Guidelines for the measurement of respiratory function

Respiratory Medicine (1994) 88, 165-194

Topical Review

Guidelines for the measurement of respiratory function

Recommendations of the British Thoracic Society and the Association of Respiratory Technicians and Physiologists

Introduction 166

Section 1 General Procedures 167

Section 2 Procedures for FEV 1 and FVC 167 2.1 Definitions 167 2.2 Equipment 168 2.3 Procedure 168

Section 3 Procedures for Short-acting Bronchodilator Response

Section 4 Procedures for Peak Expiratory Flow 4.1 Definitions 4.2 Equipment 4.3 Procedure

Section 5.1 5.2 5.3 5.4 5.5 5.6

5 Procedures for Maximal Flow Volume Curves Definitions Equipment Indications for maximal flow volume curves Procedure Additional aspects to maximal flow volume curves Examples of different maximal flow volume curves

Section 6.1 6.2 6.3 6.4 6.5 6.6

6 Procedures for Static Lung Volumes and Capacities Definitions Equipment Procedure - steady state method Sources of error Recommendations for minimum equipment requirements Calculations and examples

Section 7 Procedures for Plethysmography 7.1 Introduction 7.2 Definitions 7.3 Principle of the method 7.4 Equipment 7.5 Calibration 7.6 Procedure 7.7 Quality control

Section 8.1 8.2

8 Procedures for Single Breath Carbon Monoxide Transfer Factor Definitions Conditions for measurement

169

170 170 170 170

171 171 171 171 17i 173 173

174 174 174 174 176 177 177

178 178 178 178 178 179 179 181

182 182 182

0954-6111/94/030165 + 30 $08.00/0 �9 1994 W. B. Saunders Co mpany Ltd

166 Topical Review

8.3 Single-breath breath holding method 8.4 Quality control

Section 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.9 9.10

9 Procedures for Blood Gas Measurement Definitions Normal ranges for arterial blood gas measurements Acid-base balance Safety Arterial blood gas sampling Capillary blood gas sampling The blood gas analyser End tidal P C O 2

Pulse oximetry Transcutaneous monitoring of blood gases

Section 10.1 10.2

10 Reference Values Reference equations Presentation of results

References

182 185

186 186 187 187 187 187 188 189 190 190 191

192 192 193

194

Introduction

The assessment of respiratory function is now a routine part of clinical practice. There are many specialized laboratories in the U K and they clearly need to provide results of the highest possible accuracy and reliability. Repeated measurements over a period of time are often of particular importance and multi-centred studies have become increasingly common. Standardization of respiratory function tests both within and between laboratories is thus essential and this topic has already been treated in detail both by the European Community for Steel and Coal (ECSC) (1) and by the American Thoracic Society (ATS) (2,3). An up-dated version of the European document has recently been published (4).

Readers may therefore be wondering why yet another document on these lines is required. Good reasons for this were revealed in a survey of respiratory function laboratories which was recently carried out by the Association of Respiratory Technicians and Physiologists (ARTP). This showed that there were considerable discrepancies between laboratories in the procedures in use; it was disturbing to find that, in a number of them, essential calibration and quality control procedures were inadequate or had simply been omitted.

It was clear, therefore, that there had been no general adoption of the ECSC or ATS recommendations in the UK and a Committee of British

Thoracic Society (BTS) and ARTP members was formed to report to the two organizations through their respective Education Committees. It seemed that one problem was possibly the very size and complexity of the ECSC and ATS documents and that the educational needs of student technicians, and indeed of more senior staff, would be better served by a simpler instruction manual which could be available on the laboratory bench for immediate referral. The Committee decided to deal primarily with those methods which were already in routine use in the majority of laboratories. We have concentrated on the actual procedures, without dealing to any extent with the important matter of interpretation, which would have otherwise caused undue enlargement of this document. We have taken advice from a number of sources and, not surprisingly, at many points we were obliged to settle for a compromise position. We hope nevertheless that our recommendations will improve laboratory practice and will be generally acceptable to both ARTP and BTS members.

A number of tests described here may be performed at sites other than the respiratory function laboratory such as wards, out-patient clinics, accident and emergency departments or general practitioners' surgeries. The requirements may differ from place to place but will almost certainly include peak expiratory flows, dynamic spirometry and the means for administering a bronchodilator. Blood gas measurements should be available to the wards and

Topical Review 167

accident and emergency departments. It may well be that some of these measurements are not at present carried out by a fully trained technician but these recommendations should nevertheless be applicable under all circumstances.

These guidelines were drawn up by the BTS/ARTP Liaison Committee. Present members are: Dr D. C. S. Hutchison (Chairman), Miss S. Revill (Secretary), Dr M. Allen, Dr S. L. Hill, Dr A. H. Kendrick, Dr M. R. Miller, Dr M. D. L. Morgan. Past members were: Dr J. M. B. Hughes and Dr P. M. Tweeddale. The report was prepared for press by Dr M. R. Miller. The Committee are most grateful to Sally Sampson for her help with Section 9, and to the members of the Education Committees of the BTS and ARTP for their encouragement during the completion of this project and to the many other members of both societies who kindly tendered most helpful advice.

Section I General Procedures

1.1 The subject should be correctly prepared for the tests and various subject details recorded.

1.2 The subject's age, height and weight (wearing indoor clothes without shoes) are obtained for later use in the calculation of the reference values. The height should be measured without shoes, with the feet together, standing as tall as possible with the eyes level looking straight ahead using an accurate measuring device (5). For patients with a deformity of the thoracic cage, such as a kyphoscoliosis, the arm span from finger tip to finger tip can be used instead as an estimate of height.

1.3 The operator should record the type and dosage of any (inhaled or oral) medication and when the drugs were last administered.

1.4 Ideally the subject should be asked to avoid: (1) smoking for 24 h prior to the test, (2) consuming alcohol for at least 4 h prior to the

test, (3) vigorous exercise for at least 30 rain prior to

the test, (4) wearing clothing which substantially restricts

full chest and abdominal expansion, (5) eating a substantial meal for at least 2 h prior

to the test, (6) taking short-acting bronchodilator drugs for at

least 4 h prior to the test. These requests should be made at the time of making the appointment. On arrival, all the points should be checked, and any deviations from them recorded. Where possible corrective action should be taken.

1.5 Subjects should be as relaxed as possible before and during the tests, and should be seated for

5-10 min prior to testing. This will give time for careful instruction in all required manoeuvres. The subject should remain seated until all technically acceptable manoeuvres are completed.

1.6 For reasons of safety the patient should not stand during dynamic tests such as PEF and FVC but should sit upright in a chair with arms. The patient should be positioned correctly in relation to the equipment.

1.7 Patients should be asked to loosen tight fitting clothing. Dentures should normally be left in place; if they are loose, they may interfere with performance and are then best removed.

1.8 When patients return for repeat testing, for example at a clinic, then ideally the time of day, the equipment and the operator should be the same.

1.9 Ambient temperature and barometric pressure must be recorded in order to allow body temperature and pressure standard (BTPS) corrections to be made. When using a spirometer, the use of the actual gas temperature within the spirometer (if available) would give a more accurate correction factor.

1.10 The usual order for performing lung function tests is as follows:

(1) dynamic studies PEF, spirometry, flow volume curves,

(2) static lung volumes, (3) gas transfer, (4) inhalation of bronchodilator agent if it is to be

used, (5) repeat dynamic studies if a bronchodilator was

given. There should be appropriate delays between tests as indicated in the subsequent sections in this document.

It should be noted that static lung volumes and gas transfer may be affected by the use of bronchodilators and tidal breathing manoeuvres may be disturbed by a recently performed maximal forced expiratory manoeuvre. Evidence for a better order of testing is currently lacking.

Section 2 Procedures for FEV~ and VC

2.1 DEFINITIONS

2.1.1 ~brced Expiratory Volume in 1 second (FEV1) This is the maximal volume of gas which can be

expired from the lungs in the first second of a forced expiration from a position of full inspiration.

2.1.2 Vital Capacity (VC) When the term Vital Capacity is used without any

further qualification it conventionally refers to a Relaxed Vital Capacity measurement as defined below.

168 Topical Review

Forced Vital Capacity (FVC). This is the maximal volume of gas which can be expired from the lungs during a forced expiration from a position of full inspiration.

Relaxed Vital Capacity (RVC). This can be measured in three ways:

(a) Expiratory Vital Capacity (EVC): The maximal volume of gas which can be expired from the lungs during a relaxed expiration from a position of full inspiration.

(b) Inspiratory Vital Capacity (IVC): The maximal volume of gas which can be inspired into the lungs during a relaxed inspiration from a position of full expiration.

(c) Two stage VC: Maximal ERV and IVC are obtained from separate manoeuvres. This may be useful in some patients with severe airflow limitation.

NOTE: all these volumes should be expressed in litres at body temperature and pressure, saturated with water vapour (BTPS).

2.2 EQUIPMENT

The equipment should be capable of measuring volumes of at least 8 1 and produce a graphical display of adequate size. For further details on equipment specification see references 1-5.

Calibration checks to confirm correct equipment function with regard to volume and time should be carried out on a regular basis. Non-sealed spirometers, (e.g. pneumotachograph based systems) should be calibrated prior to each recording session. Sealed spirometers require regular checking for leaks, dry bellows spirometers should be checked before each recording session.

Any necessary cleaning and maintenance procedures should also be carried out on a regular basis according to the manufacturer's recommendations.

2.3 PROCEDURE

2.3.1 The equipment and the patient are prepared for the test and the purpose and nature of the test are explained to the patient. A nose clip is usually not needed for measurement of FEV 1 and FVC, but is required for a relaxed VC. However, better FEV1 and FVC values may be obtained from children, adolescents and some non-caucasians if a nose-clip is used.

2.3.2 A relaxed VC (RVC) should be recorded first. The patient is fitted with a nose-clip and encouraged to blow out from a position of maximal inspiration at a sustained and comfortable speed until no further gas can be exhaled.

The manoeuvre is like a deep sigh and expiration should neither be forced nor held back. The term 'slow VC' should be avoided as this implies an artificially controlled manoeuvre and will generally result in a lower value than expected.

Older subjects and patients with airflow obstruction can often achieve a larger VC if they do not exhale forcibly. This is because the FVC manoeuvre causes dynamic compression of the airways which can reduce the expired volume.

2.3.3 For FEV~ and FVC the patient is instructed to breathe as deeply as possible (i.e. to full inspiration), to place the lips tightly around the mouthpiece and then to blow out into the equipment as hard and as fast as possible until no further gas can be exhaled.

The patient should prevent the tongue from occluding the mouthpiece and the teeth should be placed around the outside of the mouthpiece if it is a rigid tube.

Some systems require the patient to insert the mouthpiece and to breathe normally prior to the maximal inspiration.

The end of the test which defines FVC occurs when (a) less than 0.05 1 has been expired over a period of 2 s, or (b) the duration of exhalation exceeds 15 s, or (c) for clinical reasons the operator has to terminate the procedure.

2.3.4 The operator should observe the patient during the manoeuvres to confirm that the patient carried out the instructions and did not exhale pre- maturely or lose expired gas around the mouthpiece.

The operator should ensure that the patient continues to exhale until the flow of gas has ceased. Patients with airflow obstruction may take more than 10 s to complete FVC or relaxed VC. Some sealed systems with chart mechanisms cease timed movement after 6 s but the patient should continue to exhale until the pen shows no further vertical movement. The manoeuvre should be terminated if the patient becomes distressed.

Display of each forced expiratory manoeuvre is essential and should be inspected to confirm the blow was satisfactory. During the blow, maximum effort must be maintained throughout. A blow should be rejected on the following grounds: (i) a leak at the mouth, (ii) an obstructed mouthpiece due to tongue or false teeth, (iii) a poorly coordinated start to the manoeuvre indicated by either a time to Peak Flow greater than 300 ms, or a back extrapolated volume of greater than 5% of FVC or 0.1 1 (whichever is the greater)- see Figure 2.1 for an example and expla- nation of back extrapolation, (iv) a cough within the first second of the manoeuvre, or a later cough if it is deemed to have interfered with the blow, (v) early

Topical Review 169

1.00

0.75

FVC = 2.2

0.50,

0.25

, o . 1 1 O l

0.00 0.05 0.I0 0.15 0.20 0.25 Time (s)

Fig. 2.1 An example of back extrapolation on the first 0-25 s of a spirogram. The slope of the steepest part of the curve is extrapolated back to the time axis. The volume that has been expired by this time is the back extrapolated volume which is 0.111 in this example, and this is 5% of the final FVC. Please note the expanded and truncated time scale used to emphasize this point.

termination of the blow, (vi) the patient did not inspire to TLC, (vii) the expiratory effort was sub- maximal.

