Hypoventilation Syndromes Treatment & Management

The treatment of hypoventilation primarily is directed at correcting the underlying disorder. Use caution when correcting chronic hypercapnia. Rapid correction of the hypercapnia can alkalinize the cerebrospinal fluid, which may cause seizures, and can induce a metabolic alkalosis placing the patient at risk for cardiac dysrhythmias. Infusion of sodium HCO₃ is not indicated for chronic hypoventilation syndromes.

• Bronchodilators such as beta-agonists (eg, albuterol, salmeterol), anticholinergic agents (eg, ipratropium bromide), and methylxanthines (eg, theophylline) are helpful in treating patients with obstructive lung disease and severe bronchospasm. Additionally, theophylline may improve diaphragm muscle contractility and stimulate the respiratory center.
• Treatment also is aimed at assisting ventilation. Therapies that may be beneficial are endotracheal intubation with mechanical ventilation and noninvasive ventilatory techniques such as bilevel positive-pressure ventilation. Ventilatory assistance may be required in patients for the following indications:

  • Symptoms of nocturnal hypoventilation such as daytime hypersomnolence, morning headaches, fatigue, nightmares, and enuresis
  • Dyspnea at rest
  • Hypoventilation that causes pulmonary hypertension and cor pulmonale
  • Nocturnal hypoxia (arterial oxygen saturation < 88%) despite supplemental oxygen
• Noninvasive ventilation using nocturnal positive-pressure ventilation (PPV) is widely accepted as the ventilatory mode of choice in patients with chronic respiratory failure related to chronic obstructive pulmonary disease (COPD), neuromuscular disease, thoracic deformities, and idiopathic hypoventilation. Nocturnal PPV may obviate the need for tracheotomy and has improved many patient-oriented outcomes. Bilevel positive-pressure ventilation is the preferred method of noninvasive ventilation.

  • Based on the available literature, the indications for noninvasive PPV for nocturnal hypoventilation syndromes have been formulated. Patients considered for this therapy should have the following: a disease known to cause hypoventilation; symptoms and signs of hypoventilation present; failure to respond to first-line therapies in mild cases of hypoventilation (ie, treatment of primary underlying disease with bronchodilators, respiratory stimulants, weight loss, supplemental oxygen, or CPAP); or moderate-to-severe hypoventilation.
  • Nocturnal PPV is indicated for use in patients with neuromuscular disorders who exhibit morning headache, daytime hypersomnolence, sleep difficulties, or cognitive dysfunction.
  • In the absence of symptoms, nocturnal PPV is recommended when the partial pressure of alveolar carbon dioxide (PaCO₂) is greater than 45 mm Hg or when the partial pressure of arterial oxygen (PaO₂) is less than 60 mm Hg on a morning blood gas measurement.^[11]
  • Daytime ventilation should be used when these patients have PaCO₂ greater than 50 mm Hg or oxygen saturation of less than 92%.^[9]
  • Studies in obesity hypoventilation syndrome (OHS) patients have shown that 1 year of treatment with nocturnal PPV improves blood gas values.^[12]
  • Nocturnal hypoventilation acts by improving nocturnal hypoventilation and improving carbon dioxide responsiveness.^[11]
  • See the related clinical guideline summary from the American Academy of Sleep Medicine, Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders.^[13]
  • Also see Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, a clinical guideline summary from the Global Initiative for Chronic Obstructive Lung Disease (GOLD).^[14]
• Consideration for intubation and invasive mechanical ventilation should be undertaken if attempts at noninvasive ventilation fail to benefit the patient.
• Drugs aimed at reversing the effects of certain sedative drugs also may be helpful in the event of an overdose. Naloxone (Narcan) may be used to reverse the effects of narcotics, and flumazenil (Romazicon) may be used to reverse the effects of benzodiazepines.
• Because many patients with hypercapnia also are hypoxemic during the day, oxygen therapy may be indicated.

  • Oxygen therapy is indicated to prevent the sequelae of long-standing hypoxemia. Patients with COPD who meet the criteria for oxygen therapy have a decreased mortality when treated with oxygen. Oxygen therapy also has been shown to reduce pulmonary hypertension. Oxygen use alone is an inadequate therapy for obesity hypoventilation syndrome (OHS).
  • Use oxygen therapy with caution because it may worsen hypercapnia in some situations. In patients with COPD, the presence of worsening hypercapnia following oxygen therapy is a consequence of ventilation-perfusion mismatching rather than reduced ventilatory drive secondary to reduction in hypoxia. Hypercapnia is best avoided by titration of oxygen delivery to maintain oxygen saturations in the range of 90-94% and a PaO₂ between 60 and 65 mm Hg. Breathing 100% oxygen may cause worsening hypercapnia in stable patients with obesity-associated hypoventilation, due to a reduction in minute ventilation, resulting in alveolar hypoventilation and an associated increase in volume of dead space to tidal volume ratio. Therefore, oxygen therapy should be administered with caution in patients who are morbidly obese.^[15]
  • Approximately half the patients with OHS require oxygen therapy in addition to nocturnal PPV.^[3]
  • Patients with neuromuscular disease should not be given oxygen therapy without ventilatory support.
• Respiratory stimulants have been used but have limited efficacy in alveolar hypoventilation.

