Upper Respiratory Tract Infection

Upper repiratory tract infections (URIs) are a common problem among young children. Children are typically infected several times a year, possibly even more frequently if they are in day care. Viruses cause the majority of URIs, with rhinoviruses constituting approximately one third to one half of etiologic species.^14,14a Other common respiratory viruses in childhood include adenoviruses and coronaviruses.

Although most URIs are short-lived, self-limited infections and are by definition limited to the upper airway, they may increase airway sensitivity to noxious stimuli or secretions for several weeks after the infection has cleared. The mechanisms probably involve a combination of mucosal invasion, chemical mediators, and altered neurogenic reflexes.¹⁴ URIs may also impair pulmonary function by decreasing FVC, FEV₁, peak expiratory flow, and diffusion capacity.^15,16

Compared with uninfected children, children with a recent or current URI have an increased incidence of perioperative laryngospasm, bronchospasm, arterial hemoglobin desaturation, severe coughing, and breath holding (Table 11-3).^{4,12,13,17–20} However, most complications can usually be predicted and successfully managed without long-term sequelae by suitably experienced and prepared clinicians.^{14,18,20–23} An approach to the child with a URI is to detect the pathologic process and associated comorbidity, establish the acuteness and severity of the URI, and then decide whether to modify the anesthetic technique or postpone surgery (Table 11-4, Fig. 11-8).

FIGURE 11-8 Suggested algorithm for assessment and management of the child with an upper respiratory tract infection (URI). ETT, Endotracheal tube; Hx, history; LMA, laryngeal mask airway.

(Modified from Tait AR, Malviya S. Anesthesia for the child with an upper respiratory tract infection: still a dilemma? Anesth Analg 2005;100:59-65.)

The basis for diagnosing a URI is a careful history and physical examination, with further investigations in limited situations. Because they are usually familiar with their child’s state of health, the parents or caregivers can provide helpful insight into the presence and severity of a URI. The child should be evaluated for fever (defined as a temperature greater than 100.4° F [38° C]), change in demeanor or behavior, dyspnea, productive cough, purulent sputum production, nasal congestion, rales, rhonchi, and wheezing. A chest radiograph may be considered if the pulmonary examination is questionable, but because the radiographic changes lag behind clinical symptoms, it is typically of limited value. Although laboratory tests may confirm the diagnosis of a viral or bacterial URI, they are not cost-effective or practical in a busy surgical setting.

For children with symptoms of an uncomplicated URI who are afebrile with clear secretions and who are otherwise healthy, anesthesia may proceed as planned, because the problems encountered are typically transient and easily managed.^{4,14,18,20–23} Elective surgery is usually postponed for children with more severe symptoms that include at least one of the following: mucopurulent secretions; lower respiratory tract signs (e.g., wheezing) that do not clear with a deep cough; a pyrexia greater than 100.4° F (38° C); or a change in sensorium (e.g., not behaving or playing normally, has not been eating properly).^14,23

The decision to proceed with surgery becomes much more difficult when the signs of the URI are between the extremes of mild and severe. For these intermediate URIs, other considerations play a greater role in assessment of the risk/benefit ratio. These include the presence of comorbidities such as asthma, cardiac disease, or obstructive sleep apnea; a history of prematurity; the frequency of URIs; prior cancellations; the type, complexity, duration, and urgency of the surgery; the age of the child; and the socioeconomic implications for the family. The comfort level and experience of the anesthesiologist may also be an underestimated but important factor in the decision to proceed with or postpone surgery, because less experienced anesthesiologists have a greater incidence of complications.⁴ The need to admit a child postoperatively because of anesthetic complications or an exacerbation of the URI may expose other children to a contagious illness.

If the decision is to proceed with general anesthesia, management is directed toward avoiding stimulation of the potentially sensitized airway. Use of an endotracheal tube (ETT) should be avoided, if possible, because it increases the risk of complications, especially in younger children.^4,18 Although airway management with a facemask is associated with the smallest frequency of airway complications,⁴ it may be inappropriate for certain cases. The laryngeal mask airway (LMA) is associated with fewer episodes of respiratory events than an ETT, but its use may similarly be contraindicated by the type of surgical procedure and the need to protect the airway from pulmonary aspiration of gastric contents.

Whichever airway technique is chosen, it is essential that the depth of anesthesia be adequate to obtund airway reflexes during placement of an airway device. The optimal depth of anesthesia at which to remove an airway device is less clearly defined. Several studies in children with and without URI did not detect a difference in emergence complications between awake and deep extubation,^4,13,18,24 whereas others found a greater incidence of arterial oxygen desaturation or coughing after removal of the ETT or LMA in awake children.^25,26

The optimal time when an anesthetic can be given after a URI without increasing the risk of adverse respiratory events remains contentious, but most clinicians wait 2 to 4 weeks after the resolution of the URI before proceeding.^4,13,27 This reflects a balance among three critical factors: the time interval to diminish both upper and lower airway hyperreactivity; the perioperative respiratory risk, which includes a recurrence of the URI; and the need to perform the procedure.

