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Transcutaneous oxygen tension in the leg during exercise in patients with chronic cardiac failure
International Journal of Cardiology, 28 (1990) 51-56 Elsevier
CARD10
51
01073
Transcutaneous oxygen tension in the leg during exercise in patients with chronic cardiac failure J.S. Elborn,
M. Riley, C.F. Stanford
and D.P. Nicholls
Royal Victoria Hospital, Belfast, Northern Ireland (Received
3 August
1989; revision
accepted
1 February
1990)
Elborn JS, Riley M, Stanford CF, Nicholls DP. Transcutaneous oxygen tension in the leg during exercise in patients with chronic cardiac failure. Int J Cardiol 1990;28:51-56. The tran~~ta~~eous partial pressure of oxygen measured in the lower limb was compared in 16 patients with chronic cardiac failure and seven normal subjects. At rest, there was no significant difference between patients and normals. At peak exercise, the partial pressure of oxygen fell significantly in those in heart failure, whereas -..I change was observed in normal subjects. No changes in arterial oxygen saturation (oximetry) were observed. These changes are likely to reflect abnormalities of peripheral perfusion of the skin. Key words: Transcutaneous
oxygen measurement;
Introduction
Transcutaneous monitors for the measurement of the partial pressure of oxygen in blood were initially developed for neonatal monitoring [l]. Since then, these monitors have found a number of uses, including the monitoring of patients in the intensive care unit [2], the monitoring of changes in blood gas concentrations during exercise [3], and as a screening test for intermittent claudication [4]. Patients with chronic cardiac failure demonstrate attenuation of peripheral blood flow during exercise [5,6]. The purpose of this study was to examine the transcutaneous partial pressure of oxygen in a group of patients with chronic cardiac
Correspondence to: Dr. D.P. Nicholls, Royal Hospital, Belfast BT12 6BA, Northern Ireland.
0167-5273/90/$03.50
Victoria
0 1990 Elsevier Science Publishers
Heart failure
failure and in a group of age- and sex-matched controls, in order to see if impairment of blood flow in the legs of such patients might be reflected in an abnormal response to exercise. Methods
In this study, 16 male patients with chronic cardiac failure aged 63 (6) years, mean (standard deviation), and body weight 69 (8) kg were compared to seven age- and sex-matched normal controls aged 60 (10) years and weight 72 (9) kg. All patients had a history and electrocardiographic evidence of ischaemic heart disease, had previously been in hospital with an episode of left ventricular failure, and had been stabilised by diuretic therapy for at least four weeks. Demographic details of the patients and their treatment are shown in Table 1. All patients had reduced exercise capacity (peak oxygen uptake of less than
B.V. (Biomedical
Division)
52
TABLE 7 Demographic details of the 16 patients with heart failure. Patient number
Age (yr)
Weight
NYHA grade
Peak CO,
LVEF
Daily therapy (mg)
(kg)
(ml/mm/kg)
(S)
Frusemide
1
51
72
II
18.6
18
80
10
2 3 4 5 6 I 8 9 10
69 71 59 68 60 56 66 69 62
65 61 12 75 76 80 62 63 60
IV III II III II III III III III
8.8 12.9 21.5 13.0 20.4 13.1 14.9 10.7 11.7
18 37 30 27 25 9 33 24 21
80 80 80 80 80 80 120 120 80
10 10 10 10 10 10 10 10 10
0.125
11 12 13
72 63 66
54 68 72
III II III
14.0 20.7 14.0
23 30 36
80 80 80
10 10 10
0.125
14 15 16 Mean Standard deviation
58 59 63 63.3
74 65 80 69.1
III II III III *
14.2 18.6 14.5 15.1
31 23 24 26.2
80 80 80 80 *
10 10 10 10 *
0.125
5.9
1.3
3.8
6.1
-
Amiloride
Digoxin
0.125
0.125 0.125 _ _
_
0.125
_
* Median. NYHA = New York Heart Association; CO2 = minute oxygen uptake; LVEF = left ventricular ejection fraction.
25 ml/mm/kg), a cardiothoracic ratio on a chest radiograph of greater than 0.50 and left ventricular ejection fraction of less than 0.45. Patients with valvar heart disease, angina pectoris, myocardial infarction within the previous six months or significant pulmonary disease were excluded. Normal subjects had no evidence of cardiovascular disease from their history or on full clinical examination, a normal resting electrocardiograph and a normal exercise test with a peak oxygen uptake of 25 ml/mm/kg or more. All normal subjects and patients had pulmonary function assessed by dry spirometry (Vitalograph) and had a forced expired volume in one second of greater than 70% predicted and a ratio of forced expired volume in one second to forced vital capacity of greater than 70%. In addition, patients or normal subjects with a history of intermittent claudication or clinical evidence of peripheral vascular disease were excluded.
