An improved rebreathing method for measuring mixed venous carbon dioxide tension and its clinical application A.C.P. POWLES,* MB, CH B, FRACP, FRCP[C]; E.J.M. CAMPBELL,t MD, PH D, FRCP, FRCP[CI, FACP
The mixed venous carbon dioxide tension (P.co2) can be measured at the bedside by a rebreathing equilibrium technique that is quick, simple and noninvasive. Only one brief period of rebreathing is required. The technique is accurate even when the lungs are not normal, and gives a graphic record that allows verification of the accuracy of the estimate. The P.co2 is affected mainly by changes in alveolar ventilation and cardiac output. It can be measured instead of the arterial carbon dioxide tension (Paco2) to follow changes in alveolar ventilation when the cardiac output is normal (Paco2 = 0.8 P.co2). When the cardiac output is abnormal, measurement of both Paco2 and P.co2 is usefuj in determining how much the cardiac output is reduced. Consideration of the relation between oxygen consumption and carbon dioxide production suggests that the equation Paco2 = 0.8 P.co2 - 12 indicates a reduction in cardiac output that may impair the oxygen supply to tissues. Simple corrections can be applied to allow for variations in arterial oxygen saturation and hemoglobin concentration that will affect this relationship. La pression veineuse mixte du gaz carbonique (P.co2) peut .tre mesur6e au lit du malade par une technique d'equilibre de reinhalation qui est A Ia fois rapide, simple et non.traumatique. Une seule breve p6riode de reinhalation est requise. La technique est precise mime lorsque les poumons sont anormaux, at elle donne un enregistrement graphique qui permet de v6rifier l'exactitude de l'evaluation. La P.co2 est affectee principalement par les changements de Ia ventilation alveolaire et du debit cardlaque. Elle peut Atre mesuree a Ia place de Ia pression arterielle en gaz carbonique (Paco2) pour suivre les changements de Ia ventilation alv6olaire quand le debit cardiaque est normal (Paco2 = 0.8 P.co2). Ouand le debit cardiaque est altere, Ia mesure de Ia Paco2 et Ia P.co2 est utile pour determiner l'importance de Ia baisse du debit cardiaque. L'examen de Ia relation entre Ia Assistant professor of medicine, and tprofessor, department of medicine, McMaster University, Hamilton Reprint requests to: Dr. A.C.P. Powles, Ambrose cardiorespiratory unit, McMaster University Medical Centre, McMaster University, Hamilton, Ont. L85 4J9
consommation d'oxyg.ne et Ia production de gaz carbonique suggAre que l.equation Paco2 = 0.8 P.co2-12 indique une diminution du debit cardiaque capable d'alterer l'apport d'oxygene aux tissus. Des corrections simples peuvent 6tre appliquees pour compenser pour les variations de Ia saturation arterielle en oxygene et de Ia concentration d'hemoglobine qui affectent ce rapport.
Measurement of arterial carbon dioxide tension (Paco2) is widely used to assess alveolar ventilation in respiratory and acid-base disturbances. Often clinical guidance can be obtained more promptly and at less cost by the use of a rebreathing method for estimating mixed venous carbon dioxide tension (P.co2). Rebreathing techniques have several advantages over arterial bloodgas analysis: they are noninvasive and can be performed quickly at the bedside by a nurse or respiratory technologist. Further, measurement of P.co2 and Paco2 can be used together in a complementary way to allow estimation of the adequacy of cardiac output. Although in many centres rebreathing methods for the estimation of Pi'co2 are well accepted, they are generally underused, being considered principally as laboratory procedures. To establish the rebreathing method as a bedside technique in a hospital, a number of obstacles must be surmounted: 1. Appreciation of the usefulness of Pi'co2 measurement by the clinician. Because of the ready availability of equipment for blood-gas analysis some of the difficulties and limitations of arterial blood-gas measurement have been ignored. 2. Choice of rebreathing method. The popularity of the two-stage method using an inexpensive chemical analyser1 has directed attention away from procedurally simpler methods, such as that of Collier and colleagues,2'3 which makes use of a rapid gas analyser. 3. Assembly and maintenance of equipment. Although this presents no difficulty to the staff of a respiratory laboratory, no one has produced a package for general hospital use. 4. Selection and training of operators. Little skill is required to measure rebreathing P.co2 provided there is an instructor available - in most hospitals there is not. In the last 4 years we have examined
these difficulties and believe we have overcome them. This paper deals with the first problem listed above. It is aimed at physicians with particular responsibility for respiratory laboratories, intensive care units and chest services. We describe briefly measurement of Pi'co2 by the equilibrium technique then discuss the clinical use of the Pi.co2 measurement. (More detailed teaching and equipment manuals are available from the authors on request.) Measurement of Pico2 by the equilibrium technique Of the rebreathing methods available for measuring P.co2 all except the twostage method of Campbell and Howell1 require a carbon dioxide analyser capable of following breath-by-breath fluctuations. The two-stage method, which uses a chemical analyser, although simple, requires a facility of the operator that is developed and maintained only by frequent practice; hence it is not suitable for the occasional user. A rapid carbon dioxide analyser permits use of the equilibrium technique.2 The patient breathes in and out of a bag containing carbon dioxide and oxygen for 30 seconds. The concentration of carbon dioxide is chosen so that during the period of rebreathing the carbon dioxide tension (Pco2) of the rebreathing bag, lungs and mixed venous blood come into equilibrium, which is recognized by a period of absence of fluctuation (plateau) in the Pco2 of the gas sampled at the mouth. The Pco2 of the plateau is the Nco2. The equilibrium technique has several advantages over other methods. Only one brief period of rebreathing is usually required; the technique is accurate even when the lungs are not normal; and the graphic record of Pco2 fluctuations allows verification of the accuracy of the measurements. We have developed a 'mobile bedside unit (Fig. 1) with which nurses, respiratory therapists or technologists can measure the Pi'co2 as part of routine patient care, taking at most only 5 minutes to complete each measurement. The unit consists of: a carbon dioxide analyser (Capnograph: Godart, Bilthoven, the Netherlands); a single channel recorder (202100 Astro-Med, Atlan-Tol Industries Inc., West Warwick, Rhode Island), two E-type gas cylinders, one containing 100% oxygen and the other 13.5% carbon dioxide
CMA JOURNAL/MARCH 4, 1978/VOL. 118
501
(approximately 96 mm Hg) in oxygen, which are used for calibration and for preparation of the rebreathing bag and valve. They key to our success in establishing the procedure, in light of the difficulties of learning and applying the method, has been in the assembly of the equipment, taps and tubing. The details of the method are contained in an instructional manual, which is available on request, but the essentials of the procedure are as follows: the analyser is calibrated and the rebreathing bag filled about half full with a mixture whose Pco2 is in the range of 60 to 65 mm Hg; the patient is asked to breathe in and out (rebreathe) for 30 seconds. The Pco2 tracing obtained will indicate whether equilibrium has been reached; if it has not, rebreathing is repeated with a higher or lower Pco2 mixture in the bag, as indicated below. The Pco2 tracing obtained (Fig. 2) may have one of three basic patterns.4 The equilibrium pattern (Fig. 2A) consists of three phases: (a) the mixing
FIG.