Anesthetic techniques may affect complication rates. An observational study of 9297 children reported significantly less laryngospasm after maintenance of anesthesia with propofol than with sevoflurane.⁴ This finding might be attributed to a differential effect of propofol versus sevoflurane on airway reflexes.²⁸ The effect of spraying the cords with lidocaine on the incidence of laryngospasm and bronchospasm is unclear.⁴ However, a randomized, controlled trial showed that topical lidocaine gel lubricant applied to the LMA in children with URIs significantly reduced the frequency of adverse airway events.²⁹ Prophylactic treatment with glycopyrrolate, ipratropium, or albuterol is not effective in preventing URI-related adverse events.^30,31 However, an observational study reported that prophylactic salbutamol was effective in reducing perioperative airway sequelae in children with URIs.³² Nasal vasoconstrictors (such as phenylephrine or oxymetazoline nose drops) have been recommended for reducing oropharyngeal secretions in children with URIs, but their efficacy remains anecdotal.²³

Lower Airway Disease

Acute lower respiratory tract infections in infants and children may result in rapid deterioration necessitating aggressive intervention, including tracheal intubation and ICU admission. Many children are treated with antibiotics on the presumption that the infection is bacterial. However, many may be affected by viruses. In infants and children up to 18 months of age, respiratory syncitial virus is a very serious and common viral infection that infects the lower respiratory tract.^32a Other viruses include parainfluenza virus, adenovirus, and human metapneumovirus.^32b Acute inflammation of the small airways may result in bronchiolitis with edema of the small airways leading to desaturation, hypercapnia, and acute respiratory failure. In many instances, bronchiolitis results in several days of tracheal intubation until the acute infection has resolved.

Croup or laryngotracheobronchitis, defined as acute inflammation of the airway (below the vocal cords), has been attributed primarily to parainfluenza virus as well as to adenovirus.

Asthma is one of the most common chronic diseases of childhood, affecting by estimate more than 6 million children in the United States.^33,34 A history of wheezing is associated with an increased risk of perioperative bronchospasm.⁴ Rare perioperative complications associated with asthma include anaphylaxis, adrenal crisis, and ventilatory barotrauma such as pneumothorax or pneumomediastinum.³⁵ An anesthetic approach to children with asthma should include a basic understanding of the disease, an assessment of the child’s current state of health, modification of anesthetic technique as appropriate, and recognition and treatment of complications if they occur.

It is difficult to define asthma with precision, because the exact pathophysiology remains unclear. The word asthma derives from the Greek aazein, which means “to breathe with open mouth or to pant.”³⁶ A working definition of asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airway obstruction, inflammation, and hyperresponsiveness of the airways.³³

Clinical expressions of asthma include wheezing, chest tightness or discomfort, persistent dry cough, and dyspnea on exertion. Severe respiratory distress can occur during acute exacerbations and may be characterized by chest wall retraction, use of accessory muscles, prolonged expiration, pneumothorax, and progression to respiratory failure and death. In some children, the development of chronic inflammation may be associated with permanent airway changes, referred to as airway remodeling, that are not prevented by or fully responsive to current available treatments. There is a strong association between asthma and atopy, or immunoglobulin E (IgE)-mediated hypersensitivity.³³

The diagnosis of asthma can be challenging because cough, wheezing, and bronchospasm may arise from many disease processes. Asthma itself is unlikely to be a single disease entity, and the disease process is markedly modified by various genetic and environmental factors.^33,36 Many young children wheeze, and there is no definitive confirmatory blood, histologic, or radiographic diagnostic test. Given the difficulty with diagnosis, the label “preschool wheezers” may be a more appropriate description for young children with reversible airway obstruction than a diagnosis of “asthma.”³⁶

The Tucson birth cohort study was the largest longitudinal study in the United States to attempt to differentiate wheezing or asthma phenotypes in children who did not subsequently develop asthma.^37–39 This study examined 826 children at ages 3 years and 6 years from a cohort of 1246 neonates. By the age of 6 years, 48.5% of the children had experienced at least one documented episode of wheezing and were categorized into three groups. “Transient wheezers” were children who wheezed only in response to viral infections, typically during the first 3 years of life. “Non-atopic wheezers” were children who wheezed beyond the first few years of life, often in response to viral infections, but who were less likely to persistently wheeze in later childhood. “Atopy-associated wheezers” were children who had a reversible wheeze together with a tendency toward IgE-mediated hypersensitivity; they had the greatest risk of persistent symptoms into late childhood and adulthood.³⁷

The development of asthma is a complex process that probably involves the interaction of two crucial elements: host factors (specifically genetic modifiers of inflammation) and environmental exposures (e.g., viral infections, environmental allergens, pollution) that occur during a crucial time in the development of the immune system.³³ Therefore, the population of young children who wheeze includes a spectrum of disorders rather than one specific pathologic process.