Exercise tests
All patients and normal subjects performed a preliminary exercise test with measurement of respiratory gas exchange to familiarise them with the equipment and with treadmill walking. We have previously shown that, after an initial test, further tests are reproducible [7]. Within two weeks of this first test, all subjects attended the exercise laboratory for a second test following a light breakfast, and the results of the second test are described. A transcutaneous probe for measurement of oxygen tension was attached to the leg 10 centimetres below the tibial tuberosity and 3 centimetres lateral to the tibia1 bone [4]. The transcutaneous oxygen tension probe used was a modified Clarke electrode [8] connected to a dedicated module (Simonson and Weel) to permit continuous monitoring. Oxygen is reduced at the platinum
53
cathode to produce a current proportional to the partial pressure of oxygen at the surface of the electrode. The operating temperature of the electrode is 44°C to allow arterialisation of capillary blood in the skin and to improve oxygen diffusion across the electrode membrane [9]. The electrode was secured to the skin by a double-sided adhesive ring and a drop of electrolyte solution placed between the membrane and skin. Prior to each exercise test, the electrode was calibrated using the concentration of oxygen in room air (20.93%) and the prevailing atmospheric pressure, and a solution of sodium sulphite of zero oxygen tension. Following a period of 20 minutes seated rest to ensure equipment equilibration each normal subject and patient performed a symptom-limited treadmill exercise test according to a modified Naughton protocol [lo] (Table 2). Each exercise stage lasted four minutes, allowing time for stabilisation. Oxygen uptake, carbon dioxide production, minute ventilation and heart rate were
NORMAL
TABLE Modified
SUBJECTS
protocol
used for exercise
testing.
Time
Speed
Incline
@in)
(km/hr)
(W)
4 8 12 16 20 24 28 32
1.6 2.4 3.2 3.2 3.2 3.2 3.2 3.2
0 0 0 3.5 7.0 10.5 14.0 17.5
CCF PATIENTS
100
so
so
h a0 I” E
G 80 I : -
70
-
70
0”
g F
Naughton
measured on-line throughout exercise by a method previously described [7]. Blood pressure was recorded during the last 30 seconds of each stage using a mercury sphygmomanometer. Arterial oxygen saturation (estimated by earlobe oximetry using a Biox II oximeter [ll]) and transcutaneous oxygen partial pressure were recorded throughout
100
k
2
b I-
60
60
50
50
40
40
-D30
_
I
I
Rest
Fig. 1. Lower limb transcutaneous
partial
Max Exercise
30
Mean
I
Rest
Max Exercise
pressure of oxygen (TCPO,) at rest and at maximum patients with chronic cardiac failure (CCF).
exercise
in normal
subjects
and in
54
exercise and values shown during the last minute of each exercise stage recorded (both analysers are slow changing). Patients and normals were instructed to exercise to their symptom-limited maximum and their predominant limiting symptom recorded at the end of the test.
oxygen uptake compared to normals (Table 3). At peak exercise, those with heart failure also had a significantly lower heart rate, systolic blood pressure and minute ventilation compared to normal subjects. There was no significant difference at rest between the two groups in the transcutaneous partial pressure of oxygen (Table 3, Fig. 1) but, at peak exercise, the pressure fell to 74 (14) mm Hg in the subjects in failure, whereas, in normal subjects, the pressure increased to 87 (11) mm Hg (P < 0.05; Fig. 1). In those with heart failure, the mean change in pressure from rest to peak exercise was -12 (12) mm Hg, compared to +6 (8) mm Hg in the normal subjects (P < 0.002). The mean change in the transcutaneous partial pressure of oxygen during the last minute of the first to the fourth stages of exercise was compared (Table 4). Only three patients completed the fifth stage, so analysis beyond stage 4 was not possible. The changes observed were significantly different between the groups. The patients with chronic cardiac failure showed a progressive decrement in pressure, whilst the normal subjects demonstrated a progressive increase (Table 4). The transcutaneous partial pressure of oxygen fell more in patients limited by fatigue (-17 (16) mm Hg; n = 7) when compared to those limited by dyspnoea (-8.6 (9) mm Hg; n = 9) but this difference was not significant (P = 0.18). Oxygen
Statistical analysis The mean values for the transcutaneous partial pressure of oxygen and for oxygen saturation during the last minute of each exercise stage were recorded. Resting and peak exercise values were compared using Student’s t-test. In addition, the changes from rest to the end of each stage were compared by analysis of variance, using the t value calculated from the combined variance [12]. The interrelationships of haemodynamic responses, functional capacity and the transcutaneous partial pressure of oxygen were examined by calculating the product-moment coefficient of correlation. Reproducibility was assessed from sequential tests by calculating the error standard deviation [ 131.
