Clinical Science and Molecular Medicine (1977) 52, 269-215.
Interaction of mental factors with hypercapnic ventilatory drive in man
J . R . A. R I G G , E . M. I N M A N , N . A . S A U N D E R S , S. R. L E E D E R A N D N . L. J O N E S Departments of Anaesthesia and Medicine, McMaster University, Hamilton, Ontario, Canada
(Received 29 July 1976; accepted 16 October 1976)
SummarY 1. The effect of mental arithmetic tasks on
ventilation, breathing pattern, oxygen intake and carbon dioxide output was studied during air breathing and carbon dioxide rebreathing in healthy subjects. 2. Ventilation and breathing frequency increased significantly on performance of the task during 4 min air breathing and 4 min rebreathing; tidal volume was unchanged. The slopes of the ventilatory, frequency and tidal volume responses to carbon dioxide changed little during task performance. 3. During 15 min air breathing, oxygen intake was unchanged with task performance. Carbon dioxide output increased significantly with task performance, as a result of wash-out of carbon dioxide from body stores by the increased ventilation . 4. Mental arithmetic had no effect on the coefficients of variation of the slope and position variables of the ventilatory, frequency and tidal volume responses to carbon dioxide. It is concluded that task performance does not improve the reproducibility of these responses.
Introduction The ventilatory response to C02 (AV,/bPco,), when measured by rebreathing, is highly reproducible in most individuals (Read, 1967; Rebuck & Read, 1971). However, we have found that many healthy people have a variable response, not only from one day to the next, but also on the same day, a finding reported by others (Jennett, Barker & Forrest, 1968; Plum, 1974; Arkinstall, Nirmel, Klissouras & Milic-Emili, 1974). In view of the known influence of wakefulness on respiratory control mechanisms (Bulow, 1963), the present experiments were designed to test the possibility that mental factors may alter the ventilatory response to hypercapnia. Mental arithmetic tasks were performed by healthy adults during air breathing and rebreathing to investigate their effects on ventilation. These tasks were chosen because they provided a simple method of maintaining a continuous process of mental activity while ventilatory measurements were made. Measurements of O2 intake and CO, output were made to exclude the possibility of an increase in metabolism causing an increase in ventilation.
Key words: hypercapnia, mental arithmetic, metabolic rate, ventilation, ventilatory responses to COz.
Metha Nineteen healthy adults, 13 men and six women, were studied. Informed consent was Obtained from each* although none was aware of the hypothesis being tested. All experiments
Correspondence: Dr J. R. A. Rim, Department of Anaesthesia, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, Canada LSS 4J9.
269
270
J . R . A . Rigg el al.
were conducted in the sitting position and all subjects fasted for 2 h before an experiment.
Procedure Three series of experiments on the effect of mental arithmetic were conducted. In the first series, the effect was studied in four subjects during rebreathing; in the second, the effect was studied in ten subjects breathing air and during rebreathing; in the third, the effect on CO, output and 0, consumption was studied in five subjects during 15 min air breathing. In rebreathing experiments (series 1 and 2), each subject performed four ventilatory response tests, two control and two during mental arithmetic; a Latin square design was used to reduce the possibility of an effect due to order. Mental arithmetic was performed continuously throughout rebreathing for 4 min. Calculations involved addition, subtraction, multiplication and division of one- or two-digit numbers. As an oral answer to calculations could not be given, each subject was told that the correct answer to each mental arithmetic step was an integer; if a fraction occurred the subject knew immediately that an error had been made. The subject then signalled by hand and the correct answer was called to permit resumption of calculations. Five sets of mental arithmetic tasks were constructed and a different set was used in each run to reduce possibility of learning, leading to transferred skill, from one experiment to the next. All sets were read slowly and clearly, from a previously prepared protocol, by the same person. In