.I. Behav. Ther. & Exp. Psyrhiat. Vol. 4, pp. 223-228. Pergamon Press, 1913. Printed in Great Britain.
EFFECTS OF CARBON DIOXIDE-OXYGEN INHALATTON ON HEART RATE, BLOOD PRESSURE, AND SUBJECTIVE ANXIETY RONALD LN* State University
of New York at Albany
HERBERT WALKER New York University
School of Medicine
Summary-Single full-capacity inhalations of a mixture of carbon dioxide (65 “/.) and oxygen (35%) were administered to 10 adult-human Ss and compressed air was administered to a second group of 10 Ss. Immediately before and 2 min after the administration of either gas we determined (a) level of anxiety (measured in terms of the sud scale-subjective units of disturbance), (b) heart rate, and (c) systolic and diastolic blood pressure. After gas inhalation, group both groups showed a decrease in anxiety and in heart rate. The carbon dioxid-xygen also showed a decrease in diastolic blood pressure, and some idiographic data suggested an increase in systolic blood pressure.
IN rmz treatment of pervasive anxiety, single full-capacity inhalations of a mixture of carbon dioxide (65%) and oxygen (35%) have been found to reduce patients’ self report of anxiety (Woipe, 1969). Since carbon dioxide is dissipated in a matter of minutes, its effect can not be a direct pharmacological one dependent upon its presence in the body; yet “one or two inhalations sometimes removes pervasive anxiety for weeks and months, and usually for at least a good many hours (Wolpe, 1969, p. 176).” Although the mechanism is not apparent, it is conceivable that the anxiety reducing properties of the gas are an indirect result of its effects on certain autonomic functions such as heart rate and blood pressure. The very rapid and strong effects of carbon dioxide inhalation suggest that it might act as the unconditioned stimulus (UCS) to an unconditioned response (UCR) consisting of “a powerful anxiety-inhibiting excitation” (Wolpe, 1969, p. 177). The cues (CS) responsible for the anxiety present at the time of the administration of the gas would be conditioned to an in-
hibition of the anxiety. The anxiety-eliciting potential of this CS would be decreased. The present experiment was conducted for the purpose of determining the immediate effects of carbon dioxide-oxygen inhalation in adult humans on (a) subjective anxiety level as measured in terms of the sud scale (subjective units of disturbance, Wolpe, 1969), (b) heart rate, (c) systolic blood pressure, and (d) diastolic blood pressure.
METHOD Subjects. The Ss were 20 adults (six females and 14 males) ranging in age from 20 to 60 yr ; mean age was 30 yr. Ten of the Ss were outpatients at the Eastern Pennsylvania Psychiatric Institute undergoing treatment for neurotic complaints. The other 10 Ss were staff employees of the Behavior Therapy Unit of the Department of Psychiatry of the Temple University Medical School and students attending the Sixth Annual Behavior Therapy Institute at the Temple University Medical School.
