Hyperventilation Syndrome

Hyperventilation syndrome is a condition in which breathing exceeds metabolic demand, lowering arterial carbon dioxide (hypocapnia, with a partial pressure of carbon dioxide below 35 mmHg or 4.7 kPa) and causing respiratory alkalosis and multiple physical symptoms, in the absence of an organic cause. It is part of the spectrum of dysfunctional breathing, and is often linked with anxiety and panic disorder.

• Mechanism: hypocapnia causes cerebral vasoconstriction (reducing cerebral blood flow by about 2 to 4% for each 1 mmHg fall in carbon dioxide), a leftward shift of the oxygen dissociation curve, a fall in ionised calcium (increased neuromuscular excitability), and sympathetic activation.
• Acute hyperventilation occurs with panic attacks and stress. Chronic hyperventilation shows a persistently low carbon dioxide with a compensatory fall in serum bicarbonate, and symptoms triggered by small changes in breathing.
• It affects about 6 to 10% of the general population, up to 30% of patients with asthma, and is commoner in women (2 to 3 times) and in adults aged 15 to 55 years.
• Triggers and associations: anxiety and panic, stress, depression, pain, asthma, exercise, pregnancy (progesterone), thyroid disease, and substance use (caffeine, nicotine, stimulants).
• Organic causes of hyperventilation that must be excluded: pulmonary embolism, asthma, pneumonia, heart failure, metabolic acidosis (diabetic ketoacidosis, renal failure, sepsis, lactic acidosis), salicylate overdose, hyperthyroidism, anaemia, hypoxia, fever and sepsis, pregnancy, central nervous system disease, pain and drugs (salbutamol, theophylline, progesterone, caffeine).

• Breathlessness (air hunger, a feeling of being unable to get a satisfying breath), frequent sighing and yawning, chest tightness or discomfort, palpitations, light headedness and dizziness, faintness, tingling (paraesthesia) around the mouth and in the hands and feet, cold hands, muscle cramps, tetany with carpopedal spasm, anxiety, a sense of unreality, headache, fatigue, bloating and belching (aerophagia), and a dry mouth.
• Acute attacks last 10 to 30 minutes, and may be triggered by stress, emotion, or a recollection of a past event. Chronic cases show a long history of vague symptoms, with sighing breathing at rest, a chest dominant pattern, irregular breathing, and an upper chest movement with little abdominal motion.
• Examination: rapid or irregular breathing, frequent sighing, and use of the upper chest, with normal oxygen saturation (97 to 100%) and a normal chest. Positive Chvostek and Trousseau signs may occur in acute severe cases.
• Differential diagnosis: asthma, pulmonary embolism, cardiac arrhythmia and ischaemia, heart failure, anaemia, thyrotoxicosis, diabetic ketoacidosis, salicylate toxicity, panic disorder, generalised anxiety disorder, vocal cord dysfunction, hypocalcaemia, hypoglycaemia, phaeochromocytoma, and drug withdrawal.
• Red flags: chest pain on exertion, syncope, exertional breathlessness with reduced oxygen saturation, haemoptysis, unilateral leg swelling, fever, weight loss, a heart rate above 120, an abnormal chest examination, and age over 50 with first presentation.
• Complications: repeated emergency visits and unnecessary investigation, avoidance behaviours, depression and anxiety, and rarely syncope and seizures like events.

• A diagnosis of exclusion that depends on a typical history, reproduction of symptoms by voluntary hyperventilation, and exclusion of organic disease.
• Initial tests: pulse oximetry (normal), electrocardiogram, blood glucose, full blood count, thyroid function tests, electrolytes, calcium and magnesium, and urine pregnancy test.
• Arterial or capillary blood gas during an attack: a low partial pressure of carbon dioxide, a raised pH, a normal partial pressure of oxygen, and a normal or slightly low bicarbonate. Chronic hyperventilation shows a normal pH with a low carbon dioxide and a low bicarbonate. End tidal carbon dioxide monitoring (capnography) below 30 mmHg at rest supports the diagnosis.
• Hyperventilation provocation test: voluntary hyperventilation for 1 to 3 minutes to reproduce symptoms, with a recovery period. This should be done only after exclusion of cardiac and cerebrovascular disease, epilepsy and pregnancy.
• A validated symptom questionnaire for dysfunctional breathing (a total score above 23 of 64 supports the diagnosis).
• Chest X-ray, spirometry (to exclude asthma), D-dimer or CT pulmonary angiography (when embolism is possible), echocardiography and exercise testing when features are atypical, as directed by risk.
• Screen for anxiety, depression and panic disorder with a validated scale.

• Acute attack:
  • Reassure the patient that the symptoms are from over breathing, not from heart or lung disease, and stay calm.
  • Coach slow breathing: breathe in through the nose for 3 to 4 seconds and out through pursed lips or the nose for 5 to 6 seconds (6 to 10 breaths per minute), using the abdomen (diaphragm), with a hand on the stomach. Breathe in a steady way for about 10 minutes.
  • Do not use a paper bag for rebreathing, because it can cause hypoxia and mask serious illness.
  • Consider lorazepam 0.5 to 1 mg sublingually or orally, or diazepam 2 to 5 mg orally, once only in severe attacks after organic causes are excluded. Avoid regular use, because of dependence.
• Breathing retraining (the mainstay of long term treatment), led by a respiratory physiotherapist, over 4 to 6 sessions of 30 to 60 minutes with daily home practice of 10 to 20 minutes twice a day:
  • Education about hyperventilation and the link between breathing and symptoms.
  • Diaphragmatic (abdominal) breathing, nasal breathing, reducing sighing and yawning, a slower breathing rate of 8 to 10 breaths per minute, and relaxation (progressive muscle relaxation).
  • Biofeedback with capnography to normalise end tidal carbon dioxide to 35 to 40 mmHg.
  • Applied relaxation during stress, and a plan for early symptoms.
• Psychological therapy: cognitive behavioural therapy for panic and anxiety (8 to 16 sessions), which produces lasting benefit.
• Drug therapy for associated panic disorder or anxiety:
  • Sertraline 25 mg orally once daily for 1 week, then 50 mg daily, increased to 100 to 200 mg daily by 25 to 50 mg every 1 to 2 weeks as needed, or escitalopram 5 mg once daily increased to 10 to 20 mg after 1 week, for at least 6 to 12 months. Warn about an early increase in anxiety and monitor for suicidal thoughts in young people.
  • Propranolol 10 to 40 mg orally 8 to 12 hourly for somatic symptoms (palpitations and tremor), when asthma is absent.
  • Avoid long term benzodiazepines.
• Lifestyle: reduce caffeine, nicotine and alcohol, take regular aerobic exercise (30 minutes on most days), maintain sleep hygiene, and manage stress.
• Treat coexisting asthma (inhaled corticosteroid, and review of overuse of salbutamol), nasal disease, reflux, and pain.
• Special groups:
  • Children and adolescents: reassurance, family education, breathing exercises and psychological support. Exclude asthma and cardiac disease.
  • Pregnancy: reassure, teach slow breathing and relaxation, and exclude embolism and anaemia. Avoid benzodiazepines when possible, and use sertraline when drug therapy is necessary.
  • Elderly: lower threshold for cardiac and pulmonary investigation, and avoid benzodiazepines because of falls.
  • Asthma: treat both conditions, because overuse of bronchodilators can mimic and worsen symptoms.
• Follow up: review at 2 to 4 weeks and at 3 months. Refer to respiratory physiotherapy for breathing retraining and to mental health services for panic disorder, and refer to a respiratory physician for diagnostic uncertainty.