Journal of Psychosomoric Printed in Great Britain.
Research,
Vol. 35, No. 213, pp. 155-162.
1991. 0
THE TEST-RETEST HYPERVENTILATION S. LINDSAY,* (Rewired
0022%3999/91 $3.00 + .oO 1991 Pergamon Press plc
RELIABILITY OF THE PROVOCATION TEST S. SAQI~
and C. BASS~
9 June 1990; in revised ,fbm
X August 1990)
Abstract--The hyperventilation provocation test (HPT) has been widely used for reproducing symptoms of panics. It is assumed that subjects experience similar symptoms on consecutive occasions of hyperventilation. Fourteen subjects with a history of panics and fourteen without such a history underwent the HPT on two occasions one week apart. In the group of 28 subjects as a whole, there were moderate similarities between the HPTs in both the choice and severity of symptoms reported, even when pre-existing symptoms were controlled statistically. Nevertheless, in the subject-by-subject analysis, many subjects showed no resemblance between the two HPTs in the choice of symptoms. This suggests that many subjects would not show any resemblance between the symptoms experienced in an HPT and those of their latest panic even if hyperventilation occurred in that panic.
INTRODUCTION IT HAS been widely suggested that hyperventilation can contribute to panic attacks in some patients [l]. To identify those patients [2], they were asked to overbreathe to produce hypocapnia: this is called the hyperventilation provocation test (HPT). If the patient reports that the symptoms during the HPT are similar to those experienced during a recent panic, it is concluded that (1) hyperventilation probably contributed to that panic [2], and/or (2) the HPT would provide a useful simulation for treatment of that panic [3]. The HPT has also been used as a screening test by cardiologists [4]. If the HPT is valid in those uses, the symptoms reported even in small samples and in single cases during one HPT, should be very similar to those reported on a subsequent occasion. To date there has been no rigorous test of this. That is surprising, given that the HPT has been widely recommended, but with reservations, in clinical practice for individual cases [2]. The HPT is much more practicable than other tests [5] and so it would be highly desirable to determine its reliability. In this study, the HPT was conducted on two occasions approximately one week apart to test whether the HPTs would be similar, for the group of subjects as a whole, in the choice and severity of symptoms. It was expected that the subjects would report some symptoms before the HPT on both occasions [6]. However, the reliability coefficients for the choice and severity of symptoms associated with the HPTs would remain significant even when baseline symptoms were controlled statistically. Also, in a subject-by-subject analysis, the two HPTs would be similar in the nature of symptoms reported by each subject. *Address correspondence to: Dr S. Lindsay, Department of Psychology, Institute of Psychiatry. De Crespigny Park, London SE5 RAF, U.K. ?Dept of Clinical Psychology. Hither Green Hospital, London SE13 6RY, U.K. $Academic Department of Psychiatry, King’s College Hospital Medical School, Denmark Hill, London SE5 9RS. U.K. 155
A rating-scale of symptoms [7], developed from earlier published lists [S] was used. Using this scale in normal subjects, Pickles [7] found that more symptoms. and of greater severity, were reported during overbreathing in air compared with overbreathing CO,. Normal subjects and patients with panic disorder were examined. Together. they would probably comprise subjects reporting a sufficient variety of symptoms for a satisfactory examination of the HPT. Also. it was appropriate to include normal subjects because previous studies have examined panics in such subjects [9]. Finally, on the assumption that the patients’ lastest panic had been influenced by hyperventilation. it was predicted that there would be significant correlations between that panic attack and the first HPT in the choice and severity of symptoms. METHOD Fourteen patients (six mtn. eight women). average age 33.45 yr + su 9.8. wcrc referred for treatment for panic attacks. Their complaints were consistent with the DSM III-R diagnosis of panic disorder or agoraphobia with panic [IO]. The other subjects wre 14 postgraduate clinical psychology students (four mtn. ten women). average age 26. I yr i SI) 3.94. none of whom had any history of panic, hyperventilatory disorder or any other psychiatric complaint. All of the latter had some knowledge of the effects of hyperventilation. Only two subjects (patients) were taking anxiolytic medication. They wcrc asked to discontinue this for the investigation. No subject had any previous or current evidcncc of serious medical illness.
The design of the study was: all patlcnts:normnl subjects baseline monitoring: (‘2) the HPT: and (3) recovery.
underwent
on two occasions,
one week apart:
(I)
According to a standard procedure [I I]. end-tidal pc’0, uas recorded with a Gould Capnograph Mark IV (Spwtramed IJ.K.) sampling continuously from a 1.2 mm diameter polythene catheter. inserted 2 4 mm inside one nostril of the subject and held in place by adhesive tape. The depcndcnt variables were: (a) total number of symptoms reported; (b) total severity of symptoms: and (c) choice of symptoms (those given greater than Tero severity). These were recorded from Pickles’ (7) checklist of 20 symptoms. 17 of which (dizziness, unreal fcchngs, tingling in the body, numbness, shahincss. muscle pain. pounding heart. irregular heart-beat. need for air. dry mouth, hcadachc. sweating, faintness, nausea. feelings of head warmth. chest pains and cold hands or feet) are commonly reported to occur during hyperventilation, and three spurious symptoms (eyes stinging. earache and low back pain). All 20 have live-point rating-scales: ‘not at all (0): ‘slight (I).’ ‘modcratc (2). ’ ‘sevcrc (3): and ‘very severe (3):
During the assessment interview, each patient was asked to describe his/her last pnmc attack, using the symptom rating-scale. Each subject was then asked tv participate in a study. on two occasions. of the ell’ects of deep rapid breathing. :I routine assessment procedure in the clinic. All agreed and one week later. in the rcsplratory laboratory. they were told that they would breathe rapidly and deeply while seated for a period of up to 5 min. monitored by the capnograph. Thq uere asked to remain vigilant for symptoms and for the pacing instruclions for the 3 min of ‘some symptoms‘ and that the pro\ocatlon test. They were advised that they might experience experimenter would ask about those afterwards. The experimenter then demonstrated the overbreathIng pwx~ by a taperecorder. Ail hubjccts agreed and were then asked to remocc’ their natches from sight. No clocks wcrc Lisible to the subjccI\. The nswl catheter for the cspnogaph was then attached. All subjects remnincd seated tht.oughtrut the procedure. End-tidal pC0, was rocordcd dut-lng ;I 5 m,n bnaelinc as the subyxts completed the symptom ratrng-scale. Fifteen ~ecc~ndsbefore the next phase. the subjects were advised that they ucrc about to bc asked to
hrcathe
deeply as dcscribcd
carher.