*Requests for reprints should be addressed to Ronald key, State University of New York at Albany, Albany, New York 12222. 223
224
RONALD
LEY and HERBERT
WALKER
blood pressure. The Ss were requested to report Apparatus. The carbon dioxide-oxygen mixtheir sud level at approximately 30-see intervals ture was administered in a ratio of 65 % carbon dioxide to 35% oxygen via a standard self- for a period of about two and + min. administration inhalation mask. Compressed air, used for half of the Ss, was administered via RESULTS a similar self-administration inhalation mask. Heart rate was measured by meads of mastoidAnxiety level. Table 1 contains the sud scores wrist surface-electrode transducers routed to a for all Ss under both the compressed air and pen recorder located in a room separate from carbon dioxide-oxygen inhalation conditions. the test room. A one-way glass between the two These data were analyzed by means of a tworooms allowed E, to observe S and El, and a factor analysis of variance in which the gas microphone located in the test room allowed Ez variable was the between-Ss factor and the preto hear El and S. The pen recorder was equipand post-treatment intervals, the within-Ss ped with an event marker which provided Es factor. Although the overall effect of the gas with the means of co-ordinating the events treatment was not significant, F (1, 18)=0*81, occurring in the test room with heart rate P>O-05; the pre- and post-treatment intervals recordings at a given moment. factorwassignificant,F(5,90)=1144,P<0401; Blood pressure was measured by means of a. but the gas by interval interaction was not, standard sphygmomanometer and mercury F(5, 90)=1*18, P>O.O5. From Fig. 1, which is column. a plot of the mean sud level for the two gas Procedure. The Ss were assigned to the experimental group (CO, group-group which inhaled the carbon dioxide-oxygen mixture) or the control group (air group-group which inhaled C---O Air compressed air) on a random basis determined co, prior to S’s arrival at the test room, with the restriction that each group contain an equal number of patients. All Ss received the same orally presented instructions from El, which in essence, (a) explained that the purpose of the experiment was to determine the effect of inhaling an innocuous gas on the ability to relax, (b) instructed S in the use of the Sud scale, (c) instructed S in the use of the self-administration inhalation apparatus, and (d) explained the function of the EKG transducers and sphygmoPm-and post -gas inhalatmn trtervols manometer. Fro. 1. Mean anxiety level in terms of Sud (subjective After the recording electrodes were secured units of disturbance) scale as a function of pre- and postand and the sphygmomanometer was attached, S gas inhalation for the carbon dioxidboxygen compressed air groups. was requested to report his sud level. Heart rate was recorded for approximately 2 min groups as a function of the pm-gas inhalation before either of the gases was administered. During this time, El obtained a measure of and post-gas inhalation intervals, it is apparent that both groups (carbon dioxide-oxygen and systolic and diastolic blood pressure. Approximately 15 set following administration of a gas, compressed air) reported a decrease in anxiety S was requested to report his sud level again. following gas inhalation. Although the differAt the same time, E, took a second measure of ence between the two groups was not significant,
EFFECTS OF CARBON DIOXIDEaXYGEN
225
INHALATION
TABLE1. PRE- AND POST-TREATMENT SUD SCORES UNDER AIR AND CARBON DIOXIDE-XYGEN
Subject*
SW S 1*
Pre sud
45 z
Air 1 15 38 10
G&S Subject*
Post treatment sud 3 4 2
5
10 38 10
10 38 10
38 1;
20
I5
15
16.8
15.8
15 38 10
S S1 s:
INHALA-I-ION
Carbon dioxide-oxygen Pre sud Post-treatment sud 4 1 2 3
5
15 10
05 5
0 5
0 5 0
0 10 10
x 12 4
26.5
14.0
11.5
11-o
12-o
9.4
SI S1* Mean
25.3
20-l
20-O
14.4 _
Mean
*The last five Ss in each group are the outpatients.
the observed means of the carbon dioxideoxygen group were less than those of the compressed air group on ail the post-inhalation intervals, whereas the two groups were essentially the same with respect to their levels of anxiety prior to gas inhalation. Heart rate. The heart rate of each S for four I-min intervals, two preceding and two following compressed air or carbon dioxide-oxygen inhalation, is given in Table 2. The two-factor analysis of variance (gas inhalation and preand post-gas inhalation intervals) resulted in no significant difference between the effects of air and carbon dioxide-oxygen inhalation on TABLET.
Subject*
HEARTRATEPOR
heartrate, F(l, 18)=1*21, P>O.O5. The interval factor was significant, F (3, 54)=3*32, P~0.05; but the gas by interval interaction was not, F (3, 54)=1*43, P>O*O5. Both the compressed air and carbon dioxide-oxygen groups showed a slight rise in heart rate from the fkst interval (two min before inhaling gas) to the second interval (I-min interval before inhaling gas), and a slight deceleration in heart rate from the second to the third and fourth intervals, i.e., slower heart rates during the post-inhalation intervals as compared with heart rates during the interval immediately preceding gas inhalation.
FOUR ONE-MMJTEWI-ERVALS,TWOPRECEDING DIOXIDE INHALATION
Air Pre-treatment heart rate 1st min 2nd min 76 79
G&3 Post-treatment heart rate 3rd min 4th min 73
S:* :
80 89
f;
:z
8: 85
5:: S4 S, S11 S 1, S 1. Mean
59 75 119 88 73 84 125 86.8
70 72 119 93 76 89 127 89.1
69 74 119 96 75 73 131 89.2
63 67 115 86 74 76 119 84.5
*The last five Ss in each group are the outpatients.
