AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Hyperventilation syndrome (HVS) represents a relatively common ED presentation that most clinicians readily recognize. However, the syndrome has defied precise definition and explanation of the underlying pathophysiology for the past 100 years.

As classically defined, HVS is a condition in which minute ventilation exceeds metabolic demands, resulting in hemodynamic and chemical changes that produce characteristic dysphoric symptoms, which can be reproduced in these patients by inducing a drop in arterial pCO₂ through voluntary hyperventilation. Recently, however, this model has been challenged with the observation that many patients with HVS do not manifest low arterial pCO₂ levels during attacks. In some cases, patients with this syndrome have demonstrated altered respiratory physiology that is manifest as a slower return to baseline of the pCO₂ after voluntary hyperventilation to a defined level of pCO₂. Current thinking suggests that the syndrome might better be termed behavioral breathlessness or psychogenic dyspnea with hyperventilation as a consequence rather than as a cause of the condition. It is also recognized that some patients may be physiologically at risk of

developingthis psychogenic dyspnea.

Symptoms of HVS and panic disorder overlap considerably, although the 2 conditions remain distinct. Approximately 50% of patients with panic disorder and 60% of patients with agoraphobia manifest hyperventilation as part of their symptomatology, whereas only 25% of patients with HVS manifest panic disorder.

Pathophysiology

HVS occurs in acute and chronic forms. Acute HVS accounts for only 1% of cases but is diagnosed more easily. Chronic HVS can present with a myriad of respiratory, cardiac, neurologic, or GI symptoms without any clinically apparent overbreathing by the patient. Hypocapnia can be maintained without any change in the absolute minute volume if the patient exhibits frequent sighs interspersed with normal respirations.

Because of the subtlety of the hyperventilation, many patients with chronic HVS are admitted and undergo extensive and expensive testing in an attempt to discover organic causes of their complaints.

The underlying mechanism by which some patients develop hyperventilation is unknown, but theories abound. A population clearly exists in whom certain stressors provoke an exaggerated respiratory response. Several such stressors have been identified, including emotional distress, sodium lactate, caffeine, isoproterenol, cholecystokinin, and CO₂.

Infusion of lactate provokes symptoms of panic in 80% of patients with panic disorder but in only 10% of controls. Approximately one half of the lactate responders develop acute hyperventilation as part of the panic reaction. Lactate levels are higher and remain elevated longer in patients with panic disorder than in controls, suggesting that abnormal metabolism of lactate is involved in the pathogenesis, although the exact abnormality has not been characterized. Whether the same abnormality is operant in pure HVS is unknown.

Part of the explanation for HVS lies in the mechanics of breathing. Normal tidal volumes range from 35-45% of vital capacity at rest. Hyperinflation of the lungs beyond that level is resisted by the elastic recoil of the chest wall, and inspiratory volumes beyond this level are perceived as effort or dyspnea.

Patients with HVS tend to breathe by using the upper thorax rather than the diaphragm, resulting in chronically overinflated lungs. When stress induces a need to take a deep breath, the deep breathing is perceived as dyspnea. The sensation of dyspnea creates anxiety, which encourages more deep breathing, and a vicious cycle is created.

The prevailing theory is that patients with panic disorder have a lower threshold for the fight or flight response. In patients who are susceptible, even minor stresses can trigger the syndrome, which then tends to manifest with primarily psychiatric complaints, such as fear of death, impending doom, or claustrophobia. In contrast, it is believed that patients with HVS tend to focus on somatic complaints related to the physiologic changes produced by hyperventilation. The initiating stimulus and the abnormal stress response may be identical in each group but are expressed differently.

Frequency

United States

As many as 10% of patients in a general internal medicine practice are reported to have HVS as their primary diagnosis, although equivalent data are not available for ED presentations. Overall up to 6% of the general population may have this condition to a variable degree.

