most reliably by an alveolar sample taken shortly after mid-expiration time.^{24},^{25} Fletcher and Jonson^{7} extended the above concept by suggesting that mean PACO_{2} could theoretically be measured as the PCO_{2} value found at the midpoint of phase III of VCap. Later, Breen et al.^{26} confirmed that the mean PACO_{2} will correspond to the midpoint of phase III in volume-based but not in time-based capnography.

These rather theoretical ideas about the true mean value of PACO_{2} in VCap have recently been confirmed and validated in an experimental model of lung injury for a broad range of V[Combining Dot Above]/Q[Combining Dot Above] conditions.^{19} A strong correlation between mean PACO_{2} as measured by VCap and the one calculated by the alveolar air equation (Equation 8) using VCO_{2} values obtained from the multiple inert gas technique (MIGET) algorithms was found (*r* = 0.99, *P* < 0.0001). Pearson correlation between VCO_{2} from capnograms and MIGET was also good (*r* = 0.96, *P* < 0.0001). These data show that mean PACO_{2} can be calculated with accuracy even under conditions of high V[Combining Dot Above]/Q[Combining Dot Above] dispersion and irrespective of the resultant deformations of the shape of the capnogram.

### Measurement of PēCO_{2}

PēCO_{2} is determined by the dilution effect that the inspired VT, a volume normally free of CO_{2}, has on the CO_{2} residing within the lungs. PĒCO_{2} is influenced not only by VD_{alv} but also by VD_{aw} and therefore, it is used in Bohr's equation to calculate VD_{phys.}^{6} PĒCO_{2} is measured using VCap as:

This measurement has been validated comparing it against reference values derived either from indirect calorimetry^{27} or from MIGET.^{19}

### The Calculation of VD_{aw} and VD_{alv}

A complete dead space analysis requires a separation of VD_{phys} 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 CO_{2} travels, either by convection within the main airways or by diffusion within the wide cross-sectional areas of the lung periphery^{29},^{30} (Fig. 2B). A limit or stationary interface between these 2 mechanisms of CO_{2} 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 airway and the alveolar compartment.^{12},^{17},^{31} According to theoretical and experimental calculations, this mean interface is found at the midpoint of phase II.^{31}^{–}^{34}

Several techniques to measure VD_{aw} 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 group^{17} have published methodologies that show a more stable and robust measurement of VD_{aw} even in deformed capnograms.

Once VD_{phys} and VD_{aw} have been obtained sequentially by Bohr's equation and Fowler's concept, the next step is to calculate VD_{alv} as follow:

### How PACO_{2} Has Been Approximated in the Past

The direct measurement of PACO_{2} by VCap has not been validated until very recently. To create a feasible approximation of dead space, in the past clinicians have replaced the lacking PACO_{2} in Bohr's equation by the surrogates PETCO_{2} or arterial PCO_{2} (PaCO_{2}).^{9},^{10},^{42} Both of these substitutes, however, lead to erroneous values for VD_{phys}, especially under pathological lung conditions.

Using PETCO_{2} instead of PACO_{2} in Bohr's formula will increase the calculated value for VD_{phys}. Whereas PACO_{2} is the average value for all ventilated alveoli, PETCO_{2} represents only those alveoli with the highest PCO_{2} resulting from ventilatory inhomogeneities within the lungs as witnessed by the positive sloping of phase III.^{29},^{30} Because PETCO_{2} is the value at the very top end of this slope, its value is higher than the value of PACO_{2} 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 CO_{2} values of the incoming blood, thereby increasing the CO_{2} concentration within these units.^{43} From the above explanation, it becomes obvious that using PETCO_{2} in Bohr's formula will systematically overestimate VD_{phys} in sicker lungs. Only in those healthy patients with flat slopes of phase III will the use of PETCO_{2} in Bohr's formula deliver dead space values similar to those where PACO_{2} is used.