Results The patients with chronic cardiac failure had significantly lower duration of exercise and peak TABLE 3
Exercise time, heart rate, systolic blood pressure, oxygen uptake, minute ventilation, transcutaneous saturation in normal subjects and patients at rest and at peak exercise (mean standard deviation). Rest
Peak exercise
Normal subjects Exercise time (set) Heart rate (beats/mm) Systolic blood pressure (mm Hg) Oxygen uptake W/mWkg) Minute ventilation (l/mm) Transcutaneous PO, (mm Hg) Oxygen saturation (W)
oxygen tension and oxygen
CCF patients
Normal subjects
83
(15)
_ 98
(11)
2 020 149
139
(19)
129
(18)
195
4.3 (0.85)
CCF patients (389) (16)
815 130
(401) * (24) *
(16)
155
(32) *
4.6 (0.9)
27.8 (2.1)
15.1 (3.9) *
11.3 (2.3)
15.4 (5.0)
59.4 (11.3)
47.4 (18.1) *
81 97
83 98
87 96
74 95
(10) (2)
(10) (3)
* P < 0.05 versus normal subjects. CCF = chronic cardiac failure.
(11) (2)
(14) * (2)
55 TABLE Lower during
4 limb transcutaneous partial pressure of oxygen in normal subjects and in patients exercise during the first four stages of exercise (mean standard deviation). Transcutaneous
Normal subjects n Patients n P value Significance the number
partial
pressure
with chronic
cardiac
failure
of oxygen (mm Hg)
Rest
Stage 1
Stage 2
Stage 3
Stage 4
80.5 (9.5) 7 82.7 (10.4) 16 _
82.6 (13.3) 7 77.9 (15.7) 16 0.033
84.4 (11.8) 7 77.2 (16) 16 0.014
84.1 (10.7) 7 75.7 (15.2) 11 0.012
84.6 (8.7) 7 74.8 (15.1) 8 0.01
values refer to the difference in pressure of subjects who finished that stage.
at rest and
from baseline
saturation was similar at rest and at peak exercise in both groups (Table 3). No significant relationship was demonstrated by linear correlation between the fall in pressure and the peak oxygen uptake, minute ventilation, heart rate, systolic blood pressure or exercise time in the patients with chronic cardiac failure. Reproducibility The mean resting transcutaneous partial pressure of oxygen for the whole group was not significantly different between the two tests (test 1, 75 (8) mm Hg and test 2, 78 (7) mm Hg). The mean change during exercise was 9 (5) mm Hg during the first test and 10 (6) mm Hg during the second. The error standard deviation for the change during exercise in transcutaneous pressure was 4 mm Hg.
Discussion The transcutaneous partial pressure of oxygen is thought to be dependent on a number of factors including arterial oxygen tension, oxygen consumption by the skin, a shift of the oxygen dissociation to the right due to the operating temperature (44OC) of the instrument, skin thickness, and skin perfusion [14]. Oxygen consumption by the skin tends to reduce the measured partial pressure, whereas the shift of the oxygen dissociation curve to the right tends to increase the pressure. These two factors, therefore, tend to move in
comparing
normal
subjects
and patients.