Asthma must be differentiated from other distinct causes that produce similar symptoms (Table 11-5). Tracheomalacia or bronchomalacia may produce wheezing, but this tends to be present from birth (which is unusual for asthma), and the wheezing is commonly of a single pitch heard loudest in the central airways, whereas asthma typically produces polyphonic sounds from the lung periphery. Breathing difficulties due to chronic aspiration are often related to feeding times. Unremitting wheeze or stridor is often caused by a fixed obstruction or foreign body.

TABLE 11-5 Causes of Wheezing in Children

ETT, Endotracheal tube.

Chronic cough is the most common manifestation of asthma in children. Many children who cough may never be heard to wheeze but still have asthma. A cough with or without wheeze may be caused by a viral infection, whereas a persistent, productive cough may suggest suppurative lung disease such as CF.³⁵ A positive response of the cough to asthma medications suggests the diagnosis of asthma.

The exact incidence of perioperative complications in the pediatric asthma population is difficult to ascertain because of variations in the definition of asthma, the definition and detection of complications, the presence of coexisting diseases, overlap with adult populations, and changing anesthetic management techniques.

A retrospective review of 706 adult and pediatric patients with a rigorous definition of asthma found an incidence of documented bronchospasm of 1.7% and no instances of pneumonia, pneumothorax, or death.⁴⁰ Of 211 children younger than 12 years of age, none developed bronchospasm at the time of surgery. A retrospective review of more than 136,000 computer-based anesthesia records found a 0.8% incidence of bronchospasm in patients with asthma.⁴¹ By contrast, older studies from the 1960s reported that 7% to 8% of asthmatic patients wheezed.^42,43 A blinded, prospective study of 59 asthmatic patients detected transient wheezing after tracheal intubation in 25% of cases; however, most events were brief and self-limited.⁴⁴ An observational study of 9297 children reported an overall incidence of 2% for bronchospasm; in the subgroup of 2256 children with a history of respiratory problems, the incidence was 6%.^4,35 An editorial review of the subject of asthma and anesthesia concluded that, although the true incidence of major complications is small, severe adverse outcomes do result from bronchospasm, and children with asthma are at heightened risk for severe morbidity.⁴⁵

Both the severity and the control of asthma must be established preoperatively. These two aspects of the current disease state should be clearly differentiated.⁴⁶ For example, asthma may be severe yet well controlled, whereas even mild asthma may be poorly controlled. Both situations may present a heightened potential for perioperative complications, because even the child with intermittent but poorly controlled asthma can have a severe exacerbation.

Severity and control may be assessed by the frequency of symptoms, limitation of effort tolerance, night awakenings, medication use, emergency department attendance, hospitalizations, and need for ventilatory support. An approach to assessment of severity and control in children aged 5 to 11 years is outlined in E-Tables 11-1 through 11-3. A history of a nocturnal dry cough, more than three wheezing episodes in the past 12 months, or a history of past or present eczema is associated with an increased risk of bronchospasm.⁴

Maintenance treatment of asthma is based on a stepwise approach, so that the type of therapy is often an indication of severity. Short-acting inhaled β-agonists are first-line therapy, with inhaled corticosteroids for those patients with persistent symptoms poorly managed by bronchodilators as the preferred second step. Alternative treatments at this step include a leukotriene receptor antagonist, a mast cell stabilizer such as cromolyn sodium or nedocromil, and a methylxanthine bronchodilator such as theophylline. The third step in therapy involves increasing the dose of inhaled corticosteroid or adding an alternative treatment to a smaller dose of corticosteroid; a long-acting β-agonist, a leukotriene receptor antagonist, or theophylline may be considered. Step 4 involves a medium dose of corticosteroid together with a long-acting β-agonist. The final steps of therapy involve a high dose of inhaled corticosteroid or commencing an oral corticosteroid (E-Fig. 11-2).

E-Figure 11-2 Stepwise approach for managing asthma in children 5 to 11 years of age.

(Reproduced from National Asthma Education and Prevention Program: Full report of the expert panel: guidelines for the diagnosis and management of asthma [EPR-3]. Bethesda, Md.: National Heart, Lung, and Blood Institute, National Institutes of Health; 2007.)

Most children with asthma have disease that is intermittent or persistent but mild and will be treated with inhaled short-acting β-agonists on an as-needed basis, alone or in combination with low-dose inhaled corticosteroids or an adjunctive therapy. Poor control may relate to poor compliance with medication, inadequate inhaler technique, or incorrect diagnosis. Severe asthma is diagnosed when symptom control is poor despite high doses of corticosteroids (steps 5 or 6 in E-Fig. 11-2). A small group of children have “brittle asthma” that is difficult to control despite optimal therapy and may lead to life-threatening respiratory compromise. A history of severe attacks or admission to intensive care is particularly ominous.