phase (I), so called because the air in the bag and lungs mixes together as shown by decreasing respiratory fluctuations in Pco2; (b) a plateau phase (II), the period during which respiratory fluctuations are less than 1 mm Hg and in which there is less than 1 mm Hg change in mean Pco2 between the beginning and the end of the phase; and (c) a recirculation phase (III), distinguished by an increase in Pco2 caused by the return to the lungs of blood that was unable to release carbon dioxide at the beginning of the rebreathing period. The equilibrium pattern is defined by the timing of the plateau, which starts within 12 seconds of the beginning of rebreathing and lasts for at least 10 seconds. During such a plateau, the carbon dioxide tension of mixed venous blood, the lungs and the rebreathing bag is in equilibrium. The Pco2 of the plateau in an equilibrium pattern is therefore the same as the Pi'co2. The second pattern is the delayed plateau (Fig. 2B), in which the plateau phase does not start until after the first 12 seconds of rebreathing. The delayed plateau does not occur until there has been recirculation of blood with a high Pco2 from the beginning of rebreathing. Hence the Pco2 of the delayed plateau is higher than the Nco2.4 The third pattern is the short plateau (Fig. 2C), in which the plateau phase lasts for less than 10 seconds. This "plateau" merely represents a completion of mixing between the bag and lungs, but not equilibrium with mixed venous blood. The Pco2 of the short plateau is therefore lower than the Nco2.4 An accurate estimate of the Nco2 can be obtained in two ways: from the Pco2 of the plateau in an equilibrium pattern, or as the mean of the Pco2s of the short and delayed plateaux, which are not more than 4 mm Hg apart. The Nco2 measurement obtained in either of these two ways will be accurate to within ± 2 mm Hg,4'5 as
2-Three
rebreathing:
A
=
(Ill) phases.
Pco2
of
initial bag
Pco2
is
too
low.
is the measurement of Paco2. An initial bag Pco, of 60 to 65 mm Hg is chosen unless there is reason to suspect that the patient's Nco1 is not in the normal range of 44 to 56 mm Hg.6 If the first rebreathing does not show an equilibrium pattern it is repeated with a more appropriate bag Pco5, if it shows a short plateau pattern the bag Pco2 is increased by 10 mm Hg, and if it shows a delayed plateau pattern the bag Pco2 is decreased by 10 mm Hg. Rebreathing is repeated until an equilibrium pattern or short and delayed plateaux of not more than 4 mm Hg are obtained. This rarely requires more than three rebreathings, taking less than 5 minutes. If the patient's approximate Pirco2 is known, for example. from previous analysis, only one rebreathing is usually necessary and the whole procedure takes about 2 minutes. The equilibrium technique can be applied to intubated patients by using a suitable connection between the rebreathing valve and the endotracheal tube. Ventilation can be continued during rebreathing by compressing the rebreathing bag if the patient is not breathing spontaneously. Each compression will be seen as a transient increase in Pco2, but equilibrium can still be recognized easily. Clinical use of Nco2
The usefulness of Nco2 measurement to a physician depends on his understanding of it and the factors that affect it. The explanation that follows emphasizes the practical aspects; more rigorous physiologic accounts have been presented previously.1'7 What is the mixed venous carbon dioxide tension? The Nco2 is the Pco2 of blood in the pulmonary artery and is so called because venous blood from various parts of the body is mixed together in the right heart. Thus the Nco2 is an average venous Pco2 and since the Pco2 of venous blood from an organ Is in equilibrium with the tissue Pco2 of that organ, the Nco2 is representative of the whole body Pco,. Rebreathing methods estimate Nco1 by measuring changes of Pco, in gas sampled at the mouth. The values of Nco2 obtained by rebreathing are higher than those obtained in blood sampled directly from the pulmonary artery. This difference is accounted for by the oxygenation of the blood in the lungs during the rebreathing procedure which uses a high oxygen mixture. As hemoglobin is oxygenated, the carbon dioxide carrying capacity of the blood is reduced and the Pco2 is increased for the same carbon dioxide content (the Christiansen-Douglas-Haldane effect8).
