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PREDICTION OF ARTERIAL PCO2 FROM END-TIDAL PCO2
British Journal of Anaesthesia 1993; 71: 917-922 CORRESPONDENCE
PE' =
/FT
KD ( ]dP/dF+PS
(1)
If V/Q mismatching was zero, doubling VT and reducing the ventilation frequency (such that the constancy of alveolar ventilation was maintained) would have no effect on PS, which would be a constant in equation (1). As VD, and dP/dV are also constant, PE' varies linearly with FT. If the tidal volume is greater than twice the deadspace, PE' > PS. Similarly, if tidal volume is less than twice the deadspace, PS >PE'.
In the following experiment, airway carbon dioxide was measured using a real-time mainstream capnometer (HP 47210A, Hewlett-Packard, Waltham, MA, U.S.A.). Expiratory volume was measured by computerized integration of theflowsignal from a Hewlett—Packard pneumotachograph. These devices were calibrated with a "Haldane" reference gas and large syringe, respectively. For a series of consecutive breaths of increasing volume in a young healthy subject, the difference between true mean alveolar Pco2 and end-tidal Pco2 (PE' C O ! —PSCOj) was plotted against tidal volume, breath by breath (fig. 2).
PA
PE' PA,peak
Expired volume
FIG. 1. Relationship between airway Pco., and expired volume. FD; = deadspace at the beginning of the breath; FD, = deadspace at the end of the breath, Pi' = "trough" value of the oscillation; PE = end-tidal Pco.,; PA,peak = peak expiratory alveolar Pco,. 0.67 0.53
S.
0.4 H
0.27 •
0.13 •
-0.13 0.5
1
2.5
1.5 VT (litre)
FIG. 2. Plot of difference between end-tidal and mean alveolar Pco2 (PE'CQJ —PA COJ ) as a function of tidal volume ( F T ) . Regression equation: (PE' COS - PA COI ) = 2.03 F T - 0 . 8 2 ; r = 0.987; P < 0.0001. Regression coefficient = 2.03; P = 0.000.
From this plot it can be seen that the end-tidal-mean alveolar discrepancy increases linearly with tidal volume. The intercept of the regression line on the x axis is 2FD (0.4 litre) and the slope of the regression line is (dP/dF)/2. dP/dV was seen to be constant within breaths, and between breaths (P < 0.0001) for a particular individual. However, because dP/dV is related to certain properties of an individual's "flow—volume loop", it shows a greater inter-individual variation and is likely to be greater in patients with obstructive airways disease, in whom an increase in tidal volume might produce a greater increase in (PE'COZ—PSCOj). From this model and these data, it seems that any change in PE' COJ in response to a change in ventilation pattern, in addition to the component proposed by Fletcher (resulting from interindividual variation in V/Q spread) has a significant component arising from the fact that, by virtue of the ventilatory oscillation of PcOj, PE'CQ, varies with tidal volume in a manner independent of V/Q homogeneity. A. D. FARMERY
Guy's Hospital London
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 13, 2015
PREDICTION OF ARTERIAL Pco2 FROM END-TIDAL Pco2 Sir,—In his abstract [1] Dr Fletcher described a series of experiments to test the hypothesis that the arterial-end-tidal Pco2 difference (PaCO] — PE' C O ! ) during anaesthesia and controlled ventilation can be predicted by what happens to end-tidal Pco2 when the ventilator frequency and tidal volume are changed. Such a prediction is important because the value of (PaCOj — PE' COJ ) is thought to represent the degree of spatial inhomogeneity of ventilation and perfusion {V/Q mismatch). The results of these experiments show that patients with a greater degree of V/Q mismatch, as shown by a greater initial value of (PaCO! —PE' CO! ), displayed a greater increase in PE' COJ when the tidal volume increased and ventilation frequency reduced simultaneously. From these results, the author suggested that patients with an increased (PaCOi — PE'CO8) can be predicted by performing this manoeuvre. In my view, these data should be interpreted more cautiously. First, it is the value of (PaCO! — PSCC,2) rather than (PaCO! —PE'CO,) which more accurately reflects V/Q mismatch, where Paco% = flow-weighted average end-capillary Pco2 and PACOS = ventilation-weighted average alveolar Pco2, of all the alveolar units. Second, it can be shown from a mathematical model, and from experimental data, that at least some change in PE' COJ in response to an alteration in ventilation rate and frequency is expected, even