Not all equipment has the capability for identifying time to PEF or for performing back extrapolation. When recording a spirogram on an already moving trace it is important, where possible, to do a back extrapolation for the purposes of defining the start of the manoeuvre from which the timing of FEV~ is made. At peak flow a back extrapolation is made with a slope equal to peak flow until it meets the time axis. This intersection is the zero start time of the manoeuvre. Back extrapolated volume is that volume expired by the subject at this point - see Figure 2.1.

The values obtained should be recorded on paper or in the computer. A hard copy display of the manoeuvre is desirable.

2.3.5 The equipment is prepared for the next measurement. The patient should perform a minimum of three manoeuvres.

A minimum of 30 s should be left between attempts to allow the patient, particularly those with airflow obstruction, to recover. Patients should not be forced into attempting manoeuvres before recovery is complete.

2.3.6 The results reported should be the greatest FEV~ and FVC values achieved from at least three technically acceptable manoeuvres, irrespective of the manoeuvre in which they occur. If technically acceptable results are not achieved e.g. patient coughing or unable to perform the manoeuvre, the reason should be explained in the report.

For FEV~, FVC and VC to be considered technically acceptable, the test should have been performed

correctly and the chosen values should not exceed the next highest by more than 5% of 0"1 1, whichever is the greater.

If a graphical presentation is to be supplied with the report then the operator should be able to choose which blow or blows (superimposed) to print out. Some equipment only prints the 'best test', being defined as the single manoeuvre yielding the highest figure when FEV 1 and FVC are added together. The selection of 'best test' in this way is not recommended for routine use.

Operators should be aware that asthmatic patients may develop bronchoconstriction as a result of performing these manoeuvres (as shown by decreasing FEVI during successive tests) and they should not be pushed further. The best value achieved should be quoted and an appropriate comment given on the report form.

2.3.7 FEV I, FVC and VC should be reported at BTPS.

Where manual systems are in use or the equipment 'assumes' a fixed room temperature which is clearly incorrect (e.g. some types of dry bellows spirometer), the room temperature should be recorded and the appropriate temperature correction applied to correct the volumes to BTPS. For automated systems the room temperature should be keyed in prior to use.

2.3.8 The FEV~/VC ratio should be calculated using the greatest FEVj obtained and expressing it as a percentage of the greatest VC - whether the V(2 is from a forced or a relaxed manoeuvre.

The common practice of only reporting the FEVJ FVC can be misleading as FVC may underestimate the true VC.

2.3.9 Reference values and reference ranges should be calculated for the patient and both should be stated on the report f o r m- see Section 10.

Section 3 Procedure for Short-acting Bronchodilator Response

3.1 It is essential that patients being formally tested for response to a bronchodilator refrain from taking short acting bronchodilators for 4 h prior to the test.

Patients should receive clear and concise instructions regarding withholding inhaled bronchodilators (short acting) when arrangements are being made for the test. If the patient is unable to comply with the instructions or fails to do so, and cannot attend on another occasion, the dose of short-acting bronchodilators taken and the time relative to the test must be reported.

170 Topical Review

Inhaled steroids, long-acting bronchodilators or oral therapy should not be stopped except by request of the clinician, though these may make a substantial difference to the measured response. A drug history should be recorded.

3.2 FEV1, FVC and relaxed VC should be recorded using the standard guidelines both before and at a suitable time after administration of the bronchodilator. Also the PEF can be used which is recommended in the BTS guidelines on the management of asthma (6).

If a technically acceptable baseline cannot be achieved, the bronchodilator would not normally be administered since the response cannot be reliably assessed. The problem should be reported to the requesting clinician.

3.3 Recommendations for reversibility testing vary from laboratory to laboratory and there is no accepted 'gold standard' method at present. Any drug administered should be given in accordance with the British National Formulary recommendations and in the dose and manner laid down in the local protocol or as requested by the clinician.

Generally the response to a therapeutic dose of bronchodilator is assessed by administration of a standard dose from an appropriate inhalation device (e.g. metered dose inhaler). It is essential that inhalers and nebulizers are used in accordance with the recommendations of the manufacturer. The drug, dose and method of administration should be recorded.

When clinicians request a comparison of response to two different bronchodilators, perhaps with different modes of delivery, then the patient may be required to attend on two separate occasions (at the same time of day) and measurements made in accordance with the guidelines on each occasion. Maximal response to bronchodilator therapy is often assessed and this is best performed by the administration of a drug (or drugs simultaneously) using a nebulizer.

Staff should observe the way in which patients use an inhaler. Any errors in technique should be noted and reported to the clinician. Such errors should, if possible, be corrected at the time.

Table 1

Time before re-test

fl-agonists Salbutamol, Terbutaline 20 rain

Anticholinergic agents Ipratropium bromide 45 min

3.4 Times recommended after drug administration are shown in Table 1. Patients should remain seated in the vicinity of the testing area and should not smoke during this time period.

3.5 The report for testing the response to a bronchodilator must include:

(a) FEV 1 and VC - reference values and reference ranges - baseline values - post-bronchodilator values

(b) Drug, dose, mode of administration and time interval between administration and recording of response.

When assessing response to short-acting bronchodilators an absolute change of 160 ml in FEVt or 330 ml in VC can be taken as indicative of a statisti- cally significant response (7). Some clinical improve- ment may, however, take place in the absence of such changes.

Section 4 Procedures for Peak Expiratory Flow

4.1 DEFINITIONS

Peak Expiratory Flow (PEF) is defined as the maximum flow achievable from a forced expiration starting at full inspiration with an open glottis. The addition of the word 'rate' after Peak Expiratory Flow is mmecessary.

4.2 EQUIPMENT

It is desirable to use a device that primarily measures flow in order to record PEF. Differentiation of volume measurements with respect to time to obtain flow accentuates any 'noise' in the signal and the frequency response of volume measuring devices may be inadequate. The equipment must be capable of measuring up to 12 1 s - 1 (7201 ra in- 1). Devices with a continuous analogue output should have a frequency response that is flat up to 20 Hz and instruments that can be independently calibrated, such as pneumotachographs, should be calibrated prior to each recording session. Any necessary cleaning and maintenance procedures should be carried out according to manufacturer's instructions.

4.3 PROCEDURE

PEF may be recorded as part of a maximal forced expiratory manoeuvre, as detailed for measuring FVC and FEV 1 when the equipment primarily records flow. In many laboratories PEF will be recorded using a hand held portable PEF meter as a separate manoeuvre from recording the FVC and FEV 1. In some asthmatic patients full expiration may

Topical Review 171

lead to increasing and distressing wheeze. It is therefore recommended in such subjects that PEF is recorded first using a portable hand held PEF meter as described below.

4.3.1 The equipment is prepared for use and any recording needle returned to zero. The purpose and nature of the test is explained to the patient.

4.3.2 The subject takes a full inspiration through the mouth and then places lips and teeth around the mouthpiece to make a tight seal. A nose clip is not required. The subject then makes a short, sharp, hard blow with an open glottis and the blow can be stopped after about 1 s. During the blow the subject's hands must not occlude any of the exhaust holes on the meter and they should not impede the movement of the pointer on the scale if it is exposed. The meter should not be gripped tightly since this may also impede the movement of the pointer.

4.3.3 The highest reading of at least three acceptable blows should be recorded with the pointer being returned to 0 between blows. It is unlikely that better repeatability will be obtained by performing more than eight blows.

4.3.4 A blow should be rejected if the subject coughed during the procedure, or a leak at the mouth was detected.

Section 5 Procedures for Maximal Flow Volume Curves

5. l DEFINITIONS

A maximal flow volume curve is the graphical presentation of the flow versus volume signal recorded from a maximal forced expiration starting from full inspiration, which is immediately followed by a maximal inspiration. This is performed as one single smooth manoeuvre. The vertical scale for flow should be 21s-1 per unit with the horizontal scale for volume being 1 1 per unit. The display should be large enough for the shape of the maximal flow volume curve to be readily visualized. Automatic scaling of the flow volume curve is not recommended as this changes the size and scaling and so distorts the shape information contained in the trace.

5,2 EQUIPMENT

It is desirable to use a device that primarily measures flow in order to record a maximal flow volume curve. Differentiation of volume measurements with respect to time to obtain flow accentuates any noise in the signal and the frequency response of volume measuring devices may be inadequate. The equipment must be capable of measuring up to 121s-J (7201min ~) and 81 in

volume. The equipment should be calibrated prior to each testing session.

Any necessary cleaning and maintenance procedures should be carried out according to manufacturer's instructions.

5.3 INDICATIONS FOR MAXIMAL F L O W VOLUME CURVES

Some laboratories will use this technique for recording all their maximal forced expiratory manoeuvres to obtain FVC, FEV 1, and PEF. Maxi- mal flow volume curves are of help in distinguishing different types of airflow limitation and may be specifically requested for this purpose. True examples are shown in Figs 5.1 to 5.7 below. The interpretation of how maximal flow volume curves distinguish between normality, fixed and variable upper airway obstruction, and intrapulmonary airflow limitation due to either asthma or emphysema, is not an exact science.

5.4 PROCEDURE

5.4.1 The equipment is prepared for use, The purpose and nature of the test is explained to the patient.

5.4.2 The subject takes a full inspiration through the mouth and then places lips and teeth around the mouthpiece to make a tight seal. A nose clip is

12

10

8

~ P E F

MEF75

MEF5o Expiration 6 :: :

~'~ 4 ~ M E F 2 5

2 0 ~ /RV - 2

Inspiration - 4

- 6

- 8 MIFac tPIF I I 0 1 2 3 4 5 6

Volume (1)

Fig. 5.1 A normal maximal flow volmne loop with two tidal breaths preceding the loop. PEF=Peak Expiratory Flow, PIF=Peak Inspiratory Flow, TLC=Total Lung Capacity, RV=Residual Volume. MEFxx=Maximal Expira- tory Flow when xx% of the FVC remains to be delivered. MIFso=Maximal Inspiratory Flow at 50% of FVC. In normals the flow trace between PEF and MEF2s is approximately a straight line due to relatively homogenous empty- ing of the lungs.

172 Topical Review

8

4

~-. 2 I

- 2

- 4

- 6

-8: i I i 0 1 2 3 4

Volume (1)

Fig. 5.2 A recording of a partial followed by a full flow volume loop. The starting position for the partial loop should start from a point below full inspiration which is at least equal to 20% of the full FVC.

lit 1

6

I m

0

i 0 1 2 3 4 5 6

Volume (1)

Fig. 5.3 An example of a maximal flow volume loop from an elderly subject showing the curvilinearity in the latter part of the expiratory limb.

12

4

"~ 2

o

2i

I . I f I 1 2 3 4 5 6

Volume (1)

Fig. 5.4 This patient with chronic obstructive lung disease shows early collapse of large airways and a sudden drop in flow early in the expiratory part of the manoeuvre. The inspiratory limb is unaffected since the airways are being opened up by transmural pressure.

1 1 I

10

-81 I I I I 0 1 2 3 4 5 6

Volume (1)

Fig. 5.5 This patient with asthma shows a smooth curvilinear drop in flow with respect to volume indicating intrapulmonary airflow limitation. The inspiratory limb is relatively unaffected.

essential. The subject then makes a maximal forced expiration until no further gas can be exhaled, followed by a maximal inspiratory effort until the lungs are absolutely full again. The manoeuvre is then complete and the subject can remove the mouthpiece. Maximal effort must be maintained throughout.

5.4.3 The flow volume curve must then be displayed for inspection. The subject should be coached

on how to improve the manoeuvre using the graphical presentation as a guide. Criteria for rejection of a blow are the same as for FVC and FEV v

5.4.4 Figure 5.1 shows some of the many indices that have been derived from the maximal flow volume curve.

MEFTs , MEFso , MEF2s refer to the Maximal Expiratory Flow when 75%, 50% and 25% of the

Topical Review 173

I 10

z-" 4 o~

2

0

- 2

- 4

- 6

- 8 I 0 1

I I L 2 3 4 Volume (1)

I 5 6

Fig. 5.6 Variable extrathoracic upper airway obstruction due to goitre showing decapitation of the expiratory part of the loop with more extreme limitation of the inspiratory limb due to collapse of the trachea during inspiration.

