Respiratory disorders

Epidemiology

Asthma is the leading childhood illness in industrialized countries and is a major cause of childhood hospitalization and intensive care unit (ICU) admission ( ). About 13% of children in the United States are thought to have asthma (7 million), and the prevalence continues to increase ( ; ). Nearly half of the children diagnosed with asthma have one or more exacerbations per year, resulting in approximately 600,000 emergency room visits ( ). Those disproportionately affected include minority children, particularly African Americans and Puerto Ricans, males (though females have a higher asthma exacerbation rate), those of lower socioeconomic status, and urban dwellers ( ; ; ; ; ). The social costs of this disease are profound: over one-third of asthmatic children suffer noticeable disability ( ; Sawicki and Haver 2015), 10.5 million school days are missed each year (Lipstein et al. 2009), and parental work absenteeism is correspondingly high. Relative to adults, mortality rates in children are low and decreasing, approaching 0.3 deaths per 10,000 ( ).

Pathophysiology

Central to the pathogenesis of asthma is chronic airway inflammation that results in increased bronchial reactivity, airway edema, and airway remodeling. Mediating this process are neutrophils and the components of the allergic response: immunoglobulin E, mast cells, eosinophils, and activated T helper cells ( ). In susceptible patients, exposure to an environmental allergen leads to a cascade of changes resulting in the activation of antibodies, release of inflammatory mediators, and the persistence of inflammation. Acute effects include bronchospasm and edema, and as additional inflammatory cells are recruited to the lungs, chronic changes consistent with ongoing inflammation, airway obstruction, and bronchial hyperresponsiveness develop ( ).

Asthma in children is thus perceived as an allergic disease. Multiple hypotheses have been put forth to explain the inception and progression of asthma, as there is a complex relationship between individuals and their response to the environment ( ; ; ; ). Genetic predisposition toward an allergic response, or atopy, as well as exposure to particular allergens and viral respiratory infections, creates the conditions necessary for this disease ( ; ). There are three main groups of allergen sensitization: pollen, dust mite, and animal/food allergens. Sensitization to the animal/food group is most strongly associated with the development of asthma ( ).

Diagnosis

Episodic airflow obstruction and bronchial hyperreactivity manifest clinically as recurrent cough, wheeze, or chest tightness. When present at night or on exposure to particular environmental triggers, these symptoms are highly suggestive of asthma ( ; Table 47.1 ).

A thorough history and examination are imperative to correct diagnosis, as other disease processes or anatomic abnormalities can also produce cough or wheezing. Of note, because of the variability in asthma, younger children may present with persistent cough as their only symptom. Physical examination may reveal chest hyperexpansion, retractions, and increased exhalation time. Wheeze may only be heard during forced exhalation. If prone to allergies, the child with asthma may also have increased nasal secretions, mucosal swelling, nasal polyps, atopic dermatitis, or eczema. Patients with a history of prematurity, low birth weight, and obesity may be at increased risk ( ).

Although all of these factors can point toward a diagnosis of asthma, spirometry is necessary to confirm the disease’s presence. The ability to at least partially reverse the airflow obstruction observed is a defining feature of asthma and is assessed by measuring lung volumes before and after inhalation of a short-acting beta-2 agonist. Typical measurements by spirometry will be forced expiratory volume in 1 second (FEV ₁ ), forced expiratory volume in 6 seconds (FEV ₆ ), forced vital capacity (FVC), and FEV ₁ /FVC.

Classification of asthma severity and control

An asthma severity classification was developed in 2007 by the National Heart, Lung, and Blood Institute to assist physicians in initiating appropriate therapy for patients newly diagnosed with asthma ( Table 47.2 ). This classification describes asthmatic severity as either intermittent or persistent, with those having persistent asthma further subdivided into mild persistent, moderate persistent, or severe persistent. Severity is determined by a combination of functional impairment and exacerbation risk. Functional impairment is defined by the patient’s frequency of symptoms, activity intolerance, and in older children, spirometry over the preceding 2 to 4 weeks. Risk of exacerbation is determined by the frequency of wheezing episodes over a defined period and the number of exacerbations requiring oral/IV corticosteroid treatment. Classification of asthma severity is dictated by the highest risk or impairment category. For those children already receiving medical management, asthma severity can be inferred by assessing the minimum regimen of medications necessary to achieve symptom control.