if there is complete homogeneity of ventilation and perfusion. The reduction in PE'COa seen in some patients after this manoeuvre might be explained by the fact that, by doubling the tidal volume and halving the frequency, there is a net increase in alveolar ventilation rate, as the deadspace ventilation rate has been reduced. The increase in PE' C( , 2 in other patients is also explicable to some extent, as follows. It has been appreciated for many years that alveolar and arterial Pco2 vary within the ventilatory cycle [2, 3]. PA CO! increases during expiration, and its time course is exponential [4]. As the decay in flow rate in expiration is also exponential, the value of the differential, dPACOj/dF is constant. This phenomenon is seen when airway Pco2 is plotted against expired volume (fig. 1). In this plot, deadspace at the beginning of the breath (FD,) differs slightly from the deadspace at the end of the breath (Fnr) which has been extrapolated, since FD varies with FT. The "trough" value of the oscillation (Pi') represents alveolar Pco2 at the end of inspiration. Peak expiratory alveolar Pco2 (PA, peak) is constructed by extrapolation of the "plateau". The slope of this plateau (dP/dV) is seen to be constant. Using this model, the mean alveolar Pco2 (PS) can be determined [5]. From the geometry of the above plot, the following equation can be derived:
918 1. Fletcher R. Can one predict arterial Pco2 from end-tidal PcOj? British Journal of Anaesthesia 1993; 71: 316P-317P. 2. Haldane JS, Priestley JG. Regulation of the lung ventilation. Journal of Physiology (London) 1905; 225-266. 3. Band DM, Wolff CB, Ward J, Cochrane GM, Prior J. Respiratory oscillations in arterial carbon dioxide tension as a control signal in exercise. Nature (London) 1980; 283: 84-85. 4. DuBois AB, Britt AG, Fenn WO. Alveolar CO2 during the respiratory cycle. Journal of Applied Physiology 1952; 4: 535-548. 5. Newstead CG, Wolff CB. The mean alveolar carbon dioxide tension in man. Journal of Physiology (London) 1983; 348: 76P.
difference is a better indicator of V/Q spread than (Pa co . — Pz Co,)However, having spent 13 years since the publication of my thesis [6] failing almost totally to get the (to my mind) simpler and more usable concept of alveolar deadspace fraction accepted by the respiratory physiological fraternity, I am not hopeful about publishing anything as advanced as PA COJ ; end-tidal Pco2 is apparently sufficient for most readers. Also, the object of the present paper was to produce an idea which had clinical appeal, and therefore it was logical to use PE' C C V
Dr Farmery states that the "slope of the plateau", is constant. This often appears to be the case, but in my thesis [6] I mentioned two situations in which phase III was concave—that is, the slope increased with VT. severe expiratory obstruction and gross obesity. In the former case, I believe that changes in alveolar Pco2 contribute to the concavity. In conclusion, Dr Farmery is correct to mention a second reason for the increase in PECOi which can be seen in patients with poor lung function; the constraints of the abstract prevented me from making the point there. While cyclical variation in PACOS is of no significance in patients with good lung function, it may be of significance in those with poor function [5]. I have presented evidence that increased Pco 2 compartments are present in patients with increased (PaCOj — PE' COJ ). R. FLETCHER
University of Lund Sweden 1. Fletcher R. Can one predict arterial Pco2 from end-tidal Pco2? British Journal of Anaesthesia 1993; 71: 316-317P. 2. Fletcher R, Jonson B. Deadspace and the single breath test for carbon dioxide. British Journal of Anaesthesia 1984; 56: 109-110. 3. West JB, Fowler KT, Hugh-Jones P, O'Donnell TV. Measurement of the ventilation-perfusion ratio inequality in the lung by the analysis of a single expirate. Clinical Science 1957; 16: 529-545. 4. West JB, Fowler KT, Hugh-Jones P, O'Donnell TV. The measurement of the inequality of ventilation and of perfusion in the lung by the analysis of single expirates. Clinical Science 1957; 16: 549-564. 5. Fletcher R, Jonson B, dimming G, Brew J. The concept of deadspace with special reference to the single breath test for carbon dioxide. British Journal of Anaesthesia 1981; 53: 77-88. 6. Fletcher R. Thesis. The single breath test for carbon dioxide. Lund: University of Lund, 1980.