Subject*
S, :: S 16 I, SI, SI S 10 ::: Mean
ANDT~~~~LL~~MOMR~R
CARBON
Carbon dioxide-oxygen Pm-treatment Post-treatment heart rate heart rate 1st mm 2nd min 4th min 3rd min 74 72 72 71 84 74
88 78
76 71
85 73
105 82 z
101 82 64 95 87 74 71 81.2
97 82 65 96 92 71 62 78.3
;;
79 75 74 80.2
;; 82 68 69 78.4
226
RONALD
LEY and HERBERT WALKER
Systolic blood pressure. The systolic blood pressure of each S immediately before and immediately after gas inhalation is given in Table 3. The results of the analysis of variance for these data indicated that (a) the observed difference in systolic blood pressure between the compressed air group and carbon dioxideoxygen group was not significant, F( 1,18) =0-O 1, P>O*O5; (b) the observed increase in systolic blood pressure from the pre-inhalation to the post-inhalation measure was not significant, F (1, 18)=2*27, P>O*O5; and (c) the interaction between these factors was not significant, F (1, 18)=0*13, P>O.O5. Diastolic blood pressure. The diastolic blood pressure of each S immediately before and TABLE3.
PRE-
AND
POST-TRBATMENT CARBGN
WSTGLIC
immediately after gas inhalation is given in Table 4. The results of the analysis of variance for these data indicated that (a) the observed difference in diastolic blood pressure between the compressed air group and carbon dioxideoxygen group was not significant, F( 1,18) = 1.23, P>O*O5; (b) the observed change in diastolic blood pressure from the pre-inhalation to the post-inhalation measure was not significant, F (1, 18)=0*72, P>O*O5; but (c) the interaction between these factors indicated a strong trend in the direction of a decrease in diastolic blood pressure following carbon dioxide-oxygen inhalation but no. change following compressed air inhalation, F (1, 18)=4.16, 0*05
&GOD
DIOXIDE-GJWGEN
PRPSSURE
(MM
G&C Subjects* :: Sir
S 18 :I0 Sa
f:: S ia MCall *The last five Ss
144 115 128 110
S* s, S. S 16
130 112 :g
112 104 112 175
155 108 130
154 108 142
2, S:
130 132 112
190 112 114
128 132
128 150 160 133.9
118 124 150 125.5
160 140 130 134.9
148
128.1
::: Sill Mean
Air Pre-treatment
Post-treatment
78.4
Sll
PRESSURE
(MM OF MERCURY)
UNDER
AIR AND
INHALATION
Gas
MlXIl
S.
BLOGD
DIOXIDE-OXYGEN
80 66 90
&
Post-treatment
in each group are the outpatients.
Sl. SI@
S II S.”__
Carbon dioxide-oxygen Pre-treatment
128 110 130 112
78 74 72 80 72
Sla
AND
Subjects*
80 80 82 72 72 90
Sa
AIR
Post-treatment
CARBON
Sa
UNDER
Air Pre-treatment
TABLE4. Paa- ANDPOGT-TREATMENT DIASTOUC
Subjects*
OF MERCURY)
lNHALATION
Subjects* Sl S, S. it:
Carbon dioxide-oxygen Post-treatment Pre-treatment 92 72 72 78 88
S.
72 82
66 68 65 90 80
92 78 100
Sta
74 72 90
82 74 72
81.0
MWl
79-2
72.9
\
72
*The last five Ss in each group are the outpatients.
-.
