SciELO - Scientific Electronic Library Online

vol.57 issue4Multiple sclerosis in Brazil: analysis of cerebrospinal fluid by standard methodsPsychiatric symptoms amongst outpatients with dementia in São Paulo, Brazil author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand




Related links


Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282X

Arq. Neuro-Psiquiatr. vol.57 n.4 São Paulo Dec. 1999 






ABSTRACT - Respiratory abnormalities are associated with anxiety, particularly with panic attacks. Symptoms such as shortness of breath, "empty-head" feeling, dizziness, paresthesias and tachypnea have been described in the psychiatric and respiratory physiology related to panic disorder. Panic disorder patients exhibit both behaviorally and physiologically abnormal responses to respiratory challenges tests. Objective: We aim to observe the induction of panic attacks by hyperventilation in a group of panic disorder patients (DSM-IV). Method: 13 panic disorder patients and 11 normal volunteers were randomly selected. They were drug free for a week. They were induced to hyperventilate (30 breaths/min) for 3 minutes. Anxiety scales were taken before and after the test. Results: 9 (69.2%) panic disorder patients and one (9.1%) of control subjects had a panic attack after hyperventilating (p< 0.05). Conclusion: The panic disorder group was more sensitive to hyperventilation than normal volunteers. The induction of panic attacks by vonluntary hyperventilation may be a useful and simple test for validating the diagnosis in some specific panic disorder patients.

KEY WORDS: panic attack, respiration, anxiety disorder, ventilation.


Transtorno do pânico e hiperventilação

RESUMO - Distúrbios respiratórios estão associados à ansiedade, especialmente aos ataques de pânico. Sufocamento, sensação de "cabeça leve", tonteira, parestesias e taquipnéia aparecem na descrição psiquiátrica e respiratória do transtorno do pânico. Pacientes com transtorno do pânico apresentam respostas comportamentais e fisiológicas anormais a testes respiratórios. Objetivo: Observamos a indução de ataques de pânico através de hiperventilação em um grupo de pacientes com transtorno do pânico (DSM-IV). Método: Selecionamos de forma randomizada 13 pacientes com transtorno do pânico e 11 voluntários normais. Todos estavam sem medicação há uma semana. Foram induzidos a hiperventilar (30 inspirações/minuto) durante 3 minutos. Escalas de ansiedade foram utilizadas antes e após o teste. Resultados: No grupo com transtorno de pânico, 9 (69,2%) pacientes apresentaram ataque de pânico após a hiperventilação e apenas 1 (9,1%) no grupo controle (p<0,05). Conclusão: Os pacientes com transtorno do pânico foram mais sensíveis à hiperventilação que o grupo controle. A indução de ataques de pânico através da hiperventilação pode ser método útil e simples para validar o diagnóstico em um grupo específico de pacientes com transtorno do pânico.

PALAVRAS CHAVE: ataque de pânico, respiração, transtorno de ansiedade, ventilação.



One of the features of the description of a panic attack is the physical nature of the symptoms. Patients with panic disorder always begin the description of their disease mentioning either the respiratory system, the heart or the gastrointestinal tract1. Symptoms such as shortness of breath, "empty-head" feeling, dizziness, paresthesias and tachypnea have been described in the psychiatric and respiratory physiology related to panic disorder2,3. Respiratory abnormalities are associated with anxiety, particularly with panic attacks1,2. Panic patients reported significantly more panic attacks and anxiety during the challenges than normal volunteers1,4. Panic disorder patients exhibit both behaviorally and physiologically abnormal responses to respiratory challenge tests4,5.

Hyperventilation is an increase in the amount of inhaled and exhaled air per minute, exceeding the amount necessary for normal cell metabolism. Hyperventilation encompasses the state where ventilation exceeds celular metabolism, resulting in an elimination of CO2 greater than its production, which causes a decline in arterial partial pressure of carbon dioxide (PCO2)1,5. During exercises the amount of CO2 produced increases as a result of an increased cell metabolism, but the PCO2 remains constant because alveolar ventilation also increases, which is responsible for an increase in CO2 elimination1,3. Hyperventilating at 30 breaths a minute, in spite of significant drops in end-tidal CO2 to conventionally accepted levels of hypocapnia, seemed less convincing panicogenic challenge than CO26,7. However, a group of panic disorder patients can have in hyperventilation a safe, easy and specific test for a more precise diagnosis.

