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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 (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 CO2 (PACO2) which can now be determined directly from the capnogram. The value derived from Enghoff’s modification of Bohr’s formula (using Pa CO2 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)

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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
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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 (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 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.

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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 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 Society
DOI: 10.1213/ANE.0b013e318247f6cc

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.7. This volume of gas free of CO2 is mixed with gases that come from ideal units with CO2.6. the NICO (Philips Respironics.11 Therefore.4 Gas exchange will depend on the overall quantitative balance of all these different subpopulations of alveoli. such as minute ventilation (V E).9. The rationale of dead space analysis is to measure the degree of dilution.7. but with V /Q ₃0 but §1) can also be found in mechanically ventilated patients. It is important that certain amounts of high V /Q areas (similar to unit C. or as an absolute volume value contributing to 1 breath known as the physiological dead space (VDphys). The main difference be-tween VCap and time-based capnography is that CO2 raw data are related point by point. as a fraction of a tidal volume (VD/VT).2. ventilation per unit of time. A normally ventilated and perfused alveolus called “ideal” unit (unit B ˙ ˙ ˙ ˙ with a V /Q of 1) can be found between the above extremes.basic understanding of the problem of dead space ventila-tion (Fig. 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). THE TOOL TO MEASURE DEAD SPACE VCaps are generated by specific capnography appara-tuses that measure flow and CO 2 with mainstream or sidestream sensors placed at the airway opening. Wallingford. which is then integrated to obtain volume. ˙ ˙ ˙ ˙ ˙ ˙ but with V /Q ₃1 but §₃) and low V /Q areas (similar to unit A.1.11: ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ VE ₃ V A VD (1) Because dead space units are not perfused. their gas compo-sition is not much different from inspired gases containing no CO 2. The most frequently used clinical VCap device is the COSMO2 Plus and its newest version. Using volume instead of time has the advantage of being able to directly derive volume-based variables . 1). is formed by an effective portion called “alveolar ventilation” (V A) and an ineffective portion called dead space ventilation (V D)6. diluting the latter to decrease expired concentrations of CO2.10 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). not to time but to expiratory flow.6 Dead space can be clinically expressed as an amount of breathing volume per unit of time (V D).12–14 Table 1 describes the main features of V Dphys and its subcomponent. CT).

PETCO2. the pure alveolar gas. PACO2. 10) VDaw Airway. mean alveolar. which are delimited by the airway-alveolar interface (dotted line). The slopes of phases II and III contain important physiological information mainly related to the distribution of ventilation within the lungs7. 2B). and (C) dead space. of gadget connectors. and PE₃CO2 are the end-tidal. respectivel Figure 2. SII and SIII are the lines following the slopes of phase II and III.br. and mixed expired partial pressures of CO2. a tidal volume is divided into an airway dead space (VDaw) and an alveolar tidal volume (VTalv). PACO2. VCap is the breath-wise tidal elimination of CO2 by measuring the area under the curve or VTCO2. Figure 2 shows the main features of VCaps. mean alveolar. respectively (Fig. Table 1. VCap is divided into phases I. VDphys is constituted by the sum of airway (VDaw) and alveolar dead space (VDalv or unit C). (B) an ideal unit. etc.15. 2A). respectively. or From ETT to the airwayseries dead space alveolar interface Any method using Absolute value or VDaw/VT Fowler’s concept VD inst Instrumental or apparatus dead space Any gadget between ETT and Water displacement Included in the calculation of VDaw the Y piece (humidifiers. physiological dead space (VDphys) is filled with air con-taining no CO2 shown as white area. PACO2. and mixed expired partial pres- sures of CO2.) . 7) units C V From airway-alveolar interface Bohr’s and Fowler’s Absolute value. PaCO2. Riley’s model of the lungs and volumetric capnography (VCap). phase II. II. mainstream sensors. B.such as dead space or the amount of CO2 eliminated per tidal breath. During inspiration. According to Fowler’s concept. and PE₃CO2 are defined as end-tidal. and PE₃CO2 are the arterial. anatomical. VCap is the plot of expired carbon dioxide (CO2) on the y-axis versus the expired volume on the x-axis. Volumetric capnography (VCap) and derived variables. It is impor-tant to address here the difference in the slope of phase III Figure 1.br (Fig. Dead Space Components Abbreviation VD phys Name Physiological dead space Alveolar or parallel dead space Limits Measurement Clinical presentation VD alv From ETT to the alveolarBohr’s formula Absolute value or VD/VT capillary membrane of (Eq. and III.16 (Fig. respectively. and phase III. PETCO2. end-tidal. VCap represents the transport of CO2 by convection (Conv) within main airways and by diffusion (Diff) within alveoli. PETCO2. or the portion of tidal volume free of CO2. Adaptation of Riley’s 3-compartment model of the lungs with (A) representing shunt. mean alveolar. and mixed expired partial pressures of CO2. VCap (top) is collected by proper sensors placed at the airway’s opening. The area under the curve in gray is the V TCO2. Dalv/VT or VDalv/VTalv until the alveolar-capillary methodologies membrane of units C together (Eq. A. 2A). representing the CO2 coming from lung units with different rates of ventilation and perfusion. The black dot in phase II is the inflection point of the whole VCap that marks the airwayalveolar interface (Aw-alv). The capnogram is divided into 3 phases: phase I.