S,
60 72
EFFECTS OF CARBON DIOXIDE-OXYGEN
C----O
Air
-
co,
* I
I Prc
Post
gas
gas
FIQ. 2. Mean diastolic blood pressure in mm of mercury as a function of pre- and post-gas inhalation for the carbon dioxidboxygen and compressed air groups.
a plot of the mean diastolic blood pressure as function of pre- and post-gas inhalation for the carbon dioxide-oxygen and compressed air groups. DISCUSSION The results of the present study indicate that anxiety measured in terms of subjective units of disturbance (suds) decreases immediately following either compressed air or carbon dioxide-oxygen inhalation. The change was greater in the carbon dioxide-oxygen group than the compressed air group (see Fig. 1). This is consistent with the tidings of Slater and Leavy (1966) who reported that a single inhalation of a 35 ‘A CO,-65 % 0, mixture was more effective in reducing subjective anxiety than inhalation of an equal volume of air. Additional data to suggest this trend are given in Table 1, where a comparison of pm-inhalation scores with the first post-inhalation scores shows that four of the 10 Ss of the compressed air group had an increase in anxiety (S,, S18, Szo, and S,k, and one S indicated no change (&), whereas only one S in the carbon dioxide-oxygen group (S,,) had an increase.
INHALATION
227
With respect to heart rate, the results indicate that it increases as the time for administration of the treatment (gas inhalation) approaches and decreases after administration of the gas. Although the observed means for the carbon dioxide-oxygen inhalation group were lower than those of the compressed air group, both groups displayed essentially the same trend with respect to the pre- and post-gas inhalation treatments. The decrease in heart rate following carbon dioxihxygen inhalation was somewhat surprising since virtually all of the Ss in this group . reported that their hearts were beating faster. It-is important to note that the sensation of an increase in heart rate is a uniform response to carbon dioxide-oxygen inhalation. Since carbon dioxide drives the respiratory centers, it is likely that the reported sensation of an increase in heart rate is actually a function of ventricular constriction and dilation. Although there was no significant difference between the compressed air and carbon dioxide-oxygen groups with respect to the increase in systolic blood pressure before and after gas inhalation, the observed increase for the carbon dioxide-oxygen group was greater than that of the compressed air group. Three Ss in the carbon dioxide-oxygen group showed a marked increase in systolic blood pressure following carbon dioxideoxygen inhalation. Table 3 shows that S,, increased from 122 to 175, S, from 132 to 190, and S,, from 118 to 160. The largest change in the compressed air group was in Sll, who showed an increase from 132 to 150. The strong trend in the direction of a decrease in diastolic blood pressure following carbon dioxideoxygen inhalation (seven of 10 Ss showing a decrease compared with three of 10 Ss in the compressed air group) strongly suggests that the commonly reported “increase” in heart rate is a function of a relatively sudden change in blood pressure. These data, especially those which suggest a decrease in blood pressure following carbon dioxide-oxygen inhalation, lend some support to the hypothesis that carbon dioxideoxygen
228
RONALD
LEY and HERBERT
inhalation serves to elicit a strong autonomic excitation (including cardio-vascular changes in the form of increased ventricular contraction and decreased ventricular dilation) which inhibits the autonomic pattern characteristic of anxiety. The reported decrease in anxiety following compressed air inhalation is probably related to participation in the experiment per se rather than the result of compressed air inhalation. The experimental setting, especially the instructions that S would be required to inhale a gas and use the gas inhalation apparatus, might well be expected to increase anxiety initially. After inhaling the compressed air, which has no known-
WALKER
effects on autonomic functioning and no reported noxious qualities, S had met the requirements of the experiment and may well have felt a reduction in anxiety to the level experienced before entering the experimental setting. The fact that both the carbon dioxide-oxygen and compressed air groups showed an increase in heart rate before the administration of their respective treatments and a decrease following their treatments, is consistent with this interpretation. The decrease in anxiety of the compressed air group was not accompanied by a change in blood pressure.
Acknowledgement-The authors wish to thank Joseph Wolpe and the staff of the Behavior Therapy Unit of the Department of Psychiatry, Temple University Medical School and the Eastern Pennsylvania Psychiatric Institute for their assistance in this experiment. REFERENCES SLATZRS. L. and LEAKYA. (1966) The effects of inhaling a 35 per cent CO+5 per cent 02 mixture upon anxiety level in neurotic patients, Behav. Res. & Therapy 4, 309-316.
WOLPE J. (1969) The Practice of Behavior Therapy, Pergamon Press, New York.
(First received 12 June 1972; in revised form 18 J-y
1973)