The value of n denotes
opposite directions [14]. Skin thickness has only a minor effect and, in this study, as the two groups were of similar age, it is unlikely to have had much effect. Thus, transcutaneous pressure may be considered primarily to reflect flow of blood of the skin and arterial oxygen tension. Patients with chronic cardiac failure in the absence of pulmonary disease do not significantly reduce arterial oxygen tension during exercise [15,16]. Although this was not directly measured in this study, none of the patients had pulmonary disease and no significant changes in oxygen saturation were demonstrated. We feel, therefore, that it is unlikely that the fall in transcutaneous pressure was due to a change in arterial oxygen tension. It is probable that the observed fall during exercise was related to abnormalities of perfusion of the skin and/or oxygenation. It has been shown that measurement of transcutaneous oxygen partial pressure is sensitive to changes in peripheral perfusion in patients with reduced cardiac output and shock, despite such patients having normal arterial oxygen tension [2]. In patients with heart failure, failure of blood flow to rise during exercise leads to muscle hypoxia [17]. The observed reduction in transcutaneous oxygen tension may, therefore, be due to both a reduction in perfusion of the skin and to hypoxia of the exercising limb. The resting and exercise values in normal subjects agree with results from previously reported studies [18,19]. Intramuscular oxygen tension increases [19] in normal subjects although perfusion
56
of blood within the skin falls as blood is diverted to the exercising muscle. Patients with intermittent claudication demonstrate a fall in transcutaneous oxygen pressure during exercise, and this is thought to relate to a reduction in muscle oxygenation and so increased steal from cutaneous blood vessels [4,20]. The fall in pressure observed in the present study may, therefore, represent a similar phenomenon in patients with heart failure as a result of impaired blood flow to the leg during exercise [5,6]. It has been suggested that limitation of exercise in heart failure is, in part, determined by impaired nutritional flow to skeletal muscle [5,17] despite exaggeration of the normal redistribution of blood away from the skin during exercise. The changes in the transcutaneous partial pressure of oxygen during exercise observed in the present study are consistent with this hypothesis. Indeed, this may be a useful non-invasive method to assess the degree of such impairment. In conclusion, in patients with stable cardiac failure, transcutaneous oxygen pressure falls significantly in the legs during exercise when compared to normals. This probably represents an abnormal steal of blood from the skin due to muscular hypoxia consequent on impaired flow of blood to the leg. This phenomenon deserves further study to elucidate the mechanisms involved, as such measurements may prove a useful method of assessing functional impairment during exercise in patients with heart failure. Acknowledgements J.S.E. was in receipt of a Royal Victoria Hospital Research Fellowship. We are grateful to Sister E. Crawford for her help with patient care.
4
5
6
7
8
9 10
11 12
13 14 15
16
17
18
References 19 1 Huch R, Lubbers DW, Huch A. Reliability of transcutaneous monitoring of arterial PO2 in newborn infants. Arch Dis Child 1974;49:213-218. 2 Tremper KK, Shoemaker WC. Transcutaneous oxygen monitoring of critically ill adults with and without low flow shock. Crit Care Med 1981;9:706-709. 3 Hughes JA, Gray BJ, Hutchinson DCS. Changes in trans-
20
cutaneous oxygen tension during exercise in pulmonary emphysema. Thorax 1984;39:424-431. Holditch TAH, Reddy RJ, Walker RJ, et al. Transcutaneous oxygen tension during exercise in patients with claudication. Br Med J 1986;292:1625-1628. Wilson JR, Wiener DH, Fink LI, et al. Vasodilatory behaviour of skeletal muscle arterioles in patients with nonoedematous chronic heart failure. Circulation 1986;74:775779. Cowley AJ, Stainer K, Rowley JM, Hampton JR. Abnormalities of the peripheral circulation and respiratory function in patients with severe heart failure. Br Heart J 1986;55;75-86. Elbom JS, Stanford CF, Nicholls DP. Reproducibility of cardiopulmonary parameters during exercise in chronic cardiac failure. The need for a preliminary test. Eur Heart J 1990;11:75-81. Clark LC Jr. Monitor and control of blood and tissue oxygen tensions. Trans Am Sot Artif Intern Organs 1956;2:41-54. Lubbers D. Cutaneous and transcutaneous POr and their measuring conditions. Birth Defects 1979;15:13-31. Patterson JA, Naughton J, Pietras RJ, Gunnar RM. Treadmill exercise in assessment of the functional capacity of patients with cardiac disease. Am J Cardiol 1972;30:757-762. Tweedale PM, Douglas NJ. Evaluation of the Biox Ha oximeter. Thorax 1985;40:825-827. Am&age P, Berry G. Statistical methods in medical research. 2nd ed. Oxford: Blackwell Scientific Publications, 1987. Bland M. An introduction to medical statistics. Oxford: Oxford University Press, 1987. Lucey JF. Clinical uses of transcutaneous oxygen monitoring. Adv Paediatr 1981;28:27-56. Rubin SA, Chatterjee K, Parmley WW. Metabolic assessment of exercise in chronic heart failure patients treated with short term vasodilators. Circulation 1980;61:543-548. Rajfer S, Nemanich JW, Surman AJ. Metabolic responses to exercise in patients with heart failure. Circulation 1987;76(suppl VI):46-53. Cohen-Solal A. Improving exercise tolerance in patients with chronic heart failure: should we treat the heart or the periphery? Eur Heart J 1989;10:866-871. McDowell JW, Triede W. Usefulness of the transcutaneous PO* monitor during exercise testing in adults. Chest 1980;78:853-855. Dowd GSE, Linge K, Bentley G. The effect of age and sex of normal volunteers upon the transcutaneous oxygen tension of the lower limb. Clin Phys Physiol Meas 1983;4:6568. Jussila EJ, Niinikoski J. Effects of vascular reconstructions on tissue gas tensions in calf muscles of patients with occlusive arterial disease. Ann Chir Gynaecol 1981;70:5660.
