Oxygen is given with a small amount of continuous positive airway pressure ("CPAP"), and intravenous fluids are administered to stabilize the blood sugar, blood salts, and blood pressure. If the baby's condition worsens, an endotracheal tube (breathing tube) is inserted into the trachea and intermittent breaths are given by a mechanical device. An exogenous preparation of surfactant, either synthetic or extracted from animal lungs, is given through the breathing tube into the lungs. Some of the most commonly used surfactants are Survanta or its generic form Beraksurf, derived from cow lungs, which can decrease the risk of death in hospitalized very-low-birth-weight infants by 30%. Such small premature infants may remain ventilated for months. A study shows that an aerosol of a perfluorocarbon such as perfluoromethyldecalin can reduce inflammation in swine model of IRDS. Chronic lung disease including bronchopulmonary dysplasia are common in severe RDS. The etiology of BPD is problematic and may be due to oxygen, overventilation or underventilation. The mortality rate for babies greater than 27 weeks gestation is less than 20%

Extracorporeal membrane oxygenation (ECMO) is a potential treatment, providing oxygenation through an apparatus that imitates the gas exchange process of the lungs. However, newborns cannot be placed on ECMO if they are under 4.5 pounds (2 kg), because they have extremely small vessels for cannulation, thus hindering adequate flow because of limitations from cannula size and subsequent higher resistance to blood flow (compare with vascular resistance). Furthermore, in infants aged less than 34 weeks of gestation several physiologic systems are not well-developed, specially the cerebral vasculature and germinal matrix, resulting in high sensitivity to slight changes in pH, PaO, and intracranial pressure. Subsequently, preterm infants are at unacceptably high risk for intraventricular hemorrhage (IVH) if administered ECMO at a gestational age less than 32 weeks.

- The INSURE Method

Henrik Verder is the inventor and pioneer of the INSURE method, a very effective approach to managing preterm neonates with respiratory distress. The method itself has been shown, through meta-analysis; to successfully decrease the use of mechanical ventilation and lower the incidence of bronchopulmonary dysplasia (BPD). Since its conception in 1989 the INSURE method has been academically cited in more than 500 papers. The first randomised study about the INSURE method was published in 1994 and a second randomised study in infants less than 30 weeks gestation was published by the group in 1999. In the last 15 years Henrik has worked with lung maturity diagnostics on gastric aspirates obtained at birth. By combining this diagnostic method with INSURE, Henrik has worked to further improve the clinical outcome of RDS. The lung maturity tests used have been the microbubble test, lamellar body counts (LBC) and measurements of lecithin-sphingomyelin ratio (L/S) with chemometrics, which involved a collaboration with Agnar Höskuldsson.

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.

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.

Surfactant appears to improve outcomes when given to infants following meconium aspiration.

It has been recommended that the throat and nose of the baby be suctioned as soon as the head is delivered. However, this is not really useful and the revised Neonatal Resuscitation Guidelines no longer recommend it. When meconium staining of the amniotic fluid is present and the baby is born depressed, it is recommended that an individual trained in neonatal intubation use a laryngoscope and endotracheal tube to suction meconium from below the vocal cords. If the condition worsens, extracorporeal membrane oxygenation (ECMO) can be useful.

Albumin-lavage has not demonstrated to benefit outcomes of MAS. Steroid use has not demonstrated to benefit the outcomes of MAS.

Giving the mother glucocorticoids speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The American College of Obstetricians and Gynecologists (ACOG), Royal College of Medicine, and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34 weeks of gestation. Multiple courses of glucocorticoid administration, compared with a single course, does not seem to increase or decrease the risk of death or neurodevelopmental disorders of the child.

In pregnancies of greater than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by amniocentesis, wherein a needle is inserted through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the lecithin-sphingomyelin ratio ("L/S ratio"), the presence of phosphatidylglycerol (PG), and more recently, the surfactant/albumin (S/A) ratio. For the L/S ratio, if the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as mg of surfactant per gm of protein. An S/A ratio 55 indicates mature surfactant production(correlates with an L/S ratio of 2.2 or greater).

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.

Treatment is primarily supportive. Management in an intensive care unit is required and the need for mechanical ventilation is common. Therapy with corticosteroids is generally attempted, though their usefulness has not been established. The only treatment that has met with success to date is a lung transplant.

Different treatments have been used to manage pulmonary interstitial emphysema with variable success. Admission/transfer to a neonatal intensive care unit (NICU) is common and expected for patients with PIE.

Treatments include:

- Lateral decubitus position with the affected side down

- High-frequency ventilation

- Lobectomy

- Selective Main Bronchial Intubation and Occlusion

Acute cardiogenic pulmonary edema often responds rapidly to medical treatment. Positioning upright may relieve symptoms. Loop diuretics such as furosemide or bumetanide are administered, often together with morphine or diamorphine to reduce respiratory distress. Both diuretics and morphine may have vasodilator effects, but specific vasodilators may be used (particularly intravenous glyceryl trinitrate or ISDN) provided the blood pressure is adequate.

