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The measurement of intrapulmonary mixing in children
10 9 8
June 1965
Brie[ clinical and laboratory observations
The measurement of intrapulmonary mixing in children M. Lertzman, M.D., ~ and G. N. Muruve, M.D. LOS GATOS~ CALIF.
T K E A L V E O L A R GAS in a normal person breathing room air contains 80 per cent of nitrogen. Cournand 1 in 1941 showed that in normal adults breathing 100 per cent oxygen, the nitrogen present will be "washed out," so that after 7 minutes, less than 2 per cent of nitrogen remains in the alveolar air. In adults with chronic obstructive pulmonary disease, there are areas of lungs which are poorly ventilated, so that nitrogen is not removed as rapidly. In these patients more than 2 per cent of nitrogen remains after 7 minutes. This value reflects the nonuniformity of distribution of the inspired air and is called the "index of intrapulmonary mixing." Because 7 minutes is a relatively long interval for a young child to remain seated, concentrating, with a mouthpiece held tightly between his lips, it is not as satisfactory for use in pediatric respiratory disease as it is in adult medicine. Accordingly, a study was attempted to modify the method for use in children in a group ranging in age from 6 to 12 years. The data indicate that the pulmonary emptying rate is shorter in children than adults and that a 2 minute breathing interval is all that is required. From the Clinical Investigation Unit o] the Children's Hospital o[ Winnipeg and the Department of Pediatrics of the University of Mannitoba, Winnipeg, Canada. Supported by a grant [rom the Canadian Cystic Fibrosis Foundation and the National Sanitarium Association, Muskoka Hospital Memorial Research Fund. ~Address, Department o[ Internal Medicine, Blossom Ridge 3,1edical Group 150G6 Los Gatos--Almaden Road, Los Gatos, CaliJ.
METHOD
The first group studied consisted of 23 male and 9 female normal children who had no clinical or functional evidence of cardiorespiratory disease. These children were selected from the psychiatric and surgical wards. Their physical characteristics and pulmonary functions are outlined in Table I. Normal values were taken from Cherniack 2 based on studies performed at the Children's Hospital of Winnipeg. The second group consisted of 8 male and 7 female children with diffuse bronchial disease of varying severity. These children were under treatment for cystic fibrosis, chronic bronchitis, bronchial asthma, and bronchiectasis. Their physical characteristics and pulmonary functions are outlined in Table I. Vital capacity, maximum breathing capacity, and maximal mid-expiratory flow rate were determined with a 9 L. Collins spirometer. Carbon dioxide tension was determined by a rebreathing technique? The intrapulmonary distribution of inspired gas was assessed by determining the breath to breath washout of nitrogen from the lungs while breathing 100 per cent oxygen, and by measurement of the concentration of nitrogen in the alveolar gas after 1 and 2 minute periods of 100 per cent oxygen breathing, using an instantaneously recording nitrogen meter. ~ Rest intervals of 15 to 20 minutes separated the periods of testing.
~Nitralvzer, Custom Englneerhlg and Development Company, St. Louis, Mo.
Volume 66 Number 6
Brie[ clinical and laboratory observations
1 099
to about 5 per cent, the sensitivity of the amplifier is increased to a u g m e n t the size of the deflection, and improve recording accuracy at the lower concentrations. Fig. 1, A demonstrates the typical normal 2 minute nitrogen washout curve. Note that the original reading of the nitrogen meter is 80 per cent and that this is rapidly and evenly reduced to below 2 per cent in less than 2 minutes. Fig. 1, B shows the curve: in a patient with uneven distribution of inspired air (cystic fibrosis). T h e rate of reduction of nitrogen concentration is not uniform and 18 per cent nitrogen remains in the alveolar sample after 2 minutes. S U M M A R Y AND C O N C L U S I O N S
Fig. 1. Index of intrapuImonary mixing.