Mortality/Morbidity

• Death attributable to the syndrome is extremely rare. A leftward shift in the HbO₂ dissociation curve and vasospasm related to low pCO₂ may cause myocardial ischemia in patients with coronary artery disease and HVS.
• Certain patients are disabled psychologically by their symptoms, and many patients carry false diagnoses. One important danger for patients with HVS is that they suffer complications from unneeded investigations (eg, angiography) or treatment (eg, thrombolytics). Withholding such therapy may be extremely difficult in a patient with crushing chest pain, dyspnea, and/or suggestive electrocardiogram (ECG) changes.
• One study reported a series of 45 patients with chest pain who had normal coronary arteries on angiography. These patients ultimately were diagnosed as having HVS. Over a 3.5-year average follow-up period, 67% of the patients had made subsequent ED visits for chest pain, and 40% of the patients had been readmitted to rule out myocardial infarction.
• Clearly HVS not only produces severe and genuine discomfort for the patient, it also accounts for considerable medical expense in excluding more serious pathology. The fact that patients with HVS appear ill prompts more and more esoteric testing which is inevitably fruitless; the chronicity of the condition often prompts different physicians to repeat these unnecessary investigations several times.

Sex

A female preponderance of HVS cases exists; the female-to-male ratio may be as high as 7:1.

Age

The peak age of incidence is from 15-55 years, but cases have been reported in all age groups except infancy.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients with acute HVS may present with great agitation and anxiety.
• Most commonly, the history is of sudden onset of chest pain, dyspnea, or neurologic symptoms (eg, dizziness, weakness, paresthesias, near syncope) following a stressful event.
• Patients with chronic HVS present with similar symptoms of recurrent chest pain, dyspnea, or neurologic deficits but usually have had numerous similar presentations in the past.
• Acute hyperventilation
• • Patients often present dramatically with agitation, hyperpnea and tachypnea, chest pain, dyspnea, wheezing, dizziness, palpitations, tetanic cramps (carpopedal spasm), paresthesias, generalized weakness, and syncope.
  • The patient often complains of a sense of suffocation. An emotionally stressful precipitating event often can be identified.
• Cardiac symptoms
• • The chest pain associated with HVS usually has atypical features, but on occasion it may closely resemble typical angina. It tends to last hours rather than minutes. It often is relieved rather than provoked by exercise. It usually is unrelieved by nitroglycerin.
  • The diagnosis of HVS should be considered in young patients without cardiac risk factors who present with chest pain, particularly if associated with paresthesias and carpopedal spasm. However, this diagnosis should be reached cautiously, because many other potentially lethal conditions can cause young patients to present with chest pain (eg, pulmonary embolus).
  • ECG changes are common in patients with HVS. Abnormalities may include prolonged QT interval, ST depression or elevation, and T-wave inversion.
  • In patients with subcritical coronary artery stenosis, the vasospasm induced by hypocarbia may be sufficient to provoke myocardial injury.
  • The incidence of HVS is high among patients with mitral valve prolapse (MVP), and the chest pain associated with MVP may be due to hyperventilation.
  • Prinzmetal angina (coronary angiospasm) is triggered by HVS, but the chest pain associated with this syndrome normally would be expected to respond to nitrates or calcium channel blockers.
• Central nervous system symptoms
• • CNS symptoms occur because hypocapnia causes reduced cerebral blood flow (CBF). CBF decreases 2% for every mm Hg decrease in pCO₂.
  • Symptoms of dizziness, weakness, confusion, and agitation are common.
  • Patients may report feelings of depersonalization and may experience visual hallucinations.
  • Rarely, syncope or seizure may be provoked by hyperventilation.
  • Paresthesias occur more commonly in the upper extremity and are usually bilateral.
  • Unilateral paresthesias are left-sided in approximately 80% of cases.
  • Perioral numbness is very common.
• GI symptoms (bloating, belching, flatus, epigastric pressure) may result from aerophagia.
• Dry mouth occurs with mouth breathing and anxiety.
• Metabolic changes
• • Acute metabolic changes result from intracellular shifts and increased protein binding of various electrolytes during respiratory alkalosis.
  • Acute secondary hypocalcemia can result in carpopedal spasm, muscle twitching, positive Chvostek and Trousseau signs, and prolonged QT interval.
  • Hypokalemia tends to be less pronounced than hypocalcemia but can produce generalized weakness.
  • Acute secondary hypophosphatemia is common and may contribute to paresthesias and generalized weakness.
• Chronic hyperventilation
• • The diagnosis of chronic HVS is much more difficult than that of acute HVS because the hyperventilation usually is not clinically apparent.
  • Often, these patients have had extensive medical investigations and have been assigned several misleading diagnoses.
  • Two thirds of patients with chronic HVS have a persistently slightly low pCO₂ with compensatory renal excretion of HCO₃, resulting in a near-normal pH level. These patients tend to have more prominent CNS symptoms than patients who maintain normal pCO₂ during attacks. These patients usually present due to dyspnea and chest pain.
  • The respiratory alkalosis can be maintained with occasional deep sighing respirations, which are observed often in patients with chronic HVS.
  • When faced with an additional stress that provokes hyperventilation, the physiologic acid-base reserve is less, and these patients become symptomatic more readily than patients without HVS.
• Many of these patients suffer from obsessive-compulsive disorders, experience sexual and marital difficulties, and have poor adaptations to stress.
• Patients with chronic HVS may have symptoms that mimic virtually any serious organic disorder, but usually they have atypical features of these diseases.

