CHAPTER 27: Pulmonology

An acute, diffuse, inflammatory lung injury that leads to increased pulmonary vascular permeability, increased lung weight, diffuse alveolar damage, and hypoxemia.

Berlin definition of acute respiratory distress syndrome (ARDS)

EPIDEMIOLOGY

• Accounts for approximately 5% of hospitalized and mechanically ventilated pediatric patients

• Incidence in children varies greatly, but in the United States ranges between 2.9 and 9.5 cases/100,000 children per year

• Mortality depends on age, etiology, pre-morbid conditions, and severity of oxygenation deficit:

  • ✓ Mortality rate in children ranges between 22 and 35%

ETIOLOGY

• Most common etiology: Sepsis

• Others include systemic inflammatory response syndrome (SIRS), pneumonia, aspiration, smoke inhalation, trauma, drowning, pancreatitis, and massive blood transfusions

• Risk of developing ARDS is higher in adults with a history of alcoholism and obesity

PATHOPHYSIOLOGY

• ARDS follows a predictable progression of histologic and clinical stages:

  • ✓ Exudative stage: Release of proinflammatory cytokines and influx of neutrophils lead to epithelial and endothelial injury, noncardiogenic pulmonary edema, impaired gas exchange, surfactant deficiency/deactivation, and diffuse alveolar damage

  • ✓ Proliferative stage: Proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of collagen

  • ✓ Fibrotic stage: Obliteration of normal lung architecture, diffuse fibrosis, collagen deposition

CLINICAL MANIFESTATIONS

• The initial presentation can include cyanosis, dyspnea, tachypnea, and diffuse crackles

DIAGNOSTICS

• Arterial blood gas: Profound hypoxemia, usually refractory to supplemental oxygen administration; elevated alveolar-arterial oxygen gradient. Calculate PaO₂/FiO₂ to determine severity of ARDS. Initially the PCO₂ is low because of hyperventilation, but later on there is CO₂ retention

• Indicators of end-organ damage and multiorgan failure: Follow liver enzyme levels, coagulation studies, cardiac enzymes

• Chest radiograph: Diffuse bilateral alveolar infiltrates

• Chest CT scan: Bilateral patchy airspace opacities in dependent areas of lung

• Expected changes in lung function and mechanics: Decreased total lung capacity, decreased functional residual capacity (FRC), large intrapulmonary shunt fraction (Q_S/Q_T), decreased pulmonary compliance

MANAGEMENT

Management involves supportive ventilation and correction of underlying causes while treating comorbidities and limiting complications.

• Ventilation: Goal is to achieve adequate (not necessarily normal) alveolar gas exchange while limiting complications by using low tidal volume to avoid alveolar overdistention, low FiO₂ to reduce oxidant injury, and high positive end-expiratory pressure (PEEP) to limit barotrauma and maximize lung recruitment:

  • ✓ Minimize tidal volume: Goal 4–8 mL/kg

  • ✓ Permissive hypercapnia: Smaller tidal volumes result in hypoventilation, therefore an elevation of PaCO₂

  • ✓ PEEP: 5–15cm H₂O to prevent or reverse atelectasis

  • ✓ Limit inflating (plateau) pressure (e.g, after an inspiratory hold) to less than 30cm H₂O if possible

  • ✓ Goal SpO₂ 88–95%; attempt to use “nontoxic” FiO₂ of less than 60% to keep PaO₂ greater than 60 mm Hg

  • ✓ Goal pH 7.25–7.40

• Adjunctive therapies have not been proven to reduce mortality but include high-frequency oscillation, inverse inspiratory-to-expiratory ratio ventilation; pressure-regulated volume control (PRVC) ventilation; airway pressure release ventilation (APRV); prone positioning; nitric oxide; exogenous surfactant administration; extracorporeal membrane oxygenation

• Supportive treatment:

  • ✓ Limited fluid resuscitation ensures adequate tissue perfusion while limiting alveolar edema. Measures to decrease oxygen demand are helpful

  • ✓ Inotropic support; blood transfusion if necessary; diuretics; sedation; paralysis if necessary; antipyretics

• Experimental therapies: Liquid ventilation, dietary antioxidant therapy, granulocyte–monocyte colony stimulating factor, statins, macrolide antibiotics, beta-agonists, steroids

• Manage comorbidities: Renal failure, cardiac failure, hepatic failure, CNS failure, disordered coagulation

• Manage complications: Ventilator-associated pneumonia, barotrauma, bacterial tracheitis, sepsis, SIRS, chronic respiratory failure, generalized deconditioning, critical illness neuropathy, central line infections, central line thrombosis, decubitus ulcer formation

An autosomal recessive defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on the long arm of chromosome 7. Abnormal transport of chloride and sodium across an epithelium results in viscid mucus secretions and elevated sweat chloride levels. Progressive chronic pulmonary disease and exocrine pancreatic insufficiency are the primary clinical manifestations.