The HPT vas dcmonstrarcd
to the subject:, who wrc
encouraged
to
Reliability
of hyperventilation
test
157
follow suit. After about 30 s all subjects continued to overbreathe, at 30 breaths per min. Overbreathing was paced by a tape recording for 3 min. end-tidal pCOz being monitored throughout. When the tape-recording ended, the subjects were told to ‘breathe normally’. After 3 min of rest, the subjects completed the check-list to record the symptoms which they had experienced during overbreathing. On the first occasion, all the normal subjects completed the 3 min of overbreathing but two patients were unable to continue after 1 min and two more stopped after 2.5 min. On the second occasion, one of the subjects who had previously stopped overbreathing after I min did so again; the other continued for 3 min. One of the two subjects who had stopped after 2.5 min. did so again; the other continued for 3 min.
RESULTS
End-tidal
pCOz
For each subject, on both occasions, the average level of pC0, during provocation was, at most 3.6 kPa (27 mm Hg). and 30% less than during the baseline. Symptoms Dummy symptoms were reported only three times and so these were omitted from further analyses. The number and total severity of symptoms during provocation were greater than for baseline for all subjects on occasion one and for all but two subjects on occasion two. Hence hyperventilation, which led to a reduction in CO>, was accompanied by an increase in both the number and severity of symptoms. Similarity between HPTs in choice of symptoms, over all subjects, uncorrected,for baseline symptoms. Each symptom, for each subject, was noted as having been experienced or not experienced during each HPT. For each symptom, therefore, a TABLE
I.-CORRESPONDENCE BETWEENTWO HPTs
OVER
ALL
SUBJECTS
IN CHOICE
OF
EACH
SYMPTrlM
Correspondence
between HPTs in choice Uncorrected for baseline symptoms
Symptom Dizziness Feelings of unreality Tingling Numbness Shakiness Muscle pain Pounding heart Irregular heart beat Need for air Dry mouth Headache Sweating Faintness Nausea Feelings of head warmth Chest pains Cold hands/feet Correspondence over all symptoms
xz
N with symptom in both HPTs
2.24 11.49**** 13.g5**** 7.04**** 7.59*** 6.60** 6.85*** 8.49*** 7.34+** 9.g7*** 5.s1** I I .s7**** 15.22**** 7.96*** 5.07* 4.73* 6.85*** 2 =
of symptoms
I I .32****
*/> < 0.05. **p < 0.02, ***p < 0.01, ****/I < 0.001.
23 13 20 II 14 5 II x I’ 20 9 14 20 8 IO 5 9
(N = 28) Corrected for baseline svmutoms zz 2.24 I1.50**** 9.X2*** 9.07*** 4.73* 6.60** x.02*** 8.49*** 7.05*** 9.82*** 5.x1*** 9.61*** 15.22**** 6.60*** 3.88* 4.73* 5.59** I = 11.17****
s.
1%
LINIISAY
Time
(‘I
r/t
Time 2 Baseline HPT
I
Baaelinc
HP-f
6.03 (4.33 3.00 (2.41)
71.06 (9.24) IO.04 (3.37)
5.57 (4.72) 3.50 (3.58)
IX.61
(I 1.03) 9.57 (3.37)
single z2 represented the similarity between the two HPTs in the choice of that symptom over all subjects (Table I). This similarity was uncorrected for baseline symptoms (Table I). Over all subjects there appeared to be a reliable similarity between HPTs for each symptom except ‘dizziness’. That is, almost all subjects who reported for example, ‘tingling’ in one HPT reported ‘tingling’ in the other HPT; those not experiencing ‘tingling’ in one HPT were unlikely to experience it on the other. Almost all subjects reported ‘dizziness’ in both HPTs (Table I) and so there was insufficient variation between the two HPTs in the choice of this symptom to allow a significant x’. According to a statistic (z) which sums all these 1’ [l2], the similarity between HPTs in the choice of all symptoms over all subjects was statistically significant. Simihrit~~
ht,cwn
t/w
HPTs
in
total
.scwrit!~
of
s~wptwmv.
owr
011 suhjmts.
The total severity of symptoms (Table 11) did not differ on average. between the HPTs (F( 1,‘26) 2.33. p > 0.05). Symptoms were rated as more severe on average by the patients (8 = 27. I I. SD = 12.9 I) than by the normal subjects (x = 12.54, SD = 7.36; F( I .‘26) 16.95. /7 < 0.001). The Spearman rank-order correlation between the two HPTs in the severity of symptoms was greater than zero (Table Ill). Therefore the total severity of symptoms during the HPT was similar on both occasions for all subjects considered together. Si~llilrrrit~’ hc~tuwu ik HPT.5. owr oil suhjccts, in tlw choicr of’srrcritj~ of' .s~wptonl.s uwrcctcrl fbr hrrscline .s~wlptonl.v. On both occasions there was a similarity between baseline and HPT in the choice of symptoms (Table 111). That is. symptoms reported during the baseline were also experienced during the HPT. Moreover, the symptoms at baseline at Time I tended to occur during baseline at Time 2 (Table III). There were similar relationships in the total severity ofsymptoms. It was possible therefore, that the similarity in symptoms between the two HPTs, noted above. was due entirely to the similarity between the two baselines in the symptoms reported. To determine the correspondence between HPTs in the choice of symptoms corrected for baseline symptoms (Table 1). the change from baseline to HPT for each tr,lc.orr.cc.trrl,for
hrwlinr
.v,mptoms.
Time I (buellne) x Time I (HPT): Time I (baseline) x Time 2 (hasdine): Time 2 (basclme) x Time 2 (HPT): Time 1 (HPT) x Time 2 (HPT).
