Treatment of the underlying cause is required. Endotracheal intubation and mechanical ventilation are required in cases of severe respiratory failure (PaO2 less than 50 mmHg). Respiratory stimulants such as doxapram are rarely used, and if the respiratory failure resulted from an overdose of sedative drugs such as opioids or benzodiazepines, then the appropriate antidote (naloxone or flumazenil, respectively) will be given.

There is tentative evidence that in those with respiratory failure identified before arrival in hospital, continuous positive airway pressure can be useful when started before conveying to hospital.

Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but offered limited effectiveness. A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects.

If the respiratory depression occurs from opioid overdose, usually an opioid antagonist, most likely naloxone, will be administered. This will rapidly reverse the respiratory depression unless complicated by other depressants. However an opioid antagonist may also precipitate an opioid withdrawal syndrome in chronic users.

Hypercapnia is generally defined as a blood gas carbon dioxide level over 45 mmHg. Since carbon dioxide is in equilibrium with carbonic acid in the blood, hypercapnia can drive serum pH down, resulting in a respiratory acidosis. Clinically, the effect of hypercapnia on pH is estimated using the ratio of the arterial pressure of carbon dioxide to the concentration of bicarbonate ion, PCO/[HCO].

Hypercapnia is generally caused by hypoventilation, lung disease, or diminished consciousness. It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, such as from volcanic or geothermal activity, or by rebreathing exhaled carbon dioxide. It can also be an initial effect of administering supplemental oxygen on a patient with sleep apnea. In this situation the hypercapnia can also be accompanied by respiratory acidosis.

As a side effect of medicines or recreational drugs, hypoventilation may become potentially life-threatening. Many different central nervous system (CNS) depressant drugs such as ethanol, benzodiazepines, barbiturates, GHB, sedatives and opioids produce respiratory depression when taken in large or excessive doses, or mixed with other depressants. Strong opiates (such as fentanyl, heroin, or morphine), barbiturates, and certain benzodiazepines (short acting ones and alprazolam) are known for depressing respiration. In an overdose, an individual may cease breathing entirely (go into respiratory arrest) which is rapidly fatal without treatment. Opioids, in overdose or combined with other depressants, are notorious for such fatalities.

Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide or both cannot be kept at normal levels. A drop in the oxygen carried in blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type I or Type II, based on whether there is a high carbon dioxide level. The definition of respiratory failure in clinical trials usually includes increased respiratory rate, abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing.

The normal partial pressure reference values are: oxygen PaO more than , and carbon dioxide PaCO lesser than .

In people with stable OHS, the most important treatment is weight loss—by diet, through exercise, with medication, or sometimes weight loss surgery (bariatric surgery). This has been shown to improve the symptoms of OHS and resolution of the high carbon dioxide levels. Weight loss may take a long time and is not always successful. Bariatric surgery is avoided if possible, given the high rate of complications, but may be considered if other treatment modalities are ineffective in improving oxygen levels and symptoms. If the symptoms are significant, nighttime positive airway pressure (PAP) treatment is tried; this involves the use of a machine to assist with breathing. PAP exists in various forms, and the ideal strategy is uncertain. Some medications have been tried to stimulate breathing or correct underlying abnormalities; their benefit is again uncertain.

While many people with obesity hypoventilation syndrome are cared for on an outpatient basis, some deteriorate suddenly and when admitted to the hospital may show severe abnormalities such as markedly deranged blood acidity (pH<7.25) or depressed level of consciousness due to very high carbon dioxide levels. On occasions, admission to an intensive care unit with intubation and mechanical ventilation is necessary. Otherwise, "bi-level" positive airway pressure (see the next section) is commonly used to stabilize the patient, followed by conventional treatment.

To date, no prospective controlled clinical trial has shown a significant mortality benefit of exogenous surfactant in adult ARDS.

In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in "Pa"CO. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:

- Acute respiratory acidosis: HCO increases 1 mEq/L for each 10 mm Hg rise in "Pa"CO.