EPIDEMIOLOGY

• Carrier frequency in certain white populations as high as 1 in 25

• More than 1900 mutations of the CFTR gene have been identified to date

• F508del-CFTR is the most common mutation in the Northern European-white population and accounts for approximately 70% of CFTR mutations in the United States

PATHOPHYSIOLOGY

• Failure of epithelial cells to conduct chloride and the associated water transport abnormalities result in tenacious secretions in the respiratory tract, pancreas, gastrointestinal tract, liver/gallbladder, and genitourinary tracts

• Decreased clearance of viscid secretions causes obstruction of progressively larger airways starting with bronchioles

• Chronic airway inflammation and bacterial colonization damage airways. This progresses to bronchiectasis, bronchiectatic cysts, and emphysematous bullae. Loss of normal airway architecture causes secondary obstructive changes with air trapping and hyperinflation

• Long-term treatment goals aim to minimize lung damage and to maintain normal lung function as long as possible, and treatment of acute pulmonary exacerbations are directed at restoring lung function to pre-illness baseline

CLINICAL MANIFESTATIONS

Respiratory Tract

• Cough is the most consistent symptom

• Infants and young children: Tachypnea, chronic or recurrent episodes of wheezing, respiratory distress with crackles and wheeze, and/or nonproductive cough; recurrent lower respiratory tract infections; respiratory cultures grow E. coli, Klebsiella pneumoniae, Staphylococcus aureus, or Haemophilus influenzae

• Older children and adolescents: Progressive respiratory symptoms including mucopurulent cough worse in morning and with activity, exercise intolerance, recurrent wheezing, and hemoptysis (occasionally massive). Physical exam findings include increased anteroposterior chest diameter, thoracic hyperresonance, persistent crackles, wheezing, and digital clubbing. Respiratory cultures usually grow Pseudomonas aeruginosa

• Progressive lung pathology includes bronchiectasis, atelectasis, fibrosis, and occasionally pneumothorax. Right heart failure is usually a late consequence of chronic hypoxemia but can present secondary to acute respiratory failure

• Pansinusitis is common and chronic; acute sinusitis is less common

• Nasal polyps can be a presenting finding

• Allergic bronchopulmonary aspergillosis (ABPA) can occur:

  • ✓ Obstructive symptoms and fall in lung function tests that do not respond to aggressive antibiotic and airway clearance therapies. Major diagnostic features include:

    • ▪ Immediate skin test reactivity to Aspergillus antigens

    • ▪ Precipitating serum antibodies to Aspergillus fumigatus

    • ▪ Elevated serum total IgE concentration (>1000 ng/mL)

    • ▪ Peripheral blood eosinophilia >500/mm³

    • ▪ Elevated specific serum IgE and IgG to Aspergillus fumigatus

    • ▪ Chest radiograph demonstrates fleeting pulmonary infiltrates while chest CT imaging usually demonstrates central bronchiectasis

  • ✓ Treatment for ABPA consists of a prolonged course of systemic corticosteroids and an antifungal agent

• Colonization with select genomovars of Burkholderia cepacia correlates with more rapid disease progression

Gastrointestinal Tract

• Obstructive symptoms due to paucity of intestinal water and large malabsorptive stools: 15% of CF newborns present with no passage of stool in the first 24–48 hours of life, abdominal distention, bilious emesis, and meconium ileus. Infants can present with rectal prolapse in association with straining. Children and adolescents can present with constipation, emesis, abdominal distention, and abdominal pain; the constellation of symptoms is referred to as distal intestinal obstruction syndrome (DIOS)

• Pancreatic insufficiency: Most (90%) patients with CF have pancreatic insufficiency and suffer from intestinal malabsorption with associated fat-soluble vitamin (A, D, E, K) deficiencies. Recurrent pancreatitis can occur

• About 20% of adolescents and 40–50% of adults patients develop CF-related diabetes which shares features of both Type I and II diabetes

• Biliary tract: Persistent neonatal direct hyperbilirubinemia, obstructive biliary cirrhosis

• Failure to thrive

• Physical exam: Rectal prolapse, protuberant abdomen, decreased muscle mass, delayed Tanner staging, right lower quadrant stool mass, hepatosplenomegaly

Genitourinary

• Average delay in sexual maturity of 2 years

• Males: Atretic epididymis, vas deferens and seminal vesicles secondary to failure of Wolffian development and inspissation of secretions; obstructive azoospermia and infertility; normal sexual function; higher incidence of anatomic defects including hernia and undescended testes

• Females: Increased rate of secondary amenorrhea with pulmonary exacerbations; tenacious cervical mucus leads to increased risk of cervicitis, but does not reduce fertility; pregnancy tolerance is correlated with lung function

Metabolic Abnormalities

• Higher risk for acute salt and volume depletion with gastroenteritis or dehydration (hyponatremic dehydration) and chronic hypochloremic metabolic alkalosis due to increased losses of sodium and chloride in sweat

• History of “tasting salty” or salt crystallization on forehead

DIAGNOSTICS

Both history/physical findings AND laboratory confirmation are required to make the diagnosis of CF (Table 27-1)

• Tests for abnormal CFTR are used to confirm a diagnosis in a patient with one or more clinical features consistent with the CF phenotype, a history of CF in a sibling, and/or a positive newborn screen

  • ✓ Sweat test (by pilocarpine iontophoresis): Sweat chloride concentration of >60 mmol/L on two separate occasions with adequate amounts (>100 mg) of sweat collected; values of 40–60 mmol/L are considered borderline and the test must be repeated

  • ✓ Identification of two CF mutations: Finding two CFTR mutations in association with clinical symptoms is diagnostic, but negative results on genotype analyses do not exclude the diagnosis

  • ✓ Nasal potential difference measurements

• Tests suggesting CF (these supporting findings need confirmation with a diagnostic test)

  • ✓ Positive newborn screen: Blood test for immunoreactive trypsinogen

  • ✓ Elevated fat content in 72-hour stool collection

  • ✓ Low Vitamin D, A, and E levels

  • ✓ Prolonged prothrombin time and elevated Proteins Induced by Vitamin K Absence (PIVKA)

  • ✓ Semen analysis: Obstructive azoospermia

  • ✓ Ultrasound finding of congenital bilateral absence of the vasa deferentia

  • ✓ Bronchoalveolar lavage fluid positive for Pseudomonas aeruginosa

  • ✓ Sputum microbiology positive for S. aureus or P. aeruginosa, especially the mucoid form

