Hyperventilation syndrome (HVS) represents a relatively common emergency department (ED) presentation that is readily recognized by most clinicians. However, the underlying pathophysiology has not been clearly elucidated.
As typically defined, HVS is a condition in which minute ventilation exceeds metabolic demands, resulting in hemodynamic and chemical changes that produce characteristic dysphoric symptoms. Inducing a decrease in arterial partial pressure of carbon dioxide (PaCO2) through voluntary hyperventilation reproduces these symptoms.
However, this model has been challenged by the observation that many patients with HVS do not manifest a low PaCO2 during attacks. In some cases, patients with this syndrome have demonstrated altered respiratory physiology that is manifested as a slower return of the PaCO2 to baseline after voluntary hyperventilation to a defined level of PaCO2.
Current thinking suggests that a better term for this syndrome might be behavioral breathlessness or psychogenic dyspnea, with hyperventilation seen as a consequence rather than a cause of the condition. It is also recognized that some patients may be physiologically at risk for the development of psychogenic dyspnea.
Symptoms of HVS and panic disorder overlap considerably, though the two conditions remain distinct. Approximately 50% of patients with panic disorder and 60% of patients with agoraphobia manifest hyperventilation as a symptom, whereas 25% of patients with HVS manifest panic disorder.
Diagnosis and management
Upon a first attack of acute HVS, the diagnosis depends on recognizing the typical constellation of signs and symptoms and ruling out the serious conditions that can cause the presenting symptoms.
A low pulse oximetry reading in a patient who is hyperventilating should never be attributed to HVS. These patients should always be evaluated for other causes of hyperventilation.
Arterial blood gas (ABG) measurement is indicated if any doubt exists as to the patient’s underlying respiratory status. In chronic HVS, ABG sampling confirms a compensated respiratory alkalosis in a majority of cases.
Electrocardiographic changes are common and may include the following:
ST depression or elevation
Prolonged QT interval
Noninvasive measurements of gas exchange during orthostatic testing are useful in the diagnosis of HVS. 
Once life-threatening conditions are eliminated, simple reassurance and an explanation of how hyperventilation produces the patient’s symptoms are usually sufficient to terminate the episode of HVS. Provoking the symptoms by having the patient voluntarily hyperventilate for 3-4 minutes often convinces the patient of the diagnosis, but it is time-consuming and may be ineffective.
Diaphragmatic breathing slows the respiratory rate, gives patients a distracting maneuver to perform when attacks occur, and provides patients with a sense of self-control during episodes of hyperventilation. This technique has been shown to be very effective in a high proportion of patients with HVS.
Several medications, including benzodiazepines and selective serotonin reuptake inhibitors (SSRIs), have been employed to reduce the frequency and severity of episodes of hyperventilation.
Stress reduction therapy, administration of beta blockers, and breathing retraining have all proved 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.
HVS occurs in acute and chronic forms. Acute HVS accounts for only 1% of cases but is more easily diagnosed. Chronic HVS can present with a myriad of respiratory, cardiac, neurologic, or gastrointestinal (GI) symptoms without any clinically apparent overbreathing by the patient. Hypocapnia can be maintained without any overt change in the minute ventilation if the patient exhibits frequent sighs interspersed with normal respirations.
Because of the subtlety of 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. 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 carbon dioxide.
Predisposition to HVS may also be rooted in childhood. Patients with HVS were shown to be more likely to have had overprotective parents when they were children. A sudden stressful situation later in life can then incite the first episode of HVS. 
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.
In addition, elevated levels of carbon dioxide have been demonstrated to induce panic symptoms in a majority of patients with panic disorder. Those patients who panicked with increased carbon dioxide levels had significantly greater baseline respiratory variability, which is also found in patients with HVS. This similarity further suggests a connection between the two disorders. 
The explanation of HVS lies partially in the mechanics of breathing. Normal tidal volume is approximately 500 mL per inspiration or 7 mL/kg of body mass. 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 HVS tend to breathe by using the upper thorax rather than the diaphragm, and this results in chronic overinflation of the 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 circle is created.
Another theory is that patients with panic disorder have a lower threshold for the fight-or-flight response. In susceptible patients, even minor stresses can trigger the syndrome, which then tends to manifest with primarily psychiatric complaints (eg, fear of death, impending doom, or claustrophobia). In contrast, it is believed that HVS patients tend to focus on somatic complaints related to the physiologic changes produced by hyperventilation. Initiating stimuli and abnormal stress responses may be identical but are expressed differently in each group.
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, which results 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 is higher in first-degree relatives than in the general population, but no clear genetic factors have been identified.
A study by D’Alba et al evaluating the prevalence of HVS in adolescents found that the rate of HVS symptoms in adolescents with asthma was 10 times higher than that in adolescents without asthma (25% vs 2.5%, respectively). The study also found that in the adolescent population scrutinized, HVS was more prevalent in females than in males (with the odds ratio [OR] for the syndrome in females being 3.2). In addition, asthma status was seen to significantly influence the probability of HVS occurrence, with the ORs for HVS in adolescents with lifetime asthma, current episodic asthma, and current active asthma calculated as 11.2, 8.9, and 41.5, respectively. 
As many as 10% of patients in a general internal medicine practice are reported to have HVS as their primary diagnosis, though equivalent data are not available for ED presentations. It is thought that up to 6% of the general population exhibits aspects of HVS.
The peak incidence is between the ages of 15 and 55 years, but cases have been reported in all age groups except infants. HVS has a strong female preponderance: the female-to-male ratio may be as high as 7:1.
Patients with chronic HVS experience multiple exacerbations throughout their lives. Children who experience acute HVS 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, benzodiazepines or selective serotonin reuptake inhibitors [SSRIs]) experience significant reductions in the frequency and the severity of exacerbations.
Death attributable to HVS is extremely rare. A leftward shift in the oxyhemoglobin dissociation curve and vasospasm related to low PaCO2 could cause myocardial ischemia in patients with coronary artery disease (CAD) and hyperventilation syndrome.
Certain patients are disabled psychologically by their symptoms, and many patients carry misdiagnoses. Patients with HVS often undergo diagnostic testing and may have complications from related interventions (eg, angiography, thrombolytics, or nasal reconstruction).  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 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 (MI).
Clearly, HVS not only causes severe and genuine discomfort for the patient but also accounts for considerable medical expense through the process of excluding more serious disorders. That patients with HVS appear ill tends to prompt further esoteric testing, which is inevitably nondiagnostic. The chronicity of the condition often causes different physicians to repeat these diagnostic investigations.
Patients should receive a clear explanation of the underlying pathophysiology and should be instructed in the technique of deflation of the upper chest followed by controlled diaphragmatic breathing.
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