*p c 0.05. **p < 0.01. ***p < 0.001.
r, = 0.74***: )‘\ = u.73***; r AL()..58*. )‘\ = 0.60**:
: _ x.74*** :=x99*** : E ‘).7x*** 1 = I I.?:***
Reliability
of hyperventilation
test
159
symptom, over all subjects, was noted as follows. For each subject at Time 1, each symptom was scored as: absent at baseline then also absent with the HPT; absent at baseline then present during the HPT; present during baseline then present during the HPT; or present at baseline then absent during the HPT. This was repeated for Time 2. Then for each symptom, over all subjects, the two HPTs were compared for these change scores. These determined the correspondence (x’) between HPTs in the symptoms corrected for baseline symptoms (Table I). Over all subjects, the correspondence between HPTs in these change scores was significant for each symptom except ‘dizziness’. The z statistic, which sums these x’, showed that over all subjects, over all symptoms, there was a similarity between the HPTs in symptoms corrected for baseline symptoms. That is, there was a reliable resemblance between the two HPTs in the symptoms produced only by the HPTs. The HPTs were then compared in the severity of symptoms, corrected for baseline symptoms. A second order partial correlation coefficient, correcting for the total severity of symptoms before provocation at Time 1 and Time 2, was greater than zero (Y,?~~= 0.57, p < 0.05). Therefore, over all subjects, the similarity between HPTs in the choice and severity of symptoms was not entirely the result of the resemblance between Time 1 and Time 2 in baseline symptoms. Test--retest reliddity, subject by subject, in choice qJ’ symptoms. The previous analyses have tested the similarity between the two HPTs in symptoms, over all subjects. However, it was possible that some subjects would show little or no similarity between the HPTs; others might show considerable similarity according to the following analyses. For each subject, every symptom was noted as having been experienced or not experienced during each HPT. A x2, uncorrected for baseline symptoms, was obtained for each subject over all symptoms (Table IV). Eight normal subjects and eight patients showed significant agreement between the two HPTs in their choice TAHLE IV.---COKKESPONI)ENCE BETWEEYTWO HPTs FOR EACH SUBJECTIN CHOICEOF SYMPTOMS
Uncorrected for baseline symptoms Patients I
3 3 4 5 6 7 x 9 10 II 12
I3 14
Correspondence between Corrected for baseline symptoms
7J
y:
16.15**** 0.26 0.26 1.56 4.43* 4.10* 7.10*** 9.38*** 1.65 0.42 12.38**** 4.62* 16.15*** 0.20
16.48****
HPTs
Normals
1.03 0.65 0.13 4.85* 5.00* 6.X1*** 16.23**** 3.10 2.46 14.x2**** I.1 I 7.10*** 0.02
*/I -=I0.05, **p < 0.02, ***p < 0.01. ****p < 0.001.
1 2 3 4 5 6 7 8 9 IO II
12 13 14
in choice of symptoms Uncorrected for Corrected for baseline symptoms baseline symptoms 7:
Y?
4.80* 9.90*** 4.44
2.86 10.77*** I .32
I .03 0.19 6.67**’ 5.71** 0.06 9.90*** 2.81 10.48*** 8.24***
I.82 1.65
0.08 0.19 7.79*** 3.81 0.09 9.90*** 9.90*** 9.73*** 3.7x 7.90*** O.S6
160
S. LINUSAYet d.
of symptoms uncorrected for baseline symptoms. That is for example, patient 7 chose similar symptoms for both HPTs. Whereas patient 10 chose very different symptoms for both HPTs. In a comparison of change scores for each subject, seven patients and six normal subjects showed a reliable correspondence between HPTs in the choice of symptoms corrected for baseline symptoms (Table IV). It has been necessary to collapse the contingency tables into 2 x 2 format for each subject because of the scarcity with which some changes occurred, notably ‘symptom present then absent’. Conzpurison het\veen latest punk und,first HPT over all patients. The severity of symptoms in the last panic attack was not significantly different, on average (2 = 29.75. SD = 11.69). from the severity of symptoms in the first HPT according to a Mann-Whitney U test (2 = 23.92, SD = 10.34: z = 1.42. II = 11. p > 0.05). The correlation. r, = 0.17, was not greater than zero (p > 0.05). Therefore, although the average severity of symptoms in the panic was similar to the average severity of symptoms in the HPT. the patients showed no consistency in reproducing the severity of symptoms. For example. among the patients who had reported intense symptoms for !heir panic, some reported intense symptoms in the HPT; others experienced mild symptoms in the HPT. However, the choice of symptoms on the first HPT did resemble the symptoms recalled for the last panic (Z = 5.63, p < 0.01). It is important to point out that these analyses were not corrected for symptoms which could have been present before the panic. No record had been made of such symptoms. DISC‘USSION
The capnograph records during the HPTs. showed that all subjects (including those terminating the test prematurely) had breathed according to instructions widely recommended for producing hypocapnia [13]. -4lthough it can occasionally be difficult to estimate pC0, during rapid, deep breathing [I I], all subjects here showed consistently reduced levels during and immediately after the HPTs to an extent consistent with hypocapnia [I 31. IJnder those conditions, all subjects considered together, there was a significant resemblance between the two consecutive HPTs, in both the choice and severity of symptoms. However. all patients and IO normal subjects reported symptoms before hyperventilation at Time 1. and average of seven and one respectively. In three patients. whose pC0, was less than 4 kPa (20 mm Hg) before the HPT, these may have been the product of mild hypocapnia. Some of these baseline symptoms could have been associated with anxiety. The symptoms experienced at baseline at Time 1 were similar to those reported for baseline at Time 2. These were. in turn. similar to those reported for the HPT on each occasion (Table III). The similarity between the HPTs in symptoms may thus have been the result of this similarity in baseline symptoms. Alternatively, other influences such as anxiety could have been similar on both occasions. As suggested by these results, the symptoms of a panic could in part be intensifications of symptoms present before the panic.