80
ASSUMING HblOg 5.02 95%
24 6
70
C(vaJC0. mi/lOG ml 10 12
P.C03 mmHg 00 40 70 70
40
95
95 70 95 P0CO.mmHg
95
100
110
CALCULATION OFThE MIXED VENOUS 02 SATURATION (59021
TISSUE METABOLISM VCO2
TRANSPORT GAS EXCHANGE -. PaCO2 0ATMOSPHERIC , PCO2
1. Mmm.P.CO.m.dP9C0.
3
diffmm.ce (C(0-.)C0.J from th, gmph CaIm.I.t. 0902 a. (albino 0002- 0902- Cla-.1C02 100 134o Hb
Coo.Oo..Eoin,.oOo.E,9.aoE C.o.9O2,o Em 0.02 .CCO.OOI4 91-0.0,1 0200oOOEIIPOCO2 ..CO.I 0016)
CARDIAC OUTPUT ALVEOLAR VENTILATiON FIG. 3-For any given carbon dioxide production, arterial carbon dioxide tension (Paco2) depends on alveolar ventilation, and the mixed venous to arterial Pco2 difference (Nco2-Paco2) on cardiac output. Thus Pico2 reflects function of both transport and gas-exchange aspects of carbon dioxide excretion.
the adequacy of cardiac output in terms more than 10 mL/dL, because it indicates a cardiac output so low that of oxygen delivery as judged by Siro,. tissue hypoxia is likely. The reasoning How is it used in clinical practice? is that, with a respiratory quotient (R) Unlike others, we measure Nco2 on of 0.8, this difference in carbon dioxide content implies a difference in arterio- a routine basis in both out- and inpavenous oxygen content of 12.5 mL/dL, tients, the measurements being made which, assuming a hemoglobin value of by nurses and respiratory technologists. 15 g/dL and an Sao2 of 95%, implies Measurement of the Nco2 provides a an S.o2 of only 33% (calculated by record of how much the patient actually breathes, rather than how much means of the equation in Fig. 5). he "can" breathe, as measured by Tissue hypoxia may result, since the corresponding venous oxygen tension is spirometry and other indices of ventilaabout 20 mm Hg; below that value cer- tory capacity. The rebreathing measurement of tain vital organs (notably the brain16) show hypoxic change. The relation be- Pi.co2 is particularly useful in the intween Paco2 and Pirco2 when cardiac tensive care unit. Its simplicity allows output is reduced to this extent and frequent assessment of alveolar ventilaoxygen delivery to tissues may be com- tion whenever required, as during the promised is given by the equation initial adjustment phases of artificial Paco2 = 0.8 P.co2 - 12 (derived from ventilation and during weaning. Measurement of Nco2 reduces the need for Fig. 5 for Siro. = 33%). arterial blood-gas analysis and, when The two equations, Paco2 = 0.8 Nco2 and Paco2 = 0.8 Nco2 - 12 combined with ear oximetry to deterare calculated on the basis of a hemo- mine arterial oxygenation,18 virtually globin value of 15 g/dL, an arterial eliminates the need for indwelling arsaturation of 95% and R = 0.8, and terial lines. When the Nco2 and Paco2 are used are approximations that will not lead to clinically significant errors. When to estimate the adequacy of cardiac values of hemoglobin or arterial satura- output, the measurements should be tion differ from this base (i.e., hemo- made within 5 minutes of each other. globin value outside the range 12 to The drawing of the arterial sample 18 g/dL or Sao, less than 90%), the should precede the rebreathing period, difference in carbon dioxide content because the high oxygen concentration should be corrected and the S.o2 cal- of the rebreathing mixture may produce culated as in Fig. 5. The respiratory erroneously high arterial oxygenation quotient is not usually measured. values for the subsequent minute or Values of R less than 0.8 are rarely so. The arterial sample should be drawn observed: the effect of assuming R = over a minute, care being taken not to 0.8 when the true value is more than disturb the patient's breathing and so 0.8 will be to overestimate the degree produce a falsely low Paco2 measureof mixed venous desaturation. It is ment from transient hyperventilation. therefore unlikely that assuming R = With these precautions, a substantial 0.8 will cause a dangerously low car- impairment of cardiac output can be detected without the need for rightdiac output to be missed. heart catheterization.14 An Svo2 of 33% may be considered Measurement of Nco2 deserves too low for adequate tissue oxygenation. The equation in Fig. 5 allows de- wider clinical use. The equilibrium termination of the Paco2-Nco2 relation technique we have described is simple whatever value of Si'o2 is considered and gives immediate information that appropriate. If an Si.o2 saturation of can be used to assess alveolar ventila50% is chosen,17 then the Pco2 relation tion and cardiac output, two vital links will be Paco2 = 0.8 Pi'co2 - 6. (The in the supply of oxygen to the tissues. venoarterial difference in oxygen content will be 10 mL/dL, which corre- We thank the nurses, in particular Mrs. T. Houston, and respiratory technologists at sponds with R = 0.8 to a difference in the Hamilton General Hospital and Mccarbon dioxide content of 8 mL/dL; Master University Medical Centre for the Pco2 relation can be read directly their assistance. from Fig. 5.) This work was performed under OnIn summary, the predominant physi- tario Ministry of Health grant PR 260. ologic factor affecting Pirco2 is alveolar ventilation; to a lesser extent Nco is affected by cardiac output, while Sao2 and hemoglobin concentration have References minor effects. With variations in alve- 1. CAMPBELL EJM, HOWELL JBL: Rebreathing method for measurement of mixed venous olar ventilation there are similar Pco2. Br Med / 2: 630, 1962 changes in Paco2 and Nco2. When 2. COLLIER CR: Determination of mixed venous CO2 tensions by rebreathing. J Appi Physlol cardiac output changes, the venoarterial 9: 25. 1956 HACKNEY JD, SEARs CH, COLLIER CR: EsPco2 difference alters in a clinically 3. timation of arterial COs tension by rebreathinformative way, allowing estimation of ing technique. I Appi Physiol 12: 425, 1958 504 CMA JOURNAL/MARCH 4, 1978/VOL. 118