T h e end alveolar nitrogen concentration was measured after a forced expiration. RESULTS All normal patients had an end alveolar nitrogen concentration below 2 per cent after breathing 100 per cent oxygen for 2 minutes (Table I). This differed significantly from the values noted in patients with chronic bronchial disease (p < 0.001), all of w h o m demonstrated values above this level at 2 minutes (Table I). T h e curves in Fig. 1, A and B, are read from right to left, are not linear, and show the change in nitrogen concentration with each breath. As indicated on the figure, when the nitrogen concentration is reduced
T h e figure showing the index of intrapulmonary mixing estimates in a semiquantitative way the n u m b e r of alveoli poorly ventilated during resting tidal breathing. T h e main value of this function is in patients with chronic obstructive bronchial disease where the degree of abnormality mirrors the extent of obstruction. A n advantage of this technique is that it provides another objective tool in the evaluation of the patient and his response to therapy. It is possible to measure the index of intrapulmonary mixing in children in 2 minutes. REFERENCES 1. Cournand, A., Baldwin, E. D., Darling, R. C., and Richards, D. W., Jr.: Studies on intrapulmonary mixture of gases: IV. The significance of the pulmonary emptying rate and a simplified open circuit measurement of residual air, J. Clin. Invest. 20: 681, 1941. 2. Cherniack, Reuben M.: Ventilator,/ function in normal children, Canad. M. A. J. 87: 80, 1962. 3. Lertzman, M., and Ciner, E.: A rebreathing technique for the estimation of arterial carbon dioxide tension in infants and children, J. PEDIAT. 63: 840, 1963.
1 10 0
Brie[ clinical and laboratory observations
June 1965
Table I
Height
Weight
Vital capacity
(Kg.)
(%)
105.5 112.5 117.5 117.5 117.5 118.0 118.5 120.0 123.0 124.0 124.5 125.0 126.0 129.5 130.0 t31.0 131.5 133.0 133.5 134.5 134.5 135.0 136.0 136.5 138.0 140.0 140.0 145.0 145.0 148.5 157.5 158.5
17.5 21.5 20.0 21.5 24.2 22.5 21.4 20.9 24.3 24.3 24.1 25.4 26.6 25.9 48.9 31.7 26.1 27.5 30.7 30.4 27.9 32.3 32.7 33.3 31.4 29.3 34.1 31.8 35.4 53.6 45.4 40.0
79 117 72
6 9 10 8 10 15 12
112 119 128 130 134 144 156
41.7 41.5 62.50 58.0 47.50 59.50
26 100 87 107 61 32 91
7 7 11 8 11
120 123 135 138.5 154
48.7 47.2 64.0 94
77 72 79 45 107
4 9 9
I04 141.2 146
39 72.0 62.0
30 95 56
No. Control subjects
Sex
Age
(cmJ
1 2 3 4 5 6 7 8 9 10 I1 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
M F F F M M M F M F M M M M M M F M M M M M M F M F M M M M M F
6 6 6 7 8 7 6 6 7 9 6 8 i0 8 12 11 9 9 9 8 9 10 10 11 10 10 8 11 12 11 12 11
F F M F F F M M M M M M
132 118 109 121 99 114 95 97 79
103 114 93 114 95 103 115 97 98 113 97 110 116 108
Cystic fibros~ 33 34 35 36 37 38 39
Asthma 40 41 42 43 44
Bronchitis and bronchiectasis 45 46 47
F M F
Volume 66
Number 6
Brie[ clinical and laboratory observations
Maximum mid-flow rate (L./sec.) Insp. ] Exp.
1 10 1
Maximum breathing capacity
~%)
Rebreathing PCO~ (mm. H~)
% nitrogen alveolar sample 2 minutes 0.1 0.1 0.1 0.2 0.1 0.3 0.3 0.3
1.17 2.34 1.60
0.54 1.91 1.91
91 116 96
34 38 35
2.73 3.17 1.93 1.95 2.72
2.46 2.81 1.73 0.95 2.04
154 127 90 74 101
41 36 43 41 37 40
1.93 2.81 1.50
2.33 1.88 2.27
117 112 100
38 39 44
2.25 2.97 2.31 2.99
2.21 2.52 1.79 1.69
106 104 84 89
37 32 32 43
2.93 3.28 3.92 1.93 3.37 2.99 2.32
1.80 1.76 2.96 1.68 2.25 1.64 2.86
80 92 133 87 92 86 80
35 36 38 36 36 39 35
3.20 4.05 3.72
2.77 3.08 2.87
91 92 90
35 36 43
0.7 0.3 0.4 0.3 0.1 0.9 0.3 0.1 0.3 0.3 0.3 0.6 0.3 0.2 1.2 0.3 0,3 0.3 0.3 1.2 0.1 0.6 0.7
0.67 1.70 2.11 1.58 2.20 2.49 2.49
0.27 0.23 0.41 0.83 0.32 0.23 0.43
28 66 87 72 40 49 60
63 40 34 42 41 51 41
13.1 12.9 11.1 3.9 19.8 14.4 4.8
1.91 1.68 2.38 1.70 4.15
0.27 0.69 0.31 0.40 1.53
43 50 50 38
37 36 36 36 36
12.0 3.5 11.6 6.5 10.5
0.59 2.83 1.17
0.41 1.16 0.25
27 77 34
35 33 39
8.4 4.8 3.8
June 1965
Brie[ clinical and laboratory observations
The measurement of intrapulmonary mixing in children M. Lertzman, M.D., ~ and G. N. Muruve, M.D. LOS GATOS~ CALIF.