Using PaCO_{2} instead of PACO_{2} in Bohr's formula also overestimates the true value of VD_{phys}. Riley and Cournand^{9},^{10} proposed the concept of ideal lungs where PACO_{2} was considered identical with PaCO_{2} assuming that all lung units have a perfect V[Combining Dot Above]/Q[Combining Dot Above] matching. Subsequently, Enghoff ingeniously modified Bohr's equation applying this concept by rewriting the formula as^{44}:

Any increase in the Bohr-Enghoff value (VD_{B-E}) beyond normal reflects the degree by which a patient's lung deviates from the assumed ideal condition. Such deviation has long been thought to be attributable to dead space only. However, 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.^{1},^{4},^{45} The VD_{B-E} equation not only measures the real VD_{alv} but also includes all other causes of venous admixture because it considers arterial blood.^{7},^{18} This effect is easy to understand in Figure 1: if pulmonary artery blood with its high PCO_{2} bypasses the lungs via shunt pathways, PaCO_{2} will exceed that of PACO_{2}, which in turn leads to an overestimation of dead space. Using Bohr's true dead space as a reference, Figure 4 shows how venous admixture increases dead space if Enghoff's approach is used. This was the reason why Suter et al.^{46} called this fictitious type of VD_{alv} shunt dead space or why Fletcher and Jonson^{7} used the term apparent dead space. Following the same line of reasoning, Wagner^{47} highlighted the effect that low V[Combining Dot Above]/Q[Combining Dot Above] areas have on PaCO_{2}.

These facts support the idea that VD_{B-E} must be considered an index of global V[Combining Dot Above]/Q[Combining Dot Above] mismatching rather than a dead space.

## COMMON MISCONCEPTIONS ABOUT DEAD SPACE

Having 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 Enghoff's modification of Bohr's original formula. By definition, only Bohr's formula is measuring true dead space (units C) because it is viewing the dilution of CO_{2} from only the alveolar side of the alveolar-capillary membrane.^{6} As we already stated above, because VD_{B-E} includes information 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 differences between VD_{Bohr} and VD_{B-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[Combining Dot Above]/Q[Combining Dot Above] areas) generate a VD_{alv}-like effect and will contribute to the calculation of VD_{alv} performed by VCap. It was postulated that this effect is caused by the intermediate solubility of CO_{2} in blood, making it impossible to differentiate high V[Combining Dot Above]/Q[Combining Dot Above] from pure dead space areas.^{14},^{18} From the physiological point of view, both V[Combining Dot Above]/Q[Combining Dot Above] mismatches have a similar diminishing effect on CO_{2} 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[Combining Dot Above]/Q[Combining Dot Above] are the same thing, no matter which one of these V[Combining Dot Above]/Q[Combining Dot Above] mismatches prevails.

### Does Bohr's Original Formula Measure VD_{alv} or VD_{phys}?

Until the end of the 19th century, the concept of alveolar dead space was ignored and VD_{Bohr} was thought to be related only to the anatomical dead space measured in cadavers. Ever since the work of Haldane and Priestley^{48} in the first years of the next century, alveolar gas could be clearly differentiated from the one within the VD_{aw}. Consequently, using the Bohr-Enghoff formula, Fletcher found that VD_{Bohr} was always higher than VD_{aw} but lower than VD_{phys}.^{11} Hence he concluded, similar to many other researchers, that VD_{Bohr} had limited clinical value because it was not adequately representing the VD_{alv} component. In other words, VD_{Bohr} was considered neither representative of VD_{aw} nor of VD_{phys}.

