Measurement of cardiac output by Alveolar gas exchange - CO 2 -O 2 based methods

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1 Measurement of cardiac output by Alveolar gas exchange - CO 2 -O 2 based methods Carlo Capelli SS.MM. Università degli Studi di Verona

2 Why CO? V O 2 = CO * (C a C v )O 2 It s a determinat of V O 2 It dictates/modulates V O 2 during sub maximal and maximal exercise

3 Alveolar-capillary diffusion Fick law M = S D J s /D x V gas = S D P/D x V O 2 = S D PO 2 /D x D: constant of diffusion D Sol/ MW Diffusion capacity D L = S D /Dx

4 Alveolar-capillary transfer limited by diffusion- CO Limited by diffusion CO affinity of Hb is so high that a negligible fraction of CO remains in solution P cco remains close to 0 increasing very slowly during the transit time P c CO does not attain equilibrium with P A CO and A-to-c pressure gradient does not zero Therefore, only diffusion problems (membrane thickness, smaller area etc. etc.) may obstacle A-c transfer

5 Alveolar Transfer of gases: soluble gases Limited by perfusion. E.g.: N 2 O, (O 2, CO 2 ) N 2 O does not bind to Hb P c N 2 O increases quickly Therefore, P c N 2 O achieves immediately the equilibrium with P A N 2 O Diffusion stops It can go on only if new venous blood without N 2 O enters the lung A-c transfer is proportional to the inflow of blood

6 Alveolar Transfer of gases: O 2 (CO 2 ) The case of oxygen At sea level, in healthy subjects, alveolar-capillary transfer of O 2 is perfusion limited

7 Fick principle and blood flow Most of these methods are based on the principle of Fick It is an application of the principle of conservation of matter It states that the blood flow (Q o ) throughout an organ can be calculated from the concentration of a tracer across the organ provided the rate (R x ) of removal (or addition) is known Q o = R x (C xout C xin )

8 Fick principle and Q Pulmonary capillary blood flow (Q L ) Q L = V x (C ax C vx ) It is the output of the right heart minus right-to-left shunts (anatomical, physiological, pathological) Invasive measurements yields Q T, which includes venous admixtures; However, venous admixture represents < 6% (rest) or <3% (exercise) of Q T

9 Fick principle and Q C ax : it can be assessed from alveolar gas pressure and converted in content knowing solubility constant (inert) or dissociation curves (O 2, CO 2 ). Or it can be measured form arterial blood samples. The crucial step, however, is the determination of C vx Inert soluble gases: it can be assumed equal to 0 before recirculation O 2, CO 2 : we need to know PvO 2 and PvCO 2 from which blood O 2 /CO 2 contents are calculated by means of the corresponding dissociation curves

10 CO 2 dissociation curve-haldane effect If blood is oxygenated without loosing CO 2 (RR = 0), PCO 2 increases If CO 2 is lost without absorbing O 2, RR is infinite If blood is oxygenated without altering PCO 2, 1,6 vol% of CO 2 are lost every 5 vol% of O 2 absorbed: RR= 0.32 Thus when RR = 0.32, P A CO 2 equals P v CO 2 When RR = 0, P A CO 2 equals P v CO 2 of fully oxygenated blood

11 Measurement with CO 2 Advantages It is virtually absent from inspired air Very soluble: end-capillary PCO 2 is almost equivalent to P A CO 2 The slope of the dissociation curve is so steep that non uniformity of P A CO 2 in the lung causes a (P A CO 2 P a O 2 ) so small that the effect of right-to-left shunts can be neglected The slope of the dissociation curve is linear over the physiological range Content is easy to calculate by applying standard dissociation curves provided appropriate Hb concentration, ph value and O 2 saturation are applied

12 Measurement with CO 2 Disadvantages P a CO 2 -P v CO 2 is very small: 1 mm Hg error would affect Q L at rest by % P v CO 2 - P a CO 2 can be increased by 6-8 mm Hg if blood is fully saturated with O 2 Lung tissue contain carbonic anhydrase which buffers alveolar CO 2 fluctuations: about 3 ml CO 2 STPD enters lung tissue when P a CO 2 increases by 1 mm Hg, whereas only 0.45 goes into the blood; ELV for CO 2 is larger than its alveolar volume P a CO 2 P A CO 2 is usually very small. However a difference of only 0.5 mm Hg would lead to a 10 % error in the calculation of Q L P A CO 2 and V CO 2 are very sensitive to changes in V E

13 CO 2 - Breath holding During breath holding with a mixture 100 % O 2, P A CO 2 rises because of rapid oxygenation of Hb and CO 2 production until it tapers of P A CO 2 = P V CO 2 λ CO 2 (P V CO 2 P A CO 2 ) e -KT K= λ CO 2 Q c (P B -47) ELV CO2 It is function of Q L, CO 2 production, ELV P V CO 2 can be measured during breath holding at different intervals after inspiring O 2