Special investigations are not routinely indicated but may be useful in specific circumstances. A chest radiograph is not usually helpful to assess the severity of asthma but can help diagnose a superimposed infection, pneumothorax, or pneumomediastinum during an acute exacerbation. Pulmonary function tests are important in monitoring long-term responses to therapy but are of little use in the immediate, routine preoperative workup of cases at a stable clinical baseline. Measurements of nitric oxide and various inflammatory markers are primarily of use as research tools at present, but their role in asthma management is evolving.⁴⁷

Although an assessment of disease severity is essential, an important caveat is that many asthma deaths in the community setting occur not in those with severe disease but in those with what was thought to be mild or moderate disease. Asthma is often undertreated,⁴⁶ so the sensitivity of medication prescription as a marker of disease activity must be viewed with some caution. Some studies have found a poor correlation between assessment of disease severity and the occurrence of perioperative bronchospasm. However, disease activity, as noted by recent asthma symptoms, use of medications for symptom treatment, and recent therapy in a medical facility for asthma, is significantly associated with perioperative bronchospasm.⁴⁰

Children should continue their regular medications before anesthesia. Midazolam has been reported to be a safe premedication for asthmatics.⁴⁸ Corticosteroids may help prevent postintubation bronchospasm in adults,⁴⁹ although controlled clinical data to substantiate this practice in children are lacking.³⁵ Inhaled β-agonists before or shortly after induction of anesthesia attenuate the increases in airway resistance associated with tracheal intubation.^50,51 Ketamine is the traditional choice of intravenous induction agent in children with severe asthma, although its superiority over other agents has not been substantiated in clinical trials.^52,53 Propofol is typically preferred over thiopentone because it causes less bronchoconstriction.^44,54 Desflurane is associated with an increased risk of bronchospasm compared with sevoflurane or isoflurane, and because it can increase airway resistance in children, should be avoided in asthmatics.⁴

Tracheal stimulation is a potent stimulus for bronchospasm.⁴ In children with URI, in whom the airways may be acutely hyperactive, the avoidance of tracheal intubation is associated with a reduced incidence of pulmonary complications.^4,17 There are inadequate clinical outcome data on the perioperative management of asthma to make definitive recommendations about airway management. Nevertheless, avoidance of tracheal and vocal cord stimulation by use of a facemask or an LMA instead of an ETT whenever possible seems a sensible approach. If tracheal intubation is mandatory, a deep plane of anesthesia is preferred to blunt airway hyperreactivity. Similarly, unless contraindicated by other factors, deep extubation is preferred for the same reason. Surgical stimulation is another trigger of bronchospasm, and anesthetic depth and analgesia should be adequate to prevent this response.

Intraoperative bronchospasm is characterized variously by polyphonic expiratory wheeze, prolonged expiration, active expiration with increased respiratory effort, increased airway pressures, a slow upslope on the end-tidal CO₂ monitor, increased end-tidal CO₂, and hypoxemia (Fig. 11-9). Other causes of wheezing must be excluded, such as partial obstruction of the ETT (secretions or herniation of the cuff causing obstruction), main-stem intubation (deep endobronchial intubation), aspiration, pneumothorax, or pulmonary edema. Mechanical obstruction of the circuit or ETT must also be excluded.

FIGURE 11-9 A, Tracing of expired carbon dioxide (PEco₂) in a child with acute bronchospasm. Notice the slowly rising PEco₂ value. B, Tracing from the same patient after administration of inhaled albuterol. Note that the PEco₂ waveform now has a flat plateau, indicating relief of the bronchospasm and efficient elimination of CO₂ from all areas of the lungs.

First-line treatment for bronchospasm involves removing the triggering stimulus if possible, deepening anesthesia, increasing the fraction of inspired oxygen (Fio₂) if appropriate, decreasing the positive end-expiratory pressure (PEEP), and increasing the expiratory time to minimize alveolar air trapping. In severe status asthmaticus, ventilation strategy focuses primarily on achieving adequate oxygenation, rather than attempting to normalize Paco₂ at the potential cost of inducing pulmonary barotrauma. All children who experience anything more than minor bronchospasm should also receive corticosteroids, if they have not already done so.

Inhaled β-agonists can be delivered by nebulizer or by a metered-dose inhaler down the airway device with specially designed adaptors (Fig. 11-10). Alternatively, a 60-mL syringe can be used to deliver doses of the nebulizer into the breathing circuit (E-Fig. 11-3). However, the efficiency of delivery through an inhaler that is actuated at the elbow of the breathing circuit is poor, especially in small-diameter ETTs.⁵⁵ To improve the delivery efficiency of the aerosol in pediatric-size ETTs, the inhaler may be actuated 10 to 20 times at the elbow or once or twice into a narrow-gauge catheter that is passed to the end of the ETT.^55,56

FIGURE 11-10 Adaptor that allows administration of albuterol through an endotracheal tube (ETT) and timing of that dose with inspirations so as to provide maximum delivery; notice that the nebulized albuterol is directed down the ETT (arrow). Use of a long intravenous catheter that extends to the tip of the ETT is an alternative method to further improve drug delivery.