Reliability
of hyperventilation
test
161
Nevertheless, over all subjects, the test-retest correspondence between the HPTs in severity and choice of symptoms remained significantly greater than zero even when the baseline symptoms were controlled statistically. It would be of greater interest if the correspondence between HPTs was high. The Y, (Table III), indicates moderate similarity [14] in severity of symptoms. Unfortunately there is no satisfactory test of the magnitude of the partial correlation coefficient which corrected for baseline symptoms [14]. Some authors have noted that the symptoms in HPTs are often not quite the same as those of panics [15] but there appears to be a scarcity of relevant, controlled investigation. The present study confirmed that, in the small sample of patients, there was a significant resemblance in the choice of symptoms recalled for their latest panic and the first HPT, not allowing for baseline symptoms. However, there was no consistent similarity between panic and HPT in the severity of the symptoms, unlike the correspondence here between two consecutive HPTs. It is possible that subjects do not recall symptoms of a panic accurately. Alternatively, influences other than hyperventilation may contribute to the panic. Hyperventilation may not have occurred in all the panics reported by the patients [l]. The symptoms reported for the first HPT were similar to those recorded for the second HPT, all subjects considered together. In spite of this, only some subjects consistently reproduced their choice of symptoms from one HPT to the next according to the subject-by-subject analysis. Hence, even where symptoms of a panic have been produced by hyperventilation, they need not be reproduced reliably by overbreathing in the clinic. In the subject-by-subject analyses (Table IV), the 11’ of the resemblance between Times 1 and 2 in the choice of symptoms would probably have been influenced by the degree to which the choice of any symptom was independent of any other. Thus a subject choosing ‘dizziness’ might also choose ‘faintness’ on Time 1. Then on Time 2, having chosen ‘dizziness’ again, he might choose ‘faintness’ again. This possible lack of independence among symptoms would favour a strong resemblance over all symptoms between the two occasions in choice of symptoms. A xX test would normally assume that the symptoms would be independent of each other. However, in spite of the possibility of a lack of independence among symptoms, many subjects showed no significant consistency from one HPT to the next in their choice of symptoms. The present study has shown that the patients, compared with the normals, reported a greater severity of symptoms during the HPT. The reasons for this were not examined. The groups did differ substantially in age and probably in knowledge of hyperventilation. However, it is not clear what influence, if any, these differences would have had. The subject-by-subject analyses showed no difference between patients and normals in the consistency with which symptoms were reproduced from one HPT to another. In conclusion, the HPT probably has sufficient temporal reliability in the choice and severity of symptoms, for groups of subjects. The symptoms produced by a group of subjects on one HPT would be similar to the symptoms produced by the same group in a subsequent HPT. In spite of this, according to the comparison of a panic and an HPT above. patients undergoing an HPT would show no consistency in the severity of symptoms from latest panic to HPT. Nevertheless, the panic and
162
s. LINDSAY Cl Ui.
HPT would be similar in the choice of symptoms over the group of patients as a whole. To account for the discrepancy in severity, further work needs to be done to determine the contribution of hyperventilation to panics and to determine the accuracy of the recall of panics. In any event, it is clear from this study that, to test the resemblance between symptoms of the HPT and a panic, the symptoms preceding both the panic and the HPT should be acknowledged by recording them in, e.g. diaries and checklists. This would be especially necessary because subjects outside the clinics would experience an infinite variety of stimulation which could provoke a wide variety of physical symptoms. With single cases, however, this study suggests that the HPT would be too unreliable to reproduce panic symptoms consistently: to identify patients whose panic symptoms had been associated with hyperventilation [16]. Many subjects who had experienced certain symptoms during a hyperventilatory panic would not report the same symptoms during hyperventilation in the clinic. Some authors have used the HPT to reproduce symptoms for treatment and have claimed a high rate of success in therapy [17]. This study suggests that an accurate of such reproduction of panic symptoms may not be an essential component treatment. REFERENCES I.
2. 3. 4.
5. 6. 7. 8. 9. IO. II. I?. 13. 14. 1s. 16. 17.
HIBHEKTG. PILSBURY D. Hyperventilation: is it a cause of panic attacks’? Br J f.yychiut 1989; 155: x05 809. STEPT~E A. Cardiovascular and respiratory disorders: investigation. In A Handbook qf’Clinicrr/ Adull Psychology (Edited by LINIXAY SJE. POWELL GE). Aldershot: Gower Publishing Co., 1987. BARLOW DH, CRASKE MG, CERNY JA, KLOSKO JS. Behavioral treatment of panic disorder. Behut. Thw 1989; 20: 261-282. NIXON PGF, FKEEMAXLJ. The think test: a further technique to elicit hyperventilation. J Roy SK Mrd 1988; 81: 277- 279. BASS C, GARUXEK W. Diagnostic issues in the hyperventilation syndrome. Br J Ps~&irr/ 1985; 146: lol~-lo2. BAKLOW DH, CRASKE MG. The phenomenology of panic. In P&c,: Ps~cho/ogicc~l Pcwpc~/icw (Edited by RACHMAN S, MASER JD). New Jersey: Erlbaum, 1988. PICKLES C. Cognitive Factors in Hyperventilation. Unpublished M.Sc. thesis University of London, Institute of Psychiatry. 1987. _. CLARK DM. HEMSLEYDR. The effects of hyperventilation: individual cariability and its relation to personality. J. B&u?. T/w Esp Psychiut 1462; 13: 41 47. NOKTON GR, HARRISON B, HAUCH J. RHOIIES L. Characteristics of people with infrequent panic attacks. J .4hmwm Psycho/ 1985; 94: 216 221. AM~KI(.AN PSYCHIATKICASSO(.IATIOX. Dia&wo.~ric~ und Stcrti.tricrrl Munucrl of Mm~ol Disorders, Third Edn. Washington DC: American Psychiatric Association. CHAMBERS JB, KIFF PJ. GAKDNEK W, JACKSON G, BASS C. Value of measuring end tidal partial pressure of carbon dioxide as an ajunct to treadmill testing. Br Mrd J 1988: 296: 12X1- 1285. EVEKITTB. The Ann/y.G.v of Conrin~my~ Tables. London: Chapman and Hall. 1977. BASS C, GAKIINEK W. Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation. Br Med J 1985: 290: I.387 1390. GUIL~OKLI JP. FKIJ(-HTEK B. Fundmwnlcrl Sru/i.t/ic~s 01 P,yvchology cmd Edum/ion. New York: McGraw-Hill, 1981. BASS C. GAKUNEK W. Emotional influences on breathlessness. J. P.syc~hosom. Re.5. 1985; 29: 599 609. HIHHEKTG, CHAN M. Respiratory control: its contribution to the treatment of panic attacks. Br J Pq~c~hicrr 1989: 154: 232 236. BECK AT. Cognitive approaches to panic disorder: theory and therapy. In Panic: P.g~cho/ogicu/ Prr.~pcctrrc~.t (Edited by RA(.HMAN S. MASER JD). New Jersey: Erlbaum. 1988.