4. JONES NL, CAMPBELL ElM MCHARDY GYR, Ct al: The estimation of' carbon dioxide pressure of mixed venous blood during exercisc. Clin Sci 32: 311, 1967 5. McEvov JD, JONES NL, CAMPBELL El: Alveolar-arterial Pcos difference during rebreathing in patients with chronic hypercapnia. I Appi Physiol 35: 542, 1973 6. SMED5TAD SEALEY KG, REDucE AS, CAMPBELL EJM: Oxygenated mixed venous Pcos in healthy subjects. Can Med Assoc 1 113: 1047, 1975 7. McEvov JDS, JONES NL, CAMPBELL EJM: Mixed venous and arterial Pco2. Br Med I 4: 687, 1974 8. CHRISTIANSEN 3, DouoLAs CG, HALDANE IS: The absorption and dissociation of carbon dioxide in human blood. I Appi Physlol 48: 244, 1914 9. McHARDY GI: The relationship between the differences in pressure and content of carbon dioxide in arterial and venous blood. Clin Sci 32: 299, 1967 10. PETERS JP JR, Bm DP, RULE FD: The carbon dioxide absorption curve and carbon dioxide tension of the blood of normal resting individuals. .1 Blol Chem 45: 489, 1921 11. DAvis CC, JONES NL, SEALEY BJ: Measurement of cardiac output in seriously ill patients using an indirect COs rebreathing method (in press) 12. FERGUSON RJ, FAULKNER JA, JULIUS 5, et al: Comparison of cardiac output determined by COs rebreathing and dye-dilution methods. I Appi Physlol 25: 450, 1968 13. KLAUSEN K: Comparison of COs rebreathing and acetylene methods for cardiac output. I Appi Physiol 20: 763, 1965 14. FRANCIOSA JA: Evaluation of the COs rebreathing cardiac output method in seriously ill patients. CirculatIon 55: 449, 1977 15. SUSKIND M, RAHN H: Relationship between cardiac output and ventilation and gas transport, with particular reference to anesthesia. I Appi Physiol 7: 59, 1954 16. LENNOX WG, Gisas FA, Ginas EL: Relationship of unconsciousness to cerebral blood flow and to anoxemia. Arch Neurol Psychiatr 34: 1001. 1935 17. SIMMoNs DH, TASHEIN DP: Predictors of hyperlactemia during arterial hypoxemia and/ or reduced cardiac output. Am Rev Respir Dis 115: 337, 1977 18. SAUNDERS NA, POWLES ACP, REDUcE AS: Ear oximetry: accuracy and practicability In the assessment of arterial oxygenation. Am Rev Respir DIs 113: 745, 1976
BOOKS continued from page 481 KIDNEY FUNCTION AND DISEASE IN PREG. NANCY. Marshall D. LlndheImer and Adrian I. Katz. 241 pp. lIlust. Lea & Febiger, Philadelphia; The Macmillan Company of Canada Limited, Toronto, 1977. Price not stated. ISBN 0.8121.0593.1 NUCLEAR MEDICINE PHYSICS, INSTRUMENTATION, AND AGENTS. Edited by F. David Rollo, 698 pp. Illust. The CV. Mosby Company, Saint Louis, 1977. $56.25. ISBN 0-8016-4181-0 PEDIATRIC RADIOLOGY. Medical Outline Series. Alan E. Qestreich. 338 pp. ilIust. Medical Examina. tion Publishing Co.. Inc., FlushIng. 1977. 615. paperbound. ISBN 0-87488-658-9 POLYPOSES INTESTINALES. Rapport pr6sentd au 79e Congr.s Fran.ais de Chirurgie, Paris, 19 au 22 aeptembre 1977. J. Loygue, M. Adioff et P. Bloch. 157 pp. Illust. Masson, Paris, 1977. Prix non mentionnd. brochd. ISBN 2-225-47730-2 THE PREMENSTRUAL SYNDROME AND PROGES. TERONE THERAPY. Katharina Dalton. 169 pp. lIlust. William Helnemann Medical Books Ltd., London; Year Book Medical Publishers. Inc., ChIcago, 1977. Price not stated. ISBN 0-8151-2265-9 PRINCIPLES OF FAMILY MEDICINE. Robert E. Rakel. 538 pp. illust. W.B. Saunders Company Canada Limited, Toronto, 1977. 316.25. ISBN 07216-7449-6 PROGRESS IN MEDICAL VIROLOGY. Vol. 23. Edited by Joseph 1. Melnlck. 211 pp. lIlust. S. Karger AG, Basel, 1977. 644. iSBN 3.8055.2423.4 PROGRESS IN PEDIATRIC RADIOLOGY. Vol. 8. Skull, Spine and Contents. Part Ii: Clinical As. pects. Edited by H.J. Kaufmann. 304 pp. lIlust. S. Karger AG, Basel, 1977. $49.75. ISBN 3-8055-2337-8 PUBLIC EDUCATION ABOUT CANCER. Recent Research and Current Programmes. A seventh series of papers. UICC Technical Report Series - Vol. 26. Edited by John Wakefield. 103 pp. Illust. International Union Against Cancer, Geneva, 1977. Price not stated, paperbound
continued on page 530
The mixed venous carbon dioxide tension (P.co2) can be measured at the bedside by a rebreathing equilibrium technique that is quick, simple and noninvasive. Only one brief period of rebreathing is required. The technique is accurate even when the lungs are not normal, and gives a graphic record that allows verification of the accuracy of the estimate. The P.co2 is affected mainly by changes in alveolar ventilation and cardiac output. It can be measured instead of the arterial carbon dioxide tension (Paco2) to follow changes in alveolar ventilation when the cardiac output is normal (Paco2 = 0.8 P.co2). When the cardiac output is abnormal, measurement of both Paco2 and P.co2 is usefuj in determining how much the cardiac output is reduced. Consideration of the relation between oxygen consumption and carbon dioxide production suggests that the equation Paco2 = 0.8 P.co2 - 12 indicates a reduction in cardiac output that may impair the oxygen supply to tissues. Simple corrections can be applied to allow for variations in arterial oxygen saturation and hemoglobin concentration that will affect this relationship. La pression veineuse mixte du gaz carbonique (P.co2) peut .tre mesur6e au lit du malade par une technique d'equilibre de reinhalation qui est A Ia fois rapide, simple et non.traumatique. Une seule breve p6riode de reinhalation est requise. La technique est precise mime lorsque les poumons sont anormaux, at elle donne un enregistrement graphique qui permet de v6rifier l'exactitude de l'evaluation. La P.co2 est affectee principalement par les changements de Ia ventilation alveolaire et du debit cardlaque. Elle peut Atre mesuree a Ia place de Ia pression arterielle en gaz carbonique (Paco2) pour suivre les changements de Ia ventilation alv6olaire quand le debit cardiaque est normal (Paco2 = 0.8 P.co2). Ouand le debit cardiaque est altere, Ia mesure de Ia Paco2 et Ia P.co2 est utile pour determiner l'importance de Ia baisse du debit cardiaque. L'examen de Ia relation entre Ia Assistant professor of medicine, and tprofessor, department of medicine, McMaster University, Hamilton Reprint requests to: Dr. A.C.P. Powles, Ambrose cardiorespiratory unit, McMaster University Medical Centre, McMaster University, Hamilton, Ont. L85 4J9