Our aim is to determine in induced panic attacks using room air hyperventilation (30 breaths/minute) during 3 minutes in panic disorder patients if there is any difference when compared to a control group.



We have randomly selected by order of arrival the 13 panic disorder patients (8 women and 5 men; mean age= 31.9 years, sd= 6,5) at the Laboratory of Panic & Respiration of the Institute of Psychiatry from the Federal University of Rio de Janeiro. The comparison group consisted of 11 subjects ( 6 women and 5 men, mean age = 30.5 years, sd= 11.7). The diagnosis was obtained using the Structured Clinical Interview ¾ SCID I8 for DSM-IV9 and the patients should not fulfill the criteria for any other psychiatry disorder. They were explained about the study and signed a voluntary written consent for their participation in this study which informed that they would be asked to hyperventilate room air and that the procedure was not dangerous but anxiety or panic could occur during the study. The protocol complying with the principles laid down in the Declaration of Helsinki was approved by our local Ethics Committee.

To participate in the study the subjects were required to be between the ages of 18 and 55 years and to report at least three panic attacks in the two weeks before the challenge test day. They were free of psychotropic drugs for at least one week and have a negative urine test for benzodiazepines and other medications. All patients underwent a physical examination and laboratory tests to ensure they were healthy enough to participate in a hyperventilation challenge test. They should have no previous history of respiratory diseases and had never smoked.

The comparison group were also assessed by the SCID ¾ I8. They were free of any lifetime history of anxiety disorders, major mood disorders, schizophrenia, and current substance use disorders. All subjects underwent medical evaluations and were in good health.

The whole test was conducted at the usual examination room, with no changes made in the environment. The selected patients were induced to relax for 10 minutes. After this period we checked the repiratory frequency and blood pressure. To measure the baseline anxiety level, subjects were asked before hyperventilating to complete the Subjective Units of Disturbance Scale (SUDS), a semiquantitative evaluation method ranging from 0 = no anxiety, 10 = the maximum anxiety10, and the Diagnostic Symptom Questionnaire - DSQ ¾11 adapted for DSM-IV in which the presence and level of disconfort of panic symptoms experienced after the inhalations were rated on a 0 - 4 point scale ( 0= none , 4 = very severe). After the test the SUDS and the DSQ were completed again. They completed them blindly to the raters.

On the basis of the Diagnostic Symptom Questionnaire, a panic attack was defined as the following: 1) four or more symptoms of a panic attack from DSM-IV; 2) at least one of the cognitive symptoms of a panic attack from DSM-IV (e.g. fear of dying or of losing sanity); 3) feeling of panic or fear, similar to spontaneous panic attacks answered on a card which the raters were not permitted to observe; and 4) clinical evaluation by two diagnosis blinded raters from the team during the test.

Afterwards we induced hyperventilation (30 respiratory movements per minute during 3 minutes), and immediately after this period we made the evaluation of the anxiety level and the induction of a panic attack.

Data Analysis

Rates of panic among the two groups, also separeted for raters' and subjects' ratings and by gender were compared with the McNemar's test. For the effects of the hyperventilation and time of observation were tested by Friedman two-way ANOVA on ranks according to the results of Kolmogorov-Smirnov (with Lilliefor's correction) test for normality and Levene median test for variances. When pairwise multiple comparisons were required, Student-Newman-Keuls method was applied. The significant level was set at 5%.



Table 1 shows the panic rates during the interventions according to the raters and to the subjects. Significant more panic patients had a panic attack in response to hyperventilation than the group control by using either ratings. 9 (69.2%) panic disorder patients, one (9.1%) of control subjects had a panic attack after hyperventilating (X² = 12.5, df=3, p< 0.05). There was no significant sex difference in any group (X² = 4.18, df=1, p=ns).



In Table 2 there is the Subjective Anxiety Level measure by SUDS before and after hyperventilating. Patients with panic disorder although not statistically significant seemed to be more sentitive to hyperventilation effects than normal volunteers. All subjects had an increase in anxiety levels after hyperventilating .




Some methodological improvements can be made in order to increase the hyperventilation challenge test sensibility. A more vigorous hyperventilation test would show better results but it would otherwise increase noncompliance in panic disorder patients. The comparison between panic disorder patients and a control group or other anxiety disorder group may be usefull for a better defining symptoms and diagnosis. Our results confirm the hyperventilation challenge test (30 breaths per minute during 3 minutes) as a usefull and easy diagnostic tool for some specific panic disorder patients diferenciating them from normal controls, increasing diagnostic validity.

