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.

Drugs aimed at reversing the effects of certain sedative drugs 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.

Ventilation

Treatment of hypoventilation 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 (PPV). 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

Consideration for intubation and invasive mechanical ventilation should be undertaken if attempts at noninvasive ventilation fail to benefit the patient.

Surgery

Surgery associated with hypoventilation includes bariatric procedures to promote weight loss and placement of an electrode on the phrenic nerve for diaphragm pacing. Some patients with thoracic deformities, such as kyphoscoliosis, may be candidates for corrective surgical procedures.

Diet

Weight loss is an ideal treatment in OHS; it 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 OSA, weight loss has been shown to decrease the number of sleep-disordered breathing events (apneas and hypopneas) and the severity of hypoxemia.

Deterrence/prevention

Alcohol and many illicit substances are known respiratory depressants. Their use in patients with hypoventilation syndromes may lead to coma and death.^[11]

Noninvasive ventilation using nocturnal PPV is widely accepted as the ventilatory mode of choice in patients with chronic respiratory failure related to COPD, neuromuscular disease, thoracic deformities, and idiopathic hypoventilation. Nocturnal ventilation acts by reducing nocturnal hypoventilation and increasing carbon dioxide responsiveness.^[12] Nocturnal PPV may obviate the need for tracheotomy and has improved many patient-oriented outcomes. Bilevel PPV is the preferred method of noninvasive ventilation.^{[13, 14]}

The indications for noninvasive PPV for nocturnal hypoventilation syndromes have been formulated based on the available literature. Patients considered for this therapy should have at least 1 of 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 continuous positive airway pressure (CPAP)
• 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 PaCO₂ is greater than 45 mm Hg or when PaO₂ is less than 60mm Hg on a morning blood gas measurement.^[12]

Daytime ventilation should be used when these patients have PaCO₂ greater than 50 mm Hg or less than 92% oxygen saturation.^[2]

Studies in patients with OHS have shown that 1 year of treatment with nocturnal PPV improves blood gas values.^[15]

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.

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 PaO₂ between 60 and 65mm Hg.

Approximately 50% of patients with OHS require oxygen therapy in addition to nocturnal PPV.^[1] However, 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 the volume of dead space-to-tidal volume ratio. Therefore, oxygen therapy should be administered with caution in patients who are morbidly obese.^[16] Oxygen use alone is an inadequate therapy for OHS.

Patients with neuromuscular disease should not be given oxygen therapy without ventilatory support.

Respiratory stimulants have been used in alveolar hypoventilation but have limited efficacy.

Medroxyprogesterone

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.^[17]

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 60mg of medroxyprogesterone in divided doses 2-3 times per day.^[18]

However, the drug does not improve apnea frequency or symptoms of sleepiness. In addition, the risk of venous thromboembolism is increased with progestational agents.^[7] Many experts do not currently recommend progesterone therapy.

Acetazolamide

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

Theophylline increases diaphragm muscle strength and stimulates the central ventilatory drive. In addition to being a stimulant, theophylline is also a bronchodilator.

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.^[1]

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 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 of the procedures require long-term dietary compliance and careful nutritional follow-up.^[19]

A National Institutes of Health (NIH) consensus statement addresses the issue of surgical treatment for obesity and obesity with associated comorbid conditions. According to these guidelines, patients who are recommended for surgical treatment include those with a body mass index greater than 40 kg/m², as well as patients with a body mass index greater than 35 kg/m² and an obesity-related comorbid condition (including OHS).

Diaphragm pacing in appropriate patients with primary alveolar hypoventilation may allow for a more normal lifestyle. In the pacing procedure, an electrode is surgically placed 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, and the phrenic nerve is stimulated by electric current, 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.^[20]

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.^[21]

If hypoventilation is severe and leads to respiratory failure, admission to an intensive care unit (ICU) may be required. ICU admission allows for more specialized nursing and respiratory care. Criteria for ICU admission are as follows:

• Confusion
• Lethargy
• Respiratory muscle fatigue
• Worsening hypoxemia
• Hypercapnia
• Respiratory acidosis with a pH of less than 7.3.

All patients requiring immediate tracheal intubation and mechanical ventilation also require ICU admission. Most acute care facilities require that all patients being treated with noninvasive ventilation be admitted to the ICU as well.

Home oxygen therapy

In the outpatient setting, continue oxygen treatment in patients who meet the specific criteria for long-term oxygen therapy. These criteria include PaO₂ less than 55 mm Hg, PaO₂ less than 59 mm Hg with evidence of polycythemia, or cor pulmonale.

Reevaluate patients in 1-3 months after initiating therapy, because some patients may improve and may not require long-term oxygen.

Again, use oxygen therapy with caution in patients with alveolar hypoventilation, because some of these patients may experience worsening of hypercapnia.

Noninvasive ventilation

Noninvasive mechanical ventilation can be continued in the outpatient setting. Bilevel PPV can be used for long-term treatment of patients with a hypoventilation syndrome.

Furthermore, patients with a hypoventilation syndrome improve with nocturnal noninvasive mechanical ventilation only. Clinical studies have shown improvements in hypercapnia and hypoxia after treatment with nocturnal noninvasive mechanical ventilation in patients with COPD with associated hypoventilation, a neuromuscular disorder, OHS, or kyphoscoliosis.

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 consultation selection.^[22] Specialists who should be considered include the following:

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