Continuous positive airway pressure and bilevel positive airway pressure (BIPAP/NIPPV) has been demonstrated to reduce the need of mechanical ventilation in people with severe cardiogenic pulmonary edema, and may reduce mortality.

It is possible for cardiogenic pulmonary edema to occur together with cardiogenic shock, in which the cardiac output is insufficient to sustain an adequate blood pressure. This can be treated with inotropic agents or by intra-aortic balloon pump, but this is regarded as temporary treatment while the underlying cause is addressed.

The initial management of pulmonary edema, irrespective of the type or cause, is supporting vital functions. Therefore, if the level of consciousness is decreased it may be required to proceed to tracheal intubation and mechanical ventilation to prevent airway compromise. Hypoxia (abnormally low oxygen levels) may require supplementary oxygen, but if this is insufficient then again mechanical ventilation may be required to prevent complications. Treatment of the underlying cause is the next priority; pulmonary edema secondary to infection, for instance, would require the administration of appropriate antibiotics.

Pulmonary interstitial emphysema often resolves gradually and may take 2–3 weeks. For longer durations of PIE the length of time of mechanical ventilation needed may increase and the incidence of bronchopulmonary dysplasia becomes higher. Some infants may develop chronic lobar emphysema, which may require surgical lobectomies.

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.

Management has three components: interventions before delivery, timing and place of delivery, and therapy after delivery.

In some cases, fetal therapy is available for the underlying condition; this may help to limit the severity of pulmonary hypoplasia. In exceptional cases, fetal therapy may include fetal surgery.

A 1992 case report of a baby with a sacrococcygeal teratoma (SCT) reported that the SCT had obstructed the outlet of the urinary bladder causing the bladder to rupture in utero and fill the baby's abdomen with urine (a form of ascites). The outcome was good. The baby had normal kidneys and lungs, leading the authors to conclude that obstruction occurred late in the pregnancy and to suggest that the rupture may have protected the baby from the usual complications of such an obstruction. Subsequent to this report, use of a vesicoamniotic shunting procedure (VASP) has been attempted, with limited success.

Often, a baby with a high risk of pulmonary hypoplasia will have a planned delivery in a specialty hospital such as (in the United States) a tertiary referral hospital with a level 3 neonatal intensive-care unit. The baby may require immediate advanced resuscitation and therapy.

Early delivery may be required in order to rescue the fetus from an underlying condition that is causing pulmonary hypoplasia. However, pulmonary hypoplasia increases the risks associated with preterm birth, because once delivered the baby requires adequate lung capacity to sustain life. The decision whether to deliver early includes a careful assessment of the extent to which delaying delivery may increase or decrease the pulmonary hypoplasia. It is a choice between expectant management and active management. An example is congenital cystic adenomatoid malformation with hydrops; impending heart failure may require a preterm delivery. Severe oligohydramnios of early onset and long duration, as can occur with early preterm rupture of membranes, can cause increasingly severe PH; if delivery is postponed by many weeks, PH can become so severe that it results in neonatal death.

After delivery, most affected babies will require supplemental oxygen. Some severely affected babies may be saved with extracorporeal membrane oxygenation (ECMO). Not all specialty hospitals have ECMO, and ECMO is considered the therapy of last resort for pulmonary insufficiency. An alternative to ECMO is high-frequency oscillatory ventilation.

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 .

Severely premature infants may have underdeveloped lungs because they are not yet producing their own surfactant. This can lead directly to respiratory distress syndrome, also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, a steroid that crosses the placental barrier and stimulates the production of surfactant in the lungs of the baby. Steroid use up to 37 weeks is also recommended by the American Congress of Obstetricians and Gynecologists. Typical glucocorticoids that would be administered in this context are betamethasone or dexamethasone, often when the pregnancy has reached viability at 23 weeks.

In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There are still some concerns about the efficacy and side-effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk. A 2015 Cochrane review supports the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course.

Beside reducing respiratory distress, other neonatal complications are reduced by the use of glucocorticosteroids, namely intraventricular bleeding, necrotising enterocolitis, and patent ductus arteriosus. A single course of antenatal corticosteroids could be considered routine for preterm delivery, but there are some concerns about applicability of this recommendation to low-resource settings with high rates of infections. It remains unclear whether one corticosteroid (or one particular regimen) has advantages over another.

Concerns about adverse effects of prenatal corticosteroids include increased risk for maternal infection, difficulty with diabetic control, and possible long-term effects on neurodevelopmental outcomes for the infants. There is ongoing discussion about when steroids should be given (i.e. only antenatally or postnatally too) and for how long (i.e. single course or repeated administration). Despite these unknowns, there is a consensus that the benefits of a single course of prenatal glucocorticosteroids vastly outweigh the potential risks.

A number of medications may be useful to delay delivery including: NSAIDs, calcium channel blockers, beta mimetics, and atosiban. Tocolysis rarely delays delivery beyond 24–48 hours. This delay however may be sufficient to allow the pregnant woman to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids to reduce neonatal organ immaturity. Meta-analyses indicate that calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days, and β2-agonist drugs delay by 48 hours but carry more side effects. Magnesium sulfate does not appear to be useful and may be harmful when used for this purpose.