SUXAMETHONIUM IN DAY-CASE ANAESTHESIA Sir,—I read with interest the paper by Alcock and colleagues [1] on intubation for day-case dental anaesthesia. I was surprised that suxamethonium should still be advocated as the neuromuscular blocking drug of choice for this procedure. The authors quoted rates of postoperative myalgia of up to 85 %, and in their study 74 % of patients reported myalgia and 42 % of these suffered severe pain. Is this really acceptable for a day-case procedure? The use of short-acting, non-depolarizing neuromuscular blocking drugs such as atracurium or vecuronium would allow excellent intubating conditions with no postoperative myalgia [2, 3]. In an unpublished study, I found no postoperative myalgia after vecuronium or atracurium, but 85 % after suxamethonium. I have abandoned the use of suxamethonium in day-case procedures, and I cannot believe that its further use in this situation can be justified. _ _ _ D. P. CARTWRIGHT
Derby City General Hospital Derby 1. Alcock R, Peachey T, Lynch M, McEwan T. Comparison of alfentanil with suxamethonium in facilitating nasotracheal intubation in day-case anaesthesia. British Journal of Anaesthesia 1993; 70: 34-37. 2. Sleigh JW, Matheson KH, Boys JE. The use of atracurium for laparoscopy. Anaesthesia 1984; 39: 277-279. 3. Raynes MA, Chisholme R, Woolmer DF, Gibbs JM. A clinical comparison of atracurium and vecuronium in women
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 13, 2015
Sir,—Thank you for the opportunity to reply to Dr Farmery, whose comments I appreciate. He suggests that my observations on what happens to end-tidal Pco2 when tidal volume is doubled and frequency halved [1] should be more cautiously interpreted. The work was preceeded by a pilot study of 30 patients, which I presented at the Edinburgh Anaesthesia Festival but did not publish because my capnograph and blood-gas analyser had not been calibrated with the same gas. Nevertheless, that series showed qualitatively the same result as the present one. For this reason I can confidently say that, whatever the mechanism involved, patients with large (Pacc,2 — PE' C 0 ! ) values at a ventilatory frequency of 20 b.p.m. do indeed show a considerable increase in PE' C O I when the ventilator setting is changed as above. Patients with small (Pa c0 , — PE' CO! ) values show a decrease in PE' C C V What happens in patients with small V/Q spread? Increasing tidal volume at the same end-expiratory lung volume hardly affects the airway deadspace [2]. Airway deadspace ventilation is thus halved, and so effective ventilation ((FT— FD,) in Dr Farmery's illustration) and alveolar ventilation (the area under the curve) are increased. PE'CO, must therefore be reduced, whilst at the same time more carbon dioxide is excreted. This is particularly true of Dr Farmery's hypothetical patient with zero V/Q spread; but this hypothetical patient has virtually no phase III slope—I have recorded carbon dioxide tracings in many such patients, children and young adults—and no increase in PE'CO2 w a s s e e n o n increasing VT. Cyclical variation in PACC>! cannot be important here. In patients with large (PaCOl — PE' CO! ) values—that is, those with large V/Q spread, changing the ventilator setting as above causes PB'CO, t 0 increase by 0.2-0.4 kPa. My explanation, that poorly ventilated, small V/Q alveoli particularly benefit from the change in ventilatory pattern, is based largely on the work of West and colleagues [3, 4] and on my own studies [2, 5]. We do not knew for certain if spatial