Although we found neither sex nor anxiety response difference among the groups, these hyperventilating sensitive panic disorder patients may be clearly identified in the future with a more sophisticated methodology.

Papp et al.5 showed that hyperventilation is a relatively mild panicogenic agent. During voluntary hyperventilation patients with panic disorder often recognize some of the symptoms felt during a panic attack12,13. For this reason hypocapnia may be an important factor in anxiety that occurs during a panic attack and hyperventilation4,7. These data suggest that hyperventilation do occur during some panic attacks.

We also observed that some clinical findings of this syndrome (anxiety, faster or deeper breathing, palpitations, tachycardia, dizziness, tremors, feelings of panic, unease, fatigue, crying spells, parestesies) are similar to the clinical findings in panic disorder, and many of its symptoms are part of the diagnostic criteria for panic attacks from the DSM classifications.

Although hyperventilation frequently occurs it may be not a cause or an important component in panic attacks. Several other studies do not give support to the theory that hyperventilation arouses panic attacks or contributes to its severity5,15. It may be that hyperventilation is a consequence of panic attacks in hyperventilation predisposed individuals4,15,16. Zanbergen et al.14 looked for evidencies of chronic hyperventilation in 18 patients with panic disorder (DSM-III-R) measuring arterial PCO2, base excess, bicarbonate (HCO3) and pH from these patients. Comparing this data with those found in 18 healthy controls and 12 patients with other anxiety disorders (obsessive-compulsive disorder, social phobia and generalized anxiety disorder) there were no significant differences found out in the base excess or HCO3 levels between patients with Panic Disorder, other anxiety disorders and healthy controls. This result also suggests that there is no sistematic chronic hyperventilation in patients with panic disorder. Bonn et al17 studied panic attacks provocation by hyperventilation with 21 patients who had the diagnosis of agoraphobia with panic attacks and with 47 normal controls. All the patients were asked to make 60 respiratory movements per minute, during 3 minutes. The authors found out that 20 (95%) of the 21 patients affirmed that the symptoms felt at the laboratory were similar to those felt in their spontaneous panic attacks, although most of them affirmed that the symptoms felt at the laboratory were less intense. All the controls felt some dizziness, paresthesies and the sensation of "being light". They confirm the prominent role of hyperventilation in agoraphobia with panic attacks, according to the authors.

There is not a methodological coherence between the various studies mentioned above. Some do not inform if the panic disorder patients are in acute symptomatic period, others do not describe wash-out periods and many times the diagnostic criteria for panic attacks are not informed. Gorman et al12 studied 12 patients with panic disorder or agoraphobia with panic attacks (DSM-III). The patients were asked to hyperventilate (30 respiratory movements/minute) for 15 minutes. After the test the patients filled in the Acute Panic Inventory, which measures the severity of the typical panic symptoms. They found out that 3 (25%) of the 12 patients have had panic attacks after this procedure, demonstrating that the induction of a respiratory alcalosis would not be enough to provoke panic attacks in all patients. Hyperventilation is a probable cause for panic attacks in a percentage of patients with panic disorder1,7,14. The losses to patients with panic disorder and their families justify greater investments in its research for a more precise diagnosis.

According to the cognitive approach18 the catastrophical interpretation of bodily sensations induced by hyperventilation would have a greater role in the panic attack. The erroneous interpretation of bodily sensations as dangerous and threatening would result in an increase in anxiety, which in turn would lead to new sensations, and thus result in a vicious circle until the panic attack. The respiratory re-training techniques may reduce the severity of the symptoms during the panic attack by decreasing the hyperventilatory response5,18.

Our previous study19 with a CO2 challenge test in panic disorder patients suggest the efficacy of the short term clonazepam therapy in attenuating panic attacks and support the usefulness of the 35% carbon dioxide challenge test as an analogue method for study the efficacy of anti-panic drugs. For sure both test needs more research with a large number of patients to help elucidate the neurobiologic vulnerability of panic disorder patients and may lead to the development of more specific and effective treatments.



Hyperventilation has been considered as a cause, a correlate and a consequence of panic attacks. Future studies will establish in which group of panic disorder patients the hyperventilation challenge test is a specific tool for diagnosis; whether it varies with age or sex of the patients and to what extent they are cognitively mediated. The evidence implicating respiratory abnormalities in the pathogenesis of panic is rapidly accumulating. While our data presented here support a theory20 advocating that some panic disorder represents a primary respiratory abnormality, these remain a number of critical areas in need of exploration before such assertion can be fully validated.



