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 developing this 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:


In the US: 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
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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


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