practice, the mental arithmetic was simple to perform; errors occurred in from 1 to 4 % of the total tasks given in any experiment and were distributed randomly throughout the 4 min of rebreathing. Subjects were not aware of the order of experiments; they did not know that they would be required to perform mental arithmetic until requested to do so after the beginning of rebreathing. Thirty minutes rest was allowed between successive studies and an estimate of oxygenated mixed venous CO, pressure (P0,co2)was obtained at the beginning of each rebreathing experiment. Air-breathing measurements were obtained immediately preceding the first rebreathing measurement; 4 min with task performance and 4 min control
ventilation was recorded before and after mental arithmetic. In the experiments to measure the effects of mental arithmetic on 0,consumption (POz) and CO, output ( k o , ) ,each subject breathed air for two successive 15 min periods, one with and one without task performance; the order of task and control experiments was alternated in successive subjects. Oxygen intake and CO, output were measured continuously, together with ventilatory variables, an on-line PDP-8/1 recorder being used for computation and display of data as detailed previously (Jones, Campbell, Edwards & Robertson, 1975). Subjects rebreathed 0,+CO, (93:7, vlv). Inspired ventilation (PI) was measured with a dry gas meter (Parkinson Cowan CD4), with a potentiometer fitted to the output shaft; full scale deflection was precise to +2%. Carbon dioxide was analysed by an infrared analyser (Godart Capnograph) with a response time of 0.1 s and precise to *0.1% over the range of &lo% CO,. Gas sampled by the analyser during rebreathing was returned to the bag. End-tidal P c o , (PETco2) and vl were recorded with an Astromed pen recorder. The resistance of the rebreathing circuit was 1.0 cm water s - ' I - ' at a flow rate of 4 I/s. Data analysis
Mean ventilation ( vl), tidal volume (V,) and breathing frequency (f) were calculated for successive 30 s intervals. All gas volumes were corrected to BTPS. The slopes of ventilatory ( A v I / A P ~ ~tidal ,), volume (A V T / A P C O ~ and ) frequency responses (AflAPco,) to CO, were calculated by leastsquares regression. To compare the position of response curves between control tests and mental arithmetic tests the following procedure was adopted. For each subject, two values of P c o , were chosen, which represented the highest (H) and lowest (L) values common to all four response curves. Ventilation (VJ, V, and f observed at these P c o , values were used to measure response curve position. This procedure was adopted because different subjects rebreathed over widely differing CO, pressures. The high and low variables represented actual measurements of each subject's ventilation during rebreathing and their use eliminated the errors due to
5 SD
Mean
14
13
12
11
10
9
8
7
6
5
4
3
MA
C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C
1
2
Study
Subjectno.
VI(H) (I/min) VdL) (litres)
+
20.2 21-8 203 22.2 208 24.0 9.8 11.6 11.2 18.10 14.0 16.3 13.7 16.5 145 19.1 12.8 19.4 8.4 9.0 21.2 21.9 18.2 22.2 15.5 21.0 24.8 249 16.10 +4.88 19.14 f 4.55 P0.3 P >0.9
(I/min)
VI(L)
0.23 0.46 0-49 0.66 + 0.27 0.53 f0.18 P 0.3
Af/APc02 AVT/APCO~ (breaths (I/kPa) min-' kPa- ') 7.15 7.15 6.78 6.78 7.02 6.92 6.76 6.76 6.92 6,68 7-25 6.98 7.16 7-32 6.68 6.68 7.21 7.38 6-72 6.85 6.69 6.85 6.56 6.38 6.32 6.18 6.68 6.57 6.85 5 028 6.82 5 0.33 P >01
0371 0.392 0.392 0.442 0.343 0.340 0.343 0.340 0.400 0446 0.461 0.422 0.566 0-592 0.396 0.416 0.408 0480 0.365 0.313 0350 0.294 0.422 0.465 0.466 0509 0.403 0.420 0.407 f 0.60 0419 k0.81 P >02
PV,COZ dp/dt (kPa) (kPa/min)
TABLE 1. Ventilation, tido1 volume and frequency at the beginning [VI(L),VAL),f ( L ) ]and at the end [VI(H),V A H ) ,f ( H ) Jof rebreathing, ventilatory (AV,/APcoz). tidal colume (AVT/APC02)and frequency (Af/APcoz) responses to COz, oxygenated mixed venous COz (PP,coz) and the rate of rise of CO2 pressure (dPcol/dt), with ( M A ) and without ( C ) mental arithmetic during rebreathing Each value is the mean of two runs for each individual. Standard deviations: 0.09-13.17, Vl(L); 0.61-11.12, Vl(H); 0.01-0.78, VAL); 0.01439, VT(H);0430-5.5, f ( L ) ; 04-46, f(H); 0.08-15.11, AVI/APcoz; 0 0 3 4 5 0 , A VT/APcoZ; 0.00-3.08, Af/APcoz ; 0.00-032, Pv,coz; 040-6*16, dPco,/dt. These variables are explained in detail in the text.