VD/VT measured by Bohr’s formula (VDBohr).12 Thus. The absolute volume of dead space.Factors that change it It is affected by factors that change both VDalv and VDaw Increases with high PEEP and/ or VT. PEEP.7. VCap separates the volume of gas that belongs to main airways from the one located within the alveolar compart-ment (Fig. and FRC.lww.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) A simple rearrangement delivers: VD/VT ₃ (FACO2 ˙ FICO2 → VD FICO2) (3) (4) FE₃CO2)/(FACO2 Because inspired gases usually do not contain CO2 (FICO2 ₃ 0). lung hypoperfusion. THE CALCULATION OF DEAD SPACE Following the above reasoning. Be-cause of the exponential passive nature of the expiratory flow. however. bothersome. fast CO2 sensors and pneumotacho-graphs placed at the airway opening allow VCap to be determined on a breath-by-breath basis. FRC ₃ functional residual capacity. 2B).6 Because this technique is time-consuming.16 The recently validated noninvasive determination of P ACO2 from VCap marks a turning point in the monitoring of VDBohr because .8. Decreases with inspiratory pause Its clinical effect depends on the size of gadget and the size of VT applied.org SPECIAL ARTICLE between time-based and volume-based capnography.6 Bohr’s dead space (VDBohr)11 was thus calculated in the following way6. pulmonary hypotension. Decreases with adequate treatment of the above conditions Increases with increased body size.7. Currently. http://links. VT. Very important in pediatric patients ETT ₃ endotracheal tube. dead space must be calcu-lated by considering both gas from Riley’s units C and the gas within the conducting airways. April 2012 • Volume 114 • Number 4 www.com/AA/A363). 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 V Dalv/VTalv ₃ alveolar dead space to alveolar tidal volume ratio. A brief explanation of our systematic analysis of VCap17 can be found in the Online Supplement (see Supplemental Digital Content 1. hypovolemia. This is what Christian Bohr proposed in 1891 using a formula based on the principle of conservation of mass of CO2. 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. and prone to handling errors. is expressed as V Dphys.anesthesia-analgesia. VDaw ₃ airway dead space and VDalv ₃ alveolar dead space. it has never reached broad clinical acceptance and has therefore rarely been applied systematically in mechanically ventilated patients. then the Bohr’s formula can be simplified as: VD/VT ₃ (FACO2 FE₃CO2)/FACO2 (5) In Bohr’s equation. VCap contains all of the information needed to calculate dead space on a breath-by-breath basis. The shallower alveolar slope of time-based capnography may lead to the erroneous assumptions of a relative equivalence of the PACO2 and PETCO2 values. PEEP ₃ positive end-expiratory pressure. VCap shows a steeper alveolar slope than the corre-sponding time-based capnogram because most of the vol-ume is exhaled early during expiration. VDphys ₃ physiological dead space. which is calculated as: VDphys ₃ VDBohr → VT (7) VDBohr was originally obtained noninvasively using a Douglas bag.