E-Figure 11-3 A and B, A 60-mL syringe may be attached to a port in the circuit to administer aerosolized drugs such as albuterol.

If intravenous salbutamol is available, the intravenous route is preferred over tracheal administration. In this case, 10 µg/kg IV salbutamol may be repeated, followed by an infusion of 5 to 10 µg/kg/min for the first hour until there is an improvement in the bronchospasm. Thereafter, salbutamol should be infused at 1 to 2 µg/kg/min until the bronchospasm resolves.

The anesthesiologist may be involved in the management of status asthmaticus when consulted to assist a child in the emergency department or on the wards. A drowsy, silent child with a quiet chest on auscultation is in imminent danger of respiratory arrest and requires emergent intubation by an experienced practitioner. Signs and symptoms to assess the severity of an asthma exacerbation are outlined in Table 11-6, and an algorithm for management issued by the American National Heart, Lung and Blood Institute is presented in E-Figure 11-4.

E-Figure 11-4 Management of asthma exacerbations in emergency department and hospital-based care. FEV₁, Forced expiratory volume in 1 second; ICS, inhaled corticosteroid; MDI, metered dose inhaler; PCO₂, partial pressure carbon dioxide; PEF, peak expiratory flow; SABA, short-acting beta₂-agonist; SaO₂, oxygen saturation.

(Reproduced from National Asthma Education and Prevention Program: Full report of the expert panel: guidelines for the diagnosis and management of asthma [EPR-3]. Bethesda, Md.: National Heart, Lung, and Blood Institute, National Institutes of Health; 2007.)

Oxygen is recommended for most children to maintain the oxygen saturation at greater than 90%. Repetitive or continuous administration of short-acting β-agonists is first-line therapy for all children and is the most effective way of reversing airflow obstruction. The addition of ipratropium to a β-agonist may produce additional bronchodilation and may have a modest effect to improve outcome. Systemic corticosteroids should be given to those who do not respond completely and promptly to β-agonists. For severe exacerbations unresponsive to the treatment listed earlier, intravenous magnesium may decrease the likelihood of intubation, although the evidence is limited. Current recommended drug doses are listed in E-Table 11-4.

There is much debate about the role of methylxanthines such as aminophylline in the management of acute exacerbations of asthma. In some countries, aminophylline is considered a first-line treatment in asthma, whereas in others it is considered second-line or used less frequently. The difference in practice may be attributed to its equivocal clinical efficacy in the treatment of acute exacerbations of asthma and to complications from toxicity (including vomiting).^57–60

Antibiotics are not recommended except for comorbid conditions. Aggressive hydration is not recommended in adults or older children, although it may be indicated in younger children who become dehydrated as a result of decreased oral intake and increased respiratory rate. In general, chest physical therapy and mucolytics are not recommended.

Children with severe atopy-associated asthma are possibly at greater risk of developing anaphylaxis in response to neuromuscular blocking drugs, antibiotics, and latex.³⁵ Bronchospasm caused by anaphylaxis is differentiated from that due to asthma; it produces additional systemic signs such as angioedema, flushing, urticaria, and cardiovascular collapse.

Adrenal crisis during major surgical stress is a potential complication associated with severe asthma due to iatrogenic suppression of the hypothalamic-pituitary-adrenal axis.³⁵ Adrenal suppression should be considered in any child who is taking significant doses of corticosteroids for a prolonged period. Short courses of prednisolone used to treat acute flares of asthma may affect function for up to 10 days, but prolonged dysfunction is unlikely. Large doses, prolonged therapy for more than a few weeks, and evening dosing may suppress adrenal function for up to 1 year. Prophylactic corticosteroid administration may be indicated for those receiving prolonged systemic corticosteroids, when their corticosteroid regimen is interrupted by the surgical schedule, or for those who have received high-dose inhaled corticosteroids in the recent past (see Chapter 25).

Cystic Fibrosis

CF is an autosomal recessive disorder that is caused by one of more than 1200 mutations in the gene coding for the CF transmembrane conductance regulator (located on chromosome 7), a protein that contributes to the regulation of chloride and other ion fluxes at various epithelial surfaces.^61,62 The incidence of CF is approximately 1 of every 2000 births in Caucasian, making it the most common fatal inherited disease in this population.

The disruption of electrolyte transport in the epithelial cells of the sweat ducts, airways, pancreatic ducts, intestine, biliary tree, and vas deferens causes increased sweat chloride concentrations, viscous mucus production, lung disease, intestinal obstruction, pancreatic insufficiency, biliary cirrhosis, and congenital absence of the vas deferens. The clinical outcome is widely variable, even among children with identical mutations at the CF locus. Absence of the gene influences expression of several other gene products, including proteins important to the inflammatory response, ion maturational processing, transport, and cell signaling. These other proteins are potential modifiers of the phenotype and may help explain the substantial differences in clinical severity.

