Hyperventilation Syndrome 

Hyperventilation syndrome (HVS) represents a relatively common ED presentation that is readily recognized by most clinicians. However, the underlying pathophysiology has not been clearly elucidated.

As classically defined, hyperventilation syndrome is a condition in which minute ventilation exceeds metabolic demands, resulting in hemodynamic and chemical changes that produce characteristic dysphoric symptoms. Inducing a drop in arterial pCO₂ through voluntary hyperventilation reproduces these symptoms. Recently, however, this model has been challenged with the observation that many patients with hyperventilation syndrome 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 developing psychogenic dyspnea.

Symptoms of hyperventilation syndrome and panic disorder overlap considerably, although the two 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 hyperventilation syndrome manifest panic disorder.

Hyperventilation syndrome occurs in acute and chronic forms. Acute hyperventilation syndrome accounts for only 1% of cases but is more easily diagnosed. Chronic hyperventilation syndrome 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 hyperventilation, many patients with chronic hyperventilation syndrome 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. One theory suggests that certain stressors provoke an exaggerated respiratory response. Several such stressors have been identified, including emotional distress, sodium lactate, caffeine, isoproterenol, cholecystokinin, and CO₂. Predisposition to hyperventilation syndrome may also be rooted in childhood. Patients with hyperventilation syndrome were shown to have a higher percentage of overprotective parents when they were children. A sudden stressful situation later in life can then incite the first episode of hyperventilation syndrome.^[1]

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 hyperventilation syndrome is unknown. In addition, elevated levels of carbon dioxide have been shown to induce panic symptoms in a majority of patients with panic disorder. Those patients who panicked with increased carbon dioxide had significantly greater baseline respiratory variability, which is also found in patients with hyperventilation syndrome, further suggesting a connection between the two.^[2]

The explanation of hyperventilation syndrome lies partially in the mechanics of breathing. Normal tidal volumes range from 35-45% of vital capacity at rest. The elastic recoil of the chest wall resists hyperinflation of the lungs beyond that level, and inspiratory volumes beyond this level are perceived as effort or dyspnea. Patients with hyperventilation syndrome 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.

Another common 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 hyperventilation syndrome 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 hyperventilation syndrome as their primary diagnosis, although equivalent data are not available for ED presentations. It is thought that up to 6% of the general population exhibits aspects of hyperventilation syndrome.

Mortality/Morbidity

Death attributable to the syndrome is extremely rare. A leftward shift in the HbO₂ dissociation curve and vasospasm related to low pCO₂ could cause myocardial ischemia in patients with coronary artery disease and hyperventilation syndrome.

Certain patients are disabled psychologically by their symptoms, and many patients carry false diagnoses. Patients with hyperventilation syndrome often undergo unnecessary testing and suffer from the complications of these interventions (eg, angiography, thrombolytics, nasal reconstruction).^[3] Withholding such therapy may be difficult in a patient with crushing chest pain and dyspnea.

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 hyperventilation syndrome. 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, hyperventilation syndrome 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 hyperventilation syndrome appear ill prompts further esoteric testing, which is inevitably nondiagnostic; the chronicity of the condition often prompts different physicians to repeat these unnecessary investigations.

Sex

A female preponderance of hyperventilation syndrome 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.