• Data used to follow clinical course

  • ✓ Chest radiograph: Hyperinflation, atelectasis, and peribronchial thickening are initial findings. Advanced findings include bowed sternum, cyst or nodule formation, extensive bronchiectasis, dilated pulmonary artery, pneumothorax, and scarring

  • ✓ Chest CT: Not recommended for routine monitoring of disease status and progression, but can be considered if patient is not responding to appropriate therapy

  • ✓ Sinus CT: Pan-opacification + failure of frontal sinus development

  • ✓ Pulmonary function testing: Initially can be normal. Early changes indicate an obstructive pattern whereas advanced disease displays a combined obstructive and restrictive pattern due to fibrosis or marked air trapping. A decrease of 10% or more from baseline FEV1 may prompt hospital admission

• Laboratory evaluation during an acute exacerbation:

  • ✓ Fluid balance, renal function, liver enzymes, glucose, magnesium (especially in patients with a history of frequent IV aminoglycoside use)

  • ✓ Complete blood cell count with differential

  • ✓ PT/international normalized ratio, PIVKA to rule out coagulation disorder secondary to vitamin K deficiency

  • ✓ Aminoglycoside levels (after institution of therapy)

  • ✓ Serum total IgE level if history of or concern for ABPA

  • ✓ Consider vitamin and mineral levels (A, E, zinc, D-25OH)

  • ✓ HgbA1c if signs or history of diabetes mellitus

  • ✓ Obtain sputum culture, cough swab, or deep throat culture before starting antibiotics. Repeat sputum cultures on day 7 of admission

  • ✓ Urinalysis to look for glucosuria, hematuria, proteinuria, and hypercalciuria

Miscellaneous Diagnostics

• DEXA (bone density scan)

  All patients over 18 years of age should have a DEXA scan and it should be repeated every 1–5 years depending on results

  • ✓ Obtain a DEXA if patient is >8 years of age and has any of the following:

    • ▪ Ideal body weight <90%

    • ▪ Body Mass Index <50%

    • ▪ FEV1 <50% predicted

    • ▪ Glucocorticoid use of ≥5 mg/day for ≥90 days/year

    • ▪ Delayed puberty

• Audiology exam (especially in those exposed frequently to aminoglycosides)

MANAGEMENT

Respiratory Management of Pulmonary Exacerbation

• Antibiotics: Empiric parenteral administration of two antipseudomonal antibiotics for 14–21 days (e.g., aminoglycoside and beta-lactam antibiotic such as tobramycin + imipenem, ticarcillin-clavulanate, or piperacillin-tazobactam). Specific therapy should be based on the identification and susceptibility testing of bacteria isolated from sputum

  • ✓ Administration of chronic aerosolized antibiotics (e.g., tobramycin, aztreonam, colistin) deliver high concentrations of medication directly to the site of infection and can reduce exacerbations, improve lung function and quality of life

  • ✓ Sputum culture should be obtained ideally at every visit, but at least quarterly, along with pulmonary function tests when the patient is able to perform them

• Non-pharmacologic secretion clearance alternatives:

  • ✓ Chest physiotherapy with postural drainage

  • ✓ High-frequency chest wall oscillation with an inflatable vest or airway oscillator

  • ✓ Intrapulmonary percussive ventilation

  • ✓ Positive expiratory pressure (PEP) device

  • ✓ Autogenic drainage, directed breathing techniques

• Pharmacologic secretion clearance:

  • ✓ Inhaled hypertonic saline can reduce the viscoelasticity of sputum

  • ✓ Inhaled human recombinant DNase can reduce the viscoelasticity of infected sputum

  • ✓ Bronchodilator therapy (beta-2-agonist) can increase ciliary beat frequency, and is also used if there is a history of airway hyperreactivity

• Anti-inflammatory therapy:

  • ✓ Azithromycin is used chronically for its anti-inflammatory effects to improve lung function and reduce number of exacerbations

  • ✓ Inhaled corticosteroids are only added when there is a concomitant history of asthma

  • ✓ Ibuprofen can be used as a chronic anti-inflammatory agent in children 6–17 years of age with FEV1 ≥60% predicted, and serum levels should be maintained 50–100 mg/mL

• CFTR targeted therapy:

  • ✓ Ivacaftor is a potentiator that activates defective CFTR at the cell surface. It is recommended for individuals with at least one G551D CFTR mutation to improve lung function and quality of life and reduce exacerbations. It also reduces sweat chloride concentrations to near normal levels

  • ✓ Combination therapy with ivacaftor/lumacaftor is approved for all patients who are homozygous for the F508del mutation, which constitutes nearly half of the CF population in the US. Lumacaftor is thought to improve CFTR protein folding and improve trafficking to the cell surface membrane. The combination therapy has been shown to improve FEV1 by up to 4% and more impressively, to reduce the rate of pulmonary exacerbations by nearly 40%

Nutritional Management

• Diet: Most patients have increased caloric needs. Children and adolescents require a high calorie, high protein, and extra salt diet

  • ✓ Oral glucose tolerance test should be done annually after 8 years of age to screen for Cystic Fibrosis-related diabetes (CF-RD)

• Pancreatic exocrine enzyme replacement

  • ✓ Doses should not exceed 2500 lipase units/kg/meal or 10,000 lipase units/kg/day to avoid fibrosing colonopathy and colonic strictures

• Vitamins A, D, E, and K in doses used for malabsorption

The expectoration of blood or blood-tinged sputum from the lower respiratory tract. The immediate danger is from suffocation, not from exsanguination.