Lung disease is the main cause of morbidity and mortality in CF, and consequently it is the focus of anesthetic concern. The pathophysiology involves mucus plugging, chronic infection, inflammation, and epithelial injury.^63–65 Mucus clearance defends the lung against inhaled bacteria. The mucociliary transport system requires two fully functioning layers to be effective. The base layer of ciliary epithelia bathed in a watery liquid (sol) is overlaid by a more viscous gel (mucus) that is responsible for transporting particles along the tips of the cilia. Normally, mucus is transported at about 10 mm/min, expelling foreign particles and pathogens from the lungs. The efficacy of clearance depends on adequate hydration of the mucus.⁶⁶ Lack of regulation of sodium absorption and chloride secretion decreases liquid on the airway luminal surfaces, slows mucus clearance, and promotes the formation of adherent plugs in the airway.⁶⁷ Increased secretions, viscous mucus, and impaired ciliary clearance contribute to airway impaction, providing a nidus for infection.

At birth, the lung structure is almost normal.⁶¹ However, chronic and recurrent bacterial infections occur early in life, assisted by the pooling of secretions and impaired neutrophil bacterial killing on airway surfaces.^63,68 Repeated and persistent infections stimulate a chronic neutrophilic inflammatory response, ultimately destroying the airway walls. Early pathogens include Staphylococcus aureus and Haemophilus influenzae. Pseudomonas aeruginosa typically invade later in life, acquire a mucoid phenotype, and form a biofilm in the lung, an event that is associated with accelerated decline in pulmonary function. The invasion of the lung by antibiotic-resistant pathogens such as certain strains of Burkholderia cepacia is often devastating, markedly increasing the death rate from lung disease.

Various insults such as bacteria, viruses, and airborne irritants can cause acute exacerbations of respiratory symptoms of cough and sputum production. This is often accompanied by systemic manifestations such as weight loss, anorexia, and fatigue. These changes from baseline are termed pulmonary exacerbations.⁶⁹

Recurrent exacerbations are associated with progressive airway obstruction, bronchiectasis, emphysema, ventilation/perfusion mismatching, and hypoxemia. Growth of blood vessels with advancing bronchiectasis predisposes to hemoptysis. Bronchial hyperreactivity and increased airway resistance are common, whereas bullae formation can lead to pneumothorax.

Pulmonary function abnormalities are commonly obstructive in nature and include increased FRC, decreased FEV₁, decreased peak expiratory flow rate, and decreased vital capacity (see Fig. 11-5). Compensatory hyperventilation typically produces a reduced Paco₂, although hypercapnia may supersede in end-stage pulmonary pathology. End-stage cor pulmonale may lead to cardiomegaly, fluid retention, and hepatomegaly.

Malnutrition is a common problem in CF that follows from pancreatic insufficiency, failure of enzyme secretion, impaired gastrointestinal motility, abnormal enterohepatic circulation of bile, increased caloric demand due to severe lung disease, and anorexia of chronic disease.⁶¹ Low weight and body mass index are closely associated with, and can predict, poor lung function.

CF-related diabetes arises from progressive pancreatic disease and scarring that compromises the pancreatic islets. More than 12% of CF teenagers older than 13 years of age have insulin-dependent diabetes, and the incidence increases with age. Evidence is accumulating that diabetes contributes to the lung disease and worse outcome.^63–65 In addition, classic diabetic complications occur in older CF patients. Hepatic dysfunction decreases plasma cholinesterase and clotting factors II, VII, IX, and X, whereas malabsorption of vitamin K may also contribute to coagulation issues.⁷⁰

When CF was first distinguished from celiac syndrome in 1938, life expectancy was approximately 6 months. Since then, substantial advances in sustained multidisciplinary supportive care have increased the median survival time to 35 years (E-Fig. 11-5).^61,71 Currently almost half of the CF population are adults.⁷⁰ The pillars of treatment include nutritional repletion, relief of airway obstruction, and antibiotic therapy for lung infection. Suppression of inflammation has been a more recent focus of therapy. Organ transplantation, and in particular lung transplantation, has been used in an attempt to improve quality of life and prolong survival, but a clear benefit remains to be demonstrated.⁷¹

E-Figure 11-5 Median survival age for patients with cystic fibrosis at various times since the first description of the disease. Data before 1970 are gleaned from the then-current literature. Data since 1985 are from the Cystic Fibrosis Foundation Data Registry and represent projections of median survival age for a child born in that year with cystic fibrosis.

(Reproduced from Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med 2006;173:475-82.)