T K E A L V E O L A R GAS in a normal person breathing room air contains 80 per cent of nitrogen. Cournand 1 in 1941 showed that in normal adults breathing 100 per cent oxygen, the nitrogen present will be "washed out," so that after 7 minutes, less than 2 per cent of nitrogen remains in the alveolar air. In adults with chronic obstructive pulmonary disease, there are areas of lungs which are poorly ventilated, so that nitrogen is not removed as rapidly. In these patients more than 2 per cent of nitrogen remains after 7 minutes. This value reflects the nonuniformity of distribution of the inspired air and is called the "index of intrapulmonary mixing." Because 7 minutes is a relatively long interval for a young child to remain seated, concentrating, with a mouthpiece held tightly between his lips, it is not as satisfactory for use in pediatric respiratory disease as it is in adult medicine. Accordingly, a study was attempted to modify the method for use in children in a group ranging in age from 6 to 12 years. The data indicate that the pulmonary emptying rate is shorter in children than adults and that a 2 minute breathing interval is all that is required. From the Clinical Investigation Unit o] the Children's Hospital o[ Winnipeg and the Department of Pediatrics of the University of Mannitoba, Winnipeg, Canada. Supported by a grant [rom the Canadian Cystic Fibrosis Foundation and the National Sanitarium Association, Muskoka Hospital Memorial Research Fund. ~Address, Department o[ Internal Medicine, Blossom Ridge 3,1edical Group 150G6 Los Gatos--Almaden Road, Los Gatos, CaliJ.
METHOD
The first group studied consisted of 23 male and 9 female normal children who had no clinical or functional evidence of cardiorespiratory disease. These children were selected from the psychiatric and surgical wards. Their physical characteristics and pulmonary functions are outlined in Table I. Normal values were taken from Cherniack 2 based on studies performed at the Children's Hospital of Winnipeg. The second group consisted of 8 male and 7 female children with diffuse bronchial disease of varying severity. These children were under treatment for cystic fibrosis, chronic bronchitis, bronchial asthma, and bronchiectasis. Their physical characteristics and pulmonary functions are outlined in Table I. Vital capacity, maximum breathing capacity, and maximal mid-expiratory flow rate were determined with a 9 L. Collins spirometer. Carbon dioxide tension was determined by a rebreathing technique? The intrapulmonary distribution of inspired gas was assessed by determining the breath to breath washout of nitrogen from the lungs while breathing 100 per cent oxygen, and by measurement of the concentration of nitrogen in the alveolar gas after 1 and 2 minute periods of 100 per cent oxygen breathing, using an instantaneously recording nitrogen meter. ~ Rest intervals of 15 to 20 minutes separated the periods of testing.
~Nitralvzer, Custom Englneerhlg and Development Company, St. Louis, Mo.
Volume 66 Number 6
Brie[ clinical and laboratory observations
1 099
to about 5 per cent, the sensitivity of the amplifier is increased to a u g m e n t the size of the deflection, and improve recording accuracy at the lower concentrations. Fig. 1, A demonstrates the typical normal 2 minute nitrogen washout curve. Note that the original reading of the nitrogen meter is 80 per cent and that this is rapidly and evenly reduced to below 2 per cent in less than 2 minutes. Fig. 1, B shows the curve: in a patient with uneven distribution of inspired air (cystic fibrosis). T h e rate of reduction of nitrogen concentration is not uniform and 18 per cent nitrogen remains in the alveolar sample after 2 minutes. S U M M A R Y AND C O N C L U S I O N S
Fig. 1. Index of intrapuImonary mixing.