• Massive or Major: >200cc in 24 hours or >100cc per day for several days

• Minor: Smaller volumes

• Life threatening: >8cc/kg/24 hour

PATHOGENESIS

The lung contains two separate blood supplies

• The pulmonary arterial circulation: High volume, low-pressure system. Its branches accompany the bronchi down to the level of the terminal bronchioles. Pulmonary vessels branch to supply the capillary bed in the walls of the alveoli and then return to the left atrium via the pulmonary veins

• The bronchial circulation: Small volume, systemic pressures. Typically there are three bronchial arteries, two that supply the left lung and one that supplies the right. These arteries usually originate from the aorta or the intercostal arteries and perfuse conducting airways approximately to the level of the terminal bronchioles

ETIOLOGY

• Minor hemoptysis: Direct mucosal injury (e.g., shearing forces dislodging mucus from airway wall, direct trauma from suction catheters)

• Massive hemoptysis: Usually from bronchial artery (high-pressure system) to pulmonary artery anastomosis

• Infection is the most common etiology of hemoptysis in children

• Bleeding from tracheostomy

• Foreign body aspiration, especially long standing

• Congenital heart disease with pulmonary vascular obstruction or enlarged collateral bronchial circulation

• Cystic fibrosis (areas of bronchiectasis and inflammation)

• Bronchiectasis

• Tuberculosis

• Nasopharyngeal bleeding (non-pulmonary source of bleeding—not true hemoptysis)

• Immune-mediated: Henoch–Schönlein purpura, granulomatosis with polyangiitis, polyarteritis nodosa, Goodpasture syndrome, systemic lupus erythematosus

• Less frequent: An infected pulmonary sequestration, pulmonary embolism, tumor, neoplasm, pulmonary arteriovenous malformation, idiopathic pulmonary hemosiderosis

DIAGNOSTICS

• Assess adequacy of ventilation

• Orthostatic pulse and blood pressure to estimate blood loss

• Chest radiograph

• CBC, PT, PTT

• If indicated: serum chemistries, BUN, creatinine, tuberculin skin test (purified protein derivative, PPD), rheumatologic markers including antinuclear antibody, double-stranded DNA, ESR, CRP, complement levels, anti-neutrophil cytoplasmic antibodies, anti-basement membrane antibodies, IgG levels

• Urinalysis

• Sputum Gram stain and culture

• Chest CT: Can help define structural abnormalities including arteriovenous malformations or masses. Spiral CT may be useful if pulmonary embolus is suspected

• Angiography in cases of severe refractory hemoptysis

• Fiberoptic bronchoscopy: Performed when bleeding is not acute to identify a source of bleeding and obtain a lavage.

  • ✓ The presence of hemosiderin-laden macrophages from bronchoalveolar lavage confirms pulmonary bleeding; they typically appear 72 hours after the event and last for several weeks

• Rigid bronchoscopy is best for acute bleeding to suction large volumes and control the airway if necessary. Allows better visualization of the airway and removal of a foreign body

• Cardiac evaluation including echocardiogram with visualization of pulmonary veins

MANAGEMENT

• Management is typically supportive except in the case of massive hemoptysis, and is otherwise directed at treating the underlying cause of bleeding

• Secure the airway and assure adequacy of ventilation; deliver increased PEEP

• Support circulating volume with crystalloid until red cell transfusion is possible

• In the case of massive hemoptysis, emergency bronchoscopy may be required. Sites of bleeding can be slowed by either balloon catheter tamponade or with the use of topical oxymetazoline, epinephrine, or cold saline

• If bleeding cannot be controlled, emergency arteriography may help to localize the area of bleeding and can allow selective embolization

Disorder of breathing during sleep characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction (obstructive apnea) that disrupts normal ventilation during sleep and normal sleep patterns.

EPIDEMIOLOGY

• Occurs at all ages, although may be more common in preschoolers

• Prevalence in school age children from 2% to 12%

ETIOLOGY

• Risk factors: Adenotonsillar hypertrophy, obesity, craniofacial anomalies, neuromuscular disorders, trisomy 21, chronic lung disease, sickle cell disease

CLINICAL MANIFESTATIONS

• Most common symptom of clinically significant OSA is snoring

• Other common manifestations: Labored breathing, restless sleep, apnea while asleep, enuresis, morning headaches, daytime sleepiness, sleeping with neck hyperextended, learning problems, attention-deficit/hyperactivity disorder

• Severe presentations: Cor pulmonale, failure to thrive, cognitive impairment

• Possible exam findings: Adenotonsillar hypertrophy, adenoidal facies, micrognathia/retrognathia, hypertension, loud pulmonary component of S2, underweight or overweight

DIAGNOSTICS

• Full polysomnography requires overnight admission to a sleep laboratory. It is the only method that quantifies ventilatory and sleep abnormalities, therefore, it is the gold standard

  • ✓ Apnea hypopnea index (AHI) <1.5 events/h is normal, >10 events/h is severe. Severe OSA is not an acute emergency

DEFINITIONS (BASED ON POLYSOMNOGRAPHIC FINDINGS)

Obstructive Apnea

• Drop in the peak signal excursion by ≥90% of the pre-event baseline using an oronasal thermal sensor

  • ✓ Lasts at least two breaths during baseline breathing

  • ✓ Respiratory effort present throughout the entire period of absent airflow

Hypopnea

• Peak signal excursions drop by ≥30% of pre-events baseline using nasal pressure

• Duration of the ≥30% drop lasts for at least two breaths

• Associated with ≥3% desaturation from pre-event baseline or the event is associated with an arousal