Treatment of infants suffering birth asphyxia by lowering the core body temperature is now known to be an effective therapy to reduce mortality and improve neurological outcome in survivors, and hypothermia therapy for neonatal encephalopathy begun within 6 hours of birth significantly increases the chance of normal survival in affected infants.

There has long been a debate over whether newborn infants with birth asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.

Treatment of CAP in children depends on the child's age and the severity of illness. Children under five are not usually treated for atypical bacteria. If hospitalization is not required, a seven-day course of amoxicillin is often prescribed, with co-trimaxazole an alternative when there is allergy to penicillins. Further studies are needed to confirm the efficacy of newer antibiotics. With the increase in drug-resistant Streptococcus pneumoniae, antibiotics such as cefpodoxime may become more popular. Hospitalized children receive intravenous ampicillin, ceftriaxone or cefotaxime, and a recent study found that a three-day course of antibiotics seems sufficient for most mild-to-moderate CAP in children.

In 2001 the American Thoracic Society, drawing on the work of the British and Canadian Thoracic Societies, established guidelines for the management of adult CAP dividing patients into four categories based on common organisms:

- Healthy outpatients without risk factors: This group (the largest) is composed of otherwise-healthy patients without risk factors for DRSP, enteric gram-negative bacteria, "pseudomonas" or other, less-common, causes of CAP. Primary microoganisms are viruses, atypical bacteria, penicillin-sensitive "streptococcus pneumoniae" and "haemophilus influenzae". Recommended drugs are macrolide antibiotics, such as azithromycin or clarithromycin, for seven to ten days.

- Outpatients with underlying illness or risk factors: Although this group does not require hospitalization, patients have underlying health problems (such as emphysema or heart failure) or are at risk for DRSP or enteric gram-negative bacteria. They are treated with a quinolone active against "streptococcus pneumoniae" (such as levofloxacin) or a β-lactam antibiotic (such as cefpodoxime, cefuroxime, amoxicillin or amoxicillin/clavulanic acid) and a macrolide antibiotic, such as azithromycin or clarithromycin, for seven to ten days.

- Hospitalized patients without risk for "pseudomonas": This group requires intravenous antibiotics, with a quinolone active against "streptococcus pneumoniae" (such as levofloxacin), a β-lactam antibiotic (such as cefotaxime, ceftriaxone, ampicillin/sulbactam or high-dose ampicillin plus a macrolide antibiotic (such as azithromycin or clarithromycin) for seven to ten days.

- Intensive-care patients at risk for "pseudomonas aeruginosa": These patients require antibiotics targeting this difficult-to-eradicate bacterium. One regimen is an intravenous antipseudomonal beta-lactam such as cefepime, imipenem, meropenem or piperacillin/tazobactam, plus an IV antipseudomonal fluoroquinolone such as levofloxacin. Another is an IV antipseudomonal beta-lactam such as cefepime, imipenem, meropenem or piperacillin/tazobactam, plus an aminoglycoside such as gentamicin or tobramycin, plus a macrolide (such as azithromycin) or a nonpseudomonal fluoroquinolone such as ciprofloxacin.

For mild-to-moderate CAP, shorter courses of antibiotics (3–7 days) seem to be sufficient.

Some patients with CAP will be at increased risk of death despite antimicrobial treatment. A key reason for this is the host's exaggerated inflammatory response. On one hand it is required to control the infection but on the other, it leads to bystander tissue damage. As a consequence of this recent research focuses on immunomodulatory therapy that can modulate the immune response to reduce injury to the lung and other affected organs such as the heart. Although the evidence for these agents has not resulted in their routine use, there potential benefits are highly promising.

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.

Although the etiology is unconfirmed, transient hyperammonemia is known to be caused by increased levels of ammonia in the blood stream, as well as a failure of the urea cycle to convert enough of the ammonia into urea. Since transamination of proteins is a leading producer of ammonia, protein restriction may be recommended as a therapy to reduce the symptoms of the episode. THAN can also be treated by avoiding amino acids in TPN or total parenteral nutrition or by giving a high caloric diet to limit catabolism of the tissues and therefore to minimize the breakdown of endogenous protein. The most common treatments are dialysis (both peritoneal and hemodialysis), sodium benzoate, and arginine. Sodium Benzoate combines with glycine to be excreted in the form of hippuric acid. The goal of these treatments is to convert nitrogen to a compound that can be excreted more easily.

Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, "Escherichia coli", and "Listeria monocytogenes" (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as "Streptococcus pneumoniae" and "Neisseria meningitidis". Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving survival.

Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was "Lactobacillus plantarum".

A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.

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.

The mortality rate for THAN is relatively high unless immediate treatment is obtained. The duration of hyperammonemia is directly correlated to morbidity as well as the associated neurological conditions. After the first hyperammonemic episode, there is no increased risk for future hyperammonemic episodes, and normal protein consumption can be continued.

Sixty percent of people with acute interstitial pneumonitis will die in the first six months of illness. The median survival is 1½ months.

However, most people who have one episode do not have a second. People who survive often recover lung function completely.