14 CO 2 - Breath holding with different P i CO 2 Different levels of P A CO 2 obtained with different P i CO 2 values Rate of change of P A CO 2 ( P A CO 2 / t) depends on P V CO 2 - P A CO 2 It can be obtained and plotted as a function of the average P A CO 2 over the same period P V CO 2 is the value of PCO 2 that satisfy P A CO 2 / t= 0 P V CO 2 refers to oxygenated blood

15 CO 2 - Breath holding Q L can be also calculated The rate of increase of CO 2 in the lung is equal to rate at which CO 2 is lost from the blood, where we assume P A CO 2 = P a CO 2 V A dp A CO 2 /dt = Q λ (P V CO 2 P A CO) dp A CO 2 /dt = (P B 47)/ V A Q L λ (P V CO 2 P A CO) P V CO 2 is constant before recirculation; V A and Q L are assumed constant during the manouvres The reciprocal value of the slope in the diagram P A CO 2 vs. ( P A CO 2 / t) is proportional to Q L

16 CO 2 - Breath holding (dp a CO 2 /dt)/p A CO 2 = (P B - 47)/V A * Q L * λ This method can not be easily accomplished during heavy intensity exercise Only trained, healthy subjects

17 CO 2 Single breath V O2 (R-0.32) Q c = S CO2 (P vco2 P aco2 ) S CO 2 : slope of the CO 2 dissociation curve (0.47 ml 100 ml -1 mm Hg -1 Prolonged expiration in lung without sequential emptying Istantaneous RR can be calculated as the ratio P A CO 2 / P A O 2 The linear relationship between PCO 2 and RR can be extrapolated to 0 to obtain oxygenated mixed venous P V CO 2 Or, for RR = 0.32, interpolation yields mixed venous true P V CO 2 During tidal ventilation this method does not work

18 CO 2 Rebreathing This method uses the closed lung-bag system as aerotonometer to estimate P V CO 2 Then, once obtained P a CO 2, by using one of the several invasive or non invasive methods, and measured V CO 2, we can calculate Q L by applying Fick principle Q L = V CO2 (C vco2 -C aco2 ) Provided we apply the right dissociation curve

19 CO 2 Rebreathing equilibrium value (Collier method) Rebreathing from a 2-4 l bag; 30 breaths/min; 5 % CO 2 at rest; % CO 2 during exercise in O 2 Plateau (less that 0.5 mm Hg PCO 2 during a complete rebreathing cycle begun with inspiration or less than 1 mmhg during at least two cycles A correct plateau appears within 6-8 seconds and breaks after 10 seconds because of recirculation P V CO 2 of oxygenated blood can be estimated to within +/- 0.8 mm Hg

20 CO 2 Rebreathing Extrapolation value If PCO 2 in the bag is greater than end-tidal value, the recording of P A CO 2 has a clear unsustained equilibrium with phase reversal below the equilibrium value After this phase PCO 2 rises toward the equilibrium value In this case, empirical equations have been developed for calculation of P V CO 2 based on inspired CO 2 and en-tidal CO 2

21 CO 2 Rebreathing Interpolation value Equilibrium is delayed beyond 10 s (recirculation) The mean of two end-tidal PCO 2 at 10 seconds between two adjacent breaths if not more that 2% of CO 2 separates the initial bag concentration In this case equilibrium value is within +/- 1 mmhg

22 CO 2 Rebreathing Downstream correction PCO 2 at equilibrium in the bag is higher than arterial PCO 2 after complete equilibrium (measured from tonometry) Lung is shrinking during rebreathing Failure of the process of CO 2 exchange in blood to reach equilibrium within capillary capillaries Jones proposed an empirical correction for calculating the difference in PCO 2 that must be subtracted from oxygenated equilibrium PCO 2 in the bag to obtain right value of PCO 2 CO2 = * V CO 2

23 CO 2 Rebreathing P a CO 2 P a CO 2 is estimated from i) end tidal ii) by applying the Bohr equation iii) estimate depending on workload: P ET CO 2 -P a CO 2 = *V CO breaths/min mm Hg (Jones et al 1966) i) End tidal At least five equations to estimate P a CO 2 from combination of ET pressure/fraction of CO 2, TV, DS i) Bohr equation (DS: physiological and apparatus dead space) P A CO 2 = TV F E CO 2 [(P B P H2 ) (TV DS)] O

24 CO 2 Rebreathing [CO2] Many dissociation curves of CO 2 that express CO 2 content as a function of PCO 2, oxygenation, temperature and ph (McHardy, 1967) Oxygenated or mixed venous blood Need of correction for ph, temperature and oxygenation otherwise we are bound to introduce an error of about 15% in the calculation of [C c -C a ]CO 2 and Q L In summary P V CO 2 estimation with rebreathing is reliable and accurate only during exercise in healthy adults and in absence of pulmonary diseases (sequential emptying) In patients with moderate to severe COPD, rebreathing can be applied with the proviso of measuring P a CO 2 after arterial blood gas analysis (not P ET CO 2!) Q L in literature tends to be low unless the downstream correction fro P V CO 2 is applied