The decision to escalate or de-escalate therapy is based on the patient’s level of asthma control ( Table 47.3 ). Asthma control, like severity, is determined by the individual’s functional impairment and risk of exacerbation and is described as well controlled, not well controlled, or very poorly controlled. A step-up or step-down approach is used to adjust medication therapy such that the minimal drugs and doses necessary to achieve adequate control are used ( Table 47.e1 ).

Pharmacologic therapy

Medications used in the treatment of asthma can be divided into those that provide immediate symptom relief and those that offer long-term control ( ; ). Quick-relief therapy focuses on minimizing the dyspnea, tachypnea, and cough that accompany acute episodes of airflow obstruction; long-acting therapy attempts to address the inflammatory process that underlies asthma. Not all patients require both classes of drugs. Those who are well controlled and at minimal risk of exacerbation may only need quick-relief therapy, whereas those with more severe or poorly controlled asthma may require multiple long-term control agents.

Quick-relief medications include inhaled anticholinergics and short-acting beta agonists (SABAs). Anticholinergics reduce the intrinsic vagal tone of the airways and cause bronchodilation through blocking muscarinic cholinergic receptors. Although not the treatment of choice to relieve mild acute asthmatic symptoms, anticholinergics like ipratropium bromide provide a benefit in moderate to severe exacerbations, particularly when combined with SABAs ( ; ; ).

The most commonly used SABA is albuterol. Albuterol is a racemic mixture of two enantiomers: (R)-albuterol, which binds beta-2-adrenergic receptors leading to bronchodilation, and (S)-albuterol, which is thought to have a detrimental effect on lung function ( ). Levalbuterol, another SABA, is a purified form of albuterol containing only the (R)-enantiomer. Though marketed as an alternative to albuterol with fewer side effects, data demonstrating the superiority of levalbuterol to albuterol have been mixed ( ; ; ). Consideration may be given to the use of levalbuterol, nonetheless, in children in whom tachycardia may be deleterious or for those requiring frequent SABAs in spite of maximal therapy.

Inhaled corticosteroids (ICSs) form the basis of long-term asthma therapy ( ). Their anti-inflammatory effect reduces airway hyperresponsiveness, inhibits inflammatory cell migration and activation, and blocks late-phase reactions to allergens. As such, they are used in all categories of persistent asthma, with dosing adjusted to meet the patient’s severity. Other long-term therapies include long-acting beta agonists (LABAs), leukotriene modifiers, cromolyn sodium, theophylline, and immunomodulators ( ). LABAs are often added as an adjunct to ICS therapy in children with moderate or severe persistent asthma; their duration of action after a single dose is at least 12 hours. Both cromolyn sodium and the leukotriene modifiers act to temper the inflammatory response to an allergen; cromolyn sodium stabilizes mast cells, whereas leukotriene modifiers inhibit the end effects of leukotrienes. Acting more upstream is the immunomodulator omalizumab ( ). Omalizumab is an anti–immunoglobulin E (IgE) monoclonal antibody that prevents the binding of IgE to basophils and mast cells, thereby preventing the release of leukotrienes, histamine, and cytokines that provoke bronchospasm, edema, and continued inflammation. This drug is reserved for patients older than 12 years of age who have severe persistent asthma.

Preoperative evaluation

The variable nature of asthma underscores the importance of a thorough preoperative assessment ( Table 47.4 ). Patients who may be currently asymptomatic can still suffer perioperative bronchospasm if their recent history suggests poor control. Alternatively, others may be well controlled, but because of a recent respiratory infection or new allergen exposure may be acutely symptomatic. Equally concerning are those children who have signs and symptoms consistent with asthma but who lack a formal diagnosis ( ). This latter category underscores the importance of questioning all patients about a history of recurrent or nighttime cough, wheeze, or chest tightness in addition to thoroughly examining the lungs.