CARD10
51
01073
Transcutaneous oxygen tension in the leg during exercise in patients with chronic cardiac failure J.S. Elborn,
M. Riley, C.F. Stanford
and D.P. Nicholls
Royal Victoria Hospital, Belfast, Northern Ireland (Received
3 August
1989; revision
accepted
1 February
1990)
Elborn JS, Riley M, Stanford CF, Nicholls DP. Transcutaneous oxygen tension in the leg during exercise in patients with chronic cardiac failure. Int J Cardiol 1990;28:51-56. The tran~~ta~~eous partial pressure of oxygen measured in the lower limb was compared in 16 patients with chronic cardiac failure and seven normal subjects. At rest, there was no significant difference between patients and normals. At peak exercise, the partial pressure of oxygen fell significantly in those in heart failure, whereas -..I change was observed in normal subjects. No changes in arterial oxygen saturation (oximetry) were observed. These changes are likely to reflect abnormalities of peripheral perfusion of the skin. Key words: Transcutaneous
oxygen measurement;
Introduction
Transcutaneous monitors for the measurement of the partial pressure of oxygen in blood were initially developed for neonatal monitoring [l]. Since then, these monitors have found a number of uses, including the monitoring of patients in the intensive care unit [2], the monitoring of changes in blood gas concentrations during exercise [3], and as a screening test for intermittent claudication [4]. Patients with chronic cardiac failure demonstrate attenuation of peripheral blood flow during exercise [5,6]. The purpose of this study was to examine the transcutaneous partial pressure of oxygen in a group of patients with chronic cardiac
Correspondence to: Dr. D.P. Nicholls, Royal Hospital, Belfast BT12 6BA, Northern Ireland.
0167-5273/90/$03.50
Victoria
0 1990 Elsevier Science Publishers
Heart failure
failure and in a group of age- and sex-matched controls, in order to see if impairment of blood flow in the legs of such patients might be reflected in an abnormal response to exercise. Methods
In this study, 16 male patients with chronic cardiac failure aged 63 (6) years, mean (standard deviation), and body weight 69 (8) kg were compared to seven age- and sex-matched normal controls aged 60 (10) years and weight 72 (9) kg. All patients had a history and electrocardiographic evidence of ischaemic heart disease, had previously been in hospital with an episode of left ventricular failure, and had been stabilised by diuretic therapy for at least four weeks. Demographic details of the patients and their treatment are shown in Table 1. All patients had reduced exercise capacity (peak oxygen uptake of less than
B.V. (Biomedical
Division)
52
TABLE 7 Demographic details of the 16 patients with heart failure. Patient number
Age (yr)
Weight
NYHA grade
Peak CO,
LVEF
Daily therapy (mg)
(kg)
(ml/mm/kg)
(S)
Frusemide
1
51
72
II
18.6
18
80
10
2 3 4 5 6 I 8 9 10
69 71 59 68 60 56 66 69 62
65 61 12 75 76 80 62 63 60
IV III II III II III III III III
8.8 12.9 21.5 13.0 20.4 13.1 14.9 10.7 11.7
18 37 30 27 25 9 33 24 21
80 80 80 80 80 80 120 120 80
10 10 10 10 10 10 10 10 10
0.125
11 12 13
72 63 66
54 68 72
III II III
14.0 20.7 14.0
23 30 36
80 80 80
10 10 10
0.125
14 15 16 Mean Standard deviation
58 59 63 63.3
74 65 80 69.1
III II III III *
14.2 18.6 14.5 15.1
31 23 24 26.2
80 80 80 80 *
10 10 10 10 *
0.125
5.9
1.3
3.8
6.1
-
Amiloride
Digoxin
0.125
0.125 0.125 _ _
_
0.125
_
* Median. NYHA = New York Heart Association; CO2 = minute oxygen uptake; LVEF = left ventricular ejection fraction.
25 ml/mm/kg), a cardiothoracic ratio on a chest radiograph of greater than 0.50 and left ventricular ejection fraction of less than 0.45. Patients with valvar heart disease, angina pectoris, myocardial infarction within the previous six months or significant pulmonary disease were excluded. Normal subjects had no evidence of cardiovascular disease from their history or on full clinical examination, a normal resting electrocardiograph and a normal exercise test with a peak oxygen uptake of 25 ml/mm/kg or more. All normal subjects and patients had pulmonary function assessed by dry spirometry (Vitalograph) and had a forced expired volume in one second of greater than 70% predicted and a ratio of forced expired volume in one second to forced vital capacity of greater than 70%. In addition, patients or normal subjects with a history of intermittent claudication or clinical evidence of peripheral vascular disease were excluded.