The multisystem nature of the disease and changing demographics mean that children present for a wide variety of surgical procedures. The most common indications for anesthesia in children are nasal polypectomy and ear, nose, and throat surgery, as a result of the frequency of upper airway pathologic processes such as chronic sinusitis and nasal polyps (Table 11-7).^72,73 The investigation or correction of gastrointestinal disorders is the next most common procedural category that requires anesthesia in the CF population. Other indications for anesthesia include bronchoscopy and pulmonary lavage, gastrointestinal endoscopy, sclerosing injection of varices due to portal hypertension, insertion of venous access devices, and incidental surgical problems.^73–75

TABLE 11-7 Most Frequent Indications for Anesthesia in Cystic Fibrosis

Modified from Della Rocca G. Anaesthesia in patients with cystic fibrosis. Curr Opin Anaesthesiol 2002;15:95-101.

Because of the increasing longevity of this population, the pediatric anesthesiologist may also be involved in the care of adults.⁷⁰ Surgical procedures in adults typically include treatment of recurrent pneumothorax, cholecystectomy, and lung or cardiac transplantation. Consultation may also be requested for obstetric cases as increasing numbers of patients survive to adulthood.

Pulmonary disease is the predominant concern when planning anesthesia for these patients. Historically, morbidity and mortality from pulmonary complications were significant, but more recently, the mortality rate has decreased. In 1964, a retrospective study reported a perioperative mortality rate of 27%,⁷⁶ but by 1972, this incidence had decreased to 4%.⁷² More recent studies confirmed a substantial morbidity rate with a low mortality rate. An observational study of 333 anesthesias for bronchoalveolar lavage reported minor complications (transient worsening of cough or low-grade postoperative fever or both) in 52% of patients; more serious problems, including prolonged intraoperative oxygen desaturation or high fever, occurred in 12% of children.^77,78 A report of 45 bronchoscopies under anesthesia noted a rate of minor intraoperative complications (coughing, desaturation) of 13.3%.⁷⁹ A study of 199 anesthesias in 53 patients for ear/nose/throat surgery reported a 5% incidence of minor pulmonary problems and no deaths.⁸⁰ A report of 126 anesthesias found no mortality and a CF-specific complication rate of 9% (predominantly pulmonary complications).⁷³ A 1984 study of 18 patients undergoing anesthesia for pleural surgery concluded that, although the risks for this procedure were great, the anesthetic hazards of CF could be minimized with careful management.⁸¹ In 11 patients undergoing anesthesia for injection of esophageal varices, there were no serious anesthetic complications, but significant deteriorations in pulmonary function tests were detected 48 hours after general anesthesia.⁸² It was unclear if these changes persisted past the immediate postoperative period. A larger study found no difference between pulmonary function tests measured 3 months before and 3 months after surgery.⁷³ Although pulmonary morbidity is a significant problem, mortality is infrequent with modern anesthetic management techniques.

An assessment of the severity, current state, and progression of pulmonary disease should guide anesthetic planning. Fitness is a positive predictor of survival,⁶¹ and exercise tolerance is a useful marker of pulmonary function. The quality and quantity of secretions, recent and chronic infections, use and effectiveness of bronchodilators, and number of hospitalizations are also important points to elucidate in the history. Examination of the cardiopulmonary systems should aim to detect compromise of cardiac, pulmonary, and hepatic function. Special investigations are not routinely indicated but may quantify organ dysfunction in end stages of the disease. Arterial blood gas analysis, chest radiography, pulmonary function tests, electrocardiography, echocardiography, and liver function tests may assist the planning of anesthetic technique in selected children.⁷⁵

Children are often emotionally vulnerable, not simply because of the usual preoperative anxieties but because of the psychological consequences of progression of an ultimately fatal disease. A preoperative visit should aim to allay distress; oral benzodiazepines have been successfully used as anxiolytics.^73,80 Prophylactic use of osmotic laxatives may be indicated if opioid-induced ileus is anticipated.⁷⁵

Because dehydration of secretions is a central pulmonary issue in CF, general anesthesia poses specific problems. During spontaneous ventilation under normal conditions, inspired gases are warmed to body temperature and saturated with water vapor, reaching this state at the isothermic saturation point just distal to the carina.^83,84 This ensures that the lower airways are kept moist and warm. The alveolar environment in optimal circumstances has a saturated water vapor pressure of 47.1 mm Hg and an absolute humidity of 43.4 g/m⁻³ at 98.6° F (37° C).

The inspiration of cold, desiccated anesthetic gases and vapors can impair the warming and humidification of the airways. The use of any airway device (oropharyngeal airway, laryngeal mask, or ETT) bypasses the nasal and oropharyngeal passages and delivers cold, dry gas farther down the airway.⁸⁵ This shifts the isothermic saturation point distally, forcing bronchi that normally function in optimal conditions to take part in heat and gas exchange.⁸⁴ These parts of the airway are less adapted to moisture exchange and tend to dehydrate more rapidly, thereby impairing the mucociliary escalator and predisposing to impaction of secretions.^86,87 Direct impairment of mucociliary motion by anesthetic medications, as well as blunting of the cough response and ventilatory drive, can further contribute to the problem.