consommation d'oxyg.ne et Ia production de gaz carbonique suggAre que l.equation Paco2 = 0.8 P.co2-12 indique une diminution du debit cardiaque capable d'alterer l'apport d'oxygene aux tissus. Des corrections simples peuvent 6tre appliquees pour compenser pour les variations de Ia saturation arterielle en oxygene et de Ia concentration d'hemoglobine qui affectent ce rapport.
Measurement of arterial carbon dioxide tension (Paco2) is widely used to assess alveolar ventilation in respiratory and acid-base disturbances. Often clinical guidance can be obtained more promptly and at less cost by the use of a rebreathing method for estimating mixed venous carbon dioxide tension (P.co2). Rebreathing techniques have several advantages over arterial bloodgas analysis: they are noninvasive and can be performed quickly at the bedside by a nurse or respiratory technologist. Further, measurement of P.co2 and Paco2 can be used together in a complementary way to allow estimation of the adequacy of cardiac output. Although in many centres rebreathing methods for the estimation of Pi'co2 are well accepted, they are generally underused, being considered principally as laboratory procedures. To establish the rebreathing method as a bedside technique in a hospital, a number of obstacles must be surmounted: 1. Appreciation of the usefulness of Pi'co2 measurement by the clinician. Because of the ready availability of equipment for blood-gas analysis some of the difficulties and limitations of arterial blood-gas measurement have been ignored. 2. Choice of rebreathing method. The popularity of the two-stage method using an inexpensive chemical analyser1 has directed attention away from procedurally simpler methods, such as that of Collier and colleagues,2'3 which makes use of a rapid gas analyser. 3. Assembly and maintenance of equipment. Although this presents no difficulty to the staff of a respiratory laboratory, no one has produced a package for general hospital use. 4. Selection and training of operators. Little skill is required to measure rebreathing P.co2 provided there is an instructor available - in most hospitals there is not. In the last 4 years we have examined
these difficulties and believe we have overcome them. This paper deals with the first problem listed above. It is aimed at physicians with particular responsibility for respiratory laboratories, intensive care units and chest services. We describe briefly measurement of Pi'co2 by the equilibrium technique then discuss the clinical use of the Pi.co2 measurement. (More detailed teaching and equipment manuals are available from the authors on request.) Measurement of Pico2 by the equilibrium technique Of the rebreathing methods available for measuring P.co2 all except the twostage method of Campbell and Howell1 require a carbon dioxide analyser capable of following breath-by-breath fluctuations. The two-stage method, which uses a chemical analyser, although simple, requires a facility of the operator that is developed and maintained only by frequent practice; hence it is not suitable for the occasional user. A rapid carbon dioxide analyser permits use of the equilibrium technique.2 The patient breathes in and out of a bag containing carbon dioxide and oxygen for 30 seconds. The concentration of carbon dioxide is chosen so that during the period of rebreathing the carbon dioxide tension (Pco2) of the rebreathing bag, lungs and mixed venous blood come into equilibrium, which is recognized by a period of absence of fluctuation (plateau) in the Pco2 of the gas sampled at the mouth. The Pco2 of the plateau is the Nco2. The equilibrium technique has several advantages over other methods. Only one brief period of rebreathing is usually required; the technique is accurate even when the lungs are not normal; and the graphic record of Pco2 fluctuations allows verification of the accuracy of the measurements. We have developed a 'mobile bedside unit (Fig. 1) with which nurses, respiratory therapists or technologists can measure the Pi'co2 as part of routine patient care, taking at most only 5 minutes to complete each measurement. The unit consists of: a carbon dioxide analyser (Capnograph: Godart, Bilthoven, the Netherlands); a single channel recorder (202100 Astro-Med, Atlan-Tol Industries Inc., West Warwick, Rhode Island), two E-type gas cylinders, one containing 100% oxygen and the other 13.5% carbon dioxide
CMA JOURNAL/MARCH 4, 1978/VOL. 118
501
(approximately 96 mm Hg) in oxygen, which are used for calibration and for preparation of the rebreathing bag and valve. They key to our success in establishing the procedure, in light of the difficulties of learning and applying the method, has been in the assembly of the equipment, taps and tubing. The details of the method are contained in an instructional manual, which is available on request, but the essentials of the procedure are as follows: the analyser is calibrated and the rebreathing bag filled about half full with a mixture whose Pco2 is in the range of 60 to 65 mm Hg; the patient is asked to breathe in and out (rebreathe) for 30 seconds. The Pco2 tracing obtained will indicate whether equilibrium has been reached; if it has not, rebreathing is repeated with a higher or lower Pco2 mixture in the bag, as indicated below. The Pco2 tracing obtained (Fig. 2) may have one of three basic patterns.4 The equilibrium pattern (Fig. 2A) consists of three phases: (a) the mixing
FIG.