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.23 DuBois et al. Experimental and theoretical studies showed that in normal lungs at rest. can be determined from VCap.26 confirmed that the mean PACO2 will correspond to the midpoint of phase III in volume-based but not in time-based capnography. 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. as seen in Figure 3. 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. 3).20. 24. for more details see Online Supplement. the 2 key constituents of Bohr’s formula. which depends on the balance between pulmonary perfusion and VA. 2B.it resolves a key limitation of the past.19 (Fig.17. Breen et al. PACO2 can be determined from VCap as the value located at the midpoint on the slope of phase III within VTalv. By definition.com/AA/A363). PACO2 must be measured within the alveolar compartment. meaning that a heteroge-neous lung is represented by a broad spectrum of PACO2 values. To avoid errors in dead space calculation because of these factors. mean PACO2 can only be determined from expiratory gases because P ICO2 is zero. Because the CO2 sensor is placed at the airway opening. which is then to be eliminated by VA. Therefore. this measurement of PACO2 has been the cause of intense debates. it is imperative to first agree on a standardized method to measure mean PACO2. these tidal swings in alveolar P CO2 are in the order of 2 to 3 mm Hg and 4 to 5 mm Hg during exercise.org Dead Space Measured by Volumetric Capnography . http://links. Thus. Fortunately. before reliable PACO2-dependent calculations such as the one for dead space can be conducted. one intuitive solution is to use the mean PACO2 for a respiratory cycle.24 showed similar mean PACO2 values for inspiration and expiration despite the fluctuation of CO2 during the respiratory cycle (Fig. Later. Below.anesthesia-analgesia.19 This implies that reliable and physiologically meaningful breath-by-breath dead space values can be obtained noninvasively using standard VCap. 868 ANESTHESIA & ANALGESIA ˙ ˙ www. which in VCap is represented by the alveolar tidal volume (VTalv).lww. 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 PE₃CO2. and (2) PACO2 changes cyclically with the respira-tory cycle. In the past. The calculated values differ depending on whether the alveolar sample is obtained at end-inspiration or at end-expiration. The Measurement of PACO2 PACO2 is the mean value of CO2 within the alveolar compartment.25 Fletcher and Jonson7 extended the above concept by sug-gesting that mean P ACO2 could theoretically be measured as the PCO2 value found at the midpoint of phase III of VCap.