  • Medroxyprogesterone increases the central respiratory drive, and it has been shown to be effective in OHS. Medroxyprogesterone also has been shown to stimulate ventilation in patients with COPD and alveolar hypoventilation. Initial studies documenting a reduction in hypercapnia with treatment with medroxyprogesterone were performed in the 1960s.^[16] More recent studies also have documented a decrease in hypercapnia in patients with OHS and COPD with associated hypercapnia while receiving total daily doses of 60 mg of medroxyprogesterone in divided doses 2-3 times per day.^[17] However, it does not improve apnea frequency or symptoms of sleepiness. In addition, the risk of venous thromboembolism is increased with progestational agents.^[6] Many experts do not currently recommend progesterone therapy.
  • Acetazolamide is a diuretic that inhibits carbonic anhydrase, increases HCO₃ excretion, and causes metabolic acidosis. The metabolic acidosis subsequently stimulates ventilation. However, this medication must be used with caution. If the patient's respiratory system cannot compensate for the metabolic acidosis it induces, the patient may suffer hyperkalemia and, potentially, a cardiac dysrhythmia.
  • Theophylline increases diaphragm muscle strength and stimulates the central ventilatory drive.
• Weight loss should be encouraged in patients with OHS. Diet regulation and exercise are prudent recommendations, and supervised weight loss programs should be offered to these patients. Unfortunately, many of these patients have numerous comorbidities that prevent them from performing an adequate level of exercise to facilitate significant weight loss. Bariatric surgical procedures such as gastric bypass procedures should be offered to patients who are appropriate surgical candidates and who are willing to accept the risk of the surgical procedure. OHS is associated with a higher operative mortality.^[3]

• The numerous surgical options available today can be grouped into 2 categories based on their weight loss mechanism. Gastric restrictive procedures include vertical banded gastroplasty (VBG), adjustable gastric banding (AGB), and Roux-en-Y gastric bypass (RYGB). The procedures causing malabsorption include biliopancreatic diversion (BPD) and biliopancreatic diversion with duodenal switch (BPD-DS). All of the procedures have been successful in improving the comorbidities associated with obesity. The most commonly performed procedure is RYGB because it has the best short- and long-term results for safety, efficacy, and durability, and it has been shown to be superior to AGB. RYBG is generally performed laparoscopically. All the procedures require long-term dietary compliance and careful nutritional follow-up.^[18]
• The National Institutes of Health consensus statement addresses the issue of surgical treatment for obesity and obesity with associated comorbid conditions. According to these guidelines, patients with a body mass index greater than 35 kg/m² and an obesity-related comorbid condition (including obesity hypoventilation syndrome) or patients with a body mass index greater than 40 kg/m² are recommended for surgical treatment.
• Some patients with thoracic deformities such as kyphoscoliosis may be candidates for corrective surgical procedures if they are acceptable candidates for thoracic surgery.
• Diaphragm pacing in appropriate patients with primary alveolar hypoventilation may allow for a more normal lifestyle. This requires surgical placement of an electrode onto the phrenic nerve, which is connected to a subcutaneous receiver. An external battery-operated transmitter and antenna are placed on the skin over the receiver. This phrenic nerve is stimulated by the electric current thereby resulting in a diaphragmatic contraction. The transmitter settings may be adjusted for respiratory rate and to give enough tidal volume to allow for adequate oxygenation and ventilation. Unfortunately, phrenic nerve stimulation results in irreversible injury to the nerve. Thus, over time, pacing of the phrenic nerve becomes ineffective.^[19]
• More recently, direct pacing of the diaphragm in patients with phrenic nerve paralysis has been of interest. Studies are ongoing to determine the utility of this treatment modality.^[20]

• Consider consultation with experts in certain medical specialties for assistance with evaluation and management of hypoventilation syndromes. The patient's history, physical examination findings, and available laboratory studies should guide the selection of consultation.^[21] Specialists who should be considered include the following:

  • Pulmonary medicine specialist
  • Neurologist
  • Physical and rehabilitation medicine specialist

Weight loss is an ideal treatment in OHS and improves the abnormal physiology and restores normal daytime gas exchange. Even a modest weight loss of 10 kg improves minute ventilation and normalizes daytime PaCO₂. In concomitant obstructive sleep apnea (OSA), weight loss has been shown to decrease the number of sleep-disordered breathing events (apneas and hypopneas) and severity of hypoxemia.