12

10

2 I

0

- 2

- 4

--6

- 8 L I L I 1 0 I 2 3 4 5 6

Volume (1) Fig. 5. 7 Intrathoracic central airway obstruction showing decapitation of the expiratory limb of the loop but little, if any, reduction in the inspiratory limb. This was due to an intrathoracic restrosternal goitre.

FVC remain to be exhaled. The American equivalent nomenclature to MEF7s is FEF2s, which refers to the forced expiratory flow when 25% of the FVC has been expired. This nomenclature is not recommended.

None of these indices is of proven value in the management of individual subjects and they may be misleading. The ratio of MEFso to MIFso has been used to help identify certain changes in the shape of maximal flow volume curve (8).

5.5 ADDITIONAL ASPECTS TO MAXIMAL FLOW VOLUME

CURVES

5.5.1 It can be helpful to see where the resting tidal breathing trace is placed on the maximal flow volume curve. However, for truly valid comparisons to be made this needs to be derived from measuring a flow volume curve in a volume displacement body plethysmograph. The subject should place the mouth round the mouthpiece after a tidal exhalation (i.e. at FRC) and then breathe in and out for one or two breaths. The subject then inhales to the point of full inspiration and then performs a maximal forced expiratory manoeuvre until no more air can be expelled from the lungs. Without taking the mouth from the mouthpiece the subject then inhales fully again to the point of full inspiration, when the inspiration is complete.

5.5.2 Partial flow volume curves have been used to indicate the difference between flows at low lung volumes before and after the relaxing effect on

airway tone of a full inhalation. The procedure is for the subject to take a small breath in from the room, as if preparing to count to ten. The mouthpiece is then inserted in the mouth and a maximal expiratory blow is performed from this point until no more gas can be exhaled from the lungs. The subject then inhales to the point of full inspiration without taking the mouth from the mouthpiece and then a maximal forced expiratory manoeuvre is performed again. The manoeuvre is then complete. Total lung capacity is taken as the reference point for displaying these curves since the point of full expiration may differ slightly between the partial and full expiratory curves. The initial inspiration at the start of the manoeuvre should not approach the point of full inspiration (TLC), but must be at least 20% of the VC below this. This is necessary to avoid relaxing the airway tone at the beginning of the (partial) manoeuvre, since this occurs whenever full inspiration is achieved. A rest of 90 s must occur between these manoeuvres to allow resting airway tone to be re-established. Figure 5.2 shows an example of this procedure.

5.6 EXAMPLES OF DIFFERENT MAXIMAL FLOW VOLUME

CURVES

Figures 5.3 to 5.7 show various characteristic abnormalities seen on maximal flow volume curves. Experienced interpretation of the shape of the maximal flow volume curve is preferred to numerical description.

174 Topical Review

Section 6 Procedures for Static Lung Volumes and Capacities

The residual volume (RV), total lung capacity (TLC) and related volumes cannot be measured directly so special techniques are required to record these volumes. There are several accepted methods for determining these volumes, which are frequently referred to as 'static lung volumes', and these methods include helium dilution, nitrogen washout and plethysmography. The helium dilution methods to determine static lung volumes comprise the steady state method, which is described in this section, and the single breath method. The single breath method for determining the alveolar volume (VA) is given in Section 8 (subsection 8.3.8), and the use of plethysmography is covered in Section 7.

6.1 DEFINITIONS

Total Lung Capacity (TLC) The volume of gas in the lungs and airways at the

position of full inspiration.

Vital Capacity ( VC) When the term Vital Capacity is used without any

further qualification it conventionally refers to a Relaxed Vital Capacity measurement which can be measured in two ways:

(a) Expiratory Vital Capacity (EVC). The maximal volume of gas which can be expired from the lungs during a relaxed expiration from a position of full inspiration.

(b) Inspiratory Vital Capacity (IVC). The maximal volume of gas which can be inspired into the lungs during a relaxed inspiration from a position of full expiration.

Residual Volume ( R V) The volume of gas in the lungs and airways at the

position of full expiration.

Tidal Volume (VT or TV) The volume of gas expired or inspired during one

breathing cycle.

Functional Residual Capacity (FRC) The volume of gas in the lungs and airways at the

end of a tidal expiration.

Expiratory Reserve Volume (ERV) The maximum volume of gas which can be expired

from the position of FRC.

Inspiratory Capacity (IC) The maximum volume of gas which can be inspired

from the position of FRC.

Inspiratory Reserve Volume (IR V) The maximum volume of gas which can be inspired

from the position of end-inspiratory tidal volume.

Lung volumes should be expressed in litres at BTPS.

6.2 EQUIPMENT

6.2.1 For the steady state method the basic components of a closed circuit steady state system include a spirometer (for example a rolling seal or water sealed device), chart recorder, circulating pump, He analyser, 0 2 source, CO: absorber, and a mouthpiece assembly with a two-way tap. An 0 2 analyser is desirable as well. All these elements should be easily accessible to the operator. Equipment can range from a totally manual arrangement to a fully computerized system.

6.2.2. Quality control The volume calibration of the spirometer should be

checked daily and its linearity weekly. The He analyser (where direct readout is available) should be checked for linearity on a quarterly basis with different gas mixtures. Alternatively, the change in He concentration can be recorded when a known volume of air is introduced into the circuit from a calibration syringe. The volume of air added can be calculated from the He dilution using the FRC equation (see subsections 6.3.5 and 6.6) and compared with the actual volume introduced.

Tubing should be checked regularly for leaks, and the CO 2 absorber replenished as soon as it shows a colour change from reaction with CO 2. Any necessary cleaning and other maintenance procedures should also be carried out on a regular basis.

6.3 PROCEDURE: STEADY STATE METHOD

6.3.1 Measurement of FRC An example of the FRC calculation and measure-

ment of circuit dead space is given in Section 6.6. The manual technique for measuring FRC is as follows.

The closed circuit is prepared according to the manufacturer's instructions with the appropriate volumes of air, O 2 and He, these volumes being marked on the chart recorder. The circuit volume is 1/1 and comprises the dead space plus the total volume of gases added to the circuit. The gases are mixed within the circuit by the circulation pump and the He concentration (He 0 recorded at equilibrium.

Topical Review 175

6.3.2 The purpose and nature of the test are explained, the subject is seated by the equipment and the height of the mouthpiece assembly adjusted as appropriate. The subject should be encouraged to sit upright, the arms should rest by the side or along the arm of the chair and both feet should be positioned on the floor directly in front of the seat. Tight clothing should be loosened. The subject should not be able to view the chart recording or display unit while performing the test. The subject, wearing a nose-clip, starts to breathe via the mouthpiece; at this stage the circuit is closed and the subject is breathing to and from room air. The chart recorder is switched on. The mouthpiece tap is turned so that the subject is connected to the spirometer circuit at the end of a normal tidal expiration, i.e. at FRC, and the subject should continue with quiet tidal breathing through the test.

6.3.3 The He concentration is recorded every 30 s until it is stable, i.e. when two consecutive readings are within :t: 0.02% (absolute) of each other (Fig. 6.1), or within • if FRC is displayed directly. At this point the final reading is noted. The recorder trace is observed and the volume of gas in the circuit kept constant by adding 0 2 as it is consumed by the subject, while CO 2 is automati- cally removed by means of the absorber. If final stability of He concentration is not achieved by 10 min then the final reading at this time should be taken and the fact that stability was not reached should be recorded.

6.3.4 The subject is then asked to perform relaxed ERV manoeuvre and then an inspiratory

capacity manoeuvre followed by a VC manoeuvre. In the presence of chronic obstructive lung disease the FRC may change during these manoeuvres due to the effect of air trapping consequent from airway collapse. Sufficient time should be allowed between manoeuvres to enable the subject to return to normal breathing at a stable FRC.

6.3.5 The unknown volume, FRC, may be determined from the initial and final helium concentrations and the circuit volume, using:

FRC=Vj (He~-He2)/H % (ATPS) (1)

Where V 1 is the circuit volume, i.e. equipment dead space (VD) plus the measured volume of gases added when preparing the circuit. He~ and He 2 are the initial and final helium concentrations, recorded during the test. See Section 6.6 for a worked example.

6.3.7 The ERV and VC are read from the chart recorder trace (see Fig. 6.1).

The manoeuvres for ERV, IVC and then VC can be carried out in one sequence, or, ERV or IVC recorded with a rest before VC is performed. The highest value from a stable baseline should be taken. The manoeuvres for ERV and VC should be performed at the end of the test as in Fig. 6.1. Some systems allow the performance of these manoeuvres earlier in the test but this is not recommended.

The largest values should be reported and RV and TLC calculated as follows:

R V = F R C - ERV (2)

TLC=RV+VC or TLC--FRC+IC (3)

Initial He (He1)

Helium 14 - - ~ ~ concentration

(%) Final helium (He2)

10

Chart - ~ } recording (1) VC

Expiration ; A I 1 1 I ~ I I I 0 1 2 3 4 5 6 7

Time (rain)

Fig. 6.1 Diagram of He and volume changes when recording FRC by steady state He dilution. The subject is connected to the circuit at FRC (point A). The circuit volume is kept constant by adding 0 2 as required while CO 2 is absorbed. The He concentration is monitored until it reaches equilibrium. The change in He concentration is initially rapid, slowing as equilibrium is approached. ERV must be recorded at the time of FRC measurement in order to calculate the RV (FRC- ERV). RV+VC=TLC. In automated systems the He concentration is generally displayed both as a graph (shown above) and as numerical values. The latter is usually shown with calculated FRC. In manual systems the He concentrations (or FRC) have to be read from the He analyser unit and written down every 30 s.

176 Topical Review

(a)

Volume (1)

Expiration

L Start volume of Finish volume of spirometer spirometer

AAAAAAAAA///A/k/) ~/~ Switch-in ERV

Time (min)

(b)

Volume (1)

Expiration

1

I sSptial;t~eO~Urme of Finish volume ~

AAAA AAAAA/AAAAI /XL _ ff Switch-in V /

V

Time (min)

Fig. 6.2 Diagram illustrating correct and incorrect 'switch- in' methods during Helium dilution. (a). Correct connection of the subject to the circuit at the end of a tidal expiration i.e. at FRC. (b). Incorrect connection of the subject to the circuit i.e. during tidal breathing. The tracing is kept at the same level throughout the test and the true FRC determined by subtracting the small volume error (V) from the calculated FRC.

6.3.8 Provided one technically acceptable result has been achieved, this result is quoted. If a duplicate measurement is to be carried out then the delay between repeated measurements by the steady state helium dilution method must be at least the same as the time taken for FRC (helium concentration) to settle as mentioned in 6.3.3.

6.3.9 The recorded ambient temperature and barometric pressure are used to correct the lung volumes to BTPS. The spirometer temperature if available gives a more accurate correction and it should be stated in the report that this adjustment has been made.

6.4 SOURCES OF ERROR

6.4.1 Position of FRC The technician should connect the subject with the

circuit at FRC by observing chest or abdominal movement and by turning the mouthpiece tap swiftly at the end of a tidal expiration. Sometimes subjects breathe erratically or the technician misjudges the breathing pattern and the tap is not turned exactly at FRC. Corrections can be made to deal with small errors of this type (Fig. 6.2) but if an error of more than 500 ml has occurred the subject should be taken off the mouthpiece and allowed to breathe room air

Topical Review 177

for 2-3 min before the test is attempted again. The 0 2 flow should not be altered at this point to 'correct' the position of the chart recorder trace as this may alter the He concentration both by dilution and by the direct effect of O2 on the He analyser.

6.4.2 02 addition The Oe consumption of each subject is different

and 02 consumption may even vary during FRC measurement. The amount of 02 added to the circuit must therefore be adjusted as required. The flow of 02 should be adjusted to keep the trace within 200 ml of the starting circuit volume.