Central Apnea

• Drop in the peak signal excursion by ≥90% of the pre-event baseline using an oronasal thermal sensor and one of the following conditions:

  • ✓ The event lasts 20 seconds or longer

  • ✓ The event lasts at least the duration of two breaths during baseline breathing and is associated with an arousal or ≥3% oxygen desaturation

  • ✓ For infants younger than 1 year of age, the event lasts at least the duration of two breaths during baseline breathing and is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds

  • ✓ If full polysomnography is not available: Nocturnal pulse oximetry, audio or videotaping, and abbreviated polysomnography or nap sleep study can be done. These all have weaker positive and negative predictive values than full nocturnal polysomnography so a normal study does not rule out sleep disordered breathing

• Adjunctive tests: ECG to evaluate for right ventricular hypertrophy; elevated serum bicarbonate reflects chronic hypoventilation

MANAGEMENT

Acute

• Positioning: Upright, sniffing position. In the case of hypotonia or tracheomalacia, prone positioning may relieve obstruction

• Nasal airway: Use preformed nasal trumpet or trimmed down endotracheal tube (ETT). Positive pressure can be delivered through a nasopharyngeal ETT

• Antibiotics: If acute infection

• Anti-inflammatories: May acutely help reduce swelling, consider dexamethasone.

  • ✓ Intranasal corticosteroids can be used as treatment for mild OSA

• Oxymetazoline nasal spray or nebulized racemic epinephrine can diminish intranasal or extrathoracic airway obstruction

• Tracheal intubation/tracheostomy placement: Reserved for refractory cases

Chronic

• Adenotonsillectomy: First line of treatment for pediatric OSA

  • ✓ Reassess OSA signs and symptoms 6–8 weeks after surgery to determine if repeat polysomnogram indicated

• Continuous positive airway pressure: Used in patients with specific contraindications to adenotonsillectomy, minimal adenotonsillar tissue, persistent OSA after adenotonsillectomy or for those who prefer nonsurgical alternatives

• Weight loss: Improves OSA if patient is obese

Step 1: Acidemia or Alkalemia?

• Alkalemia: pH greater than 7.40

• Acidemia: pH less than 7.40

Step 2: Metabolic or Respiratory?

• Primary respiratory alkalosis: pH greater than 7.40 and PaCO₂ less than 40

• Primary metabolic alkalosis: pH greater than 7.40 and PaCO₂ greater than 40

• Primary respiratory acidosis: pH less than 7.40 and PaCO₂ greater than 40

• Primary metabolic acidosis: pH less than 7.40 and PaCO₂ less than 40

Step 3: Is the problem acute or chronic

• For respiratory acidosis/alkalosis, a 10-mm Hg change in PaCO₂ causes a 0.08 change in pH in the acute setting or a 0.03 change in the chronic setting

• For metabolic acidosis/alkalosis, a 10-mEq/L change in HCO₃ ⁻ causes a 0.15 change in pH

• For acute respiratory acidosis, expect an increase in HCO₃ ⁻ of 1 mEq/L for every increase in PaCO₂ of 10 mm Hg

• For acute respiratory alkalosis, expect a decrease in HCO₃ ⁻ of 1–3 mEq/L for every decrease in PaCO₂ of 10 mm Hg

• For chronic respiratory acidosis, expect an increase in HCO₃ ⁻ of 4 mEq/L for every increase in PaCO₂ of 10 mm Hg

• For chronic respiratory alkalosis, expect a decrease in HCO₃⁻ of 2–5 mEq/L for every decrease in PaCO₂ of 10 mm Hg

Step 4: Is there a second primary problem?

In other words, are changes in pH greater than expected from the primary disorder alone? Example: An infant with bronchopulmonary dysplasia is receiving diuretics and is hypochloremic with a pH of 7.42, PCO₂ 75, and HCO₃⁻ 34. The blood gas values reflect not only the patient’s chronic respiratory acidosis but also a second primary problem (i.e., hypochloremic metabolic alkalosis).

• A compensatory process alone never restores pH completely back to normal

• For metabolic acidosis, expect a decrease in PaCO₂ of 1–1.5 mm Hg for every decrease in HCO₃ ⁻ of 1 mEq/L

• For metabolic alkalosis, expect an increase in PaCO₂ of 0.5–1 mm Hg for every increase in HCO₃ ⁻ of 1 mEq/L

Step 5: In metabolic acidosis, calculate the anion gap.

• Normal anion gap is less than 12 mEq/L

• In normal gap metabolic acidosis, hyperchloremic acidosis results from the loss of HCO₃ in the gut or kidneys

• Anion-gap acidosis results from addition of nontitratable acid to the system. Etiologies include “MUDPILES”: Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde/Propylene glycol, Isoniazid/Iron/Infections, Lactic acidosis, Ethanol, Salicylates

Step 6: If there is an anion-gap metabolic acidosis you should consider the possibility of a second metabolic abnormality.

• This is done by calculating the delta–delta gap:

  $Δ−Δ Gap=(MeasuredAG-NormalAG)/(Normal [ HCO 3 − ]-Measured [ HCO 3 − ])$

• If Δ–Δ Gap

  • ✓ <1, there is a concurrent non-anion gap acidosis

  • ✓ =1, there is a pure anion-gap acidosis

  • ✓ >1, there is a concurrent metabolic alkalosis

  • ✓ Example: A 12-year-old with diabetic ketoacidosis has an anion gap of 22, pH of 7.2, and an HCO₃ ⁻ of 17

  • ✓ You calculate the Δ–Δ gap: (22−12)/(24−17) = 1.4. This tells you that there is a metabolic acidosis with a concurrent metabolic alkalosis (e.g., from vomiting) present

PULMONARY CAUSES OF HYPOXEMIA

• V/Q mismatch

• Hypoventilation

• Shunt

• Diffusion Block

• Low FiO₂

ALVEOLAR-ARTERIAL GRADIENT (A-a GRADIENT)

• A measure of the difference between the alveolar and arterial concentration of oxygen. It is useful in determining the cause of hypoxemia (Table 27-2)

where

PAO₂ = partial pressure of oxygen in alveoli.