In patients with known asthma, disease severity can be assessed through a review of functional impairment and exacerbation risk, including current symptoms, recent exacerbations, and baseline use of rescue/controller medications (see Table 47.2 ). Patients with well-controlled asthma do not appear to be at increased risk for perioperative pulmonary complications compared with the general population, in contrast to those with uncontrolled or severe disease ( ). Factors corresponding with severe disease include frequent exacerbations, emergency department visits, and hospitalizations and previous ventilatory support in the setting of an asthma exacerbation ( ). The use of multiple long-term control medications or systemic steroids in the past year are also indicators of significant disease. Particularly worrisome are those children with an increasing frequency of symptoms and/or inhaler use who have not had a “step up” in their therapy and those with asthma exacerbations severe enough to have required intubation. Respiratory infections, although relevant in all children undergoing anesthetics, are particularly important in asthma because they can trigger exacerbations. Such patients should be identified and optimized before elective surgery. Optimization may entail the initiation of adjuvant therapy, a course of oral steroids, or simply time to allow airway healing to occur after an infection.

Other relevant history to assess includes any prior adverse response to nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen. In a small percentage of children, these analgesics can trigger asthma symptoms. Moreover, any history of respiratory complications with previous anesthetics or significant medication side effects should be elicited ( ; ). Chronic systemic steroids can affect growth and cause hyperglycemia, hypertension, weight gain, and muscle weakness ( ). Beta agonists can result in increased lactate levels, hypokalemia, and hyperglycemia ( ).

Additional investigations in the form of blood tests or chest radiographs are rarely necessary in the preoperative setting unless indicated by concerns for infection, pneumothorax, or pulmonary parenchymal disease ( ). Spirometry, though used to confirm diagnosis in patients older than 5 years of age, correlates poorly with clinical asthma severity ( ) and does not exclude asthma, even if the results are normal (>80% of predicted) ( ).

Anesthetic considerations

The ideal anesthetic for the asthmatic patient minimizes the risk of bronchospasm while also providing the conditions necessary to allow surgery. Though no anesthetic technique has been demonstrated to be superior to any other, general recommendations can be followed to reduce risk ( Table 47.5 ).

Preoperatively, all asthma medications should be continued, including the day of surgery ( ). Consideration should be given to the empiric administration of albuterol via a metered-dose inhaler or nebulizer even in the absence of symptoms, as this has been shown to improve preoperative lung function and decrease bronchospasm after endotracheal intubation ( ; ; ). Intravenous steroids may also be of benefit in those needing emergent surgery who are inadequately controlled or in those undergoing procedures associated with significant inflammation ( ). Those at risk for steroid-induced adrenal insufficiency should be identified and treated with stress-dose steroids. These include children who have received greater than 2 weeks of systemic steroids in the previous 6 months ( ). Inhaled steroids are unlikely to be associated with adrenal suppression in doses less than or equal to 400 mcg budesonide/day ( ) (see Chapter 46 , “Endocrine Disorders”).

Premedication with an anxiolytic or sedative such as midazolam, dexmedetomidine, or clonidine can calm the patient and decrease work of breathing. The alpha-2 agonists, dexmedetomidine and clonidine, have the additional effect of blunting the reflex bronchoconstriction associated with intubation ( ). Other prophylactic agents to be considered include anticholinergics such as glycopyrrolate to dry airway secretions and suppress upper airway vagal responses, albeit with the potential side effect of tachycardia.

Intraoperatively, induction with sevoflurane, propofol, and/or ketamine can be beneficial in the context of asthma. Sevoflurane appears to have the greatest bronchodilatory effect of any inhalational agent (von ; ). Desflurane, in comparison, is associated with an increased risk for bronchospasm and should be avoided in asthmatic patients ( ). Relative to the volatile agents, propofol is superior at blunting airway reflex bronchoconstriction but is inferior at bronchodilation ( ). Concerns regarding propofol include the potential for metabisulphite-containing formulations to induce bronchospasm ( ). Of note, propofol may be used safely in patients with egg or soy allergies ( ). Ketamine acts to induce bronchodilation and minimize reflex bronchoconstriction ( ). Any associated increase in secretions may be counteracted by the administration of an antisialogogue. Often used as an adjuvant to induction, lidocaine administration is controversial in patients with asthma. Although intravenous lidocaine can attenuate the response to airway stimulation, inhaled forms may actually precipitate bronchospasm through airway irritation ( ; ; ).