1. Papp LA, Martinez JM, Klein DF, et al.. Respiratory psychophysiology of panic disorder: three respiratory challenges in 98 subjects. Am J Psychiatry 1997;154:1557-1565.

2. Bandelow B, Amering M, Benkert O, et al.. Cardio-respiratory and other symptom clusters in panic disorder. Anxiety 1996;2:99-101.

3. Bataglia M, Perna G: The 35% CO2 challenge in panic disorder: optimization by receiver operating characteristic (roc) analysis. J Psychiat Res 1995;29:111-119.

4. Papp LA, Klein DF, Gorman JM. Carbon dioxide hypersensivity, hyperventilation and panic disorder. Am J Psychiatry 1993;150:1149-1157.

5. Gorman JM, Papp LA, Coplan JD, et al.. Anxiogenic effects of CO2 and hyperventilation in patients with panic disorder. Am J Psychiatry 1994;151:547-553.

6. Rapee R, Brown T, Antony M, Barlow D. Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders. J Abnorm Psychol 1992;101:538-552.

7. Maddock RJ, Carter CS: Hyperventilation-induced panic attacks in panic disorder with agoraphobia. Biol Psychiatry 1991;29:843-854.

8. First MB, Spitzer RL, Gibbon M, Williams JBM. Structured clinical interview diagnostic (SCID) for DSM-IV axis I disorders - clinician version (SCID-CV). Washington: American Psychiatric Press, 1997.

9. American Psychiatric Association. Diagnostic and statistical manual for mental disorders, 4Ed. DSM-IV. Washington: American Psychiatric Press, 1994.

10. Bech P, Kastrup M, Rafaelsen OJ: Mini-compendium of rating scales for states of anxiety, depression, mania, schizophrenia with corresponding DSM III syndromes. Acta Psychiatr Scand 1986;73(Suppl 326):1-37.

11. Sanderson WC, Rapee RM, Barlow DH : The influence of an illusion of control on panic attacks induce via inhalation of 5.5% carbon dioxide-enriched air. Arch Gen Psychiatry 1989;46:157-162.

12. Gorman JM, Askanazi J, Liebowitz MR, et al.. Response to hyperventilation in a group of patients with panic disorder. Am J Psychiatry 1984;141:857-861.

13. Garssen B, Buikhuisen M, Dick R. Hyperventilation and panic attacks. Am J Psychiatry 1996;153:513-518.

14. Zanbergen J, Lousberg HA, Pols H, Loof C, Griez E. Hypercarbia versus hypocarbia in panic disorder. J Affective Disord 1990;18:75-81.

15. Bass C. Hyperventilation syndrome: a chimera? J Psychosom Res 1997;42:421-426.

16. Humble M. Aetiology and mechanisms of anxiety disorders. Acta Psychiatr Scand 1987;76(Suppl 335):15-30.

17. Bonn JA, Readhead CPA: Enhanced adaptative behavioural response in agoraphobic patients pretreated with breathing retraining. Lancet 1984;22:665-669.

18. Salkovskis PM, Jones DO, Clark DM: Respiratory control in treatment of panic attacks: replication and extension with concurrent measurement of behaviour and PCO2. Br J Psychiatry 1986;148:526-532.

19. Nardi AE, Valença A, Zin WA, Nascimento I. Carbon dioxide induced panic attack and short term clonazepam treatment: preliminary study. Arq Neuropsiquiatr 1999;57:361-365.

20. Klein DF. Panic disorder and agoraphobia: hypothesis hothouse. J Clin Psychiatry 1996;57(Suppl 6):21-27.



The research was conducted at the Laboratory of Panic & Respiration. Institute of Psychiatry. Federal University of Rio de Janeiro. Brazil: *Laboratory of Panic & Respiration. Institute of Psychiatry, Federal University of Rio de Janeiro. Brazil; **Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Brazil. Supported by the Brazilian Council for Scientific and Technological Development (CNPq). Aceite: 1-setembro-1999.

Dr. Antonio Egidio Nardi - R. Visconde de Pirajá 407/702 - 22410-003. Rio de Janeiro RJ - Brazil. Fax. 5521 523 6839. E-mail:

Creative Commons License All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License