PaO₂ = partial pressure of O₂ measured in arterial blood. Normally 80–100 mm Hg.

PCO₂ = partial pressure of CO₂ measured in arterial blood. Normally 35–45 mm Hg.

P_atm (atmospheric pressure: at sea level) approximately equal to 760 mm Hg, but will vary with altitude

$P H 2 O$ (water vapor pressure at 37^oC) = 47 mm Hg

R (respiratory quotient) = 0.8 under normal circumstances

Normal A-a Gradient: <10 mm Hg

A method to mechanically support/assist or replace spontaneous breathing.

• Common indications for initiating mechanical ventilation are to improve alveolar ventilation, improve arterial oxygenation, prevent or reverse atelectasis, reverse hypoxemic or hypercarbic respiratory failure, and to prevent or reverse respiratory muscle fatigue

• Most ventilators use positive pressure to augment the work of the respiratory muscles, although negative pressure devices are still occasionally used

• A ventilator can use either pressure control (PC) or volume control (VC) to assist breathing

• Pressure control: The clinician sets the desired pressure to be delivered by the ventilator. The tidal volume varies from breath to breath depending on respiratory system compliance and resistance. The inspiratory flow depends on the pressure being delivered and how quickly the peak pressure is set to be achieved. The resulting flow pattern is one of decelerating flow. Because you are able to deliver a uniform pressure over a set inspiratory time, this mode is useful in children with a large leak around a tracheostomy tube or noninvasive interface

• Volume control: The clinician sets the volume of the breath to be delivered. Inspiratory flow rate can also be set by the operator; the flow is delivered with a square wave pattern (e.g., flow is constant) to a set tidal volume (V_T), allowing the pressure to vary as the compliance and resistance of the system changes

• Breaths are classified according to what triggers (starts) or cycles (stops) inspiration. These events can be either patient or ventilator initiated. Trigger variables include time, pressure, and flow. A few ventilators can also use abdominal movement or diaphragm EMG as trigger variables, but this is less common. Cycle variables can include pressure, volume, flow, or time

• If a positive pressure breath is triggered by the patient and cycled by the patient (or by the inherent mechanical characteristics of the patient’s respiratory system as with Pressure Support) the breath is considered to be spontaneous

• If the ventilator triggers OR cycles a breath independent of the patient’s effort or mechanics, the breath is considered to be mandatory

THREE BASIC BREATH SEQUENCES OF A VENTILATOR

• Intermittent mandatory ventilation (IMV): Mandatory breaths are interspersed with breaths that are spontaneous. (This would include modes that are commonly referred to as intermittent mandatory ventilation [IMV], synchronized IMV [SIMV], SIMV with pressure support, or APRV)

• Continuous spontaneous ventilation (CSV): All breaths are spontaneous. (This would include modes like CPAP or CPAP with Pressure Support). Pressure Support (PS) is considered to be a pressure limited, flow or pressure triggered, and flow cycled spontaneous breath. The breath is supported to a preset pressure by the ventilator and terminated based on characteristics of the patient’s respiratory system. This mode enhances the patient’s native respiratory drive, reducing respiratory work while allowing the patient to determine respiratory rate as well as the length and depth of breaths. Pressure support is often used in conjunction with mandatory ventilation as a tool for weaning

• Continuous mandatory ventilation: No breaths are spontaneous. (This would include modes that are commonly referred to as Control ventilation, Assist/Control ventilation)

TYPES OF SUPPORTED VENTILATION (ALL BREATHS ARE SPONTANEOUS)

• Continuous positive airway pressure (CPAP): Supplies a constant airway pressure above atmospheric pressure during both inspiratory and expiratory phases of spontaneous ventilation. It is often used to overcome upper airway obstruction or to maintain FRC

• Bi-level positive airway pressure (BLPAP): Supplies both an inspiratory positive airway pressure (IPAP) and an expiratory positive airway pressure (EPAP). The patient triggers inspiration and cycle variables are set to end inspiration and allow exhalation. BLPAP can also be a form of assisted ventilation if a respiratory rate is set. It is often used to improve ventilation

TYPES OF MANDATORY VENTILATION (NO SPONTANEOUS BREATHS)

• High-frequency ventilation (high-frequency oscillatory ventilation [HFOV]): Delivers low tidal volume breaths (1–3 mL/kg) at very high rates (3–15Hz = 180–900 breaths per minute). HFOV settings are mean airway pressure, frequency (Hz), and amplitude or power. Indications include severe neonatal respiratory distress syndrome (RDS), ARDS, and severe air leak syndromes

TYPES OF ASSISTED VENTILATION (MIXTURE OF MANDATORY AND SPONTANEOUS BREATHS)

• Synchronized intermittent mandatory ventilation (SIMV): The most frequently used mode of ventilation in most pediatric institutions. SIMV allows spontaneous breathing between ventilator breaths that are delivered in either PC or VC mode. Mechanical breaths can be programmed to trigger with patient-initiated breaths or independent of the patient’s respiratory effort and are synchronized so as not to occur while the patient is exhaling