Physical

• Acute hyperventilation
• • Obvious tachypnea and hyperpnea are present.
  • Although chest wall tenderness is common in patients with HVS, the finding is not helpful, because chest wall tenderness also is found in pneumonia, pneumothorax, pulmonary embolism, coronary artery syndromes, and a wide variety of other serious and benign thoraco-abdominal diseases.
  • Carpopedal spasm occurs when acute hypocarbia causes reduced ionized calcium and phosphate levels, resulting in involuntary contraction of the feet or (more commonly) the hands.
  • Chvostek or Trousseau signs may be positive because of hypocalcemia.
  • Wheezing may be heard because of bronchospasm from hypocarbia.
  • Tremor, mydriasis, pallor, tachycardia, and other manifestations of anxiety can occur.
  • Evidence of depersonalization or hallucination may be noted.
• Chronic HVS
• • Hyperventilation usually not readily apparent
  • Frequent sighing respirations, 2-3 per minute; frequent yawning
  • Chest wall tenderness, numbness, tingling
  • Characteristically, multiple complaints without much supporting physical evidence of disease

Causes

• The cause of HVS is unknown, but some persons who are affected appear to have an abnormal respiratory response to stress, sodium, lactate, and other chemical and emotional triggers, thereby resulting in excess minute ventilation and hypocarbia. In most patients, the mechanics of breathing are disordered in a characteristic way. When stressed, these patients rely on thoracic breathing rather than diaphragmatic breathing, resulting in a hyperexpanded chest and high residual lung volume. Because of the high residual volume, they are then unable to take a normal tidal volume with the next breath and consequently experience dyspnea. Proprioceptors in the lung and chest wall signal the brain with a "suffocation alarm" that triggers release of excitatory neurotransmitters that are responsible for many of the symptoms such as palpitations, tremor, anxiety, and diaphoresis.
• The incidence of HVS in first-degree relatives is higher than in the general population, but no clear genetic factors have been identified.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Upon a first attack of acute HVS, the diagnosis depends on recognizing the typical constellation of signs and symptoms and ruling out the serious etiologies that can cause the presenting symptoms. Coronary artery disease and pulmonary embolism are the two most serious entities that must be ruled out with specific diagnostic tests, but this evaluation needs to be performed only once. On subsequent attacks, the diagnosis is made clinically, without repeating an extensive workup on each occasion.
• Patients with a history of HVS who have undergone an appropriate workup at some earlier time may not need any further laboratory evaluation in the face of a recurrence. Recognition of the typical constellation of dyspnea, agitation, dizziness, atypical chest pain, tachypnea and hyperpnea, paresthesias, and carpopedal spasm in a young, otherwise healthy patient with an adequate prior evaluation is sufficient to make the diagnosis.
• Pulse oximetry can identify the occasional patient with pulmonary embolism or other primary pulmonary disease who is so severely hypoxemic that even with hyperventilation the saturation cannot be maintained. A normal pulse oximetry test is not helpful, because a severe defect in gas exchange easily can be masked by hyperventilation. Some fraction of patients with chronic pulmonary embolism will have compensated chronic hyperventilation that may mimic primary chronic hyperventilation.
• ABG
• • An ABG is indicated if any question exists as to the patient's underlying respiratory status; it may be helpful when HVS-induced acidosis is suspected, or when shunting or impaired pulmonary gas exchange is being considered.
  • ABG sampling confirms a compensated respiratory alkalosis in a majority of cases. The pH in these cases is near normal, with a low pCO₂ and low HCO₃.
• Other tests
• • Toxicology screen
  • If acute pulmonary embolism is being considered, a quantitative ELISA D-dimer assay may be helpful. Latex agglutination tests for D-dimer are not sensitive and cannot be used to rule out thromboembolic disease.