If there is an imbalance between 02 consumed and 02 returned to the system then the tracing of tidal breathing will have a constant and gradual slope up or down depending on whether too much or too little 02 is being supplied. Large deviations or sudden inconstant changes should lead to rejection of the test. For small deviations of the baseline the following equations can be used to calculate FRC,

FRC=(V I x HeffHe2)- V 2

Where V 1 is the initial volume of the apparatus including the dead space and V 2 is the final volume. This adjustment will also correct for errors concern- ing the switch in point as discussed in 6.4.1.

6.4.3 Length of" test The time taken for the He concentration in the

lungs and the circuit to reach equilibrium will vary. In normal subjects and those with restrictive disorders equilibrium is reached in 3-5 rain. In subjects with airflow obstruction who have poorly ventilated areas in the lungs the time taken to reach equilibrium will be extended. It is recommended that the test is regarded as complete after 10 rain from the beginning of the measurement.

6.4.4 Measurement of E R V The ERV can be taken from the VC or recorded

separately from VC. At least three relaxed VC manoeuvres should be performed which can be either expiratory or inspiratory. Occasionally subjects may change their FRC after they have been connected to the circuit and it is therefore important that ERV and IC manoeuvres are performed while the subject is still breathing on the circuit. The volumes recorded will then reflect the subject's FRC at the time and a reliable value can be calculated for RV.

6.4.5 Equipment fitults Operators should always be alert for equipment

problems such as leaks in the tubing, faulty recording speeds and non-linearity of the He analyser.

6.4.6 Other problems (1) Gas can leak from the circuit because the subject

does not hold the lips tightly enough around the mouthpiece.

(2) Subjects may find the mouthpiece or nose-clip uncomfortable, become restless and develop an irregular or excessive breathing pattern. I f the subject does not relax, even when reassured, the test should be stopped.

(3) Unstable He values can occur because the nose- clip is not fitting tightly enough or the subject has perforated eardrums (if the Eustachian tube is patent then it is believed that Helium may be lost by this route).

6,5 RECOMMENDATIONS FOR MINIMUM EQUIPMENT REQUIREMENTS Volume: at least 8 1 volume displacement, tolerance 5: 2% or i 50 ml whichever is the greater. Resol-

ution 25 ml. Driving Pressure: less than 0-03 kPa. Temperature: measurement inside the spirometer. Calibration: Calibrated syringe, at least 1 1. For further details on equipment specifications see references (1) and (2).

6.6 CALCULATIONS AND EXAMPLES

6.6.1 Calculation of FRC [rom the steady state He dilution method

The calculation of FRC requires an estimate of equipment dead space volume. The dead space volume is defined as the volume in the circuit when the spirometer is isolated from room air. It will be affected by the length of the breathing tubes, the mouthpiece assembly and the level of absorbent present in the CO 2 absorber unit. In theory the dead space should be calculated each time the circuit is prepared anew, but in practice, if the procedure is rigidly standardized and the circuit components remain unchanged, the mean value can be measured on one occasion and assumed to be constant for several subsequent tests. Some systems do not display the He concentration and dead space cannot be determined directly, in which case the manufacturer is presumed to have allowed for the dead space in the calculation of FRC; the accuracy of this must be checked regularly and not assumed to be correct for the lifetime of the instrument.

6.6.2 Dead space equation A technique for measuring dead space in systems

which display He concentration is as follows:

178 Topical Review

The spirometer is emptied completely and the circuit closed to air. About 500 ml of He are introduced into the spirometer. The pump is switched on and the He mixed with the gas already in the circuit until equilibrium is reached.

The pump is switched off, the circuit is opened to air, the spirometer is again emptied and the circuit closed again.

The pump is switched on and the He concentration at equilibrium noted (Heo).

The pump is switched off, the circuit is opened and 2 1 of air are drawn in. The exact volume added, V~, is read from the chart recorder trace. The circuit is closed again, the pump restarted and when a new equilibrium is reached, He concentration is again recorded (He 0.

VD=He x VJ(He o - Hex) (1)

where VD=equipment dead space. When the dead space volume is to be used in

further tests the measurement should be made in duplicate. If the figures agree within 50 ml, the mean dead space can be used in the FRC calculation. If the values do not agree, the tubing and absorber canister connections should be checked for leaks.

6.6.3 Example of calculation of FRC and lung volumes Barometric Pressure (PB) 756 mmHg Room temp 20~ BTPS factor 1.103 Dead space of equipment (VD) 3"3 1 Volume of gases (in 1 ATPS) added when setting up circuit: Air 2.8 0 2 0"2 He 1 "0 Total volume of gases added (Vadaed) 4"0 1 Initial He concentration (Hel) 13-70% Final He concentration (H%) 9.56% VC 3'65 1 ERV 0.95 1

FRC=(VD+ gadded) (Hel - Hez)/He2

FRC (ATPS)=(3.14+4.0) (13-70 - 9.56)19.56=3.09 1

RV (ATPS)=3'09 - 0.95=2.14 1

TLC (ATPS)=2.14+3.65=5.79 1

RV/TLC=(2.14/5-79) x 100=37%

Volumes expressed in litres at BTPS (using the factor 1.103) are:

FRC=3.41 1 RV=2.36 1 VC=4'03 1 TLC=6'39 1

Section 7 Procedures for Static Lung Volumes by Body Plethysmography

7.1 ~NTRODUCTION An alternative method to estimating the TLC and

RV is to use a body plethysmography of which there are essentially two t y p e s - the constant volume (i.e. patient sealed inside) and the variable volume (i.e. patient breathes from the room). Although both may be used to estimate TLC, the constant volume box is generally used for routine clinical measurements, whilst the variable volume box is more suited to studies of lung mechanics,/ 'or example measurement of lung compliance. The latter will not be considered further.

7.2 DEFINITIONS

The terminology is the same as in helium dilution lung volume measurements, with the exception that FRC is replaced by the term Thoracic Gas Volume (TGV). This is the volume of air in the thorax at which the measurement is made, which may be higher or lower than the FRC. When reporting the results, TGV should be the quoted volume, not FRC. All lung volumes are reported in litres at BTPS.

7.3 PRINCIPLE OF THE METHOD

The body plethysmograph uses Boyle's Law as its basis for operation. This states that at a constant temperature, the product of pressure (P) and volume (V) in a sealed vessel will be a constant. Thus, if pressure increases, volume will decrease. Mathemati- cally, this relationship is given by

PV=Constant (1)

If a respiratory effort is made against a shutter, with the glottis open, pressure changes will occur within the thoracic cavity which will result in compression and rarefaction of the air within the cavity. Alveolar pressure is assumed to be equal to mouth pressure, and changes in thoracic volume are recorded either by direct volume recording or by changes in box pressure.

7.4 EQUIPMENT

The equipment varies widely in its complexity, particularly with the automated or computerized systems. Essentially, there is a large box, of known volume, in which the subject is sealed during the measurement (Fig. 7.1). A shutter mechanism is located at the mouth, which includes a pneumotachograph to record flow, and hence expired volume, and a differential pressure transducer port to record changes in mouth pressure (PMouth)" Another

Topical Review 179

9

S pn

Fig. 7.1 Constant Volume Plethysmograph. The subject is completely enclosed and breathes from within the box. Mouth pressure (PM,,,th) and box pressure (PBox) are measured by individual transducers. The mouthpiece is attached to a shutter assembly .(S) and a pneumotachograph (pn) across which flow (V) is measured. Usually flow is integrated to give volume. Modified with permission from Gibson GJ. Clinical Tests of Respiratory Function. McMillan Press, London.

differential pressure transducer is located in the box wall, recording changes in box pressure (Pno• A vent is located in the wall of the box to allow excess pressure build-up in the box to be released.

7.5 C A L I B R A T I O N

The body plethysmograph must be calibrated at least once per day. The calibration performed should be as stated by the manufacturer and should include calibration of the pressure transducers and the pneumotachograph (usually done as volume rather than flow) and leak tests on the door seals and shutter assembly. Records of the calibrations should be kept.

7.6 P R O C E D U R E

Careful instruction is required prior to closing the door. The height of the shutter assembly should be adjusted so that the subject is sitting upright, and that when attached to the mouthpiece, the chin is perpen- dicular to the chest. As most shutters are noisy the subject should be given a demonstration of shutter closure.

I

(a)

(b)

Q Thermal Drift Equlibrium

Box pressure (kPa)

Thermal Drift Equilibrium

Time (s)

Fig. 7.2 Example of (a) flow and box pressure, and (b) volume and time from a body plethysmograph which has not achieved thermal equilibrium, and after thermal equilibrium has been achieved. The first trace in section (b) would also be obtained if the FRC was progressively changing.

7.6.1 The subject is seated in the box, the door closed and the subject asked to relax for approximately 2 rain.

This allows the temperature of the box to equili- brate with the body temperature of the subject. During this time, the box should be sealed periodi- cally and changes in Pnox noted. If pressure drift occurs, then thermal equilibrium has not yet occurred. The box vent should be opened to allow the increased pressure to be released (Fig. 7.2).

7.6.2 The subject is then attached to the mouthpiece with a nose-clip in place and with the flats of the hands placed against the cheeks and thumbs supporting beneath the chin.

Visual inspection is necessary to ensure the mouthpiece has been inserted correctly. The hands are placed on the sides of the face to reduce the movement of the cheeks and the floor of the mouth whilst the shutter is closed.

7.6.3 The subject breathes normally. Ensure that the subject is breathing in a relaxed

manner by observing the tidal breathing pattern. 7.6.4 Close the shutter, record the changes in Box

and Mouth pressure and then release shutter. This part of the procedure may be either manual or

automatic. The shutter is closed at the end of a normal tidal expiration and the subject is asked to pant quietly against the shutter. Some manufacturers suggest the subject should try to breathe quietly against the shutter but the instruction to pant is usually best. The resultant trace will show changes in

180 Topical Review

(a) (b)

TLC - - - Mout

fi ox A B[ ! " ~ . : - ~ I iC

I ERV

RV Fig. 7.3 Recording of a single complete measurement of thoracic gas volume, showing tidal volume; (a) showing tidal volume with respect to time, changes in box pressure, mouth pressure and the measurement of static lung volumes. (b) an alternative display of (a).

PBox and PMouth (Fig. 7.3). One or two complete loops of these changes should be recorded before the shutter is opened.

7.6.5 The subject exhales to RV, then inhales fully to TLC, then breathes normally.

Immediately the shutter opens, the subject should be instructed to breathe in fully to the point of maximal inspiration and then breathe out fully. This will allow recording of the IVC and ERV. Some equipment allows these manoeuvres to be recorded before the shutter has been closed (i.e. in section 7.6.3).

7.6.6 The box vent is opened, the pressure stabil- ized momentarily, and then the vent closed.

There may be a small pressure build up in the box during the manoeuvre. Venting the box at the end of each recording ensures pressure stability.

7.6.7 Repeat steps 7.6.3 to 7.6.6. A minimum of three technically acceptable traces

are required. Many normal subjects will be able to manage ten or more attempts over a period of about 5 min but patients with severe airflow limitation may manage only five or less.

7.6.8 Calculation. The basic equation for the calculation of TGV is

T G V = ( P b - 6"3) AVL/APA (2)

where Pb is the barometric pressure (kPa), 6"3 is the partial pressure (kPa) of water vapour at 37~ AVL is the change in lung volume and APA is the change in alveolar pressure when the subject makes inspiratory and expiratory efforts against the shutter. APA is measured indirectly as changes in mouth pressure PMouth'

Changes in volume are obtained from the product of changes in box pressure and the compliance of

the box (CBox) , the latter being obtained during calibration. Thus equation 2 becomes

T G V = ( P b - 6"3) CBo x (APBox/APMouth) (3)

APBoxlAPMouth is obtained from the tangent of the angle (0) from the pressure changes recorded during each manoeuvre (Fig. 7.3). Thus equation 3 becomes

T G V = ( P b - 6.3) CBox (1/tan0) (4)

The line to obtain the slope of the relationship between box pressure and mouth pressure should pass through the centre of a closed loop at the point where the inspiration/expiration commenced. At about 2 cmH20 above and below this centre point, the line should pass through the centre of the curve.