Research,
Vol. 35, No. 213, pp. 155-162.
1991. 0
THE TEST-RETEST HYPERVENTILATION S. LINDSAY,* (Rewired
0022%3999/91 $3.00 + .oO 1991 Pergamon Press plc
RELIABILITY OF THE PROVOCATION TEST S. SAQI~
and C. BASS~
9 June 1990; in revised ,fbm
X August 1990)
Abstract--The hyperventilation provocation test (HPT) has been widely used for reproducing symptoms of panics. It is assumed that subjects experience similar symptoms on consecutive occasions of hyperventilation. Fourteen subjects with a history of panics and fourteen without such a history underwent the HPT on two occasions one week apart. In the group of 28 subjects as a whole, there were moderate similarities between the HPTs in both the choice and severity of symptoms reported, even when pre-existing symptoms were controlled statistically. Nevertheless, in the subject-by-subject analysis, many subjects showed no resemblance between the two HPTs in the choice of symptoms. This suggests that many subjects would not show any resemblance between the symptoms experienced in an HPT and those of their latest panic even if hyperventilation occurred in that panic.
INTRODUCTION IT HAS been widely suggested that hyperventilation can contribute to panic attacks in some patients [l]. To identify those patients [2], they were asked to overbreathe to produce hypocapnia: this is called the hyperventilation provocation test (HPT). If the patient reports that the symptoms during the HPT are similar to those experienced during a recent panic, it is concluded that (1) hyperventilation probably contributed to that panic [2], and/or (2) the HPT would provide a useful simulation for treatment of that panic [3]. The HPT has also been used as a screening test by cardiologists [4]. If the HPT is valid in those uses, the symptoms reported even in small samples and in single cases during one HPT, should be very similar to those reported on a subsequent occasion. To date there has been no rigorous test of this. That is surprising, given that the HPT has been widely recommended, but with reservations, in clinical practice for individual cases [2]. The HPT is much more practicable than other tests [5] and so it would be highly desirable to determine its reliability. In this study, the HPT was conducted on two occasions approximately one week apart to test whether the HPTs would be similar, for the group of subjects as a whole, in the choice and severity of symptoms. It was expected that the subjects would report some symptoms before the HPT on both occasions [6]. However, the reliability coefficients for the choice and severity of symptoms associated with the HPTs would remain significant even when baseline symptoms were controlled statistically. Also, in a subject-by-subject analysis, the two HPTs would be similar in the nature of symptoms reported by each subject. *Address correspondence to: Dr S. Lindsay, Department of Psychology, Institute of Psychiatry. De Crespigny Park, London SE5 RAF, U.K. ?Dept of Clinical Psychology. Hither Green Hospital, London SE13 6RY, U.K. $Academic Department of Psychiatry, King’s College Hospital Medical School, Denmark Hill, London SE5 9RS. U.K. 155
A rating-scale of symptoms [7], developed from earlier published lists [S] was used. Using this scale in normal subjects, Pickles [7] found that more symptoms. and of greater severity, were reported during overbreathing in air compared with overbreathing CO,. Normal subjects and patients with panic disorder were examined. Together. they would probably comprise subjects reporting a sufficient variety of symptoms for a satisfactory examination of the HPT. Also. it was appropriate to include normal subjects because previous studies have examined panics in such subjects [9]. Finally, on the assumption that the patients’ lastest panic had been influenced by hyperventilation. it was predicted that there would be significant correlations between that panic attack and the first HPT in the choice and severity of symptoms. METHOD Fourteen patients (six mtn. eight women). average age 33.45 yr + su 9.8. wcrc referred for treatment for panic attacks. Their complaints were consistent with the DSM III-R diagnosis of panic disorder or agoraphobia with panic [IO]. The other subjects wre 14 postgraduate clinical psychology students (four mtn. ten women). average age 26. I yr i SI) 3.94. none of whom had any history of panic, hyperventilatory disorder or any other psychiatric complaint. All of the latter had some knowledge of the effects of hyperventilation. Only two subjects (patients) were taking anxiolytic medication. They wcrc asked to discontinue this for the investigation. No subject had any previous or current evidcncc of serious medical illness.
The design of the study was: all patlcnts:normnl subjects baseline monitoring: (‘2) the HPT: and (3) recovery.
underwent
on two occasions,
one week apart:
(I)
According to a standard procedure [I I]. end-tidal pc’0, uas recorded with a Gould Capnograph Mark IV (Spwtramed IJ.K.) sampling continuously from a 1.2 mm diameter polythene catheter. inserted 2 4 mm inside one nostril of the subject and held in place by adhesive tape. The depcndcnt variables were: (a) total number of symptoms reported; (b) total severity of symptoms: and (c) choice of symptoms (those given greater than Tero severity). These were recorded from Pickles’ (7) checklist of 20 symptoms. 17 of which (dizziness, unreal fcchngs, tingling in the body, numbness, shahincss. muscle pain. pounding heart. irregular heart-beat. need for air. dry mouth, hcadachc. sweating, faintness, nausea. feelings of head warmth. chest pains and cold hands or feet) are commonly reported to occur during hyperventilation, and three spurious symptoms (eyes stinging. earache and low back pain). All 20 have live-point rating-scales: ‘not at all (0): ‘slight (I).’ ‘modcratc (2). ’ ‘sevcrc (3): and ‘very severe (3):
During the assessment interview, each patient was asked to describe his/her last pnmc attack, using the symptom rating-scale. Each subject was then asked tv participate in a study. on two occasions. of the ell’ects of deep rapid breathing. :I routine assessment procedure in the clinic. All agreed and one week later. in the rcsplratory laboratory. they were told that they would breathe rapidly and deeply while seated for a period of up to 5 min. monitored by the capnograph. Thq uere asked to remain vigilant for symptoms and for the pacing instruclions for the 3 min of ‘some symptoms‘ and that the pro\ocatlon test. They were advised that they might experience experimenter would ask about those afterwards. The experimenter then demonstrated the overbreathIng pwx~ by a taperecorder. Ail hubjccts agreed and were then asked to remocc’ their natches from sight. No clocks wcrc Lisible to the subjccI\. The nswl catheter for the cspnogaph was then attached. All subjects remnincd seated tht.oughtrut the procedure. End-tidal pC0, was rocordcd dut-lng ;I 5 m,n bnaelinc as the subyxts completed the symptom ratrng-scale. Fifteen ~ecc~ndsbefore the next phase. the subjects were advised that they ucrc about to bc asked to
hrcathe
deeply as dcscribcd
carher.