Black dots represent the mean PACO2 during both inspi-ration and expiration. 29.35– 40 All of them use Fowler’s original concept to determine the position of the airway-alveolar interface. is located at the end of inspiration at different depths within the lungs. these interfaces move mouthward and reach the gas sensor at different times.9. lead to erroneous values for VDphys. Point c is the highest PCO2 found at the end of expiration. P § 0. 39 and our group17 have published methodologies that show a more stable and robust measurement of VDaw even in deformed capnograms. has on the CO2 residing within the lungs. Point a represents the reinhalation of CO2 at the beginning of inspiration coming from the airways and from instrumental dead spaces.Figure 3. A limit or station-ary interface between these 2 mechanisms of CO2 transport is found in each bronchiole.99. thereby causing the typical wide spread in gas concentrations of phase II.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. which is the result of the dilution by the CO2-free inhaled tidal volume. it is used in Bohr’s equation to calculate VDphys. This is best done following Fowler’s concept. capnograms represent the way CO 2 travels. because of airway asymmetry. Whereas PACO2 is the average value for all ventilated alveoli.19 Additionally.0001).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.12.0001).31 According to theoretical and experimental calculations.10. Thus. thereby increasing the CO2 concentration within these units. Alveolar CO2 during the respiratory cycle and its relation-ship with volumetric capnography. Wolff et al. Pearson correlation between VCO2 from capnograms and MIGET was also ˙ ˙ good (r ₃ 0.17.20).25. 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. 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.19. which. alveolar gas is sampled and PACO2 can be measured directly in capnograms at the middle point of phase III (modified from DuBois et al. During expiration.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.31–34 Several techniques to measure VDaw by means of VCap have been published. Changes in the partial pressure of CO2 within the alveolar compartment during the respiratory cycle are represented by the dotted line. Once the gas in the airway dead space has been washed out during expiration.96. espe-cially under pathological lung conditions.12 The limitations of these methodologies were highlighted by Wolff et al. however. they have more time to equilibrate with the higher CO2 values of the incoming blood. These data show that mean P ACO2 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. it be-comes obvious that . in the past clinicians have replaced the lacking P ACO2 in Bohr’s equation by the surrogates P ETCO2 or arterial PCO2 (PaCO2). its value is higher than the value of PACO2 located at the middle of such slope (Figs.19 A strong correlation between mean PACO2 as measured by VCap and the one calculated by the alveolar air equation (Equation 8) using V CO2 values obtained from the multiple inert gas technique (MIGET) algorithms was found (r ₃ 0. a volume normally free of CO2. 39 and Tang et al.7. the next step is to calculate VDalv as follow: VDalv ₃ 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.30 Because PETCO2 is the value at the very top end of this slope. Once VDphys and VDaw have been obtained sequentially by Bohr’s equation and Fowler’s concept. either by convection within the main airways or by diffusion within the wide cross-sectional areas of the lung periphery29. Using PETCO2 instead of PACO2 in Bohr’s formula will increase the calculated value for V Dphys. 2B and 3). this mean inter-face is found at the midpoint of phase II. These rather theoretical ideas about the true mean value of P ACO2 in VCap have recently been confirmed and validated in an ˙ ˙ experimental model of lung injury for a broad range of V /Q conditions.43 From the above explanation. Point b is the lowest PCO2 found at the end of inspiration. it does not measure any CO2 in the inspired fresh gas (PICO2 ₃ 0). Measurement of PE₃CO2 PE₃CO2 is determined by the dilution effect that the inspired VT. 2B).30 (Fig. To create a feasible approxi-mation of dead space.19 The Calculation of VDaw and VDalv A complete dead space analysis requires a separation of VDphys into the airway and alveolar components. PE₃CO2 is influenced not only by VDalv but also by VDaw and therefore.42 Both of these substitutes. because these lung units have a longer expiratory time constant than the remainder of the alveoli. P § 0. As the CO2 sensor is placed at the airway opening.