Three further modifications are required to equation 4. (a) Standardization to BTPS. (b) Correction of the box calibration for the volume

of the subject, which is indirectly estimated from body mass, using the equation

Masscor = rBox,cal • [VBox- (Body mass/l'O7)]/VBo x (5)

(c)

where V B . . . . . , is the box calibration factor, VBo x is the volume of the box and 1.07 is the average density of the human body and body mass is in kilograms. Standardization of units. To convert millilitres to litres multiply by 1/1000. The pressure inside the box is measured in cmH20, but Pb is in kPa, so to convert from cmH20 to kPa, (Pb-6 '3 ) is multiplied by 10.2. Equation 4 then becomes

Topical Review 181

PMouth

/~

(a) (b)

(c) (d)

b- Fig. Z4 Examples of poor quality results. (a) too forceful an inspiration and expiration, (b) poor panting/quiet breathing against the shutter so it is not possible to determine the angle from this tracing, (c) open loops which may be seen when mouth and box pressure changes are out of phase, either due to the patient or due to the mechanical performance of the box, so the positioning of the line to obtain the angle is difficult to determine, (d) shutter occluded the airway at the end of a tidal inspiration, and not after a tidal expiration. *Pen deflection.

TGV (BTPS)=(Pb - 6"3) x CBo x (1/tan0) Massco ,. (I l l000) 10-2 (6)

7.7 QUALITY CONTROL

Apart from the physiological variability inherent in the test, two sources of variability are possible. These are test technique and computat ional algorithms.

The magnitude of the variability due to test technique is about 10%, but can be much greater. The computational algorithms used are fairly standard, but a number of corrections are required. Further- more, the selection of reference values will alter the mean reference value and hence the reference range, leading to variations in interpretation.

7.7.1 Methodological Assuming the patient has been correctly instructed

and carefully prepared for the manoeuvre, there should be few problems of methodological quality control. However, on occasions poor co-operation can be observed from the recorder tracing, and it is therefore always important that technicians look carefully at the trace to determine its technical acceptability.

7.7.2 Number of tests A minimum of three technically acceptable tests

should be obtained, and the mean of these reported.

There should be a short period of time between each test to allow the patient to recover, the length of which depends on the patient. If after ten or so attempts, no acceptable measurements are obtained, the test should be abandoned and helium dilution performed if necessary. Figure 7.4 shows some poor quality results.

7.7.3 Reporting of test results It is helpful to the reporting officer to have avail-

able the spirometric trace for each test, the raw data used in the calculations, and the technician's comments. The latter are particularly important if the tests are suboptimal. The reporting officer may make use of this information when making the report, especially if the tests are of poor quality or the results are not consistent with other measures of lung function.

7.7.4 Equipment The recommended specifications and quality assur-

ance for equipment is given overleaf. A useful final check on the whole system may be performed using a normal subject. Reported values should agree to within 10% of previous estimates in the same subject, allowing for any physiological variation. If a greater than 10% difference occurs, the test should be repeated. I f the repeat test confirms the findings then

182 Topical Review

Table 2 Quality assurance methods for body plethysmography

Recommendation Checks/tests

Volume -Pneumotachograph • 3% over 7 l range Daily Pressure -Box • 1% of expected Twice daily*

-Mouth • 1% of expected Daily -Flow • 1% of expected Daily

Time -XY-t recorder • 2% if using a stopwatch Quarterly Leaks -Door seal A decay time of >5 s for an applied Daily

pressure signal -Shutter None should be present Daily

Response -XY-t recorder • 5% of stated response time Quarterly

*or more often when the ambient pressure is rapidly changing during the recording session.

the system should be regarded as 'out of control' and evaluated carefully for leaks, and pressure/volume/ timing accuracy.

agreement as to whether gas transfer is measured before or after bronchodilator. Values recorded after bronchodilator may be subject to less error due to labile bronchoconstriction.

Section 8 Procedures for Single Breath Carbon Monoxide Transfer Factor

8.1 DEFINITIONS 8.1.1 The ability of the lungs to transfer oxygen

from air to blood is termed the transfer factor of the lung (TL). In North America the term 'diffusing capacity' is often used instead.

8.1.2 The gas exchange characteristics of the lung are usually assessed by the measurement of the transfer factor of the lung using carbon monoxide (TLCO). Measurement of TLCO gives information about the amount of functioning capillary bed in contact with ventilated alveoli and reflects the presence of certain types of pulmonary vascular and parenchymal disorders. The additional index of the transfer coefficient (KCO) is used to provide information on gas transfer per unit of lung volume.

8.1.3 The SI units of transfer factor are mmol r a in - lkPa-1 . To convert from traditional units (ml m i n - l m m H g 1) to SI units the former are multiplied by 0"335. The units represent the uptake of a gas (mmol ra in- l ) per unit of pressure gradient (kPa).

The units of the transfer coefficient are mmol min l k P a 11 1.

8.2 CONDITIONS FOR MEASUREMENT The requirements under General Procedures in

Section 1.4 should ideally be met. The measurement of the gas transfer of the lungs may be influenced by the prior use of bronchodilator and if a nitrogen washout using oxygen has been performed to measure FRC then time must be allowed for equili- bration again with air. There seems to be no general

8.3 SINGLE-BREATH BREATH HOLDING METHOD 8.3.1 The equipment varies widely in complexity,

particularly with automated or computerized systems. Volume can be measured by a bag-in-box or by integrating the signal from a pneumotachograph. Other measurement systems are available but they will not be addressed here.

8.3.2 The apparatus generally consists of a 9 121 bag containing the test gas mixture, a 11 bag to collect the expired sample, a multi-way tap, spirometer, chart recorder run at a speed of 10 mm s 1 and gas analysers for CO and He. The use of an 02 analyser is optional for routine measurements. All these elements must be easily accessible to the operator. The spirometer and chart recorder allow monitoring of the test procedure. All circuit resistance should be as low as possible to avoid prolonging inspiratory and expiratory times. The sample bag must be fully evacuated before the test and must not be overfilled.

8.3.3 The gas mixture used to estimate 7LCO needs four components- CO, 02, N2 and the inert gas helium (He). The recommended gas mixtures are 0"3% CO and 14% He in Air (or other inert gas instead of He), or 0"3% CO and 10% He in Air, the choice being dependent on the working range of the helium analyser. For both mixtures, the percentage of 02 is approximately 18%. The mixture should be produced with a 'gas of medical quality' certificate.

8.3.4 The technique requires the subject to be connected to the system using a rubber or plastic mouthpiece and a nose-clip. The subject breathes room air for a few tidal breaths and is then instructed

Topical Review 183

TLC ........................... /,,

Og, we t .1; Fig. 8.1 Tracing obtained from a breath-hold manoeuvre. The breath-hold time for the Ogilvie method is calculated from the start of inspiration to the beginning of the sample collection. The Jones and Meade method is the preferred technique where the breath-hold time includes 0.7 of the inspiratory time and half of the sample time.

t o

(1) Take a small breath in. This step is optional, but many subjects find it much easier to perform the subsequent manoeuvres.

(2) Blow out as far as possible. This is a maximal exhalation and should be to RV. How- ever subjects with significant lung disease, particularly those with emphysema, may find blowing to a 'true' RV extremely difficult. A compromise between a 'true' RV and as close as possible to RV may then be needed.

(3) Maximally inhale as far as possible. This should be at least to 90% of the subject's VC. At lung volumes of greater than 90% of the subject's VC, both 7LCO and KCO have reached an approximate plateau and therefore further increases will have little effect on the estimate. The VI should be at least 90% of the subject's maximally recorded VC, the time of inhalation between 1'5 and 2 s in both normal subjects and in patients with an FEVJVC% of greater than 50%. In patients with an FEV~/ VC% of less than 0.5, 95% of the VI should be inhaled within 4 s.

(4) Hold the breath for 10 s without straining. In this step the subject should relax against the shutter (if there is one) and should be encouraged not to breathe out or breathe in against it, as this will alter the intrathoracic pressure and the pulmonary haemodynamics, resulting in either an increase (breathing in) or a decrease (breathing out) in 7LCO. The time of breath- holding should be set at 10 s, but may need to be reduced where the subject is dyspnoeic. The time set should be recorded.

(5) Blow out as far as possible. During this exhalation, the initial portion is discarded

(washout) since this contains gas from the anatomical and instrument dead space. This is followed by a second portion (sample), representative of alveolar gas, which is collected in the expired bag. The settings for the washout volume should be between 0"75 and 1.0 1. The sample volume should range from 0.50 to 1.0 1 and should ideally be collected in less than 3 s. If the patient's VC is less than 2.0 1, this washout and sample volume may be reduced accordingly. The settings for washout and sample volumes should be recorded. If the patient is dyspnoeic they need only blow out to just beyond the point of the sample collection.

8.3.5 On completion of the above the subject is disconnected from the circuit, and should remain seated before repeating the test at least once more. At least two technically acceptable measurements should be made and the mean of two or more acceptable tests is the reported value. If after five attempts an acceptable measurement cannot be achieved then the procedure should be abandoned. Since the dead space of the bag for the first measurement is filled with air a correction for this can be applied (3) although the effect is small. The time between manoeuvres should be at least 4 min. The resultant trace is shown in Fig. 8.1.

8.3.6 The concentrations of CO and He in the inspired and expired bags should be analysed at the same flow rate. The volume inspired and the actual breath-hold time should be recorded from the chart recorder (Fig. 8.1). Where possible, the helium analyser should be adjusted to allow for differences in 0 2 concentration in the inspired and expired gas samples because 02 affects the values of helium obtained from a thermal conductivity analyser. For

184 Topical Review

the recommended gas mixtures, the inspired concentration of 02 is about 18%, whilst the expired 02 is about 15%. Where an 02 analyser is present within the system the actual concentration can be measured and this value should be used.

8.3.7 Calculation of TLCO The basic equation to calculate 7LCO by this

method is

TLCO= VA ln(FACO{o)/FACO(r)) �9 (60 / t ) [ 1 / ( P b - 6 " 3 ) 1 (1)

where 60 converts seconds to minutes, t is the breath- hold time (s), ( P b - 6 . 3 ) converts tractional concentration to partial pressure of dry gas, Pb is barometric pressure, and In means the natural logarithm, with ln(FACO(o)/FACO(~)) reflecting the uptake of CO at time zero and at time t.

This basic equation translates into the working equation below.

TLCO-~( VI- VD,inst- 150) FIHe/[(0"95- FAH20 ) FAHe] ln[(FAHe/F~He) (bqCO/FACO)]

x 60/[t(Pb-6.3)] (2)

The subsequent sections (8.3.9 to 8.3.13) explain the derivation of its various components.

The transfer coefficient KCO is then calculated from

KCO = TLCO / VAeff (3)

where VAeff is the effective alveolar volume standardized to BTPS (see Section 8.3.8). VAeff is the preferred divisor for KCO, but if the VA measured in a plethysmograph is used then this must be stated in the report.

Corrections for back pressure of carbon monoxide and the effect of alveolar POe can be made if this is deemed necessary (3).

8.3.8 Measurement of Vae~ "c The volume of inhaled He and CO are diluted in

the RV of the lungs. Since He does not readily pass across the alveolar-capillary membrane, the volume of alveolar gas involved in gas exchange (VAeff) can be estimated from the dilution of He during the breath-hold, knowing the volume of gas inhaled (VI). Thus

VAeff = VIFIHe/FAHe (4)

where FIHe and FAHe are the fractional concentrations of inhaled and alveolar He respectively�9 Where VAeff is used in the calculation of TL, then TL is referred to as 'effective TL' An alternative calculation for VA is

VA=Residual Volume+ VT (5)

where the residual volume is obtained either from helium dilution or body plethysmography estimates of lung volumes. In normal subjects and in patients with mild airflow obstruction or a restrictive lung defect the difference between the two estimates is about 200-300ml. In patients with moderate to severe airflow obstruction, the VAeff will be smaller than VA. VAeffis the estimate of choice and should be reported in litres (BTPS)�9

8.3.9 Measurement of FaCO~o ~ Since the initial dilution of He and CO in the RV is

assumed to be equal, the alveolar concentration of CO at time zero can be calculated from the concentration of CO in the test gas mixture and the ratio of inhaled to alveolar He

FACO(o)= FAHe/FIHe (6)

8.3.10 Measurement of FACOI, ) The concentration of alveolar CO at any given

instant in time is taken to be that in the expired sample bag. Since the uptake of CO is approximately exponential, it is not possible to take any point in time to obtain FACO(t ) as the rate of uptake is constantly changing. By using the logarithm to the base e (ln), the curvilinear relationship is 'linearized', permitting any point on the x and y axis to be used.