V/Q variation (between units) is more important than temporal (within-units) variation. However, one indication of the relative roles of the two forms of V/Q mismatch is that the alveolar deadspace fraction is greatly reduced when tidal volume is increased and frequency reduced [2]. This would not have been the case had cyclical V/Q variation been important at large tidal volumes. The most striking increases in PE' COI are seen in patients with severe expiratory obstruction—that is, patients with intrinsic PEEP or auto-PEEP. In these, if the ventilator setting is momentarily increased early in expiration, extending expiratory time but not inspiratory volume for that breath, PE' COJ increases and the volume of carbon dioxide in that breath is greatly increased. This suggests that a significant volume of increased Pco 2 compartments were present at the old ventilator setting, but that they were poorly ventilated so that their contributions did not reach the airway opening. (I showed tracings from such a patient when I presented the paper.) A second time line of proof, obtained from the patients demonstrated in paper [2] is that those patients who show the greatest change in (Pa COi —PE' COI ) when the ventilator is changed are those with the greatest deadspace. Therefore I believe that, in such patients, spatial variation in V/Q is important. However, Brew's mathematical model of changes in alveolar carbon dioxide partial pressure during passive ventilation [5] shows that alveolar PA COJ does in fact increase more steeply in lungs with increased time constants. To extend West's work: the alveoli that empty last have two reasons to have the greatest Pco2. Dr Farmery's experiments confirm the theory put forward previously on the effects of tidal volume on the difference between mean alveolar Pco2 (PACOI) and Pe'COt [5]. I take the point that this
BRITISH JOURNAL OF ANAESTHESIA
PE' =
/FT
KD ( ]dP/dF+PS
(1)
If V/Q mismatching was zero, doubling VT and reducing the ventilation frequency (such that the constancy of alveolar ventilation was maintained) would have no effect on PS, which would be a constant in equation (1). As VD, and dP/dV are also constant, PE' varies linearly with FT. If the tidal volume is greater than twice the deadspace, PE' > PS. Similarly, if tidal volume is less than twice the deadspace, PS >PE'.
In the following experiment, airway carbon dioxide was measured using a real-time mainstream capnometer (HP 47210A, Hewlett-Packard, Waltham, MA, U.S.A.). Expiratory volume was measured by computerized integration of theflowsignal from a Hewlett—Packard pneumotachograph. These devices were calibrated with a "Haldane" reference gas and large syringe, respectively. For a series of consecutive breaths of increasing volume in a young healthy subject, the difference between true mean alveolar Pco2 and end-tidal Pco2 (PE' C O ! —PSCOj) was plotted against tidal volume, breath by breath (fig. 2).
PA
PE' PA,peak
Expired volume
FIG. 1. Relationship between airway Pco., and expired volume. FD; = deadspace at the beginning of the breath; FD, = deadspace at the end of the breath, Pi' = "trough" value of the oscillation; PE = end-tidal Pco.,; PA,peak = peak expiratory alveolar Pco,. 0.67 0.53
S.
0.4 H
0.27 •
0.13 •
-0.13 0.5
1
2.5
1.5 VT (litre)
FIG. 2. Plot of difference between end-tidal and mean alveolar Pco2 (PE'CQJ —PA COJ ) as a function of tidal volume ( F T ) . Regression equation: (PE' COS - PA COI ) = 2.03 F T - 0 . 8 2 ; r = 0.987; P < 0.0001. Regression coefficient = 2.03; P = 0.000.