T h e end alveolar nitrogen concentration was measured after a forced expiration. RESULTS All normal patients had an end alveolar nitrogen concentration below 2 per cent after breathing 100 per cent oxygen for 2 minutes (Table I). This differed significantly from the values noted in patients with chronic bronchial disease (p < 0.001), all of w h o m demonstrated values above this level at 2 minutes (Table I). T h e curves in Fig. 1, A and B, are read from right to left, are not linear, and show the change in nitrogen concentration with each breath. As indicated on the figure, when the nitrogen concentration is reduced
T h e figure showing the index of intrapulmonary mixing estimates in a semiquantitative way the n u m b e r of alveoli poorly ventilated during resting tidal breathing. T h e main value of this function is in patients with chronic obstructive bronchial disease where the degree of abnormality mirrors the extent of obstruction. A n advantage of this technique is that it provides another objective tool in the evaluation of the patient and his response to therapy. It is possible to measure the index of intrapulmonary mixing in children in 2 minutes. REFERENCES 1. Cournand, A., Baldwin, E. D., Darling, R. C., and Richards, D. W., Jr.: Studies on intrapulmonary mixture of gases: IV. The significance of the pulmonary emptying rate and a simplified open circuit measurement of residual air, J. Clin. Invest. 20: 681, 1941. 2. Cherniack, Reuben M.: Ventilator,/ function in normal children, Canad. M. A. J. 87: 80, 1962. 3. Lertzman, M., and Ciner, E.: A rebreathing technique for the estimation of arterial carbon dioxide tension in infants and children, J. PEDIAT. 63: 840, 1963.
1 10 0
Brie[ clinical and laboratory observations
June 1965
Table I
Height
Weight
Vital capacity
(Kg.)
(%)
105.5 112.5 117.5 117.5 117.5 118.0 118.5 120.0 123.0 124.0 124.5 125.0 126.0 129.5 130.0 t31.0 131.5 133.0 133.5 134.5 134.5 135.0 136.0 136.5 138.0 140.0 140.0 145.0 145.0 148.5 157.5 158.5
17.5 21.5 20.0 21.5 24.2 22.5 21.4 20.9 24.3 24.3 24.1 25.4 26.6 25.9 48.9 31.7 26.1 27.5 30.7 30.4 27.9 32.3 32.7 33.3 31.4 29.3 34.1 31.8 35.4 53.6 45.4 40.0
79 117 72
6 9 10 8 10 15 12
112 119 128 130 134 144 156
41.7 41.5 62.50 58.0 47.50 59.50
26 100 87 107 61 32 91
7 7 11 8 11
120 123 135 138.5 154
48.7 47.2 64.0 94
77 72 79 45 107
4 9 9
I04 141.2 146
39 72.0 62.0
30 95 56
No. Control subjects
Sex
Age
(cmJ
1 2 3 4 5 6 7 8 9 10 I1 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
M F F F M M M F M F M M M M M M F M M M M M M F M F M M M M M F
6 6 6 7 8 7 6 6 7 9 6 8 i0 8 12 11 9 9 9 8 9 10 10 11 10 10 8 11 12 11 12 11
F F M F F F M M M M M M
132 118 109 121 99 114 95 97 79
103 114 93 114 95 103 115 97 98 113 97 110 116 108
Cystic fibros~ 33 34 35 36 37 38 39
Asthma 40 41 42 43 44
Bronchitis and bronchiectasis 45 46 47
F M F
Volume 66
Number 6
Brie[ clinical and laboratory observations
Maximum mid-flow rate (L./sec.) Insp. ] Exp.
1 10 1
Maximum breathing capacity
~%)
Rebreathing PCO~ (mm. H~)
% nitrogen alveolar sample 2 minutes 0.1 0.1 0.1 0.2 0.1 0.3 0.3 0.3
1.17 2.34 1.60
0.54 1.91 1.91
91 116 96
34 38 35
2.73 3.17 1.93 1.95 2.72
2.46 2.81 1.73 0.95 2.04
154 127 90 74 101
41 36 43 41 37 40
1.93 2.81 1.50
2.33 1.88 2.27
117 112 100
38 39 44
2.25 2.97 2.31 2.99
2.21 2.52 1.79 1.69
106 104 84 89
37 32 32 43
2.93 3.28 3.92 1.93 3.37 2.99 2.32
1.80 1.76 2.96 1.68 2.25 1.64 2.86
80 92 133 87 92 86 80
35 36 38 36 36 39 35
3.20 4.05 3.72
2.77 3.08 2.87
91 92 90
35 36 43
0.7 0.3 0.4 0.3 0.1 0.9 0.3 0.1 0.3 0.3 0.3 0.6 0.3 0.2 1.2 0.3 0,3 0.3 0.3 1.2 0.1 0.6 0.7
0.67 1.70 2.11 1.58 2.20 2.49 2.49
0.27 0.23 0.41 0.83 0.32 0.23 0.43
28 66 87 72 40 49 60
63 40 34 42 41 51 41
13.1 12.9 11.1 3.9 19.8 14.4 4.8
1.91 1.68 2.38 1.70 4.15
0.27 0.69 0.31 0.40 1.53
43 50 50 38
37 36 36 36 36
12.0 3.5 11.6 6.5 10.5
0.59 2.83 1.17
0.41 1.16 0.25
27 77 34
35 33 39
8.4 4.8 3.8