Choice of airway management often hinges on the patient’s procedure and comorbidities. Endotracheal intubation is associated with an increased risk for bronchospasm relative to a laryngeal mask airway (LMA) or face mask ( ). Inadequate depth of anesthesia, however, regardless of airway device, can provoke bronchoconstriction. If intubation is indicated, ventilatory settings should be adjusted to maximize expiratory time, limit respiratory rate, and allow permissive hypercapnia if evidence of obstruction arises ( ; ). Cuffed endotracheal tubes (ETTs) may be preferable to uncuffed tubes, as they decrease the need for airway reinstrumentation and allow more reliable end-tidal carbon dioxide (ETCO ₂ ) monitoring and lower fresh gas flows. Neuromuscular blocking agents may be used as needed with the exception of the histamine-releasing drugs mivacurium and atracurium. Succinylcholin e, although not contraindicated, can also promote histamine release. Reversal of a muscle relaxant with cholinesterase inhibitors may precipitate airflow obstruction, even when combined with anticholinergics; thus the minimum dose necessary to achieve adequate muscle strength (if needed at all) should be used ( ). Alternatively, sugammadex can be administered, but has also been associated with bronchospasm in at-risk patients ( ; ). If feasible, deep extubation is preferred to avoid airway irritation and reflexive bronchoconstriction.

Analgesic options in children with asthma are largely comparable to those in otherwise healthy patients. Meriting caution are acetaminophen, NSAIDs, and morphine. Though morphine can blunt the airway response to noxious stimuli, it can also cause histamine release with subsequent bronchospasm ( ). NSAIDs, through mediating an increase in leukotriene production, may induce an exacerbation in a subset of patients with both asthma and nasal polyps ( ; ). Given the frequent use of over-the-counter NSAIDs and the relative lack of asthma-related complications, the risk associated with NSAID use is likely low. Acetaminophen, on the other hand, has been associated with concurrent asthma symptoms and decreased lung function in observational studies ( ; ; ; ). Further, a post hoc analysis comparing the use of ibuprofen and acetaminophen for fever in children demonstrated a higher relative risk of unscheduled visits for asthma after the use of acetaminophen ( ). A randomized control trial, however, showed no difference between acetaminophen and ibuprofen in the risk of asthma exacerbation, use of rescue albuterol, or unscheduled visits for asthma in children with mild persistent asthma ( ). Likewise, another randomized control trial comparing spirometry and clinical changes in asthmatic and healthy children 60 minutes after the ingestion of acetaminophen observed no significant differences between the groups ( ). Therefore although its effects on patients with more severe asthma are unclear, the use of acetaminophen as either a single dose or repeated doses does not appear to be associated with an increased risk of exacerbation in comparison to ibuprofen ( ; ).

Perioperative asthma complications

Perioperative complications resulting from asthma can be categorized into those resulting from air trapping and/or noxious stimuli and provocative medications ( ; ; ). Air trapping, or dynamic hyperinflation, can lead to respiratory and hemodynamic sequelae if prolonged and unrecognized. As new breaths are taken before prior breaths are exhaled, lung volumes and end-expiratory pressure progressively increase, causing a decrease in venous return and cardiac output and an increase in intra-alveolar pressure. Pneumothorax, subcutaneous emphysema, hypotension, tachycardia, and ultimately cardiac arrest may result ( ; ). If air trapping is suspected in the intubated patient, a brief ventilator disconnect may allow for the passive exhalation of trapped gas and a subsequent improvement in hemodynamics ( ). On resuming mechanical ventilation, a longer expiratory time, decreased respiratory rate, and permissive hypercapnia can be employed. Concurrent therapy to address the bronchospasm leading to dynamic hyperinflation is often necessary.

An asthmatic response to provocative medications or noxious stimuli such as airway manipulation or surgery can entail bronchospasm, laryngospasm, mucus plugging, and atelectasis. Bronchospasm manifests intraoperatively in intubated patients as increased peak inspiratory pressure, an increase in and up-sloped ETCO ₂ , bilateral expiratory wheeze, and desaturation. If isolated, bronchospasm can be treated with increasing fraction of inspired oxygen (Fio ₂ ) to 100%, deepening the level of anesthesia with a volatile agent and/or propofol, and administering albuterol to the inspiratory limb of the ventilator circuit (2.5 mg, < 30 kg; 5 mg, > 30 kg) ( Table 47.6 , Fig. 47.1 ). Continuous rather than intermittent administration of albuterol results in greater improvements in peak expiratory flow ( ). Higher doses are also necessary in mechanically ventilated patients because of poor drug delivery.