phase (I), so called because the air in the bag and lungs mixes together as shown by decreasing respiratory fluctuations in Pco2; (b) a plateau phase (II), the period during which respiratory fluctuations are less than 1 mm Hg and in which there is less than 1 mm Hg change in mean Pco2 between the beginning and the end of the phase; and (c) a recirculation phase (III), distinguished by an increase in Pco2 caused by the return to the lungs of blood that was unable to release carbon dioxide at the beginning of the rebreathing period. The equilibrium pattern is defined by the timing of the plateau, which starts within 12 seconds of the beginning of rebreathing and lasts for at least 10 seconds. During such a plateau, the carbon dioxide tension of mixed venous blood, the lungs and the rebreathing bag is in equilibrium. The Pco2 of the plateau in an equilibrium pattern is therefore the same as the Pi'co2. The second pattern is the delayed plateau (Fig. 2B), in which the plateau phase does not start until after the first 12 seconds of rebreathing. The delayed plateau does not occur until there has been recirculation of blood with a high Pco2 from the beginning of rebreathing. Hence the Pco2 of the delayed plateau is higher than the Nco2.4 The third pattern is the short plateau (Fig. 2C), in which the plateau phase lasts for less than 10 seconds. This "plateau" merely represents a completion of mixing between the bag and lungs, but not equilibrium with mixed venous blood. The Pco2 of the short plateau is therefore lower than the Nco2.4 An accurate estimate of the Nco2 can be obtained in two ways: from the Pco2 of the plateau in an equilibrium pattern, or as the mean of the Pco2s of the short and delayed plateaux, which are not more than 4 mm Hg apart. The Nco2 measurement obtained in either of these two ways will be accurate to within ± 2 mm Hg,4'5 as
2-Three
rebreathing:
A
=
(Ill) phases.
Pco2
of
initial bag
Pco2
is
too
low.
is the measurement of Paco2. An initial bag Pco, of 60 to 65 mm Hg is chosen unless there is reason to suspect that the patient's Nco1 is not in the normal range of 44 to 56 mm Hg.6 If the first rebreathing does not show an equilibrium pattern it is repeated with a more appropriate bag Pco5, if it shows a short plateau pattern the bag Pco2 is increased by 10 mm Hg, and if it shows a delayed plateau pattern the bag Pco2 is decreased by 10 mm Hg. Rebreathing is repeated until an equilibrium pattern or short and delayed plateaux of not more than 4 mm Hg are obtained. This rarely requires more than three rebreathings, taking less than 5 minutes. If the patient's approximate Pirco2 is known, for example. from previous analysis, only one rebreathing is usually necessary and the whole procedure takes about 2 minutes. The equilibrium technique can be applied to intubated patients by using a suitable connection between the rebreathing valve and the endotracheal tube. Ventilation can be continued during rebreathing by compressing the rebreathing bag if the patient is not breathing spontaneously. Each compression will be seen as a transient increase in Pco2, but equilibrium can still be recognized easily. Clinical use of Nco2
The usefulness of Nco2 measurement to a physician depends on his understanding of it and the factors that affect it. The explanation that follows emphasizes the practical aspects; more rigorous physiologic accounts have been presented previously.1'7 What is the mixed venous carbon dioxide tension? The Nco2 is the Pco2 of blood in the pulmonary artery and is so called because venous blood from various parts of the body is mixed together in the right heart. Thus the Nco2 is an average venous Pco2 and since the Pco2 of venous blood from an organ Is in equilibrium with the tissue Pco2 of that organ, the Nco2 is representative of the whole body Pco,. Rebreathing methods estimate Nco1 by measuring changes of Pco, in gas sampled at the mouth. The values of Nco2 obtained by rebreathing are higher than those obtained in blood sampled directly from the pulmonary artery. This difference is accounted for by the oxygenation of the blood in the lungs during the rebreathing procedure which uses a high oxygen mixture. As hemoglobin is oxygenated, the carbon dioxide carrying capacity of the blood is reduced and the Pco2 is increased for the same carbon dioxide content (the Christiansen-Douglas-Haldane effect8).