Exercise tests
All patients and normal subjects performed a preliminary exercise test with measurement of respiratory gas exchange to familiarise them with the equipment and with treadmill walking. We have previously shown that, after an initial test, further tests are reproducible [7]. Within two weeks of this first test, all subjects attended the exercise laboratory for a second test following a light breakfast, and the results of the second test are described. A transcutaneous probe for measurement of oxygen tension was attached to the leg 10 centimetres below the tibial tuberosity and 3 centimetres lateral to the tibia1 bone [4]. The transcutaneous oxygen tension probe used was a modified Clarke electrode [8] connected to a dedicated module (Simonson and Weel) to permit continuous monitoring. Oxygen is reduced at the platinum
53
cathode to produce a current proportional to the partial pressure of oxygen at the surface of the electrode. The operating temperature of the electrode is 44°C to allow arterialisation of capillary blood in the skin and to improve oxygen diffusion across the electrode membrane [9]. The electrode was secured to the skin by a double-sided adhesive ring and a drop of electrolyte solution placed between the membrane and skin. Prior to each exercise test, the electrode was calibrated using the concentration of oxygen in room air (20.93%) and the prevailing atmospheric pressure, and a solution of sodium sulphite of zero oxygen tension. Following a period of 20 minutes seated rest to ensure equipment equilibration each normal subject and patient performed a symptom-limited treadmill exercise test according to a modified Naughton protocol [lo] (Table 2). Each exercise stage lasted four minutes, allowing time for stabilisation. Oxygen uptake, carbon dioxide production, minute ventilation and heart rate were
NORMAL
TABLE Modified
SUBJECTS
protocol
used for exercise
testing.
Time
Speed
Incline
@in)
(km/hr)
(W)
4 8 12 16 20 24 28 32
1.6 2.4 3.2 3.2 3.2 3.2 3.2 3.2
0 0 0 3.5 7.0 10.5 14.0 17.5
CCF PATIENTS
100
so
so
h a0 I” E
G 80 I : -
70
-
70
0”
g F
Naughton
measured on-line throughout exercise by a method previously described [7]. Blood pressure was recorded during the last 30 seconds of each stage using a mercury sphygmomanometer. Arterial oxygen saturation (estimated by earlobe oximetry using a Biox II oximeter [ll]) and transcutaneous oxygen partial pressure were recorded throughout
100
k
2
b I-
60
60
50
50
40
40
-D30
_
I
I
Rest
Fig. 1. Lower limb transcutaneous
partial
Max Exercise
30
Mean
I
Rest
Max Exercise
pressure of oxygen (TCPO,) at rest and at maximum patients with chronic cardiac failure (CCF).
exercise
in normal
subjects
and in
54
exercise and values shown during the last minute of each exercise stage recorded (both analysers are slow changing). Patients and normals were instructed to exercise to their symptom-limited maximum and their predominant limiting symptom recorded at the end of the test.
oxygen uptake compared to normals (Table 3). At peak exercise, those with heart failure also had a significantly lower heart rate, systolic blood pressure and minute ventilation compared to normal subjects. There was no significant difference at rest between the two groups in the transcutaneous partial pressure of oxygen (Table 3, Fig. 1) but, at peak exercise, the pressure fell to 74 (14) mm Hg in the subjects in failure, whereas, in normal subjects, the pressure increased to 87 (11) mm Hg (P < 0.05; Fig. 1). In those with heart failure, the mean change in pressure from rest to peak exercise was -12 (12) mm Hg, compared to +6 (8) mm Hg in the normal subjects (P < 0.002). The mean change in the transcutaneous partial pressure of oxygen during the last minute of the first to the fourth stages of exercise was compared (Table 4). Only three patients completed the fifth stage, so analysis beyond stage 4 was not possible. The changes observed were significantly different between the groups. The patients with chronic cardiac failure showed a progressive decrement in pressure, whilst the normal subjects demonstrated a progressive increase (Table 4). The transcutaneous partial pressure of oxygen fell more in patients limited by fatigue (-17 (16) mm Hg; n = 7) when compared to those limited by dyspnoea (-8.6 (9) mm Hg; n = 9) but this difference was not significant (P = 0.18). Oxygen
Statistical analysis The mean values for the transcutaneous partial pressure of oxygen and for oxygen saturation during the last minute of each exercise stage were recorded. Resting and peak exercise values were compared using Student’s t-test. In addition, the changes from rest to the end of each stage were compared by analysis of variance, using the t value calculated from the combined variance [12]. The interrelationships of haemodynamic responses, functional capacity and the transcutaneous partial pressure of oxygen were examined by calculating the product-moment coefficient of correlation. Reproducibility was assessed from sequential tests by calculating the error standard deviation [ 131.