The HPT vas dcmonstrarcd
to the subject:, who wrc
encouraged
to
Reliability
of hyperventilation
test
157
follow suit. After about 30 s all subjects continued to overbreathe, at 30 breaths per min. Overbreathing was paced by a tape recording for 3 min. end-tidal pCOz being monitored throughout. When the tape-recording ended, the subjects were told to ‘breathe normally’. After 3 min of rest, the subjects completed the check-list to record the symptoms which they had experienced during overbreathing. On the first occasion, all the normal subjects completed the 3 min of overbreathing but two patients were unable to continue after 1 min and two more stopped after 2.5 min. On the second occasion, one of the subjects who had previously stopped overbreathing after I min did so again; the other continued for 3 min. One of the two subjects who had stopped after 2.5 min. did so again; the other continued for 3 min.
RESULTS
End-tidal
pCOz
For each subject, on both occasions, the average level of pC0, during provocation was, at most 3.6 kPa (27 mm Hg). and 30% less than during the baseline. Symptoms Dummy symptoms were reported only three times and so these were omitted from further analyses. The number and total severity of symptoms during provocation were greater than for baseline for all subjects on occasion one and for all but two subjects on occasion two. Hence hyperventilation, which led to a reduction in CO>, was accompanied by an increase in both the number and severity of symptoms. Similarity between HPTs in choice of symptoms, over all subjects, uncorrected,for baseline symptoms. Each symptom, for each subject, was noted as having been experienced or not experienced during each HPT. For each symptom, therefore, a TABLE
I.-CORRESPONDENCE BETWEENTWO HPTs
OVER
ALL
SUBJECTS
IN CHOICE
OF
EACH
SYMPTrlM
Correspondence
between HPTs in choice Uncorrected for baseline symptoms
Symptom Dizziness Feelings of unreality Tingling Numbness Shakiness Muscle pain Pounding heart Irregular heart beat Need for air Dry mouth Headache Sweating Faintness Nausea Feelings of head warmth Chest pains Cold hands/feet Correspondence over all symptoms
xz
N with symptom in both HPTs
2.24 11.49**** 13.g5**** 7.04**** 7.59*** 6.60** 6.85*** 8.49*** 7.34+** 9.g7*** 5.s1** I I .s7**** 15.22**** 7.96*** 5.07* 4.73* 6.85*** 2 =
of symptoms
I I .32****
*/> < 0.05. **p < 0.02, ***p < 0.01, ****/I < 0.001.
23 13 20 II 14 5 II x I’ 20 9 14 20 8 IO 5 9
(N = 28) Corrected for baseline svmutoms zz 2.24 I1.50**** 9.X2*** 9.07*** 4.73* 6.60** x.02*** 8.49*** 7.05*** 9.82*** 5.x1*** 9.61*** 15.22**** 6.60*** 3.88* 4.73* 5.59** I = 11.17****
s.
1%
LINIISAY
Time
(‘I
r/t
Time 2 Baseline HPT
I
Baaelinc
HP-f
6.03 (4.33 3.00 (2.41)
71.06 (9.24) IO.04 (3.37)
5.57 (4.72) 3.50 (3.58)
IX.61
(I 1.03) 9.57 (3.37)
single z2 represented the similarity between the two HPTs in the choice of that symptom over all subjects (Table I). This similarity was uncorrected for baseline symptoms (Table I). Over all subjects there appeared to be a reliable similarity between HPTs for each symptom except ‘dizziness’. That is, almost all subjects who reported for example, ‘tingling’ in one HPT reported ‘tingling’ in the other HPT; those not experiencing ‘tingling’ in one HPT were unlikely to experience it on the other. Almost all subjects reported ‘dizziness’ in both HPTs (Table I) and so there was insufficient variation between the two HPTs in the choice of this symptom to allow a significant x’. According to a statistic (z) which sums all these 1’ [l2], the similarity between HPTs in the choice of all symptoms over all subjects was statistically significant. Simihrit~~
ht,cwn
t/w
HPTs
in
total
.scwrit!~
of
s~wptwmv.
owr
011 suhjmts.
The total severity of symptoms (Table 11) did not differ on average. between the HPTs (F( 1,‘26) 2.33. p > 0.05). Symptoms were rated as more severe on average by the patients (8 = 27. I I. SD = 12.9 I) than by the normal subjects (x = 12.54, SD = 7.36; F( I .‘26) 16.95. /7 < 0.001). The Spearman rank-order correlation between the two HPTs in the severity of symptoms was greater than zero (Table Ill). Therefore the total severity of symptoms during the HPT was similar on both occasions for all subjects considered together. Si~llilrrrit~’ hc~tuwu ik HPT.5. owr oil suhjccts, in tlw choicr of’srrcritj~ of' .s~wptonl.s uwrcctcrl fbr hrrscline .s~wlptonl.v. On both occasions there was a similarity between baseline and HPT in the choice of symptoms (Table 111). That is. symptoms reported during the baseline were also experienced during the HPT. Moreover, the symptoms at baseline at Time I tended to occur during baseline at Time 2 (Table III). There were similar relationships in the total severity ofsymptoms. It was possible therefore, that the similarity in symptoms between the two HPTs, noted above. was due entirely to the similarity between the two baselines in the symptoms reported. To determine the correspondence between HPTs in the choice of symptoms corrected for baseline symptoms (Table 1). the change from baseline to HPT for each tr,lc.orr.cc.trrl,for
hrwlinr
.v,mptoms.
Time I (buellne) x Time I (HPT): Time I (baseline) x Time 2 (hasdine): Time 2 (basclme) x Time 2 (HPT): Time 1 (HPT) x Time 2 (HPT).