8.3.11 Breath-hold time There are two methods of calculating the breath-

hold time (Fig�9 8�9 but the Jones-Meade method is recommended. The breath-hold time allows for the time of contact between the test gas mixture and the erthyrocytes when gas exchange is occurring. There- fore the time starts during the inspiration of the test gas mixture, continues during the breath-hold and ends during the expiration at the end of the test. The two methods yield similar results except in the presence of airflow obstruction which affects the Ogilvie but not the Jones-Meade method. Hence the latter is recommended.

8.3.12 Inspired dead space The volume of inspired test gas mixture (Vt) will

include the volume of the instrument dead space and the anatomical dead space of the subject. This must be accounted for, otherwise 7LCO will be overestimated. Instrument dead space (VDinst) should be less than 100 ml (including mouthpiece), the actual volume being supplied by the manufacturer. Anatomical dead space may be given an arbitrary value of 150 ml. Thus

VI,ad= VI - VD,inst- 150 ml (7)

where V~,ad is the adjusted volume inspired.

Topical Review 185

8.3.13 Adjustment for absorption of CO 2 and 1120 Before the expired gas sample is passed through

the helium analyser, CO 2 and H20 are absorbed. This reduces the total volume of the sample by the percentage of the gases absorbed. Consequently, the percentage of helium within the sample appears to rise. To overcome this, a CO2 adjustment must be applied to the FAHe used in calculation VA. For the estimation of FACO the correction appears in both denominator and numerator and therefore cancels out. Thus

FAHe,ad=FAHe (1-FACO 2 - FAH20 ) (8)

where FAHe,ad, FACO 2 and FAH20 are the adjusted helium and measured concentrations of He, CO 2 and H20 respectively. Where direct measurement of CO 2 is not available, an average value of 0.05 for FACO 2 can be used, so equation 8 becomes

FAHe,ad=FAHe(1 - 0.05 - FAH20 ) (9) =FAHe(0.95 - FAH20 )

The percentage of H20 in the sample may be estimated from tables, and is dependent on the ambient temperature. Failure to correct for CO 2 and H20 absorption results in an underestimation of TLCO of about 5%. In some systems no CO 2 absorption occurs and this correction should not be used.

8.3.14 Haemoglobin concentration If the haemoglobin is 19 g dl ~ or 11.7 g d l - l then

the adjusted transfer factor will be 10% lower or higher respectively than that recorded. To obtain measurements of haemoglobin on every patient undergoing routine clinical assessment will increase the cost of the procedure, add inconvenience to the patient and may raise ethical issues. It is however desirable that measurements of TLCO be reported at a standard haemoglobin of 14.6 g d l - 1. The equation is

TLCO,ad= TLCO,ob [10'22+Hb)/l.7Hb] (10)

where TLCO,ad and TLCO,ob are the adjusted and observed TLCO respectively, and Hb is the patient's measured Haemoglobin concentration. If this correction has been made then this should be made clear on the report form.

8.4 Q U A L I T Y C O N T R O L

8.4.1 Apart from the physiological variability inherent in the test, three sources of variability are possible. These are test technique, gas analysis and computational algorithms.

The acceptable magnitude of the variability due to test technique can be up to 10%, but potentially could be much greater. Errors in gas analysis are clearly a

Stepwise TLC ~ inspiration or

~ . . . . . ~ : ' . . . . . .~xpiration . . . . ..: "%......

/ / 1~oo slow / / inspiration

_ ~ Inspiration not".. ~ from residual ~ ".. ~-- volume ...... RV

Time Fig. 8.2 Some of the more common problems observed on the single-breath TLCO tracing. All should lead to rejection of the test. Modified with permission from Cotes JE. Lung Function--Assessment and Application in Medicine. Fifth edn. Oxford: Blackwell.

problem and can alter TLCO considerably, whilst 7LCO may vary by up to 41% depending on the computational algorithms used. Furthermore, the selection of reference values will alter the mean reference value and hence the reference range, leading to variations in interpretation.

8.4.2 Methodological Assuming the patient is correctly instructed and is

carefully prepared for the manoeuvre, there should be few problems of methodological quality control. However, on occasions poor co-operation can be observed from the recorder tracing, and it is therefore always important that technicians look carefully at the trace to determine its technical acceptability. Some of the common faults are shown in Fig. 8.2. All these faults should lead to rejection of the test which should be repeated after a delay of at least 4 min.

8.4.3 Inspired volume and flow Inadequate inspiration is the commonest problem.

Inspiratory time should be under 2 s in normals and below 4 s in patients with airflow limitation. The 7LCO will be reduced by about 13% if the inspiratory time is allowed to increase to 5 s. The equipment inspiratory resistance should be kept to a minimum since a high resistance will lead to an increase in lung capillary blood volume. For most equipment a VC of less than 11 renders the test impossible or the results invalid.

8.4.4 Breath-hold time This should be ideally between 9 and 10 s. Re-

ducing the time to below 9 s may increase TLCO. However, in patients with severe airflow obstruction, a reduced breath-hold time will be necessary. This should be noted and taken into account when

186 Topical Review

Table 3 Quality assurance methods for transfer factor

Recommendation Checks/tests

Volume i 3% over 71 range Weekly spirometer Daily pneumotachograph

CO, He, 02 concentrations Two- point-Daily Linearity-Quarterly

Quarterly

Daily

Time Chemical absorbers Leaks

CO range: 0-0.35% He range: ~14.0% 02 range: 0 100% • 2% using a stopwatch Changed at least daily None should be present

interpretation of the results is made. The time should not be set to below 6 s.

8.4.5 Number of tests and time between tests' A minimum of two technically acceptable tests

should be performed, and the mean of these reported. Reporting a maximum value is not acceptable. There should be at least 4 min between tests to allow as complete a washout of the test gas mixture as possible. A maximum number of five tests should be attempted. If after all five attempts no acceptable measurements are obtained, the test should be abandoned. Greater than five attempts will lead to an increasing effect of COHb on the estimated of TL,co

8.4.6 Test specification not met The test specifications are fairly rigidly set, and not

all patients will be able to meet them. Results, after several attempts where V is 85% of the VC or the

i

breath-hold time is 7 s after three or four genuine attempts by the subject, need not be rejected outright. It is recommended that those results which are 'close but suboptimal' be reported and clearly labelled as such for the interpreter to take into account. Inter- preters should be able to identify the discrepancy and the direction and magnitude of the potential error involved and decide whether the discrepancy is clinically significant.

8.4.7 Reporting of test results It is helpful to the reporting officer to have avail-

able the spirometric trace for each test, the raw data used in the calculations, the breath-hold time, washout and sample volumes settings and the technician's comments. The latter are particularly important if the tests are suboptimal. The reporting officer may make use of this information when making the report, especially if the test are of poor quality or the TLc o results are not consistent with other measures of lung function.

8.4.8 Equipment The recommended specification and quality assur-

ance for equipment is given above. 8.4.9 A useful final check on the whole system may

be performed either by using a 'dummy' subject such as a large (3-7 1) syringe or another spirometer, or by performing a physiological check using a normal subject. Using the large syringe (or spirometer), such as a 7 1 calibration syringe, a volume of 1-2 1 is set to simulate an RV. The test procedure is then performed, as for a subject. The ' VA' of the syringe can then be calculated knowing V1 and the inspired and expired concentration of helium. No correction for CO 2 is required. The 'VA' should agree to within 5% of the set lung volume. The expected dilution of CO by the syringe can also be calculated.

When a physiological control is used, reported values should agree to within 10% of those previously estimated in the same subject, allowing for any physiological variation. If a difference greater than 10% occurs, the test should be repeated. If this repeat test confirms the error then the TLCO system should be regarded as 'out of control' and evaluated carefully for leaks, non-linearity of the analysers, volume and timing accuracy.

Section 9 Procedures for Blood Gas Measurement

This document covers the procedures required to monitor blood gases by both direct and indirect methods.

9.1 D E F I N I T I O N S

PaO 2 is the partial pressure of oxygen in the arterial blood. PaO 2 and PaCO 2 are measured in kPa, which replaces the older unit, mmHg. (kPa=mmHg/ 7"5).

PaCO 2 is the partial pressure of carbon diox- ide in arterial blood.

Topical Review 187

70- 100- / / / / / 5 10 15 2O 25 /

90 -- HCO3-isopleths mmol 1-1

7.1 80 -- ~,o,-~ / 30 j

70 -- \ ~,4"" / ,

I ~ 1 I 1 I I I 0 2 4 6 8 10 12

kPa

I 1 I I I I I 0 15 30 45 60 75 90 mmHg

Arterial PCO2

Fig. 9.1 Acid-base diagram showing the relationship between PaCO 2 ([H +] or pH) and HCO 3- in various disorders. From Flenley 1978 (11), by courtesy of the British Journal of Hospital Medicine. (1~) Normal range, (=) significance.

[H +1

pH

SaO2

[ H C O 3 ]

Base excess

Base deficit

is the Hydrogen ion concentration with the units being nmol 1 is the negative logarithm of [H +] when expressed in nmol 1 1 is the percentage of haemoglobin which is oxygenated (oxyhaemoglobin), i.e. the oxygen saturation. is the serum concentration of bicarbonate ion in mmol 1-~. is the quantity of acid or base necessary to titrate 1 1 of blood to pH 7.4 at 37~ with a PaCO 2 of 5"3 kPa. is a negative base excess.

9.2 NORMAL RANGES FOR ARTERIAL BLOOD GAS

MEASUREMENTS

PaO 2 10.0-13.5 kPa PaCO 2 4.8-6.0 kPa [H+] 35.0~5.0 nmol 1 l pH 7.35--7.45 units SaO 2 96"0 98"0 (%) [HCO3- ] 23"0 270 mmol 1- i Base excess • 3'0 mmol 1- 1

9.3 ACID-BASE BALANCE The relationship between

[HCO 3 ] is shown in Fig. 9.1. PaCO 2 [H +] and

9.4 SAFETY

This is of paramount importance when taking blood, or handling blood samples. All blood samples must be handled carefully and regarded as potentially infective. The Health and Safety Commission describes the necessary procedures (9,10) and each department must have its own safety code, which should be followed exactly. (1) Blood must only be taken in designated areas. (2) Gloves must be worn at all times when taking

blood, handling samples, or cleaning blood gas analysers.

(3) 'Sharps' must be disposed of correctly. Samples should never be transport with a needle still attached, but always have a syringe cap in place. Needles must not be re-sheathed.

(4) Blood spills must be cleared up immediately, and blood waste must be disposed of, following local safety procedures.

(5) Any accident, however small, must be reported immediately.

9.5 ARTERIAL BLOOD GAS SAMPLING

9.5.1 This is usually performed by a clinician, as a blood sample is taken directly from an artery. However, the technique will be described briefly, as the technician may be required to assist. All blood samples must be mixed with an anticoagulant

188 Topical Review

(usually heparin) before analysis, or the blood will clot and prevent the blood gas analyser from working correctly.

9.5.2 Equipment 5 ml syringe & 25 G needle (or use a commercially available ready heparinized, low-resistance syringe & needle) Heparin (1000 IU ml 1) Syringe cap 2 ml syringe 23 g needle which is used to administer the local anaesthetic 1% lignocaine Gauze swabs Crepe bandage Adhesive plaster

9.5.3 Procedure NB: Arterial puncture should be avoided in

patients receiving anticoagulant therapy or who are receiving or about to receive streptokinase therapy for thromboembolic disease or myocardial infarction. (1) Blood is taken from a site where the pulse is

palpable, usually the radial or brachial artery of the non-dominant hand.

(2) The patient should preferably be reclining on a couch, but if not possible, in a comfortable chair, and the procedure explained.

(3) Local anaesthetic should always be used otherwise this is a painful procedure; it is injected close to the proposed site of arterial puncture. By abolishing pain, this should help to prevent hyperventilation, which can alter blood gases. Allow sufficient time for the anaesthetic to take effect before proceeding.

(4) If an ordinary syringe is to be used, it must be washed with heparin. One millilitre of heparin is drawn into the syringe and the barrel drawn back. The heparin in then expelled, leaving approximately 0" 1 ml in the dead space of the syringe, which is sufficient to prevent coagulation of the blood sample. Excess heparin will affect PCO2, and to a lesser extent pH and P O 2. No air bubbles should be left in the syringe.