80
ASSUMING HblOg 5.02 95%
24 6
70
C(vaJC0. mi/lOG ml 10 12
P.C03 mmHg 00 40 70 70
40
95
95 70 95 P0CO.mmHg
95
100
110
CALCULATION OFThE MIXED VENOUS 02 SATURATION (59021
TISSUE METABOLISM VCO2
TRANSPORT GAS EXCHANGE -. PaCO2 0ATMOSPHERIC , PCO2
1. Mmm.P.CO.m.dP9C0.
3
diffmm.ce (C(0-.)C0.J from th, gmph CaIm.I.t. 0902 a. (albino 0002- 0902- Cla-.1C02 100 134o Hb
Coo.Oo..Eoin,.oOo.E,9.aoE C.o.9O2,o Em 0.02 .CCO.OOI4 91-0.0,1 0200oOOEIIPOCO2 ..CO.I 0016)
CARDIAC OUTPUT ALVEOLAR VENTILATiON FIG. 3-For any given carbon dioxide production, arterial carbon dioxide tension (Paco2) depends on alveolar ventilation, and the mixed venous to arterial Pco2 difference (Nco2-Paco2) on cardiac output. Thus Pico2 reflects function of both transport and gas-exchange aspects of carbon dioxide excretion.
the adequacy of cardiac output in terms more than 10 mL/dL, because it indicates a cardiac output so low that of oxygen delivery as judged by Siro,. tissue hypoxia is likely. The reasoning How is it used in clinical practice? is that, with a respiratory quotient (R) Unlike others, we measure Nco2 on of 0.8, this difference in carbon dioxide content implies a difference in arterio- a routine basis in both out- and inpavenous oxygen content of 12.5 mL/dL, tients, the measurements being made which, assuming a hemoglobin value of by nurses and respiratory technologists. 15 g/dL and an Sao2 of 95%, implies Measurement of the Nco2 provides a an S.o2 of only 33% (calculated by record of how much the patient actually breathes, rather than how much means of the equation in Fig. 5). he "can" breathe, as measured by Tissue hypoxia may result, since the corresponding venous oxygen tension is spirometry and other indices of ventilaabout 20 mm Hg; below that value cer- tory capacity. The rebreathing measurement of tain vital organs (notably the brain16) show hypoxic change. The relation be- Pi.co2 is particularly useful in the intween Paco2 and Pirco2 when cardiac tensive care unit. Its simplicity allows output is reduced to this extent and frequent assessment of alveolar ventilaoxygen delivery to tissues may be com- tion whenever required, as during the promised is given by the equation initial adjustment phases of artificial Paco2 = 0.8 P.co2 - 12 (derived from ventilation and during weaning. Measurement of Nco2 reduces the need for Fig. 5 for Siro. = 33%). arterial blood-gas analysis and, when The two equations, Paco2 = 0.8 Nco2 and Paco2 = 0.8 Nco2 - 12 combined with ear oximetry to deterare calculated on the basis of a hemo- mine arterial oxygenation,18 virtually globin value of 15 g/dL, an arterial eliminates the need for indwelling arsaturation of 95% and R = 0.8, and terial lines. When the Nco2 and Paco2 are used are approximations that will not lead to clinically significant errors. When to estimate the adequacy of cardiac values of hemoglobin or arterial satura- output, the measurements should be tion differ from this base (i.e., hemo- made within 5 minutes of each other. globin value outside the range 12 to The drawing of the arterial sample 18 g/dL or Sao, less than 90%), the should precede the rebreathing period, difference in carbon dioxide content because the high oxygen concentration should be corrected and the S.o2 cal- of the rebreathing mixture may produce culated as in Fig. 5. The respiratory erroneously high arterial oxygenation quotient is not usually measured. values for the subsequent minute or Values of R less than 0.8 are rarely so. The arterial sample should be drawn observed: the effect of assuming R = over a minute, care being taken not to 0.8 when the true value is more than disturb the patient's breathing and so 0.8 will be to overestimate the degree produce a falsely low Paco2 measureof mixed venous desaturation. It is ment from transient hyperventilation. therefore unlikely that assuming R = With these precautions, a substantial 0.8 will cause a dangerously low car- impairment of cardiac output can be detected without the need for rightdiac output to be missed. heart catheterization.14 An Svo2 of 33% may be considered Measurement of Nco2 deserves too low for adequate tissue oxygenation. The equation in Fig. 5 allows de- wider clinical use. The equilibrium termination of the Paco2-Nco2 relation technique we have described is simple whatever value of Si'o2 is considered and gives immediate information that appropriate. If an Si.o2 saturation of can be used to assess alveolar ventila50% is chosen,17 then the Pco2 relation tion and cardiac output, two vital links will be Paco2 = 0.8 Pi'co2 - 6. (The in the supply of oxygen to the tissues. venoarterial difference in oxygen content will be 10 mL/dL, which corre- We thank the nurses, in particular Mrs. T. Houston, and respiratory technologists at sponds with R = 0.8 to a difference in the Hamilton General Hospital and Mccarbon dioxide content of 8 mL/dL; Master University Medical Centre for the Pco2 relation can be read directly their assistance. from Fig. 5.) This work was performed under OnIn summary, the predominant physi- tario Ministry of Health grant PR 260. ologic factor affecting Pirco2 is alveolar ventilation; to a lesser extent Nco is affected by cardiac output, while Sao2 and hemoglobin concentration have References minor effects. With variations in alve- 1. CAMPBELL EJM, HOWELL JBL: Rebreathing method for measurement of mixed venous olar ventilation there are similar Pco2. Br Med / 2: 630, 1962 changes in Paco2 and Nco2. When 2. COLLIER CR: Determination of mixed venous CO2 tensions by rebreathing. J Appi Physlol cardiac output changes, the venoarterial 9: 25. 