Therefore, the question arises what VD_{Bohr} really is. The answer to this key question can be found in the definition of PACO_{2}. Because Fletcher and others used the ideal PACO_{2} in their dead space calculations, they overestimated VD_{phys} because of the inadvertent addition of a fictitious VD_{alv} from other sources. Today, we understand that these pioneers erroneously thought that VD_{Bohr} underestimated VD_{phys}. Following this reasoning, we firmly believe that VD_{Bohr} encompasses a well-defined airway as well as an alveolar component provided that the mean PACO_{2} is used to 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 of VD_{aw} and VD_{Bohr} have been clearly differentiated from one another.^{6},^{12} Fowler's concept determines VD_{aw}, 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 VD_{phys} based on the dilution effect of inspired gases on CO_{2} of the entire tidal breath, using phase III of the capnograms.^{6},^{19} Thus, it would not be plausible to confuse VD_{aw} with VD_{Bohr} 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[Combining Dot Above]/Q[Combining Dot Above] develop even in healthy patients undergoing anesthesia or mechanical ventilation.^{4} Using VCap and Bohr's formula, we found in 70 anesthetized patients with healthy lungs that VD_{alv} constituted approximately one-third of the VD_{phys} (personal unpublished 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 that V_{phys} obtained by Bohr's formula would be the same as the one obtained using Enghoff's approach, provided the latter was corrected for shunt effects using the formula described by Kuwabara and Duncalf^{49} as follow:

where PV[Combining Macron]CO_{2} is the partial pressure of CO_{2} in mixed venous blood and Qs/Qt the right-to-left shunt.

Correcting our experimental data this way revealed a Pearson correlation of *r*^{2} = 0.93 (*P* < 0.0001) between VD_{Bohr} and the corrected VD_{B-E}. The corresponding Bland-Altman plot showed a mean bias of 0.0025 and limits of agreement between −0.0375 and 0.0425 (Fig. 5).

These results confirm that, by removing the effects of venous admixture from Enghoff's formula, VD_{phys} becomes similar to the one obtained by Bohr's original equation. Thus, VD_{Bohr} comprises a true VD_{alv} component and VD_{phys} 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}:

Fletcher proposed that VA should be measured by Enghoff's approach and not by Bohr's original equation because he postulated that VD_{Bohr} underestimated VD_{phys}.^{7},^{11} As has been pointed out above, we now know that VD_{Bohr} measures VD_{phys} accurately and that VD_{B-E} underestimates VA because of the addition of a shunt-related apparent or fictitious VD_{alv}.^{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 calculation of VA 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 ENGHOFF

Table 2 shows the main differences between the formulas of Bohr and Enghoff that are of clinical relevance. 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. What we are trying to convey is the simple fact that true dead space can only be determined by 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[Combining Dot Above]/Q[Combining Dot Above]. 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 embolism.^{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 VD_{alv} is increased by high shunt and low V[Combining Dot Above]/Q[Combining Dot Above]. If clinicians misinterpret 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. 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. 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 extubation,^{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[Combining Dot Above]/Q[Combining Dot Above] relationship in mechanically ventilated patients. Although this technique may not be as precise and detailed as the investigational “gold standard” of MIGET, it can easily be applied at the bedside.

Currently, the novel direct determination of PACO_{2} by VCap allows the calculation of wasted ventilation (true dead space together with areas of high V[Combining Dot Above]/Q[Combining Dot Above]) 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[Combining Dot Above]/Q[Combining Dot Above] matching considering both, wasted ventilation and wasted perfusion (shunt plus low V[Combining Dot Above]/Q[Combining Dot Above] 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 clinician with useful complementary information when monitoring mechanically ventilated patients at the bedside. We think it is time to call these important physiological variables by their appropriate names.

## DISCLOSURES

**Name:** Gerardo Tusman, MD.

**Contribution:** This author helped prepare the manuscript, figures, and tables.

**Conflicts of Interest:** Gerardo Tusman is the inventor and applicant of patent EP 04007355.3: non-invasive method and apparatus for optimizing the respiration of atelectatic lungs.

**Name:** Fernando Suarez Sipmann, MD, PhD.

**Contribution:** This author helped prepare the manuscript.

**Conflicts of Interest:** This author has no conflicts of interest to declare.

**Name:** Stephan H. Bohm, MD.

**Contribution:** This author helped prepare the manuscript.

**Conflicts of Interest:** Stephan H. Bohm is the inventor and applicant of patent EP 04007355.3: non-invasive method and apparatus for optimizing the respiration of atelectatic lungs.

**This manuscript was handled by:** Steven L. Shafer, MD.

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