Intravenous steroids such as methylprednisolone (1–2 mg/kg, max 50 mg) or hydrocortisone (4 mg/kg, max 100 mg) should be administered early in spite of their delayed onset of action. In refractory cases, magnesium sulfate and systemic epinephrine should be promptly considered. Magnesium induces bronchial smooth muscle relaxation and can be administered intravenously (50 mg/kg, max 2 g, over 20 minutes) or as an inhaled preparation ( ; ). Systemic epinephrine is useful when severe airway obstruction limits the delivery of inhaled bronchodilators (1 to 10 mcg/kg depending on clinical severity) or when hypotension ensues that is not reversible by a simple ventilator disconnect ( ; ). In these circumstances, a mixture of helium and oxygen (Heliox) may enhance drug delivery beyond areas of proximal obstruction ( ). Clinical use, though, is limited by the lower Fio ₂ inherent to such a mixture.

Other causes of wheezing include mainstem intubation, pneumothorax, airway foreign body, acute pulmonary edema, pulmonary embolism, or aspiration ( Table 47.7 ). In children, the possibility of coincident congenital anomalies like bronchomalacia or a vascular ring is also possible ( ). Because airway secretions are increased at baseline in asthma, high circuit pressures and rhonchi may be the result of mucus plugging rather than bronchospasm ( ). Adequate anesthetic depth should be ensured before suctioning to avoid airway hyperreactivity. Anaphylaxis may also mimic the bronchospasm of asthma ( ). If cardiovascular collapse coincides with the onset of bronchospasm, the diagnosis of anaphylaxis rather than an asthma exacerbation should guide management.

Epidemiology

BPD affects 10,000 to 15,000 infants annually in the United States and is the most common chronic lung disease in infancy ( ; ). Those at greatest risk include infants of low birth weight (<1000 grams) and correspondingly young gestational age (<30 weeks) ( ). Approximately 40% of infants with a birth weight less than 1000 grams develop BPD, and in those patients weighing between 500 and 699 grams, the incidence may be as high as 85% ( ; ). Unlike other diseases associated with prematurity, the incidence of BPD has not consistently decreased, likely because of the increased survival of lower-birth-weight patients ( ; ).

Pathogenesis

An interplay of lung immaturity, acute lung injury, and impaired healing contributes to the development of BPD ( Fig. 47.2 ). Oxygen exposure alone can halt the septation of lungs and directly cause lung injury through the generation of cytotoxic oxygen free radicals ( ; ; ). Preterm infants are particularly susceptible to oxygen because of deficient antioxidant systems at birth. Ventilator-induced lung injury in the forms of barotrauma or volutrauma also has a role. In animals, mechanical ventilation alone in the absence of oxygen was sufficient to generate the pathologic lesions of BPD. Central to these processes is inflammation. Inflammatory cells and proinflammatory cytokines are noted in the airspaces of such patients early on and contribute to endothelial cell dysfunction, inhibition of surfactant synthesis, elastase production, and fibroblast proliferation ( ; ; ; ). Other risk factors include a history of intrauterine and postnatal infection, patent ductus arteriosus, poor nutritional status, and certain genetic polymorphisms ( ).

Old versus new bronchopulmonary dysplasia

Two types of BPD have been described, which reflects the advances in perinatal medicine over the past 30 years (see Fig. 47.2 ). As initially characterized, “old” BPD was a disease of diffuse lung injury marked by parenchymal fibrosis, smooth muscle hypertrophy, and neutrophilic inflammation ( ). Lung injury was multifactorial, but primarily the result of surfactant deficiency and the subsequent effects of mechanical ventilation and oxygen toxicity. The introduction of intratracheal surfactant, antenatal steroids, and lung-protective ventilation thus heralded the end of “old” BPD. In its place, as survival of very premature infants improved, a new type of lung disease with a different pathology and presentation emerged ( ; ).

The defining characteristic of this “new” BPD is a disruption in lung development rather than lung injury. As such, the airways demonstrate less fibrosis and inflammation, the alveoli are fewer and larger, and the pulmonary microvasculature is correspondingly dysplastic and small ( ; ; ). The end result is a decreased surface area for gas exchange. The outcome is determined by the influence of genetic predisposition, injurious perinatal exposures, and comorbidities on the developing lungs ( ).