- Chronic respiratory acidosis: HCO rises 3.5 mEq/L for each 10 mm Hg rise in "Pa"CO.

The expected change in pH with respiratory acidosis can be estimated with the following equations:

- Acute respiratory acidosis: Change in pH = 0.008 X (40 − "Pa"CO)

- Chronic respiratory acidosis: Change in pH = 0.003 X (40 − "Pa"CO)

Respiratory acidosis does not have a great effect on electrolyte levels. Some small effects occur on calcium and potassium levels. Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels. In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia.

Positive airway pressure, initially in the form of "continuous" positive airway pressure (CPAP), is a useful treatment for obesity hypoventilation syndrome, particularly when obstructive sleep apnea co-exists. CPAP requires the use during sleep of a machine that delivers a continuous positive pressure to the airways and preventing the collapse of soft tissues in the throat during breathing; it is administered through a mask on either the mouth and nose together or if that is not tolerated on the nose only (nasal CPAP). This relieves the features of obstructive sleep apnea and is often sufficient to remove the resultant accumulation of carbon dioxide. The pressure is increased until the obstructive symptoms (snoring and periods of apnea) have disappeared. CPAP alone is effective in more than 50% of people with OHS.

In some occasions, the oxygen levels are persistently too low (oxygen saturations below 90%). In that case, the hypoventilation itself may be improved by switching from CPAP treatment to an alternate device that delivers "bi-level" positive pressure: higher pressure during inspiration (breathing in) and a lower pressure during expiration (breathing out). If this too is ineffective in increasing oxygen levels, the addition of oxygen therapy may be necessary. As a last resort, tracheostomy may be necessary; this involves making a surgical opening in the trachea to bypass obesity-related airway obstruction in the neck. This may be combined with mechanical ventilation with an assisted breathing device through the opening.

Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in COPD involves multiple mechanisms, including decreased responsiveness to hypoxia and hypercapnia, increased ventilation-perfusion mismatch leading to increased dead space ventilation, and decreased diaphragm function secondary to fatigue and hyperinflation.

Chronic respiratory acidosis also may be secondary to obesity hypoventilation syndrome (i.e., Pickwickian syndrome), neuromuscular disorders such as amyotrophic lateral sclerosis, and severe restrictive ventilatory defects as observed in interstitial lung disease and thoracic deformities.

Lung diseases that primarily cause abnormality in alveolar gas exchange usually do not cause hypoventilation but tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia. Hypercapnia only occurs if severe disease or respiratory muscle fatigue occurs.

Inhaled nitric oxide (NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for gas exchange. Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS. Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity.

The rate of BPD varies among institutions, which may reflect neonatal risk factors, care practices (e.g., target levels for acceptable oxygen saturation), and differences in the clinical definitions of BPD.

There is evidence to show that steroids given to babies less than 8 days old can prevent bronchopulmonary dysplasia. However, the risks of treatment may outweigh the benefits.

It is unclear if starting steroids more than 7 days after birth is harmful or beneficial. It is thus recommended that they only be used in those who cannot be taken off of a ventilator.

People generally require tracheostomy and lifetime mechanical ventilation on a ventilator in order to survive. However, it has now been shown that biphasic cuirass ventilation can effectively be used without the need for a tracheotomy. Other potential treatments for Ondine's curse include oxygen therapy and medicine for stimulating the respiratory system. Currently, problems arise with the extended use of ventilators, including fatal infections and pneumonia.

Most people with CCHS (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is diaphragm pacing.

Preventing alveolar overdistension – Alveolar overdistension is mitigated by using small tidal volumes, maintaining a low plateau pressure, and most effectively by using volume-limited ventilation.

Preventing cyclic atelectasis (atelectotrauma) – Applied positive end-expiratory pressure (PEEP) is the principal method used to keep the alveoli open and lessen cyclic atelectasis.

Open lung ventilationn – Open lung ventilation is a ventilatory strategy that combines small tidal volumes (to lessen alveolar overdistension) and an applied PEEP above the low inflection point on the pressure-volume curve (to lessen cyclic atelectasis).