Imaging Studies

• Imaging studies are not indicated when the diagnosis of HVS is clear. In less obvious cases of HVS, if imaging studies are done, findings are normal.
• Because pulmonary embolism can present with findings identical to those of HVS, a first-ever episode of acute HVS may warrant a V/Q scan or computed tomography pulmonary angiogram to rule out perfusion defects.
• Chest radiography is indicated for patients at high risk of cardiac or pulmonary pathology. Chest x-ray also is indicated when the diagnosis is not clear.

Other Tests

• ECG: Changes are common and may include the following:
• • Prolonged QT interval
  • ST depression or elevation
  • T-wave inversion
  • Sinus tachycardia

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Because respiratory distress or chest pain has many potentially serious causes, this diagnosis should never be made in the field. Even when a patient carries a prior diagnosis of HVS, transporting patients with these complaints for a more complete evaluation than is available in the field is prudent.
• Rebreathing into a paper bag is not recommended in the field. Rebreathing should not be initiated in the ED until after more serious etiologies have been excluded. Deaths have occurred in patients with acute myocardial infarction (MI), pneumothorax, or pulmonary embolism misdiagnosed as HVS and treated with paper bag rebreathing.

Emergency Department Care

ED treatment of HVS is often ineffective. Techniques of rebreathing into a paper bag are no longer recommended because significant hypoxia and death have been reported.

• In patients who are hyperventilating for organic reasons (eg, pulmonary edema, metabolic acidosis), increasing pCO₂ and decreasing O₂ may be disastrous.
• In addition, paper bag rebreathing is often unsuccessful in reversing the symptoms of HVS because patients have difficulty complying with the technique and because CO₂ itself may be a chemical trigger for anxiety in these patients.
• Once life-threatening conditions have been eliminated, simple reassurance and an explanation in layman's terms of how hyperventilation produces the patient's symptoms is usually sufficient to terminate the episode.
• Provoking the symptoms by having the patient voluntarily hyperventilate for 3-4 minutes often convinces the patient of the diagnosis but is time-consuming and may be ineffective.
• Most patients with HVS tend to breathe using the upper thorax and have hyperinflated lungs throughout the respiratory cycle. Because the residual lung volume is high, the patient is unable to take a full tidal volume and experiences dyspnea.
• • Physically compressing the upper thorax and having the patient exhale maximally decreases hyperinflation of the lungs.
  • Instructing the patient to breathe abdominally, using the diaphragm more than the chest wall, often leads to improvement in subjective dyspnea and eventually corrects many of the associated symptoms. Diaphragmatic breathing slows the respiratory rate, gives the patient a distracting maneuver to perform when attacks occur, and gives the patient a sense of self-control during the episode. This technique has been shown to be very effective in a high proportion of patients with HVS.
  • The patient should be instructed in the technique of diaphragmatic breathing and referred to a specialist (ie, physiotherapist, psychologist, psychiatrist, family physician, internist, or respiratory therapist) who can reinforce this approach.
• Use of benzodiazepines for stress relief and for resetting the trigger for hyperventilation is effective, but patients may require prolonged treatment.
• Although acute chemical sedation may be effective and humane in selected severe cases, prolonged use of these medications should not be initiated in the ED.
• Stress reduction therapy, beta-blockers, tricyclic antidepressants, and breathing retraining all have proven effective in reducing the intensity and the frequency of episodes of hyperventilation. If the diagnosis of HVS has been established, the patient should be referred to an appropriate therapist to implement these techniques over the long term.

Consultations

Acute consultation usually is not required. The patient can be referred to the primary physician or to a therapist to help control this disease.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Benzodiazepines are effective in reducing stress that may provoke HVS and are thought to reset the CNS response to a variety of "panic-ogens."

Beta-blockade and tricyclic antidepressants have been reported to reduce the frequency and the severity of episodes of hyperventilation.

Drug Category: Benzodiazepines

These agents are useful in the treatment of hyperventilation resulting from anxiety and panic attacks. By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and to facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Drug Name	Lorazepam (Ativan)
Description	Sedative hypnotic in benzodiazepine class that has short onset of effect and relatively long half-life. By increasing action of GABA, a major inhibitory neurotransmitter, may depress all levels of CNS, including limbic and reticular formation.
Adult Dose	1-10 mg/d PO divided bid/tid
Pediatric Dose	0.05 mg/kg/dose PO q4-8h
Contraindications	Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Interactions	Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease

Drug Category: Selective serotonin reuptake inhibitors

These agents are useful in treating hyperventilation associated with anxiety.