From this plot it can be seen that the end-tidal-mean alveolar discrepancy increases linearly with tidal volume. The intercept of the regression line on the x axis is 2FD (0.4 litre) and the slope of the regression line is (dP/dF)/2. dP/dV was seen to be constant within breaths, and between breaths (P < 0.0001) for a particular individual. However, because dP/dV is related to certain properties of an individual's "flow—volume loop", it shows a greater inter-individual variation and is likely to be greater in patients with obstructive airways disease, in whom an increase in tidal volume might produce a greater increase in (PE'COZ—PSCOj). From this model and these data, it seems that any change in PE' COJ in response to a change in ventilation pattern, in addition to the component proposed by Fletcher (resulting from interindividual variation in V/Q spread) has a significant component arising from the fact that, by virtue of the ventilatory oscillation of PcOj, PE'CQ, varies with tidal volume in a manner independent of V/Q homogeneity. A. D. FARMERY
Guy's Hospital London
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 13, 2015
PREDICTION OF ARTERIAL Pco2 FROM END-TIDAL Pco2 Sir,—In his abstract [1] Dr Fletcher described a series of experiments to test the hypothesis that the arterial-end-tidal Pco2 difference (PaCO] — PE' C O ! ) during anaesthesia and controlled ventilation can be predicted by what happens to end-tidal Pco2 when the ventilator frequency and tidal volume are changed. Such a prediction is important because the value of (PaCOj — PE' COJ ) is thought to represent the degree of spatial inhomogeneity of ventilation and perfusion {V/Q mismatch). The results of these experiments show that patients with a greater degree of V/Q mismatch, as shown by a greater initial value of (PaCO! —PE' CO! ), displayed a greater increase in PE' COJ when the tidal volume increased and ventilation frequency reduced simultaneously. From these results, the author suggested that patients with an increased (PaCOi — PE'CO8) can be predicted by performing this manoeuvre. In my view, these data should be interpreted more cautiously. First, it is the value of (PaCO! — PSCC,2) rather than (PaCO! —PE'CO,) which more accurately reflects V/Q mismatch, where Paco% = flow-weighted average end-capillary Pco2 and PACOS = ventilation-weighted average alveolar Pco2, of all the alveolar units. Second, it can be shown from a mathematical model, and from experimental data, that at least some change in PE' COJ in response to an alteration in ventilation rate and frequency is expected, even if there is complete homogeneity of ventilation and perfusion. The reduction in PE'COa seen in some patients after this manoeuvre might be explained by the fact that, by doubling the tidal volume and halving the frequency, there is a net increase in alveolar ventilation rate, as the deadspace ventilation rate has been reduced. The increase in PE' C( , 2 in other patients is also explicable to some extent, as follows. It has been appreciated for many years that alveolar and arterial Pco2 vary within the ventilatory cycle [2, 3]. PA CO! increases during expiration, and its time course is exponential [4]. As the decay in flow rate in expiration is also exponential, the value of the differential, dPACOj/dF is constant. This phenomenon is seen when airway Pco2 is plotted against expired volume (fig. 1). In this plot, deadspace at the beginning of the breath (FD,) differs slightly from the deadspace at the end of the breath (Fnr) which has been extrapolated, since FD varies with FT. The "trough" value of the oscillation (Pi') represents alveolar Pco2 at the end of inspiration. Peak expiratory alveolar Pco2 (PA, peak) is constructed by extrapolation of the "plateau". The slope of this plateau (dP/dV) is seen to be constant. Using this model, the mean alveolar Pco2 (PS) can be determined [5]. From the geometry of the above plot, the following equation can be derived:
918 1. Fletcher R. Can one predict arterial Pco2 from end-tidal PcOj? British Journal of Anaesthesia 1993; 71: 316P-317P. 2. Haldane JS, Priestley JG. Regulation of the lung ventilation. Journal of Physiology (London) 1905; 225-266. 3. Band DM, Wolff CB, Ward J, Cochrane GM, Prior J. Respiratory oscillations in arterial carbon dioxide tension as a control signal in exercise. Nature (London) 1980; 283: 84-85. 4. DuBois AB, Britt AG, Fenn WO. Alveolar CO2 during the respiratory cycle. Journal of Applied Physiology 1952; 4: 535-548. 5. Newstead CG, Wolff CB. The mean alveolar carbon dioxide tension in man. Journal of Physiology (London) 1983; 348: 76P.