1956 HACKNEY JD, SEARs CH, COLLIER CR: EsPco2 difference alters in a clinically 3. timation of arterial COs tension by rebreathinformative way, allowing estimation of ing technique. I Appi Physiol 12: 425, 1958 504 CMA JOURNAL/MARCH 4, 1978/VOL. 118
4. JONES NL, CAMPBELL ElM MCHARDY GYR, Ct al: The estimation of' carbon dioxide pressure of mixed venous blood during exercisc. Clin Sci 32: 311, 1967 5. McEvov JD, JONES NL, CAMPBELL El: Alveolar-arterial Pcos difference during rebreathing in patients with chronic hypercapnia. I Appi Physiol 35: 542, 1973 6. SMED5TAD SEALEY KG, REDucE AS, CAMPBELL EJM: Oxygenated mixed venous Pcos in healthy subjects. Can Med Assoc 1 113: 1047, 1975 7. McEvov JDS, JONES NL, CAMPBELL EJM: Mixed venous and arterial Pco2. Br Med I 4: 687, 1974 8. CHRISTIANSEN 3, DouoLAs CG, HALDANE IS: The absorption and dissociation of carbon dioxide in human blood. I Appi Physlol 48: 244, 1914 9. McHARDY GI: The relationship between the differences in pressure and content of carbon dioxide in arterial and venous blood. Clin Sci 32: 299, 1967 10. PETERS JP JR, Bm DP, RULE FD: The carbon dioxide absorption curve and carbon dioxide tension of the blood of normal resting individuals. .1 Blol Chem 45: 489, 1921 11. DAvis CC, JONES NL, SEALEY BJ: Measurement of cardiac output in seriously ill patients using an indirect COs rebreathing method (in press) 12. FERGUSON RJ, FAULKNER JA, JULIUS 5, et al: Comparison of cardiac output determined by COs rebreathing and dye-dilution methods. I Appi Physlol 25: 450, 1968 13. KLAUSEN K: Comparison of COs rebreathing and acetylene methods for cardiac output. I Appi Physiol 20: 763, 1965 14. FRANCIOSA JA: Evaluation of the COs rebreathing cardiac output method in seriously ill patients. CirculatIon 55: 449, 1977 15. SUSKIND M, RAHN H: Relationship between cardiac output and ventilation and gas transport, with particular reference to anesthesia. I Appi Physiol 7: 59, 1954 16. LENNOX WG, Gisas FA, Ginas EL: Relationship of unconsciousness to cerebral blood flow and to anoxemia. Arch Neurol Psychiatr 34: 1001. 1935 17. SIMMoNs DH, TASHEIN DP: Predictors of hyperlactemia during arterial hypoxemia and/ or reduced cardiac output. Am Rev Respir Dis 115: 337, 1977 18. SAUNDERS NA, POWLES ACP, REDUcE AS: Ear oximetry: accuracy and practicability In the assessment of arterial oxygenation. Am Rev Respir DIs 113: 745, 1976
BOOKS continued from page 481 KIDNEY FUNCTION AND DISEASE IN PREG. NANCY. Marshall D. LlndheImer and Adrian I. Katz. 241 pp. lIlust. Lea & Febiger, Philadelphia; The Macmillan Company of Canada Limited, Toronto, 1977. Price not stated. ISBN 0.8121.0593.1 NUCLEAR MEDICINE PHYSICS, INSTRUMENTATION, AND AGENTS. Edited by F. David Rollo, 698 pp. Illust. The CV. Mosby Company, Saint Louis, 1977. $56.25. ISBN 0-8016-4181-0 PEDIATRIC RADIOLOGY. Medical Outline Series. Alan E. Qestreich. 338 pp. ilIust. Medical Examina. tion Publishing Co.. Inc., FlushIng. 1977. 615. paperbound. ISBN 0-87488-658-9 POLYPOSES INTESTINALES. Rapport pr6sentd au 79e Congr.s Fran.ais de Chirurgie, Paris, 19 au 22 aeptembre 1977. J. Loygue, M. Adioff et P. Bloch. 157 pp. Illust. Masson, Paris, 1977. Prix non mentionnd. brochd. ISBN 2-225-47730-2 THE PREMENSTRUAL SYNDROME AND PROGES. TERONE THERAPY. Katharina Dalton. 169 pp. lIlust. William Helnemann Medical Books Ltd., London; Year Book Medical Publishers. Inc., ChIcago, 1977. Price not stated. ISBN 0-8151-2265-9 PRINCIPLES OF FAMILY MEDICINE. Robert E. Rakel. 538 pp. illust. W.B. Saunders Company Canada Limited, Toronto, 1977. 316.25. ISBN 07216-7449-6 PROGRESS IN MEDICAL VIROLOGY. Vol. 23. Edited by Joseph 1. Melnlck. 211 pp. lIlust. S. Karger AG, Basel, 1977. 644. iSBN 3.8055.2423.4 PROGRESS IN PEDIATRIC RADIOLOGY. Vol. 8. Skull, Spine and Contents. Part Ii: Clinical As. pects. Edited by H.J. Kaufmann. 304 pp. lIlust. S. Karger AG, Basel, 1977. $49.75. ISBN 3-8055-2337-8 PUBLIC EDUCATION ABOUT CANCER. Recent Research and Current Programmes. A seventh series of papers. UICC Technical Report Series - Vol. 26. Edited by John Wakefield. 103 pp. Illust. International Union Against Cancer, Geneva, 1977. Price not stated, paperbound
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