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B
3
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J . R . A . Rigg et at.
272
TABLE 2. Ventilation (v,),frequency ( f ) , ridal volume ( VT), end-tidol CO, pressure ( P ~ T c o ~COz ), output (VCO,) and oxygen uptake (Po2) during 12-15 min air breathing with ( M A ) and without ( C ) niental arithmetic ~~~
f
Subject no.
Study
15
C MA
16 17
18 19 Mean f SD
C MA C MA
C MA C MA C
MA
PI (I/min) (breathslmin) 9.53 11.13 9.07 9.72 5.22 6.83 5.72 6.82 5.00 7.05 6.9 1 f2.21 8.3 I +2.00
15.6 17.4 15.7 17.3 1 7.95 11.65 12.0 15.2 5.7 6.8 11.39 f4.50 13.67 k4.49
extrapolation that would result if a single Pcoz value was chosen to express response curve position for all subjects. The low-position variables for ventilation, tidal volume and frequency were assigned the symbols vi(L), VT(L) and f(L) respectively; corresponding high-position variables were assigned the symbols vl(H), V T ( H ) and f(H) respectively (Tables 1 and 2, Fig. 1). The effect of mental arithmetic on the reproducibility of the CO, response was assessed by computing coefficients of variation for each variable measured. The effects of mental arithmetic on all variables were tested with a two-tailed paired t-test.
Results Air breathing
Mental arithmetic during air breathing was associated with an increase of ventilation (mean increase = 1.8 I/min, P
Interaction of mental factors with hypercapnic ventilatory drive in man
J . R . A. R I G G , E . M. I N M A N , N . A . S A U N D E R S , S. R. L E E D E R A N D N . L. J O N E S Departments of Anaesthesia and Medicine, McMaster University, Hamilton, Ontario, Canada
(Received 29 July 1976; accepted 16 October 1976)
SummarY 1. The effect of mental arithmetic tasks on
ventilation, breathing pattern, oxygen intake and carbon dioxide output was studied during air breathing and carbon dioxide rebreathing in healthy subjects. 2. Ventilation and breathing frequency increased significantly on performance of the task during 4 min air breathing and 4 min rebreathing; tidal volume was unchanged. The slopes of the ventilatory, frequency and tidal volume responses to carbon dioxide changed little during task performance. 3. During 15 min air breathing, oxygen intake was unchanged with task performance. Carbon dioxide output increased significantly with task performance, as a result of wash-out of carbon dioxide from body stores by the increased ventilation . 4. Mental arithmetic had no effect on the coefficients of variation of the slope and position variables of the ventilatory, frequency and tidal volume responses to carbon dioxide. It is concluded that task performance does not improve the reproducibility of these responses.
Introduction The ventilatory response to C02 (AV,/bPco,), when measured by rebreathing, is highly reproducible in most individuals (Read, 1967; Rebuck & Read, 1971). However, we have found that many healthy people have a variable response, not only from one day to the next, but also on the same day, a finding reported by others (Jennett, Barker & Forrest, 1968; Plum, 1974; Arkinstall, Nirmel, Klissouras & Milic-Emili, 1974). In view of the known influence of wakefulness on respiratory control mechanisms (Bulow, 1963), the present experiments were designed to test the possibility that mental factors may alter the ventilatory response to hypercapnia. Mental arithmetic tasks were performed by healthy adults during air breathing and rebreathing to investigate their effects on ventilation. These tasks were chosen because they provided a simple method of maintaining a continuous process of mental activity while ventilatory measurements were made. Measurements of O2 intake and CO, output were made to exclude the possibility of an increase in metabolism causing an increase in ventilation.