Respiratory function

Patients with BPD appear to be at greatest respiratory risk early on in life. Analysis of forced expiratory flows in survivors demonstrates significant airflow limitation beginning in the first month and continuing to 3 years ( ; ). Respiratory infection, a common event in childhood, can lead to a further decline in pulmonary function. Because of alterations in the lungs’ defenses and an already abnormal substrate, the risk and severity of infection are both increased in children with BPD ( ; ; ). Underscoring this fact is that nearly half of all infants with BPD require hospital readmission during early childhood for respiratory issues ( ; ).

Though most children with BPD experience improvement in pulmonary function over time, with few requiring oxygen beyond 2 years, airflow abnormalities may persist. Spirometric evaluation has documented worse airway obstruction and alveolar hyperinflation in survivors of BPD at any age relative to controls (Giacola et al. 1997; ; ; ). These findings likely reflect the fixed airway narrowing that results from blunted lung development ( ). As such, patients may appear clinically well despite having diminished reserve. The degree of airflow limitation in the first years of life seems to predict later pulmonary function (Fillippone et al. 2003), placing those with severe, early airflow obstruction at highest risk.

Diminished lung compliance and airway hyperresponsiveness may also accompany airflow obstruction ( ). Lung compliance is affected by interstitial fibrosis, edema, narrowing of the airways, and atelectasis. Airway hyperresponsiveness occurs in as many as 50% to 60% of adolescents with BPD ( ; ) but appears to be unrelated to the allergic inflammation that occurs in childhood asthma ( ; ; ). Whereas eosinophilic airway inflammation is the hallmark of allergic asthma, BPD patients have only neutrophilic inflammation ( ). Moreover, the response to bronchodilator or inhaled corticosteroid therapies is variable, with some responding only partially and others not at all.

Other respiratory comorbidities accompanying BPD can include altered breathing patterns and laryngotracheal abnormalities ( ). Apneas and hypopneas, which are common in preterm infants, can result in more profound hypoxemia in the infant with BPD, particularly during quiet sleep ( ). Obstructive sleep apnea is also more prevalent throughout the age range in children with a history of prematurity ( ). The common airway abnormalities are those that are a by-product of prolonged intubation and mechanical ventilation: vocal fold paresis, subglottic stenosis, airway granulomas, and tracheomalacia.

Respiratory support currently consists of endotracheal intubation in those infants with cardiopulmonary failure, and noninvasive ventilatory support in all others who need assistance to maintain oxygen saturations >90% ( ). These latter modes include nasal synchronized positive pressure ventilation, nasal continuous positive airway pressure, and high-flow nasal cannulae ( ; ; ). Long-term support in those unable to wean from invasive mechanical ventilation entails tracheostomy placement.

Cardiovascular function

Alveolar and pulmonary vascular growth are intertwined. Deficiencies in alveolar number and maturation thus correspond with impaired pulmonary vascular development that can contribute to elevated pulmonary vascular resistance (PVR) and pulmonary hypertension (PH) ( ; ). Beyond a reduction in pulmonary vascular cross-sectional area, the vessels themselves in BPD are abnormal. Endothelial cells are injured as a result of oxidant injury because of either hyperoxia or inflammation ( ). Vascular remodeling also occurs as smooth muscle cells and fibroblasts proliferate within the media of pulmonary arteries ( ). The pulmonary vasculature can further develop abnormal vasoreactivity, resulting in exaggerated elevations in PVR in response to acute hypoxia ( ; ).

PH is thus common in BPD and correlates with the extent of lung injury. Prevalence is estimated at 30% to 50% of infants with moderate to severe BPD, and the associated morbidity and mortality are high ( ; ). The persistence of echocardiographic evidence of PH beyond the first few months of life is associated with up to 40% mortality ( ). Sequelae of PH include right ventricular dysfunction, decreased cardiac output, increased pulmonary edema, prolonged ventilatory support, and increased mortality.

Other cardiovascular abnormalities associated with BPD include systemic hypertension, left ventricular hypertrophy, and the development of aortopulmonary collaterals ( ). The etiology of these findings is unclear, and they are variable in whom they occur. All of these conditions, however, have the potential to worsen pulmonary function.