25 One step CO 2 Rebreathing The volume of CO 2 added to alveolar gas measures gas output from the capillary blood only if P A CO 2 is constant If P A CO 2 varies, lung tissue gas stores will readjust and gain CO 2 This amount is equal to the algebraic difference between CO 2 eliminated from the blood and the CO 2 gained by the gas phase This amount can be large enough to produce sizeable errors in method based on CO 2 rebreathing To circumvent this problem, Farhi et al (1976) proposed a onestep rebreathing method with 50 % O 2 and 50 % N 2 The manouvre, after an initial drop in PCO 2, induces a subsequent and smooth rise in PCO 2 When, at time T, PCO 2 in the bag becomes identical to end-tidal PCO 2 before rebreathing (P 0 A), the net change in CO 2 lung stores is zero

26 One step CO 2 Rebreathing At time T, net change in CO 2 lung store is zero. Hence VCO 2, the volume of CO 2 gained by alveolar space plus bag, is the cumulative loss of CO 2 from capillary blood Q L = ΔV CO2 / T Cv CO2 CC CO2

27 One step CO 2 Rebreathing 1. At time T, therefore, both lung tissue and alveolar gas CO 2 contents should be returned to initial value 2. Thus, VCO 2 could be calculated from the increase of FCO 2 in the bag knowing the initial volume of the bag 3. But only in rare occasions T (after s) will coincide with FRC 4. Under all the other circumstances part of the initial bag volume is in the lung and the PCO 2 has risen from P 0 RB to P 0 A 5. The remainder will be in the bag at slightly lower PCO 2

28 One step CO 2 Rebreathing P RB P RB V RB V AG Alveolar gas V RB V AG Alveolar gas At time T the bag is 1/3 of V 0 CO 2 output has exceeded O 2 uptake causing an increase of total gas volume V Tiss Tissue V Tiss Tissue P A 0 P A 0

29 One step CO 2 Rebreathing VCO2 Initial CO2 This panel compares the conditions and shows the distribution of CO 2 at time T V P VCO2 Initial CO2 A virtual system where VCO 2 is present in a volume V that represents the difference between total gas volume at T and lung volume at 0 This defines P, the partial pressure that would result if the excess lung volume coudl be added to and mixed with the gas in the RB P is estimated from graphycal analysis of the traces

30 One step CO 2 Rebreathing Advantages One step: no needs of measuring in a separate session V CO 2 It solves the problems of the uptake of CO 2 by the lung tissue Disadvantages Cumbersome and long graphycal analysis to calculate P and C eq CO 2 - C c CO 2 from P eq CO 2 and average P A CO 2 during rebreathing

31 O 2 Rebreathing Rebreathing in a bag (V = FRC) with 8-9 % O 2 in N 2 P A O 2 stabilises after about 6 seconds and is believed to reflect P V O 2 To convert in C V O 2, the right (ph and T) dissociation curve must be applied This manouvre exposes the subject to severe hypoxia Trials and errors ph and T unknown P a O 2 from arterial sample

32 References Farhi LE, Nesarajah MS, Olszowka AJ, Metildi LA, Ellis AK. Cardiac output determination by simpel one-step rebreathing technique. Resp Physiol 28: , Jones NL, Campbell EJM, McHardy GJR, Higgs BE, Clode M. The estimation of carbon dioxide pressure of mixed venous blood during exercise. Clin Sci 32: , Kim TS, Rahn H, Farhi LE. Estimation of true venous and arterial PCO2 by gas analysis of a single breath. J Appl Physiol 21: , Marks C, Katch V, Rocchini A, Beekman R, Rosenthal A. Validity and reliability of cardiac outptu by CO 2 rebreathing. Sports Med 2: , 1985.

33 References Sackner MA, Measurement of cardiac ouptu by alveoalr gas exchange, In: Fahri LE, Tenney SM, editors. Handbook of physiology, sec 3: the respiratory system. vol IV. Bethesda, MD: American Physiological Society; pp Warburton DER, Haykowsky MJF, Quinney HA, Humen DP, Teo KK. Reliability and validity of measures of cardiac output during incremental to maximal exercise. Part 1: Conventional techniques. Sports Med 27: 23-41, 1999.

Measurement of cardiac output by Alveolar gas exchange - Inert gas rebreathing

Measurement of cardiac output by Alveolar gas exchange - Inert gas rebreathing Carlo Capelli SS.MM. Università degli Studi di Verona Soluble Inert gas They dissolve and do not form bonds with haemoglobyn