Drug Category: Tricyclic antidepressants

These agents are used both for their antidepressant and their anxiolytic effects. Effects are caused through central and peripheral anticholinergic effects and through changes in CNS serotonin and norepinephrine reuptake.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Inpatient care is not indicated, but many patients with chronic HVS are admitted because their symptomatology resembles many serious organic problems and because no simple way to confirm the diagnosis in the ED is available.

Further Outpatient Care

• Patients should be referred to a consultant psychiatrist, psychologist, or family physician with expertise and interest in managing HVS. Some physiotherapists and respiratory therapists have extensive experience in retraining patients in proper breathing techniques and should be consulted (if available).

In/Out Patient Meds

• Several medications, including benzodiazepines, tricyclic antidepressants, and beta-blockers, are effective in reducing the frequency and the severity of hyperventilation. These agents require prolonged use and are best managed by a consultant on an ongoing outpatient basis rather than through sporadic prescriptions following an ED visit.

Complications

• Complications are related mainly to invasive procedures and investigations (eg, angiography) or to symptoms produced indirectly by hyperventilation (eg, injuries sustained in a fall during a syncopal episode due to hyperventilation).

Prognosis

• Patients with chronic HVS experience multiple exacerbations throughout their lives.
• Children who experience acute hyperventilation often continue this pattern into adulthood.
• Many patients have associated disorders (eg, agoraphobia) that may dominate the clinical picture.
• Management of these underlying disorders affects the course of hyperventilation.
• Patients who are treated with breathing retraining, stress reduction therapy, and various medications (eg, beta-blockers, benzodiazepines, tricyclics) experience significant reductions in the frequency and the severity of exacerbations.

Patient Education

• Patients should have the underlying pathophysiology explained in layman's terms and should be instructed in the technique of deflating the upper chest followed by controlled diaphragmatic breathing.
• For excellent patient education resources, visit eMedicine's Anxiety Center. Also, see eMedicine's patient education articles, Anxiety, Panic Attacks, and Hyperventilation.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Hyperventilation can be a symptom of serious underlying pathology, including pulmonary embolism, asthma, and other respiratory disorders. The diagnosis of HVS should not be made in patients with a prior history of organic causes for respiratory insufficiency. Particular care must be exercised when considering a diagnosis of HVS in an elderly person or in those with comorbid disease.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Blau JN, Wiles CM, Solomon FS. Unilateral somatic symptoms due to hyperventilation. Br Med J (Clin Res Ed). Apr 2 1983;286(6371):1108. [Medline].
• Callaham M. Hypoxic hazards of traditional paper bag rebreathing in hyperventilating patients. Ann Emerg Med. Jun 1989;18(6):622-8. [Medline].
• DeGuire S, Gevirtz R, Hawkinson D. Breathing retraining: a three-year follow-up study of treatment for hyperventilation syndrome and associated functional cardiac symptoms. Biofeedback Self Regul. Jun 1996;21(2):191-8. [Medline].
• Evans RW. Neurologic aspects of hyperventilation syndrome. Semin Neurol. Jun 1995;15(2):115-25. [Medline].
• Folgering H. The pathophysiology of hyperventilation syndrome. Monaldi Arch Chest Dis. Aug 1999;54(4):365-72. [Medline].
• Gardner WN. The pathophysiology of hyperventilation disorders. Chest. Feb 1996;109(2):516-34. [Medline].
• Han JN, Stegen K, Schepers R, et al. Subjective symptoms and breathing pattern at rest and following hyperventilation in anxiety and somatoform disorders. J Psychosom Res. Dec 1998;45(6):519-32. [Medline].
• Hornsveld H, Garssen B. The low specificity of the Hyperventilation Provocation Test. J Psychosom Res. Nov 1996;41(5):435-49. [Medline].
• Lum LC. Hyperventilation syndromes in medicine and psychiatry: a review. J R Soc Med. Apr 1987;80(4):229-31. [Medline].
• Papp LA, Klein DF, Gorman JM. Carbon dioxide hypersensitivity, hyperventilation, and panic disorder. Am J Psychiatry. Aug 1993;150(8):1149-57. [Medline].
• Tavel ME. Hyperventilation syndrome--hiding behind pseudonyms?. Chest. Jun 1990;97(6):1285-8. [Medline].

Article Last Updated: Sep 26, 2005