(5) If the sample is to be taken from the brachial artery, the arm should be fully extended and well supported. If from the radial artery, the wrist should be supported in a hyper-extended position. The needle is inserted at an angle of about 45 ~

(6) Self-filling syringes are much more convenient and should be used routinely; the arterial pressure will push back the plunger, and quickly fill

the syringe. Two millilitres is sufficient for most analysers. Ordinary syringes will need to be drawn back as usual.

(7) Remove needle, and immediately apply pressure to the puncture site, and maintain for at least 5 rain. The application of a crepe bandage ensures that a constant pressure is applied. Fail- ure to do so may result in haemorrhage or formation of a thrombosis. Once the bandage is removed, the puncture site should be examined for any sign of further bleeding. If this occurs, pressure should be reapplied. Once bleeding has ceased, an adhesive plaster should be applied. The patient should be advised to return to the hospital accident and emergency department should any further bleeding or swelling occur.

(8) Air bubbles must be removed from the sample immediately. Remove the needle, hold syringe upright, and encourage bubbles to float to the surface by gently tapping the syringe. Bubbles can then be expelled and the sample is then capped in order to maintain anaerobic conditions. Samples with one or two small bubbles are acceptable for analysis. Samples containing froth will be irreversibly contaminated and should not be accepted.

(9) If the sample is not be analysed immediately, it should be stored in a mixture of ice and water in order to slow white cell metabolism thus prevent- ing changes in the blood gases. Do not use ice alone, as this may freeze the blood and haemo- lyse the red blood cells.

9.5.4 Sampling from an arterial cannula An indwelling arterial cannula may have been

inserted in the intensive care patient. The cannula is connected by a series of 3-way taps to a solution of 0"9% saline containing 1000IU of heparin per 500 ml. This flush solution is maintained at greater than systolic blood pressure.

To sample from the cannula, a 2 ml syringe is attached to the 3-way tap closest to the patient. The tap is opened to the syringe and a 2 ml arterial blood sample is drawn. The tap is then closed. This initial sample is discarded as it will have been diluted by flush solution. A second sample is then taken. It is then very important to flush the cannula with the flush solution (usually by pressing an in-line valve mechanism) in order to maintain the patency of the cannula.

9.6 CAPILLARY BLOOD GAS SAMPLING

In adults this is taken from the ear lobe (12). Correct sampling will give values close to arterial

Topical Review 189

levels. All blood samples must be mixed with an anticoagulant (usually heparin) before analysis, or the blood will clot and prevent the blood gas analyser from working correctly.

9.6.1 Equipment Pre-heparinized nylon cannula or glass capillary tubes and caps Rubber bung Sterile scalpel blade or lancet Green towel Vasodilator cream Gauze swabs Adhesive plaster Scissors

9.6.2 Procedure (1) The procedure is explained to the patient. Ear

rings should be removed, and the hair pinned back away from the ear. A surgical towel is placed on the patient's shoulder to protect clothing.

(2) The circulation to the ear is stimulated by vigorous rubbing with a gauze swab. This is assisted by the application of a vasodilator cream such as 'Algipan', which is applied to the ear lobe approximately 10 rain prior to sampling.

(3) The cream is removed, and the ear rubbed vigor- ously again.

(4) The earlobe is held firmly, and supported by placing a rubber bung behind the lobe. A sterile number 15 scalpel blade or lancet is used to quickly stab the ear about 3 mm from the edge of the earlobe, and to a depth of about 3 mm. Blood flow from the puncture site should be rapid.

(5) Blood flow can be encouraged by placing a finger behind the stab, and stroking gently. Do not squeeze the ear, or the sample will consist of a mixture of blood and tissue fluid and result in a lower pH, PaO 2 and 0 2 saturation, and an increase in PaCO>

(6) The blood sample (approximately 125/al) is collected into a capillary tube or a nylon intravenous cannula, which have been heparized before use. (a) A capillary tube should be held horizontally with one end placed into the well of blood. The tube will fill by capillary action. (b) The luer end of the cannula is held up to the well of blood, and blood flow into this is controlled by pressing or releasing a piece of rubber tubing attached to the far end of the cannula.

(7) To maintain anaerobic conditions prior to analysis, the capillary tube is capped after the addition of a metal stirring rod, and the cannula is closed

using surgical damps. The sample must be well mixed before analysis.

(8) Gauze swabs, or a cotton wool ball, are placed on the patient's ear lobe, and the patient asked to apply pressure until bleeding stops.

(9) A plaster is applied to the puncture site. This should remain in place for at least 12h, as removal can often trigger bleeding again.

The cannula method has the advantage of provid- ing a larger blood sample than a capillary tube, so minimizing the possibility of contamination with air. Frequent practice is needed in order to control blood flow sufficiently. If blood flow is slow, the sample should be discarded as it will not reflect true arterial blood gas levels.

9.7 THE BLOOD GAS ANALYSER

Blood gas analysers incorporate three electrode systems for the direct measurement of pH, PCO2, and PO> All other values reported are derived measurements.

To ensure reliability of measurements made, quality control procedures must be regularly conducted, and the machine must be correctly maintained.

9.7.1 Maintenance of blood gas analysers Maintenance procedures for individual analysers

will be provided by the manufacturer, and should be followed precisely. (1) The analyser and surrounding area must be kept

clean. Local safety procedures must be followed. To encourage safe working practice, 'sharps' bins, a tray on which to place the syringe while the sample is analysed, disposable gloves and cleaning materials should be immediately to hand. Hand washing facilities must be located nearby. Local safety rules must be followed at all times.

(2) Reagents and calibration gases should be checked daily, and replenished as necessary.

(3) Humidifiers must be topped up with sterile water. (4) Waste should be rendered harmless and suitably

disposed of at least once a day, and more often if the machine is in frequent use.

(5) The inlet to the analyser should be cleaned after each sample has been introduced into the machine, and any other blood spills cleaned immediately.

(6) Additional maintenance procedures should be carried out at intervals recommended by the manufacturers.

(7) The machine should be serviced twice a year by a qualified service engineer.

190 Topical Review

Cleaning the blood gas analyser is a professional responsibility of all those that use the equipment.

9.7.2 Calibration The majority of blood gas analysers are pro-

grammed to perform automatic one and two point calibrations every 1 2 h. The printout of the analyser will alert the operator to calibration errors, which must be rectified before samples can be analysed.

9.7.3 Quality control The technician must be aware of the reproduci-

bility and accuracy of results from the blood gas analyser and be able to take appropriate remedial action to correct deviations from accepted limits. Accuracy is defined as the difference between a measured value and the estimated true value, whereas reproducibility is a measure of the day to day variation of measurements.

9.7.4 Quality control material Commercially available aqueous buffer solutions

provide a simple way of performing quality control. Buffers are contained in glass ampoules and are equilibrated to a known P O 2 , P C O 2 and pH. Usually levels equivalent to normal blood gases, acidaemia, alkalaemia and high oxygen are supplied. Ampoules must be tested at the correct temperature, and according to the manufacturer's instructions. One of each level should be tested on a daily basis, and checked against the range supplied by the manufacturer. This gives information on the accuracy of the electrodes, but gives no information on the day to day variability. To find this, each batch of quality control ampoules should be tested daily for a minimum of 10 days, then the mean and error limits ( :t: 2 standard deviations) calculated. Future values should be plotted, and if they fall outside these calculated limits, the operator should take remedial action. Other methods of quality control less commonly used include blood tonometry, or quality control solutions containing human erythrocytes, or with a viscosity similar to blood.

9.8 END TIDAL P C O 2

This is an indirect measurement of arterial PCO 2 commonly used during sleep studies or to detect hyperventilation. In subjects without significant airflow obstruction, expired PCO 2 during tidal breathing rises until a plateau is reached, which is close to PaCO 2. The measurement should be taken as the mean of at least five breaths.

End tidal P C O 2 c a n be recorded at the mouth or nose, using narrow bore tubing. The CO 2 analyser must have a rapid response time, and must be

calibrated with 5% CO 2 immediately before each test procedure. The weakness of this method is that, in patients with airflow obstruction, a plateau is not achieved during expiration and PaCO 2 cannot therefore be estimated.

9.9 PULSE OXIMETRY

9.9.1 The pulse oximeter gives an indirect measurement of oxygen saturation which is used for continuous monitoring, thus obviating the need for frequent arterial sampling. Oximeter probes have been designed for the earlobe or finger tip. A light source is sited on one side of the probe, and a photodetector on the other.

The light source consists of two light-emitting diodes, usually at wavelengths of 660 nm (red) and 940 nm (infra-red), which have different absorption spectra with respect to oxyhaemoglobin and reduced haemoglobin.

The instrument is designed to separate the pulsatile component of the light signal (representing arterial blood) from the non-pulsatile components, which include skin, bone, and other tissues, together with blood in the veins and capillaries.

9.9.2 Limitations (1) Different makes of oximeter differ in accuracy,

the 95% confidence limits for the measurement being of the order of i 4%. Thus an oximeter reading of 95% could indicate a PaO 2 between 8.0kPa (91% saturation) and 21.3kPa (99% saturation). Their accuracy is considerably reduced when SaO 2 falls below 80%.

(2) Pulse oximetry is of limited use in monitoring blood gases, as large changes in PO 2 are necessary to produce a significant SaO 2 change in the upper flat section of the oxyhaemoglobin dissociation curve.

(3) Operators should ensure that there is good circulation to the finger or ear. Poor circulation will result in a low quality signal and unreliable estimation of 0 2 saturation.

(4) Nail varnishes (especially blue, green or black) are likely to cause a reduction in the SaOz reading. Nail varnish should be removed, or the probe mounted sideways on the finger in order to eliminate this problem. Avoid siting ear probes over holes for pierced ears.

(5) The readings may be affected by the degree of skin pigmentation, as calibration curves have usually been established in white subjects. Differ- ences are unlikely to be of clinical significance.

(6) Abnormal haemoglobins: oximeters that operate on two wavelengths are unable to distinguish

Topical Review 191

oxyhaemoglobin fiom carboxyhaemoglobin or methaemoglobin. Thus SaO 2 may appear normal by this method, even if the true SaO 2 is grossly reduced. Polarographic methods are unaffected. In anaemic subjects, the accuracy of the method is reduced.

(7) Dyes: intravenous administration of dyes such as indocyanine green or methylene blue (used for diagnostic purposes) can cause serious underestimation of Sa02.

9.10 TRANSCUTANEOUS MONITORING OF BLOOD GASES

The arterial P O 2 and PCO 2 can be monitored by means of electrodes fixed to the skin surface. This type of electrode was originally developed for use in newborn infants but can readily be used in adult s u b j e c t s . P O 2 and PCO 2 can be measured either by separate electrodes or by a single combined electrode. Each type incorporates a thermostatically controlled heating element within the electrode structure, designed to increase the blood flow in the immediately underlying tissues. The normal electrode oper- ating temperature is 44-45~ at which temperature the gas tensions at the skin surface should theoreti- cally approach those of the arterial blood.

9.10.1 Transcutaneous P02 (teP02) A polarographic electrode is used, similar in prin-

ciple to the electrode used in blood-gas equipment, but designed in such a way that the platinum cathode is separated from the skin surface by a thin polythene membrane permeable to gases only.

Calibration requires only a two point procedure as the output from the electrode is virtually linear over the whole usable range. A number of models have a built-in calibration device otherwise the calibration points must be established as below. Calibration gases mixtures in small cylinders are usually provided by the manufacturer.

Lower point calibration (zero PO2): this can quite simply be obtained by exposing the electrode to pure nitrogen, placing a drop of a reducing solution such as saturated sodium sulphite on the electrode surface, or by disconnecting the electrode from the power source (electrical zero).

Upper point calibration: By the conventional method, air or a gas mixture of known 02 compo- sition is used. The PO2 of the calibrating gas should be near to the top of the expected range, and the electrode should be at the working temperature. Dry gases are sufficiently accurate for this purpose.

Greater accuracy can be obtained by using the subject's own arterial blood (or arterialized earlobe sample) for the upper calibration point. The gas

calibration method is first used as a rough guide; the electrode is then attached to the skin and when a stable reading has been obtained, the apparatus is recalibrated to the arterial value. Recalibration of the lower point is not necessary as this remains unchanged.