Key words: hypercapnia, mental arithmetic, metabolic rate, ventilation, ventilatory responses to COz.
Metha Nineteen healthy adults, 13 men and six women, were studied. Informed consent was Obtained from each* although none was aware of the hypothesis being tested. All experiments
Correspondence: Dr J. R. A. Rim, Department of Anaesthesia, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, Canada LSS 4J9.
269
270
J . R . A . Rigg el al.
were conducted in the sitting position and all subjects fasted for 2 h before an experiment.
Procedure Three series of experiments on the effect of mental arithmetic were conducted. In the first series, the effect was studied in four subjects during rebreathing; in the second, the effect was studied in ten subjects breathing air and during rebreathing; in the third, the effect on CO, output and 0, consumption was studied in five subjects during 15 min air breathing. In rebreathing experiments (series 1 and 2), each subject performed four ventilatory response tests, two control and two during mental arithmetic; a Latin square design was used to reduce the possibility of an effect due to order. Mental arithmetic was performed continuously throughout rebreathing for 4 min. Calculations involved addition, subtraction, multiplication and division of one- or two-digit numbers. As an oral answer to calculations could not be given, each subject was told that the correct answer to each mental arithmetic step was an integer; if a fraction occurred the subject knew immediately that an error had been made. The subject then signalled by hand and the correct answer was called to permit resumption of calculations. Five sets of mental arithmetic tasks were constructed and a different set was used in each run to reduce possibility of learning, leading to transferred skill, from one experiment to the next. All sets were read slowly and clearly, from a previously prepared protocol, by the same person. In practice, the mental arithmetic was simple to perform; errors occurred in from 1 to 4 % of the total tasks given in any experiment and were distributed randomly throughout the 4 min of rebreathing. Subjects were not aware of the order of experiments; they did not know that they would be required to perform mental arithmetic until requested to do so after the beginning of rebreathing. Thirty minutes rest was allowed between successive studies and an estimate of oxygenated mixed venous CO, pressure (P0,co2)was obtained at the beginning of each rebreathing experiment. Air-breathing measurements were obtained immediately preceding the first rebreathing measurement; 4 min with task performance and 4 min control
ventilation was recorded before and after mental arithmetic. In the experiments to measure the effects of mental arithmetic on 0,consumption (POz) and CO, output ( k o , ) ,each subject breathed air for two successive 15 min periods, one with and one without task performance; the order of task and control experiments was alternated in successive subjects. Oxygen intake and CO, output were measured continuously, together with ventilatory variables, an on-line PDP-8/1 recorder being used for computation and display of data as detailed previously (Jones, Campbell, Edwards & Robertson, 1975). Subjects rebreathed 0,+CO, (93:7, vlv). Inspired ventilation (PI) was measured with a dry gas meter (Parkinson Cowan CD4), with a potentiometer fitted to the output shaft; full scale deflection was precise to +2%. Carbon dioxide was analysed by an infrared analyser (Godart Capnograph) with a response time of 0.1 s and precise to *0.1% over the range of &lo% CO,. Gas sampled by the analyser during rebreathing was returned to the bag. End-tidal P c o , (PETco2) and vl were recorded with an Astromed pen recorder. The resistance of the rebreathing circuit was 1.0 cm water s - ' I - ' at a flow rate of 4 I/s. Data analysis
Mean ventilation ( vl), tidal volume (V,) and breathing frequency (f) were calculated for successive 30 s intervals. All gas volumes were corrected to BTPS. The slopes of ventilatory ( A v I / A P ~ ~tidal ,), volume (A V T / A P C O ~ and ) frequency responses (AflAPco,) to CO, were calculated by leastsquares regression. To compare the position of response curves between control tests and mental arithmetic tests the following procedure was adopted. For each subject, two values of P c o , were chosen, which represented the highest (H) and lowest (L) values common to all four response curves. Ventilation (VJ, V, and f observed at these P c o , values were used to measure response curve position. This procedure was adopted because different subjects rebreathed over widely differing CO, pressures. The high and low variables represented actual measurements of each subject's ventilation during rebreathing and their use eliminated the errors due to
5 SD
Mean
14
13
12
11
10
9
8
7
6
5
4
3
MA
C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C MA C
1
2
Study
Subjectno.