High frequency ventilation is thought to reduce ventilator-associated lung injury, especially in the context of ARDS and acute lung injury.

Permissive hypercapnia and hypoxaemia allow the patient to be ventilated at less aggressive settings and can thererfore mitigate all forms of ventilator associated lung injury

In those who are not palliative the primary treatment of shortness of breath is directed at its underlying cause. Extra oxygen is effective in those with hypoxia; however, this has no effect in those with normal blood oxygen saturations, even in those who are palliative.

Individuals can benefit from a variety of physical therapy interventions. Persons with neurological/neuromuscular abnormalities may have breathing difficulties due to weak or paralyzed intercostal, abdominal and/or other muscles needed for ventilation. Some physical therapy interventions for this population include active assisted cough techniques, volume augmentation such as breath stacking, education about body position and ventilation patterns and movement strategies to facilitate breathing.

VALI is most common in patients receiving mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ALI/ARDS).

Possible reasons for predisposition to VALI include:

- An injured lung may be at risk for further injury

- Cyclic atelectasis is particularly common in an injured lung

After a patient receives a diagnosis, the diagnosing physician can provide different options for treatment.

- Mechanical regulation of airflow and/or airway pressure:

- An experimental pacemaker for the diaphragm has shown promising results in overcoming central sleep apnea.

The conditions of hypoxia and hypercapnia, whether caused by apnea or not, trigger additional effects on the body. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures, how short is the interval between failures to breathe, and the presence or absence of independent conditions whose effects amplify those of an apneic episode.

- Brain cells need constant oxygen to live, and if the level of blood oxygen remains low enough for long enough, brain damage and even death will occur. These effects, however, are rarely a result of central sleep apnea, which is a chronic condition whose effects are usually much milder.

- Drops in blood oxygen levels that are severe but not severe enough to trigger brain-cell or overall death may trigger seizures even in the absence of epilepsy.

- In severe cases of sleep apnea, the more translucent areas of the body will show a bluish or dusky cast from cyanosis, the change in hue ("turning blue") produced by the deoxygenation of blood in vessels near the skin.

- Compounding effects of independent conditions:

Administration of oxygen at 15 litres per minute by face mask or bag valve mask is often sufficient, but tracheal intubation with mechanical ventilation may be necessary. Suctioning of pulmonary oedema fluid should be balanced against the need for oxygenation. The target of ventilation is to achieve 92% to 96% arterial saturation and adequate chest rise. Positive end-expiratory pressure will generally improve oxygenation. Drug administration via peripheral veins is preferred over endotracheal administration. Hypotension remaining after oxygenation may be treated by rapid crystalloid infusion. Cardiac arrest in drowning usually presents as asystole or pulseless electrical activity. Ventricular fibrillation is more likely to be associated with complications of pre-existing coronary artery disease, severe hypothermia, or the use of epinephrine or norepinephrine.

The mortality rate of meconium-stained infants is considerably higher than that of non-stained infants; meconium aspiration used to account for a significant proportion of neonatal deaths. Residual lung problems are rare but include symptomatic cough, wheezing, and persistent hyperinflation for up to five to ten years. The ultimate prognosis depends on the extent of CNS injury from asphyxia and the presence of associated problems such as pulmonary hypertension. Fifty percent of newborns affected by meconium aspiration would die fifteen years ago; however, today the percent has dropped to about twenty.

MAS is difficult to prevent. Amnioinfusion, a method of thinning thick meconium that has passed into the amniotic fluid through pumping of sterile fluid into the amniotic fluid, has not shown a benefit.

Extrapulmonary restriction is a type of restrictive lung disease, indicated by decreased alveolar ventilation with accompanying hypercapnia. It is characterized as an inhibition to the drive to breathe, or an ineffective restoration of the drive to breathe.

Extrapulmonary restriction can be caused by central and peripheral nervous system dysfunctions, over-sedation, or trauma (such as a broken rib).