• Pressure-regulated volume control (PRVC): The delivered tidal volume is set by the practitioner, but the ventilator monitors both the volume delivered and the pressure used to deliver the breath. The pressure is adjusted from breath to breath to meet the targeted tidal volume. Flow is delivered with a decelerating wave form. This allows the ventilator to respond to changes in compliance and resistance in the system, thereby limiting volutrauma and barotrauma

• Airway pressure release ventilation (APRV): Allows spontaneous ventilation while maintaining mean airway pressure (MAP) with a high level of CPAP for a preset time (T high) and a “release” that intermittently drops the MAP to a lower CPAP level for a shorter period of time (T low). This is designed to open and maintain collapsed alveoli and enhance ventilation of lungs with poor compliance without excessive PIP

INITIAL VENTILATOR SETTINGS

The following should be used as a general guide: Evaluation of the patient’s response and care by physicians experienced with managing the mechanically ventilated child are critical to ensure the settings provide an appropriate level of support.

Initial settings depend on the age and indication.

• In patients with decreased lung or chest wall compliance, a short inspiratory time and higher pressure would be recommended to deliver a set V_T. Examples would include premature infants with RDS, or a child with severe interstitial lung disease

• In obstructive lung patterns where the time constant of the lung (the product of resistance and compliance) is long, a slow mandatory rate with a relatively short inspiratory time and longer expiratory time are recommended to allow adequate time for the lungs to empty before inspiration is initiated. Examples would include a child with asthma or patient with CF

Conventional Ventilation

• Mode: In order to pick one of five main modes listed below (VC-continuous mandatory ventilation, VC-IMV, PC-continuous mandatory ventilation, PCIMV, and PC-CSV), you will need to decide if breaths will be mandated, spontaneous, or a combination of the two

• Continuous mandatory ventilation in pressure control (PC-continuous mandatory ventilation) or volume control (VC-continuous mandatory ventilation)

• Intermittent mandatory ventilation in pressure control (PC-IMV) or volume control (VC-IMV)

• Continuous spontaneous ventilation in pressure control (PC-CSV)

• Mandated respiratory rate (per minute): Typical starting ventilator rates assuming minimal spontaneous respiration: 30–40 neonates, 20–30 infants, 15–20 children. If allowing for the patient to take some spontaneous breaths, begin supporting at one-half to two-thirds of the normal respiratory rate for age

• FiO₂: Set at 1.0 (or last known effective FiO₂) and wean to desired SpO₂

• Positive end-expiratory pressure (PEEP): 3–5cm H₂O is considered “physiologic” and helps to maintain FRC. Neonates with severe lung disease may require much higher levels of PEEP to treat parenchymal disease or to support collapsible airways. Older children with ARDS may require PEEP of 12–15cm H₂O to recruit surfactant-deficient lung units and prevent injury from recruitment–derecruitment cycling

• V_T: Set to 8–12 mL/kg; if low tidal volume strategy is desired begin with 4–6 mL/kg as tolerated

• T_i (inspiratory time): Neonates 0.3–0.4 seconds; infants 0.4–0.7 seconds; children 0.5–1.0 seconds. Shorter inspiratory times are favored in heterogeneous disease (e.g., ARDS, asthma)

• I/E ratio: 1:2, with longer E times in obstructive disease to prevent breath stacking and the development of dynamic hyperinflation

• Positive inspiratory pressure: In PC mode, set PC to achieve adequate chest wall movement and desired tidal volume

High-Frequency Ventilation

• Frequency: Set at 10–15Hz in neonates; may need 5–7 in severe ARDS

• Mean airway pressure (MAP): Set 1–4cm H₂O higher than that needed on conventional ventilation. Wean slowly once recruitment established

• Amplitude: Set to level with best chest wall movement

ADJUSTING VENTILATOR SETTINGS

Ventilator settings are manipulated in order to minimize iatrogenic injury while providing adequate ventilation and oxygenation to support cellular function (Table 27-3).

• Conventional ventilation: To increase CO₂ exchange, increase either RR or V_T. To increase oxygenation, increase MAP or FiO₂. MAP increase can be achieved by increasing PEEP, PIP, or inspiratory time

• High-frequency ventilation: To increase CO₂ exchange, increase amplitude or decrease frequency. Increase oxygenation by increasing FiO₂ or MAP

WEANING VENTILATION

The most common weaning modes are SIMV, PSV, and T-piece trials.

• Weaning with SIMV: Gradually wean rate of ventilator as the rate of spontaneous breaths increases. Once all breaths are spontaneous, consider supporting each breath to allow adequate oxygenation and ventilation. This method may increase the metabolic cost of breathing for the patient during the weaning process

• Weaning with PSV (two options):

  • ✓ Using SIMV mode with PSV, initiate short trials of only PSV, gradually lengthening the time off SIMV until the patient is maintained only on minimal PSV

  • ✓ Place patient on full PSV mode to produce a fully supported tidal volume. Gradually wean down the PSV until the patient is minimally supported. If tolerated, wean off support

INDICATORS OF READINESS TO WEAN

Negative inspiratory force (NIF): Measures maximum negative deflection during inspiration after occlusion of airway. Used to assess adequacy of spontaneous breaths. A NIF less than −15 cm H₂O in an adult has 97% sensitivity for weaning failure. There is, however, poor positive predictive value for this test in children.