VI(H) (I/min) VdL) (litres)
+
20.2 21-8 203 22.2 208 24.0 9.8 11.6 11.2 18.10 14.0 16.3 13.7 16.5 145 19.1 12.8 19.4 8.4 9.0 21.2 21.9 18.2 22.2 15.5 21.0 24.8 249 16.10 +4.88 19.14 f 4.55 P0.3 P >0.9
(I/min)
VI(L)
0.23 0.46 0-49 0.66 + 0.27 0.53 f0.18 P 0.3
Af/APc02 AVT/APCO~ (breaths (I/kPa) min-' kPa- ') 7.15 7.15 6.78 6.78 7.02 6.92 6.76 6.76 6.92 6,68 7-25 6.98 7.16 7-32 6.68 6.68 7.21 7.38 6-72 6.85 6.69 6.85 6.56 6.38 6.32 6.18 6.68 6.57 6.85 5 028 6.82 5 0.33 P >01
0371 0.392 0.392 0.442 0.343 0.340 0.343 0.340 0.400 0446 0.461 0.422 0.566 0-592 0.396 0.416 0.408 0480 0.365 0.313 0350 0.294 0.422 0.465 0.466 0509 0.403 0.420 0.407 f 0.60 0419 k0.81 P >02
PV,COZ dp/dt (kPa) (kPa/min)
TABLE 1. Ventilation, tido1 volume and frequency at the beginning [VI(L),VAL),f ( L ) ]and at the end [VI(H),V A H ) ,f ( H ) Jof rebreathing, ventilatory (AV,/APcoz). tidal colume (AVT/APC02)and frequency (Af/APcoz) responses to COz, oxygenated mixed venous COz (PP,coz) and the rate of rise of CO2 pressure (dPcol/dt), with ( M A ) and without ( C ) mental arithmetic during rebreathing Each value is the mean of two runs for each individual. Standard deviations: 0.09-13.17, Vl(L); 0.61-11.12, Vl(H); 0.01-0.78, VAL); 0.01439, VT(H);0430-5.5, f ( L ) ; 04-46, f(H); 0.08-15.11, AVI/APcoz; 0 0 3 4 5 0 , A VT/APcoZ; 0.00-3.08, Af/APcoz ; 0.00-032, Pv,coz; 040-6*16, dPco,/dt. These variables are explained in detail in the text.
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9.
a
B
3
2
C
.c
8'
f
&
0
-+ r, .c
J . R . A . Rigg et at.
272
TABLE 2. Ventilation (v,),frequency ( f ) , ridal volume ( VT), end-tidol CO, pressure ( P ~ T c o ~COz ), output (VCO,) and oxygen uptake (Po2) during 12-15 min air breathing with ( M A ) and without ( C ) niental arithmetic ~~~
f
Subject no.
Study
15
C MA
16 17
18 19 Mean f SD
C MA C MA
C MA C MA C
MA
PI (I/min) (breathslmin) 9.53 11.13 9.07 9.72 5.22 6.83 5.72 6.82 5.00 7.05 6.9 1 f2.21 8.3 I +2.00
15.6 17.4 15.7 17.3 1 7.95 11.65 12.0 15.2 5.7 6.8 11.39 f4.50 13.67 k4.49
extrapolation that would result if a single Pcoz value was chosen to express response curve position for all subjects. The low-position variables for ventilation, tidal volume and frequency were assigned the symbols vi(L), VT(L) and f(L) respectively; corresponding high-position variables were assigned the symbols vl(H), V T ( H ) and f(H) respectively (Tables 1 and 2, Fig. 1). The effect of mental arithmetic on the reproducibility of the CO, response was assessed by computing coefficients of variation for each variable measured. The effects of mental arithmetic on all variables were tested with a two-tailed paired t-test.
Results Air breathing
Mental arithmetic during air breathing was associated with an increase of ventilation (mean increase = 1.8 I/min, P