PETCO2. hypovolemia. and PE₃CO2 ₃ the arterial. because VDB-E includes information from both the blood and the alveolar gas side. COPD. PACO2. 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. 6 As we already stated above. pneumonia. VDBohr ₃ VD/VT measured by Bohr’s formula. VDaw ₃ airway dead space and VDalv ₃ alveolar dead space.org 869 Figure 4. pulmonary embolism. Wagner 47 highlighted the effect that low V /Q areas have on PaCO2. respectively. PaCO2. By defini-tion. and mixed expired partial pressures of carbon dioxide. of the differ- .anesthesia-analgesia. end-tidal. discontinuous provides information only when arterial blood samples are obtained Idem Bohr’s approach plus all causes of shunt and low ˙ ˙ V/Q: atelectasis. PETCO2. COPD ₃ chronic obstructive pulmonary disease. respectively SPECIAL ARTICLE Table 2. etc. the clinical implications. Only in those healthy patients with flat slopes of phase III will the April 2012 • Volume 114 • Number 4 www. Graphical representation of the ap-proaches of Bohr and Enghoff. Differences Between the Approaches of Bohr and Enghoff Table 2. Following the same line of reasoning. V T ₃ tidal volume. Differences Between the Approaches of Bohr and Enghoff Formula Origin of PACO2 Type of V/Q analyzed ˙ ˙ Bohr’s approach VDBohr ₃ (PACO2 ₃ PE₃CO2)/PACO2 Mean PACO2 as the average PCO2 coming from all lung units ˙ ˙ ˙ ˙ V/Q of ₃ (units C) High V/Q ₃1 but §₃ Enghoff’s approach VDB-E ₃ (PaCO2 ₃ PE₃CO2)/PaCO2 PaCO2 replaces PACO2 following Riley’s concept of an ideal lung ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ V/Q of ₃ (units C) High V/Q ₃1 but §₃ V/Q of 0 (unit A) Low V/Q §1 but ₃0 Type of measurement Physiological factors having an influence on parameter Noninvasive. V /Q ₃ ventilation/perfusion ratio. breath by breath Alveolar overdistension by excessive PEEP and/ or VT. ˙ ˙ ˙ ˙ COMMON MISCONCEPTIONS ABOUT DEAD SPACE Having introduced the rationale for a meaningful dead space analysis. and PACO2 are the arterial. continuous. asthma. however.using PETCO2 in Bohr’s formula will systematically overestimate VDphys in sicker lungs. and mean alveolar partial pressures of carbon dioxide. we discuss below the main misconceptions and misunderstandings around the topic. mean alveolar. 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. 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. ˙ ˙ used the term apparent dead space. end-tidal. it must not be called dead space (Table 2). PEEP ₃ positive end-expiratory pressure. pulmonary hypotension Invasive. Although these differences seem to be nothing more than simple semantic problems.

the concept of alveolar dead space was ignored and VDBohr was thought to be related only to the anatomical dead space measured in cadavers. 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. 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. 12. 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. These results confirm that. for clinical purposes. 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. making it impossible to differ-entiate high V /Q from pure dead space areas. 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.11 Hence he concluded. it would not be plausible to confuse VDaw with VDBohr neither from a theoretical nor from a clinical point of view. Therefore. no matter which one of these V /Q mismatches prevails.31. Following this reasoning. VDBohr comprises a true VDalv component and VDphys is not underestimated by this formula.12 Fowler’s concept determines VDaw.lww. First. http://links. Ever since the work of Haldane and Priestley 48 in the first years of the next century.33 Bohr’s formula. In other words. measures VDphys based on the dilution effect of inspired gases on CO2 of the entire tidal breath.com/AA/A363. 5). similar to many other researchers.0025 and limits of agreement between ₃0. provided the latter was corrected for shunt effects using the formula described by Kuwabara and Duncalf49 as follow: PvCO2 VD/VT ₃ PvCO2 ₃ PaCO2 ↨ PaCO2 PE₃C O2 ˙ ˙ ₃ PvCO2 1 Qs/Qt 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. Con-sequently. both V /Q mismatches have a similar diminishing effect on CO2 clearance and can thus be considered part of the same problem.4 Using VCap and Bohr’s formula. the question arises what VDBohr really is. The following facts support this point of view.0425 (Fig.6. Because Fletcher and others used the ideal PACO2 in their dead space calculations. It was postulated that this effect is caused by the intermediate solubility of CO 2 in blood. by removing the effects of venous admixture from Enghoff’s formula. ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ ˙ Does Bohr’s Original Formula Measure VDalv or VDphys? Until the end of the 19th century. We hypothesized that Vphys obtained by Bohr’s formula would be the same as the one obtained using Enghoff’s approach. The answer to this key question can be found in the definition of PACO2.18 From the physiological point of view. Thus. The corresponding Bland-Altman plot showed a mean bias of 0. Therefore. Third. to provide even stronger support for this point of view. however. Second. V Dphys becomes similar to the one obtained by Bohr’s original equation.0001) between VDBohr and the corrected VDB-E. using the Bohr-Enghoff formula. we understand that these pioneers erroneously thought that V DBohr underestimated VDphys.ences between VDBohr and VDB-E may be enormous (see below).0375 and 0.93 (P § 0. making use of phase II and thus detects the gas interface that marks the limit between conducting and gas-exchanging airways (Fig. Issues Related to the Calculation of VA . that VDBohr had limited clinical value because it was not adequately representing the V Dalv component. they overestimated VDphys because of the inadvertent addition of a fictitious VDalv from other sources. Today. 2B). alveolar gas could be clearly differentiated from the one within the VDaw. VDBohr was considered neither representative of VDaw nor of VDphys.6.19 Thus. Fletcher found that VDBohr was always higher than VDaw but lower than VDphys.14. Correcting our experimental data this way revealed a Pearson correlation of r2 ₃ 0. it seems legitimate to assume that dead space and high V /Q are the same thing. we found in 70 anesthe-tized patients with healthy lungs that VDalv constituted approximately one-third of the VDphys (personal unpub-lished data). using phase III of the capnograms.