*p c 0.05. **p < 0.01. ***p < 0.001.
r, = 0.74***: )‘\ = u.73***; r AL()..58*. )‘\ = 0.60**:
: _ x.74*** :=x99*** : E ‘).7x*** 1 = I I.?:***
Reliability
of hyperventilation
test
159
symptom, over all subjects, was noted as follows. For each subject at Time 1, each symptom was scored as: absent at baseline then also absent with the HPT; absent at baseline then present during the HPT; present during baseline then present during the HPT; or present at baseline then absent during the HPT. This was repeated for Time 2. Then for each symptom, over all subjects, the two HPTs were compared for these change scores. These determined the correspondence (x’) between HPTs in the symptoms corrected for baseline symptoms (Table I). Over all subjects, the correspondence between HPTs in these change scores was significant for each symptom except ‘dizziness’. The z statistic, which sums these x’, showed that over all subjects, over all symptoms, there was a similarity between the HPTs in symptoms corrected for baseline symptoms. That is, there was a reliable resemblance between the two HPTs in the symptoms produced only by the HPTs. The HPTs were then compared in the severity of symptoms, corrected for baseline symptoms. A second order partial correlation coefficient, correcting for the total severity of symptoms before provocation at Time 1 and Time 2, was greater than zero (Y,?~~= 0.57, p < 0.05). Therefore, over all subjects, the similarity between HPTs in the choice and severity of symptoms was not entirely the result of the resemblance between Time 1 and Time 2 in baseline symptoms. Test--retest reliddity, subject by subject, in choice qJ’ symptoms. The previous analyses have tested the similarity between the two HPTs in symptoms, over all subjects. However, it was possible that some subjects would show little or no similarity between the HPTs; others might show considerable similarity according to the following analyses. For each subject, every symptom was noted as having been experienced or not experienced during each HPT. A x2, uncorrected for baseline symptoms, was obtained for each subject over all symptoms (Table IV). Eight normal subjects and eight patients showed significant agreement between the two HPTs in their choice TAHLE IV.---COKKESPONI)ENCE BETWEEYTWO HPTs FOR EACH SUBJECTIN CHOICEOF SYMPTOMS
Uncorrected for baseline symptoms Patients I
3 3 4 5 6 7 x 9 10 II 12
I3 14
Correspondence between Corrected for baseline symptoms
7J
y:
16.15**** 0.26 0.26 1.56 4.43* 4.10* 7.10*** 9.38*** 1.65 0.42 12.38**** 4.62* 16.15*** 0.20
16.48****
HPTs
Normals
1.03 0.65 0.13 4.85* 5.00* 6.X1*** 16.23**** 3.10 2.46 14.x2**** I.1 I 7.10*** 0.02
*/I -=I0.05, **p < 0.02, ***p < 0.01. ****p < 0.001.
1 2 3 4 5 6 7 8 9 IO II
12 13 14
in choice of symptoms Uncorrected for Corrected for baseline symptoms baseline symptoms 7:
Y?
4.80* 9.90*** 4.44
2.86 10.77*** I .32
I .03 0.19 6.67**’ 5.71** 0.06 9.90*** 2.81 10.48*** 8.24***
I.82 1.65
0.08 0.19 7.79*** 3.81 0.09 9.90*** 9.90*** 9.73*** 3.7x 7.90*** O.S6
160
S. LINUSAYet d.
of symptoms uncorrected for baseline symptoms. That is for example, patient 7 chose similar symptoms for both HPTs. Whereas patient 10 chose very different symptoms for both HPTs. In a comparison of change scores for each subject, seven patients and six normal subjects showed a reliable correspondence between HPTs in the choice of symptoms corrected for baseline symptoms (Table IV). It has been necessary to collapse the contingency tables into 2 x 2 format for each subject because of the scarcity with which some changes occurred, notably ‘symptom present then absent’. Conzpurison het\veen latest punk und,first HPT over all patients. The severity of symptoms in the last panic attack was not significantly different, on average (2 = 29.75. SD = 11.69). from the severity of symptoms in the first HPT according to a Mann-Whitney U test (2 = 23.92, SD = 10.34: z = 1.42. II = 11. p > 0.05). The correlation. r, = 0.17, was not greater than zero (p > 0.05). Therefore, although the average severity of symptoms in the panic was similar to the average severity of symptoms in the HPT. the patients showed no consistency in reproducing the severity of symptoms. For example. among the patients who had reported intense symptoms for !heir panic, some reported intense symptoms in the HPT; others experienced mild symptoms in the HPT. However, the choice of symptoms on the first HPT did resemble the symptoms recalled for the last panic (Z = 5.63, p < 0.01). It is important to point out that these analyses were not corrected for symptoms which could have been present before the panic. No record had been made of such symptoms. DISC‘USSION
The capnograph records during the HPTs. showed that all subjects (including those terminating the test prematurely) had breathed according to instructions widely recommended for producing hypocapnia [13]. -4lthough it can occasionally be difficult to estimate pC0, during rapid, deep breathing [I I], all subjects here showed consistently reduced levels during and immediately after the HPTs to an extent consistent with hypocapnia [I 31. IJnder those conditions, all subjects considered together, there was a significant resemblance between the two consecutive HPTs, in both the choice and severity of symptoms. However. all patients and IO normal subjects reported symptoms before hyperventilation at Time 1. and average of seven and one respectively. In three patients. whose pC0, was less than 4 kPa (20 mm Hg) before the HPT, these may have been the product of mild hypocapnia. Some of these baseline symptoms could have been associated with anxiety. The symptoms experienced at baseline at Time 1 were similar to those reported for baseline at Time 2. These were. in turn. similar to those reported for the HPT on each occasion (Table III). The similarity between the HPTs in symptoms may thus have been the result of this similarity in baseline symptoms. Alternatively, other influences such as anxiety could have been similar on both occasions. As suggested by these results, the symptoms of a panic could in part be intensifications of symptoms present before the panic.