difference is a better indicator of V/Q spread than (Pa co . — Pz Co,)However, having spent 13 years since the publication of my thesis [6] failing almost totally to get the (to my mind) simpler and more usable concept of alveolar deadspace fraction accepted by the respiratory physiological fraternity, I am not hopeful about publishing anything as advanced as PA COJ ; end-tidal Pco2 is apparently sufficient for most readers. Also, the object of the present paper was to produce an idea which had clinical appeal, and therefore it was logical to use PE' C C V
Dr Farmery states that the "slope of the plateau", is constant. This often appears to be the case, but in my thesis [6] I mentioned two situations in which phase III was concave—that is, the slope increased with VT. severe expiratory obstruction and gross obesity. In the former case, I believe that changes in alveolar Pco2 contribute to the concavity. In conclusion, Dr Farmery is correct to mention a second reason for the increase in PECOi which can be seen in patients with poor lung function; the constraints of the abstract prevented me from making the point there. While cyclical variation in PACOS is of no significance in patients with good lung function, it may be of significance in those with poor function [5]. I have presented evidence that increased Pco 2 compartments are present in patients with increased (PaCOj — PE' COJ ). R. FLETCHER
University of Lund Sweden 1. Fletcher R. Can one predict arterial Pco2 from end-tidal Pco2? British Journal of Anaesthesia 1993; 71: 316-317P. 2. Fletcher R, Jonson B. Deadspace and the single breath test for carbon dioxide. British Journal of Anaesthesia 1984; 56: 109-110. 3. West JB, Fowler KT, Hugh-Jones P, O'Donnell TV. Measurement of the ventilation-perfusion ratio inequality in the lung by the analysis of a single expirate. Clinical Science 1957; 16: 529-545. 4. West JB, Fowler KT, Hugh-Jones P, O'Donnell TV. The measurement of the inequality of ventilation and of perfusion in the lung by the analysis of single expirates. Clinical Science 1957; 16: 549-564. 5. Fletcher R, Jonson B, dimming G, Brew J. The concept of deadspace with special reference to the single breath test for carbon dioxide. British Journal of Anaesthesia 1981; 53: 77-88. 6. Fletcher R. Thesis. The single breath test for carbon dioxide. Lund: University of Lund, 1980.