Results The patients with chronic cardiac failure had significantly lower duration of exercise and peak TABLE 3
Exercise time, heart rate, systolic blood pressure, oxygen uptake, minute ventilation, transcutaneous saturation in normal subjects and patients at rest and at peak exercise (mean standard deviation). Rest
Peak exercise
Normal subjects Exercise time (set) Heart rate (beats/mm) Systolic blood pressure (mm Hg) Oxygen uptake W/mWkg) Minute ventilation (l/mm) Transcutaneous PO, (mm Hg) Oxygen saturation (W)
oxygen tension and oxygen
CCF patients
Normal subjects
83
(15)
_ 98
(11)
2 020 149
139
(19)
129
(18)
195
4.3 (0.85)
CCF patients (389) (16)
815 130
(401) * (24) *
(16)
155
(32) *
4.6 (0.9)
27.8 (2.1)
15.1 (3.9) *
11.3 (2.3)
15.4 (5.0)
59.4 (11.3)
47.4 (18.1) *
81 97
83 98
87 96
74 95
(10) (2)
(10) (3)
* P < 0.05 versus normal subjects. CCF = chronic cardiac failure.
(11) (2)
(14) * (2)
55 TABLE Lower during
4 limb transcutaneous partial pressure of oxygen in normal subjects and in patients exercise during the first four stages of exercise (mean standard deviation). Transcutaneous
Normal subjects n Patients n P value Significance the number
partial
pressure
with chronic
cardiac
failure
of oxygen (mm Hg)
Rest
Stage 1
Stage 2
Stage 3
Stage 4
80.5 (9.5) 7 82.7 (10.4) 16 _
82.6 (13.3) 7 77.9 (15.7) 16 0.033
84.4 (11.8) 7 77.2 (16) 16 0.014
84.1 (10.7) 7 75.7 (15.2) 11 0.012
84.6 (8.7) 7 74.8 (15.1) 8 0.01
values refer to the difference in pressure of subjects who finished that stage.
at rest and
from baseline
saturation was similar at rest and at peak exercise in both groups (Table 3). No significant relationship was demonstrated by linear correlation between the fall in pressure and the peak oxygen uptake, minute ventilation, heart rate, systolic blood pressure or exercise time in the patients with chronic cardiac failure. Reproducibility The mean resting transcutaneous partial pressure of oxygen for the whole group was not significantly different between the two tests (test 1, 75 (8) mm Hg and test 2, 78 (7) mm Hg). The mean change during exercise was 9 (5) mm Hg during the first test and 10 (6) mm Hg during the second. The error standard deviation for the change during exercise in transcutaneous pressure was 4 mm Hg.
Discussion The transcutaneous partial pressure of oxygen is thought to be dependent on a number of factors including arterial oxygen tension, oxygen consumption by the skin, a shift of the oxygen dissociation to the right due to the operating temperature (44OC) of the instrument, skin thickness, and skin perfusion [14]. Oxygen consumption by the skin tends to reduce the measured partial pressure, whereas the shift of the oxygen dissociation curve to the right tends to increase the pressure. These two factors, therefore, tend to move in
comparing
normal
subjects
and patients.