Reliability
of hyperventilation
test
161
Nevertheless, over all subjects, the test-retest correspondence between the HPTs in severity and choice of symptoms remained significantly greater than zero even when the baseline symptoms were controlled statistically. It would be of greater interest if the correspondence between HPTs was high. The Y, (Table III), indicates moderate similarity [14] in severity of symptoms. Unfortunately there is no satisfactory test of the magnitude of the partial correlation coefficient which corrected for baseline symptoms [14]. Some authors have noted that the symptoms in HPTs are often not quite the same as those of panics [15] but there appears to be a scarcity of relevant, controlled investigation. The present study confirmed that, in the small sample of patients, there was a significant resemblance in the choice of symptoms recalled for their latest panic and the first HPT, not allowing for baseline symptoms. However, there was no consistent similarity between panic and HPT in the severity of the symptoms, unlike the correspondence here between two consecutive HPTs. It is possible that subjects do not recall symptoms of a panic accurately. Alternatively, influences other than hyperventilation may contribute to the panic. Hyperventilation may not have occurred in all the panics reported by the patients [l]. The symptoms reported for the first HPT were similar to those recorded for the second HPT, all subjects considered together. In spite of this, only some subjects consistently reproduced their choice of symptoms from one HPT to the next according to the subject-by-subject analysis. Hence, even where symptoms of a panic have been produced by hyperventilation, they need not be reproduced reliably by overbreathing in the clinic. In the subject-by-subject analyses (Table IV), the 11’ of the resemblance between Times 1 and 2 in the choice of symptoms would probably have been influenced by the degree to which the choice of any symptom was independent of any other. Thus a subject choosing ‘dizziness’ might also choose ‘faintness’ on Time 1. Then on Time 2, having chosen ‘dizziness’ again, he might choose ‘faintness’ again. This possible lack of independence among symptoms would favour a strong resemblance over all symptoms between the two occasions in choice of symptoms. A xX test would normally assume that the symptoms would be independent of each other. However, in spite of the possibility of a lack of independence among symptoms, many subjects showed no significant consistency from one HPT to the next in their choice of symptoms. The present study has shown that the patients, compared with the normals, reported a greater severity of symptoms during the HPT. The reasons for this were not examined. The groups did differ substantially in age and probably in knowledge of hyperventilation. However, it is not clear what influence, if any, these differences would have had. The subject-by-subject analyses showed no difference between patients and normals in the consistency with which symptoms were reproduced from one HPT to another. In conclusion, the HPT probably has sufficient temporal reliability in the choice and severity of symptoms, for groups of subjects. The symptoms produced by a group of subjects on one HPT would be similar to the symptoms produced by the same group in a subsequent HPT. In spite of this, according to the comparison of a panic and an HPT above. patients undergoing an HPT would show no consistency in the severity of symptoms from latest panic to HPT. Nevertheless, the panic and
162
s. LINDSAY Cl Ui.
HPT would be similar in the choice of symptoms over the group of patients as a whole. To account for the discrepancy in severity, further work needs to be done to determine the contribution of hyperventilation to panics and to determine the accuracy of the recall of panics. In any event, it is clear from this study that, to test the resemblance between symptoms of the HPT and a panic, the symptoms preceding both the panic and the HPT should be acknowledged by recording them in, e.g. diaries and checklists. This would be especially necessary because subjects outside the clinics would experience an infinite variety of stimulation which could provoke a wide variety of physical symptoms. With single cases, however, this study suggests that the HPT would be too unreliable to reproduce panic symptoms consistently: to identify patients whose panic symptoms had been associated with hyperventilation [16]. Many subjects who had experienced certain symptoms during a hyperventilatory panic would not report the same symptoms during hyperventilation in the clinic. Some authors have used the HPT to reproduce symptoms for treatment and have claimed a high rate of success in therapy [17]. This study suggests that an accurate of such reproduction of panic symptoms may not be an essential component treatment. REFERENCES I.
2. 3. 4.
5. 6. 7. 8. 9. IO. II. I?. 13. 14. 1s. 16. 17.
HIBHEKTG. PILSBURY D. Hyperventilation: is it a cause of panic attacks’? Br J f.yychiut 1989; 155: x05 809. STEPT~E A. Cardiovascular and respiratory disorders: investigation. In A Handbook qf’Clinicrr/ Adull Psychology (Edited by LINIXAY SJE. POWELL GE). Aldershot: Gower Publishing Co., 1987. BARLOW DH, CRASKE MG, CERNY JA, KLOSKO JS. Behavioral treatment of panic disorder. Behut. Thw 1989; 20: 261-282. NIXON PGF, FKEEMAXLJ. The think test: a further technique to elicit hyperventilation. J Roy SK Mrd 1988; 81: 277- 279. BASS C, GARUXEK W. Diagnostic issues in the hyperventilation syndrome. Br J Ps~&irr/ 1985; 146: lol~-lo2. BAKLOW DH, CRASKE MG. The phenomenology of panic. In P&c,: Ps~cho/ogicc~l Pcwpc~/icw (Edited by RACHMAN S, MASER JD). New Jersey: Erlbaum, 1988. PICKLES C. Cognitive Factors in Hyperventilation. Unpublished M.Sc. thesis University of London, Institute of Psychiatry. 1987. _. CLARK DM. HEMSLEYDR. The effects of hyperventilation: individual cariability and its relation to personality. J. B&u?. T/w Esp Psychiut 1462; 13: 41 47. NOKTON GR, HARRISON B, HAUCH J. RHOIIES L. Characteristics of people with infrequent panic attacks. J .4hmwm Psycho/ 1985; 94: 216 221. AM~KI(.AN PSYCHIATKICASSO(.IATIOX. Dia&wo.~ric~ und Stcrti.tricrrl Munucrl of Mm~ol Disorders, Third Edn. Washington DC: American Psychiatric Association. CHAMBERS JB, KIFF PJ. GAKDNEK W, JACKSON G, BASS C. Value of measuring end tidal partial pressure of carbon dioxide as an ajunct to treadmill testing. Br Mrd J 1988: 296: 12X1- 1285. EVEKITTB. The Ann/y.G.v of Conrin~my~ Tables. London: Chapman and Hall. 1977. BASS C, GAKIINEK W. Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation. Br Med J 1985: 290: I.387 1390. GUIL~OKLI JP. FKIJ(-HTEK B. Fundmwnlcrl Sru/i.t/ic~s 01 P,yvchology cmd Edum/ion. New York: McGraw-Hill, 1981. BASS C. GAKUNEK W. Emotional influences on breathlessness. J. P.syc~hosom. Re.5. 1985; 29: 599 609. HIHHEKTG, CHAN M. Respiratory control: its contribution to the treatment of panic attacks. Br J Pq~c~hicrr 1989: 154: 232 236. BECK AT. Cognitive approaches to panic disorder: theory and therapy. In Panic: P.g~cho/ogicu/ Prr.~pcctrrc~.t (Edited by RA(.HMAN S. MASER JD). New Jersey: Erlbaum. 1988.