SUXAMETHONIUM IN DAY-CASE ANAESTHESIA Sir,—I read with interest the paper by Alcock and colleagues [1] on intubation for day-case dental anaesthesia. I was surprised that suxamethonium should still be advocated as the neuromuscular blocking drug of choice for this procedure. The authors quoted rates of postoperative myalgia of up to 85 %, and in their study 74 % of patients reported myalgia and 42 % of these suffered severe pain. Is this really acceptable for a day-case procedure? The use of short-acting, non-depolarizing neuromuscular blocking drugs such as atracurium or vecuronium would allow excellent intubating conditions with no postoperative myalgia [2, 3]. In an unpublished study, I found no postoperative myalgia after vecuronium or atracurium, but 85 % after suxamethonium. I have abandoned the use of suxamethonium in day-case procedures, and I cannot believe that its further use in this situation can be justified. _ _ _ D. P. CARTWRIGHT
Derby City General Hospital Derby 1. Alcock R, Peachey T, Lynch M, McEwan T. Comparison of alfentanil with suxamethonium in facilitating nasotracheal intubation in day-case anaesthesia. British Journal of Anaesthesia 1993; 70: 34-37. 2. Sleigh JW, Matheson KH, Boys JE. The use of atracurium for laparoscopy. Anaesthesia 1984; 39: 277-279. 3. Raynes MA, Chisholme R, Woolmer DF, Gibbs JM. A clinical comparison of atracurium and vecuronium in women
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 13, 2015
Sir,—Thank you for the opportunity to reply to Dr Farmery, whose comments I appreciate. He suggests that my observations on what happens to end-tidal Pco2 when tidal volume is doubled and frequency halved [1] should be more cautiously interpreted. The work was preceeded by a pilot study of 30 patients, which I presented at the Edinburgh Anaesthesia Festival but did not publish because my capnograph and blood-gas analyser had not been calibrated with the same gas. Nevertheless, that series showed qualitatively the same result as the present one. For this reason I can confidently say that, whatever the mechanism involved, patients with large (Pacc,2 — PE' C 0 ! ) values at a ventilatory frequency of 20 b.p.m. do indeed show a considerable increase in PE' C O I when the ventilator setting is changed as above. Patients with small (Pa c0 , — PE' CO! ) values show a decrease in PE' C C V What happens in patients with small V/Q spread? Increasing tidal volume at the same end-expiratory lung volume hardly affects the airway deadspace [2]. Airway deadspace ventilation is thus halved, and so effective ventilation ((FT— FD,) in Dr Farmery's illustration) and alveolar ventilation (the area under the curve) are increased. PE'CO, must therefore be reduced, whilst at the same time more carbon dioxide is excreted. This is particularly true of Dr Farmery's hypothetical patient with zero V/Q spread; but this hypothetical patient has virtually no phase III slope—I have recorded carbon dioxide tracings in many such patients, children and young adults—and no increase in PE'CO2 w a s s e e n o n increasing VT. Cyclical variation in PACC>! cannot be important here. In patients with large (PaCOl — PE' CO! ) values—that is, those with large V/Q spread, changing the ventilator setting as above causes PB'CO, t 0 increase by 0.2-0.4 kPa. My explanation, that poorly ventilated, small V/Q alveoli particularly benefit from the change in ventilatory pattern, is based largely on the work of West and colleagues [3, 4] and on my own studies [2, 5]. We do not knew for certain if spatial V/Q variation (between units) is more important than temporal (within-units) variation. However, one indication of the relative roles of the two forms of V/Q mismatch is that the alveolar deadspace fraction is greatly reduced when tidal volume is increased and frequency reduced [2]. This would not have been the case had cyclical V/Q variation been important at large tidal volumes. The most striking increases in PE' COI are seen in patients with severe expiratory obstruction—that is, patients with intrinsic PEEP or auto-PEEP. In these, if the ventilator setting is momentarily increased early in expiration, extending expiratory time but not inspiratory volume for that breath, PE' COJ increases and the volume of carbon dioxide in that breath is greatly increased. This suggests that a significant volume of increased Pco 2 compartments were present at the old ventilator setting, but that they were poorly ventilated so that their contributions did not reach the airway opening. (I showed tracings from such a patient when I presented the paper.) A second time line of proof, obtained from the patients demonstrated in paper [2] is that those patients who show the greatest change in (Pa COi —PE' COI ) when the ventilator is changed are those with the greatest deadspace. Therefore I believe that, in such patients, spatial variation in V/Q is important. However, Brew's mathematical model of changes in alveolar carbon dioxide partial pressure during passive ventilation [5] shows that alveolar PA COJ does in fact increase more steeply in lungs with increased time constants. To extend West's work: the alveoli that empty last have two reasons to have the greatest Pco2. Dr Farmery's experiments confirm the theory put forward previously on the effects of tidal volume on the difference between mean alveolar Pco2 (PACOI) and Pe'COt [5]. I take the point that this
BRITISH JOURNAL OF ANAESTHESIA