Pharmacologic interventions

Therapy used in the postnatal management and prevention of BPD is varied and dependent on the patient’s clinical symptoms. Agents used for prevention include caffeine and vitamin A ( ). Those used for symptom control or escalating severity include inhaled nitric oxide, sildenafil, systemic corticosteroids, diuretics, and bronchodilators ( ). Both sildenafil and inhaled nitric oxide act as pulmonary vasodilators that may be of use in patients with PH; they also have the ancillary benefit of promoting lung growth. Steroids, although capable of reducing chronic oxygen dependency and inflammatory cell counts, have also been associated with increased mortality and adverse effects on growth and neurodevelopmental outcomes ( ). Use of systemic steroids is thus recommended only in those who have difficulty weaning from high ventilatory settings or in whom respiratory status is rapidly deteriorating ( ). Diuretics and bronchodilators have inconsistent efficacy, as not all patients are volume overloaded or demonstrate bronchospasm; their use is guided by clinical response.

Anesthetic considerations

Patients with BPD can span the range of clinical severity, from micropreemies on maximal ventilatory settings, inhaled nitric oxide, and inotropic support to asymptomatic children presenting as outpatients on no medications. Clinical status thus dictates anesthetic management ( Table 47.9 ).

Those at highest risk are low-birth-weight infants scheduled to undergo major surgery ( ; ). Assessment begins with a review of the patient’s ventilatory support, hemodynamics, and end-organ function. Based on these data, if there is concern for instability or the safety of transport, consideration should be given to performing the procedure at bedside. If not feasible, planning for the operating room (OR) should entail the immediate availability of (1) an ICU ventilator should the OR ventilator prove inadequate (patients with high baseline ventilator settings or <1 kg weight); (2) inhaled nitric oxide; and (3) blood, inotropes, and vasopressors. For those patients who are not yet intubated, the choice of ETT should allow an adequate seal to accurately monitor ETCO ₂ and deliver the necessary tidal volumes. Although a reasonable starting goal is to allow permissive hypercapnia and the lowest Fio ₂ that allows for a pulse oximetry (SpO ₂ ) >90%, a higher Fio ₂ and a lower partial pressure of carbon dioxide (Pa co ₂ ) may be needed to avoid increases in PVR in patients at risk for PH crises. Vascular access and invasive monitoring should be commensurate to the risk of the procedure and the patient’s clinical status. Of note, given that these patients may have had significant and lengthy exposures to sedatives in the ICU, they may demonstrate tolerance to the usual doses of opioids and benzodiazepines.

Children with BPD who present from home tend to have a larger weight and more mature end-organ function. Nonetheless, because recovery of lung function is variable, the preanesthetic evaluation is unchanged. As such, questions about asthmalike symptoms, activity tolerance, oxygen requirements, and the need for bronchodilator therapy can give insight into respiratory risk. Because respiratory infection can unmask or exacerbate underlying pulmonary disease ( ; ), its presence should lead to rescheduling elective procedures 4 to 6 weeks after resolution of symptoms. Ongoing issues with PH can be discerned by evaluating current medications and recent echocardiograms or cardiac catheterizations. Patients on home oxygen to maintain saturations or those with a history of moderate or severe BPD may reflect a subset at greater risk for PH and fixed airway obstruction. Intraoperatively, common concerns include bronchospasm and acute increases in PVR. If intubation is needed, adequate anesthetic depth with airway instrumentation and the use of lower respiratory rates may prevent bronchospasm and lung hyperinflation, respectively.

The stable low-birth-weight infant with mild BPD presenting for low-risk surgery represents an intermediate-risk category and merits discussion. Airway strategies and anesthetic techniques to consider in these patients include the use of an LMA, supplemental analgesia in the form of epidural anesthesia, or a sole spinal anesthetic. Selection depends on patient and procedural factors in addition to institutional practice. Advantages to the LMA may include decreased respiratory complications commonly associated with endotracheal intubation, but must be weighed against procedural length, the potential for hemodynamic compromise, and the risk of aspiration. Procedures in which the LMA has been used successfully in infants with BPD include vitrectomy and cryotherapy for retinopathy of prematurity ( ; ). Likewise, spinal anesthesia may be beneficial for short abdominal procedures like inguinal hernia repair. Its theoretic benefits when performed without additional sedation include a decreased risk of postprocedural intubation or apnea compared with general anesthesia. But it is limited by technical difficulty and the block’s duration ( ; ; ). To date, the risks of postoperative apnea and bradycardia are comparable in ex-premature infants who undergo either general or neuraxial anesthesia alone ( ; ).