• Measured vital capacity: Adequate vital capacity is 10–15 mL/kg

• Spontaneous tidal volume: At least 4 mL/kg

• Able to maintain PaO₂ greater than 60 mm Hg in FiO₂ less than 0.35

• Respiratory rate: Physiologic (lack of rapid shallow breathing); in adults, a respiratory frequency/tidal volume (in liters) ratio <105 during a spontaneous breathing (T-piece) trial is associated with weaning success (rapid shallow breathing index)

• Rapid shallow breathing index (RSBI): RSBI adapted for children (see formula listed below) of 8 or less has both a sensitivity and specificity of 74% in predicting successful extubation in some studies. In children, RSBI occasionally used in clinical practice

Pulmonary function tests (PFTs) are used to diagnose, assess severity, and assess response to therapy in pulmonary disease. To assess reversible airway obstruction or bronchodilator responsiveness, the patient is given an inhaled bronchodilator and the test is repeated. Histamine, methacholine, exercise, isocapneic cold dry air, and hypertonic or hypotonic aerosol challenges may also help assess airway reactivity.

SPIROMETRY

• Forced vital capacity (FVC): Volume that can be maximally forcefully exhaled after a complete inspiration

• FEV1: Volume of air that is forcefully exhaled in the first second following a complete inspiration

• FEV1/FVC: Ratio of FEV1 to FVC, expressed as a percentage

• FEV 25–75: Average forced expiratory flow over the mid portion of the FVC

• Peak expiratory flow (PEF): Peak expiratory flow rate during forced exhalation

LUNG VOLUMES (FIGURE 27-1)

A volume is the amount that describes a compartment of the lung; when two or more volumes are added together, the new amount is called a capacity. All volumes except the residual volume (RV) can be measured by spirometry; any capacity that includes the RV requires specialized equipment for its measurement.

• Expiratory Reserve Volume (ERV): Volume that can still be exhaled following normal exhalation

• Functional residual capacity (FRC): Volume remaining in the lungs at the end of normal exhalation (RV + ERV)

• Inspiratory capacity (IC): Volume in the lungs at full inspiration (IRV + V_T)

• Inspiratory reserve volume (IRV): Volume that can still be inhaled after normal inspiration

• Residual volume (RV): Volume remaining in the lungs after maximal expiration (FRC-ERV, or TLC-VC)

• Tidal volume (V _T): Volume inhaled and exhaled during normal breathing

• Total lung capacity (TLC): Total volume of gas in the lungs at full inspiration (VC + RV, or IC + FRC, or IRV + V_T + ERV + RV)

• Vital capacity (VC): Maximal volume that can be expired from a full inspiration (IRV + TV + ERV; TLC-RV)

EQUIPMENT COMMONLY USED TO MEASURE LUNG FUNCTION

• Body plethysmograph: Apparatus for measurement of FRC, RV, TLC, and airway resistance. Fractional lung volumes can also be measured with dilution techniques using helium or nitrogen

• Spirometer: Apparatus for measuring lung volumes (except RV) and flow rates. Spirometry is used to plot a volume–time curve and a flow–volume loop

ANTHROPOMETRIC MEASUREMENTS AFFECTING LUNG FUNCTION

• Height: Taller individuals have larger lung volumes and airways

• Age: Lung volumes change with increasing age in the pediatric population; RV and FRC increase, ERV decreases

• Sex: Males have larger lung volumes than females

• Ethnicity: TLC is generally lower in African Americans when compared to Caucasians because African Americans have smaller upper-to-lower body segment ratios

OBSTRUCTIVE LUNG DISEASE

Obstruction to airflow during expiration leads to gas trapping, increased RV, decreased, increased, or normal VC, and increased to normal TLC (Figure 27-1). Common causes include asthma, bronchiolitis, chronic bronchitis, CF, and bronchiectasis. Spirometry demonstrates a low FEV1 (<80% predicted), low FVC (<80% predicted), low FEV1/FVC (<75% predicted), decreased FEF 25–75, and an expiratory flow–volume curve that is concave to the volume axis (Figure 27-2B).

• Small airway obstruction is represented by low FEV 25–75

• Significant response to bronchodilators defined as >12% increase in the FEV1 and/or FVC

• Methacholine challenge that results in a decrease in FEV1 20% or greater from baseline at a dose less than 16 mg/dL, or exercise or cold dry air challenge that results in 15% or greater decrease in FEV1 from baseline are used to diagnose airway hyperreactivity

RESTRICTIVE LUNG DISEASE

Restrictive lung diseases cause reductions in lung volumes due to decreased lung compliance, decreased chest wall compliance, or muscle weakness. Etiologies include interstitial lung disease, neuromuscular diseases, and chest wall or spine abnormalities. TLC is decreased whereas flow rates are proportionally normal or slightly increased. Spirometry reveals a low FEV1 (<80% predicted), low FVC (<80% predicted), normal FEV1/FVC ratio, and “miniaturized” appearance to flow–volume curve (Figure 27-2C).

VARIABLE EXTRATHORACIC OBSTRUCTION

During inhalation, narrowing of the extrathoracic airway accentuates any obstruction, and airflow through the narrowed portion of the extrathoracic airway decreases. This results in flattening of the inspiratory flow–volume loop (Figure 27-2D). If the narrowing is not present during exhalation, the expiratory flow–volume curve is normal. Spirometry reveals a normal FVC and FEV1, but the ratio of forced expiratory to inspiratory flow at 50% of vital capacity (FEF50/FIF50) is usually greater than 1. Etiologies include vocal cord dysfunction or vocal cord paralysis.

FIXED AIRWAY OBSTRUCTION

There is no change in the caliber of the airway with a fixed intrathoracic or extrathoracic obstruction during the entire respiratory cycle. As a result, airflow limitation through the obstruction is independent of the phase of respiration and results in flattening of both inspiratory and expiratory flow–volume loops (Figure 27-2E). Etiologies include tumors, tracheal or subglottic stenosis, and foreign bodies in the airway.