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. 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.e. Data were obtained in an experimental model of acute lung injury (n ₃ 12 pigs.11 As has been pointed out above. The formula to calculate VA is a direct derivative of Equation (1)6.” they might want to decrease the level of PEEP while in fact more PEEP is needed to overcome the atelectatic and shunting state.55 or to predict survival in acute respiratory distress syndrome patients.54 to detect lung collapse. Thus. i. in atelectatic lungs where the fictitious V Dalv is increased by high shunt and low V/Q.7. the question of which formula we must use at the bedside deserves an answer. However. Bohr’s formula cannot detect what is happening at the capillary side of the alveolar-capillary membrane. This is the case.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). (A) Pearson correlation and (B) Bland-Altman plot showing the mean bias and limit of agreement between variables. Bohr’s approach is useful to determine the balance between effective and wasted ventilation. If clinicians misinter-pret such a scenario as PEEP-induced lung “overdistension.50 Enghoff’s approach includes a similar but less specific calculation. or embo-lism. 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.52 to guide the weaning process and to predict tracheal extuba-tion.11: ˙ ˙ ˙ VA ₃ V E 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. Enghoff’s approach has important clinical applications: it has been used to diagnose pulmonary embolism. 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. On the one hand. VA is a real volume that can be adjusted on the ventilator whereas the fictitious volume is not. This answer is. What we are trying to convey is the simple fact that true dead space can only be determined by SPECIAL ARTICLE . 53 to adjust PEEP. depending on the clinical problem or disease to be addressed. 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. For example. 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. for example. both.18. 144 data points). 51. pulmonary hypotension.. Was mortality really related to dead space or was it more related to the ˙ ˙ ˙˙ . it can give a false-positive diagnosis of an increment in dead space or type C units. 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.19 Conceptually but also practically. 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). Figure 5.56 Despite these ample publications. Nuckton et al. Bohr’s formula. Therefore. we encourage caution and a critical reappraisal of some of these results. 56 demonstrated that VD/VT obtained by Enghoff’s approach seems to be a predictor of mortality in acute respiratory distress syndrome patients.

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? .

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. ˙ ˙ matching considering both.In future studies. the novel direct determination of P ACO2 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. Enghoff’s approach uses an arterial blood sample and delivers an index of global V/Q ˙˙ V /Q areas). 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. it can easily be applied at the bedside. Contrarily. wasted ventilation and wasted perfusion (shunt plus low . Therefore. Currently. We think it is time to call these important physiological vari-ables by their appropriate names. Following both approaches separately provides the cli-nician with useful complementary information when moni-toring mechanically ventilated patients at the bedside. to avoid misunderstanding using dead space as a descriptor of the output of Enghoff’s formula is no longer justified.