9.10.2 Transcutaneous PC02 (tcPC02) A modification of the Severinghat~s electrode is

used. CO 2 diffuses from the skin across a polythene membrane and into a bicarbonate solution, the pH of which is measured by a glass electrode.

For calibration two gas mixtures are needed, with tcPCO 2 values spanning the expected range. Small cylinders containing CO 2 at 5 and 10% are often provided. A gas mixture with z e r o PCO 2 cannot be used as the electrode is unstable at that point. The tcPCO 2 value so measured is always substantially greater than the true arterial value and a correction factor must be applied.

The 95% response time of tcPCO2 electrodes is much slower than that of the tcPCO 2 electrodes (3 rain or longer) and they cannot be used to monitor rapidly altering changes.

9.10.3 Placement of electrodes The electrode should be fixed to a readily acces-

sible and hairless area of skin. Suitable sites are the flexor aspect of the forearm, over the biceps muscle or on the anterior upper chest. The skin should first be rubbed with an alcohol impregnated swab (abrasion of the skin is sometimes recommended but is not necessary). The electrode is then fixed to the skin using a suitable adhesive device which is normally provided by the manufacturer. A warm-up time of 15-20 rain is required before stable readings can be obtained.

The electrode should not be left at one site for more than 4 h at a time (during sleep studies, for example), otherwise a blister may be formed. If the site is to be changed, it would be wise to recalibrate the electrode though it is not yet known whether this is absolutely necessary. No transcutaneous electrodes will give accurate readings in states where the skin is poorly perfused such as shock or heart failure.

9.10.4 Uses or transcutaneous monitoring (a) Continuous monitoring: The method was intro-

duced for monitoring of newborn infants and can be used in adults for studies in sleep or assessment and management of hypoventilation. The monitoring site should be changed after 4 h.

(b) Oxygen administration: The method gives accurate estimates of PaO 2 at levels up to 100 kPa

192 Topical Review

Table 4

Index Unit Regression Equation RSD

Men FVC 1 FEV l 1 PEF 1 s 1 TLC 1 RV 1 FRC 1 RV% % FEVffVC % 7LCO mmolmin ~ kPA 1

Women FVC 1 FEV 1 1 PEF 1 s- TLC 1 RV 1 FRC 1 RV% % FEVI/VC % TLCO mmol min- 1 kPA- t

5.76H- 0.026A- 4.34 0.61 4-30H- 0.029A 2.49 0.51 6.14H - 0.043A+0.15 1.21 7.99H - 7.08 0.70 1.31H+0-022A- 1.23 0-41 2.34H+0.009A- 1-09 0.60 0-39A+ 13"96 5.46 -0.18A+87.21 7.17 11.11H- 0-066A- 6.03 1.41

4.43H-0.026A 2.89 0.43 3.95H - 0.025A - 2.60 0.38 5-50H - 0-030A- 1.11 0.90 6.60H - 5.79 0.60 1.81H+0.016A-2.00 0-35 2-24H+0.001A- 1-00 0.50 0.34A+18.96 5.83 - 0.19A+89-10 6.5i 8.18H - 0.049A- 2.74 1.17

where A is age in years, H is height in metres and RSD is the residual standard deviation. These equations have the problem that they are not internally consistent. Thus the ratio for FEVJVC calculated from the individual reference values for FEVI and VC may differ from the ratio calculated directly from the FEVjVC equation given above. Although these summary equations have yet to be perfected they are still recommended for use.

and can thus be used in studies involving hyper- oxia or assessment of equipment for oxygen administration.

(c) Exercise testing: Due to their fast response time, tcPO2 electrodes can follow blood gas changes accurately during any form of exercise.

9.10.5 Compar&ons with pu&e oximetry The transcutaneous PO2 method is a much more

useful moni tor when SaO2 is greater than 90% and arterial PO~ values up to 100 kPa can be measured. There is a discrepancy between P a O ; and tcPO 2 if the arterial calibration method is not used.

Pulse oximetry requires no skin heating and there is no danger of skin damage; no warm-up time is needed and no calibration is required. Pulse rate can be obtained simultaneously.

9.10.6 For further reading see references 13-15.

Sect ion 10 Reference Values

10.1 REFERENCE EQUATIONS

10.1.1 Adults It is desirable that reference values (often known

as 'predicted' or 'normal ' values) should be standardized. Summary equations for subjects of

caucasian descent have been produced for standardization purposes by the European Community for Steel and Coal (1,4). The relevant equations are shown for ages between 18 and 70 years. NB: for subjects between 18 and 25 years an age of 25 should be entered because of the lack of decline in function between these ages in the 'normal ' population.

10.1.2 The size of lungs varies between ethnic groups. Fo r FEV 1 and FVC (and possibly also for TLC) the predicted value should be multiplied by a factor of 0.9 for Japanese, Polynesian, Indian, Pakistani and African subjects or those of African descent (4). No adjustment needs to be made for Hong Kong Chinese. Therefore the above predic- tion equations can still be used and this final adjustment is made to the predicted value. The residual standard deviations for the equations remain unchanged. On the report it must be made clear if this adjustment for ethnicity has been made. Adjust- ments to other indices are not recommended.

10.1.3 Children No summary equations have yet been published

for children although a comprehensive list of reference equations is available (16). There is particular

Topical Review 193

Table 5

Index Unit Regression Equation RSD Reference

Boys FVC 1 5.00H+0.078A- 5.51 0.54 (a) FEV1 1 4-60H+0.045A- 4.81 0-52 (a) PEF 1 s i 7.80H+0.166A-8.06 1.65 (a) PEF 1 min 1 529H-423 50 (b) TLC l 6 2 3 H - 5.00 0.51 (c) RV 1 0.96H - 0.48 0-40 (c) FRC 1 3.64H - 3-00 0.38 (c) RV% % 22.6 8.89 (c) FEVJFVC % - 8.7H - 0.14A+ 103.6 6-72 (a) 7LCO mmol min-1 kPA a (t"956 x TLC)+l-23 1'08 (d)

Girls FVC 1 3"30H+0-092A- 3-47 0"50 (a) FEV l 1 270H+0.085A - 2.70 0.42 (a) PEF 1 s -1 4.90H+0.157A 3.92 1.34 (a) PEF 1 min - 1 528H - 423 41 (b) TLC 1 5.67H - 4.41 0.46 (c) RV 1 0.97H- 0.51 0.40 (c) FRC 1 3.35H- 2.69 0.37 (c) RV% % 23"9 7"92 (c) FEVIPr % - 11 "IH -0.11A+ 107.4 7-66 (a) TLCO mmol min- l kPA i (1.956 • TLC)+l-23 1.08 (d)

(a) Knudson, 1976, Pneumotachograph. (b) Godfrey, 1970, Wright PEF meter. (c) Haluszka, 1976, Plethysmograph. (d) Haluszka, 1981, Single Breath Method.

difficulty in adolescence and discretion should be used as to whether adult of paediatric reference values are appropriate. The choice of which equat ion to use will depend on age range and equipment. The equations given below are presented in reference 16 and are from large samples with as wide an age range (usually 5-17) as possible, Staff should establish which reference values are in use (or are programmed into the equipment) in their laboratory and why they are being used.

10.1.4 For KCO the ERS recommendat ion is to divide the predicted 7LCO by the predicted TLC. The residual standard deviation for this predicted KCO is not defined.

10.2 PRESENTATION OF RESULTS 10.2.1 The expected variation or range about the

reference value can be calculated by multiplying the RSD by 1"645 (1,4). This represents the limits that will include 90% of the populat ion in a normal distribution; thus 5% of the populat ion will lie outside this range at the lower end of the normal distribution and 5% at the upper end.

For example, the mean reference value for FEV 1 in a man of height 1.70 m and aged 45 years is 3.52 l

BTPS with R S D 0.51 I. The reference range is then given by R S D x 1.645=0.841. The mean reference value and range can be reported as:

3.52 4- 0.84 1 or 3.52 1 (range 2.684.36)

10.2.2 If a patient is having lung function tests performed over several years the above ranges will be changing with time. The preferred method (17) for making comparisons year by year under these circumstances is that of Standardized Residuals (SR). They are derived from:

SR=(Observed - Predicted)/RSD

where RSD is the residual standard deviation taken from the regression equation used to derive the predicted value. The predicted value is the mean value found for subjects o f the same sex, age, height and ethnic extraction. SR expresses the subject's deviation from this predicted value in terms of the expected variat ion within the normal population. An SR of zero means the subject's result is the same as the predicted value. An SR of - 1.645 means that the subject's value is at the lower 90% confidence limit, that is 1"645 standard deviations below the predicted value. SR values are independent of age, height and

194 Topical Review

sex bias, and they have the same scale and uni tary value for all lung funct ion indices.

Example calculation o j S R

Consider a m a n aged 70 years of height 1-60 m and using the ECSC equa t ion where the R S D is 0.51 1 it follows:

Predicted FEV~ =2.36 1 Observed = 1"34 1 Percent predicted =57% S R = ( 1 " 3 4 - 2.36)/0-51 = - 2-00

Fo r a m a n aged 25 years of height 1.80 metres:

Predicted FEVt =4.52 1 Observed =3"50 1 Percent predicted =77% SR=(3"50 - 4.52)/0.51 = - 2.00

The elderly m a n has an F E V 1 tha t is 57% of predicted and this is 2.00 s tandard deviat ions below predicted (SR= - 2 . 0 0 ) whereas the younger m a n has an FEV~ tha t is 77% of predicted which is also 2"0 s tandard deviat ions below predicted. Therefore percent of predicted falsely suggests tha t the older m a n has 'worse ' lung funct ion t han the young m a n when their results are equivalent in terms of devia t ion f rom the popu la t ion mean.

References

1. Quanjer Phil. Standardised Iung function testing. Report Working Party for the European Community for Steel and Coal. Bull Eur Physiopath Respir 1983; 19: Suppl. 15.

2. American Thoracic Society. Standardisation of spirometry - 1987 update. Am Re~, Respir Dis' I987; 136: 1285 1298.

3. American Thoracic Society. Single Breath carbon monoxide diffusing capacity (transfer factor). Recom-

mendations for a standardized technique. Am Rev Respir Dis 1987; 136" 1299-1307.

4. Quanjer Phil, ed. Standardization of Lung Function Tests 1993 Update. Report Working Party for the European Community for Steel and Coal. Eur Respir J 1993; 6: Suppl. 16.

5. Cotes JE, ed. Lung Funetion: Assessment and Appli- cation in Medicine. Fifth edn. Blackwell Scientific Pub- lications 1993.

6. Statement by the British Thoracic Society. Guidelines on the management of asthma. Thorax 1993; 48: Supplement S1 $24.

7. Tweeddale PM, Alexander F, McHardy GJR. Short term variability in FEV 1 and bronchodilator respon- siveness in patients with obstructive ventilatory defects. Thorax 1987; 42: 487490.

8. Miller RD, Hyatt RE. Obstruction lesions of the larynx and trachea: clinical and physiologic characteristics. Mayo Clin Pror 1969; 44: 145-161.

9. H.M.S.O. Safe working and the prevention of infection in clinical laboratories. London, 1991.

10. H.M.S.O. Safe working and the prevention of infection in clinical laboratories - model rules for staff and visi- tors. London, 1991.

11. Flenley DC. Clinical physiology: interpretation of blood gas and acid base data. Br J Hosp Med 1978; 20: 384-394.

12. Spiro SG, Dowdeswell 1RG. Arterialized ear lobe blood samples for blood gas tensions. Br JDis Chest 1976; 70: 263-268.

13. Jubran A. Pulse oximetry. In: Tobin MJ, ed. Res'pira- tory Monitoring. New York: Churchill Livingstone, 1991.

14. Gray BJ, Hutchinson DCS. Transcutaneous and transconjunctival oxygen monitoring. In: Tobin MJ, ed. Respirator), Monitoring. New York: Churchill Livingstone, 1991.

15. Clark JS, Votteri B, Ariagno RL et al. Noninvasive assessment of blood gases. Am Rev Respir Dis' 1992; 145: 220-232.

16. Quanjer Phil, Helms P, Bjure J, Gaultier C1. Standard- isation of lung function tests in paediatrics. Eur Respir J 1989; 2" Suppl. 4.

17. Miller MR, Pincock AC. Predicted values: how should we use them? Thorax 1988; 43: 265-267.

Documents

Guidelines for the measurement of respiratory function