The value of n denotes
opposite directions [14]. Skin thickness has only a minor effect and, in this study, as the two groups were of similar age, it is unlikely to have had much effect. Thus, transcutaneous pressure may be considered primarily to reflect flow of blood of the skin and arterial oxygen tension. Patients with chronic cardiac failure in the absence of pulmonary disease do not significantly reduce arterial oxygen tension during exercise [15,16]. Although this was not directly measured in this study, none of the patients had pulmonary disease and no significant changes in oxygen saturation were demonstrated. We feel, therefore, that it is unlikely that the fall in transcutaneous pressure was due to a change in arterial oxygen tension. It is probable that the observed fall during exercise was related to abnormalities of perfusion of the skin and/or oxygenation. It has been shown that measurement of transcutaneous oxygen partial pressure is sensitive to changes in peripheral perfusion in patients with reduced cardiac output and shock, despite such patients having normal arterial oxygen tension [2]. In patients with heart failure, failure of blood flow to rise during exercise leads to muscle hypoxia [17]. The observed reduction in transcutaneous oxygen tension may, therefore, be due to both a reduction in perfusion of the skin and to hypoxia of the exercising limb. The resting and exercise values in normal subjects agree with results from previously reported studies [18,19]. Intramuscular oxygen tension increases [19] in normal subjects although perfusion
56
of blood within the skin falls as blood is diverted to the exercising muscle. Patients with intermittent claudication demonstrate a fall in transcutaneous oxygen pressure during exercise, and this is thought to relate to a reduction in muscle oxygenation and so increased steal from cutaneous blood vessels [4,20]. The fall in pressure observed in the present study may, therefore, represent a similar phenomenon in patients with heart failure as a result of impaired blood flow to the leg during exercise [5,6]. It has been suggested that limitation of exercise in heart failure is, in part, determined by impaired nutritional flow to skeletal muscle [5,17] despite exaggeration of the normal redistribution of blood away from the skin during exercise. The changes in the transcutaneous partial pressure of oxygen during exercise observed in the present study are consistent with this hypothesis. Indeed, this may be a useful non-invasive method to assess the degree of such impairment. In conclusion, in patients with stable cardiac failure, transcutaneous oxygen pressure falls significantly in the legs during exercise when compared to normals. This probably represents an abnormal steal of blood from the skin due to muscular hypoxia consequent on impaired flow of blood to the leg. This phenomenon deserves further study to elucidate the mechanisms involved, as such measurements may prove a useful method of assessing functional impairment during exercise in patients with heart failure. Acknowledgements J.S.E. was in receipt of a Royal Victoria Hospital Research Fellowship. We are grateful to Sister E. Crawford for her help with patient care.
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13 14 15
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References 19 1 Huch R, Lubbers DW, Huch A. Reliability of transcutaneous monitoring of arterial PO2 in newborn infants. Arch Dis Child 1974;49:213-218. 2 Tremper KK, Shoemaker WC. Transcutaneous oxygen monitoring of critically ill adults with and without low flow shock. Crit Care Med 1981;9:706-709. 3 Hughes JA, Gray BJ, Hutchinson DCS. Changes in trans-
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cutaneous oxygen tension during exercise in pulmonary emphysema. Thorax 1984;39:424-431. Holditch TAH, Reddy RJ, Walker RJ, et al. Transcutaneous oxygen tension during exercise in patients with claudication. Br Med J 1986;292:1625-1628. Wilson JR, Wiener DH, Fink LI, et al. Vasodilatory behaviour of skeletal muscle arterioles in patients with nonoedematous chronic heart failure. Circulation 1986;74:775779. Cowley AJ, Stainer K, Rowley JM, Hampton JR. Abnormalities of the peripheral circulation and respiratory function in patients with severe heart failure. Br Heart J 1986;55;75-86. Elbom JS, Stanford CF, Nicholls DP. Reproducibility of cardiopulmonary parameters during exercise in chronic cardiac failure. The need for a preliminary test. Eur Heart J 1990;11:75-81. Clark LC Jr. Monitor and control of blood and tissue oxygen tensions. Trans Am Sot Artif Intern Organs 1956;2:41-54. Lubbers D. Cutaneous and transcutaneous POr and their measuring conditions. Birth Defects 1979;15:13-31. Patterson JA, Naughton J, Pietras RJ, Gunnar RM. Treadmill exercise in assessment of the functional capacity of patients with cardiac disease. Am J Cardiol 1972;30:757-762. Tweedale PM, Douglas NJ. Evaluation of the Biox Ha oximeter. Thorax 1985;40:825-827. Am&age P, Berry G. Statistical methods in medical research. 2nd ed. Oxford: Blackwell Scientific Publications, 1987. Bland M. An introduction to medical statistics. Oxford: Oxford University Press, 1987. Lucey JF. Clinical uses of transcutaneous oxygen monitoring. Adv Paediatr 1981;28:27-56. Rubin SA, Chatterjee K, Parmley WW. Metabolic assessment of exercise in chronic heart failure patients treated with short term vasodilators. Circulation 1980;61:543-548. Rajfer S, Nemanich JW, Surman AJ. Metabolic responses to exercise in patients with heart failure. Circulation 1987;76(suppl VI):46-53. Cohen-Solal A. Improving exercise tolerance in patients with chronic heart failure: should we treat the heart or the periphery? Eur Heart J 1989;10:866-871. McDowell JW, Triede W. Usefulness of the transcutaneous PO* monitor during exercise testing in adults. Chest 1980;78:853-855. Dowd GSE, Linge K, Bentley G. The effect of age and sex of normal volunteers upon the transcutaneous oxygen tension of the lower limb. Clin Phys Physiol Meas 1983;4:6568. Jussila EJ, Niinikoski J. Effects of vascular reconstructions on tissue gas tensions in calf muscles of patients with occlusive arterial disease. Ann Chir Gynaecol 1981;70:5660.