It is therefore particularly important to minimize mucus desiccation in the perioperative period. Inhalation of hypertonic saline (7% sodium chloride) accelerates mucus clearance, increases lung function, and improves quality of life^88–90; this is now typically part of the routine maintenance management of CF. Nebulized saline treatments should continue up to the start of anesthesia and recommence after the procedure. Inhaled gases should be humidified, or an artificial “nose” should be inserted into the circuit to conserve airway moisture and minimize inspissation of secretions.

Although removal of pulmonary secretions is considered important in principle, a small prospective trial of intraoperative bronchial wash-out and physical therapy reported an acute increase in airway resistance with no significant long-term benefit in measures of lung function.⁹¹

At the conclusion of surgery, complete reversal of neuromuscular blockade should be confirmed. Whenever possible, the trachea should be extubated and the child encouraged to breathe spontaneously. A 30- to 40-degree head-up position assists movement of the diaphragm and ventilation. Postoperatively, physiotherapy, airway humidification, close attention to analgesia, and early mobilization should enhance clearance of secretions and minimize atelectasis. The use of regional or local anesthesia, as well as nonopioid analgesics, is useful to avoid respiratory depression. Ambulatory surgery is optimal, if feasible, because it minimizes disruption to the patient’s schedule and decreases exposure to nosocomial infection.

Sickle Cell Disease

SCD is an inherited hemoglobinopathy that results from a point mutation on chromosome 11. The mutant gene codes for the production of hemoglobin S, a mutant variant of the normal hemoglobin A. This leads to widespread and progressive vascular damage.^92,93 Clinical features of the disease include acute episodes of pain, acute and chronic pulmonary disease, hemorrhagic and occlusive stroke, renal insufficiency, and splenic infarction, with mean life expectancy shortened to just over 3 decades.⁹⁴ Perioperative problems and management are covered in more detail in Chapter 9, and the discussion here is limited to a brief review of the pulmonary pathology of SCD.

Acute chest syndrome (ACS) is an acute lung injury caused by SCD. Diagnostic criteria include a new pulmonary infiltrate involving at least one lung segment on the radiograph (excluding atelectasis) combined with one or more symptoms or signs of chest pain, pyrexia greater than 101.3° F (38.5° C), tachypnea, wheezing, or cough.^95–97 Precipitants include infection, fat embolism after bone marrow infarction, pulmonary infarction, and surgical procedures.^97–99 Potential risk factors for the development and severity of perioperative ACS include a history of lung disease, recent clustering of acute pulmonary complications, pregnancy, increased age, and the invasiveness of the surgical procedure.⁹² A study of 60 laparoscopic surgeries noted that ACS was associated with younger-age patients, reduced body temperature, and greater blood loss.¹⁰⁰

Minor procedures such as inguinal hernia repair or distal extremity surgery have a reduced risk of pulmonary complications (<5%), whereas intraabdominal or major joint surgery has an ACS rate of 10% to 15%.^99,101,102 Although the overall perioperative mortality from SCD is quite small, <1%,⁹⁹ ACS can lead to prolonged postoperative hospitalization, respiratory failure, and death. One study of 604 patients noted that ACS typically developed about 3 days postoperatively and persisted for approximately 8 days; 2 patients died in approximately 60 episodes.⁹⁸

SCD also causes chronic lung damage, known as sickle cell lung disease (SCLD).¹⁰³ Because lung function has not yet been assessed longitudinally in a cohort from early childhood to adulthood, the precise pathology of and relationship between the obstructive and restrictive patterns of lung disease is unclear.¹⁰⁴ Children appear to have a predominantly obstructive pattern,¹⁰⁵ whereas adults have more restrictive pulmonary findings.^103,106,107 The later stages of lung damage involve decreased vital and total lung capacities, impaired gas diffusion, pulmonary fibrosis, pulmonary artery hypertension, right-sided cardiomyopathy, and progressive hypoxemia.^103,107 The development of pulmonary artery hypertension, which can precede clinically apparent lung damage, is a particularly ominous sign of disease progression and is associated with a heightened risk of sudden death.¹⁰⁶ Recurrent ACS is an independent risk factor for the development of end-stage SCLD, but subtle evidence of parenchymal and vascular damage commonly precedes clustered episodes of ACS.¹⁰³

Assessment of lung function should include a history of the occurrence, frequency, severity, and known precipitants of ACS and a search for progression of chronic lung damage. A recent chest radiograph can serve as a baseline for comparison if postoperative radiographs are needed and can also delineate lung pathology. Early features of lung damage include decreased distal pulmonary vascularity and diffuse interstitial fibrosis, whereas later stages are characterized by pulmonary fibrosis, pulmonary hypertension, and right ventricular hypertrophy.^103,108 Pulmonary function testing can reveal the need for bronchodilators and the presence of obstructive or restrictive lung disease.

The efficacy of preoperative or intraoperative management techniques beyond basic standards of care has not been clearly demonstrated; well-delivered anesthetic and postoperative care may be the best guarantor of a good outcome.^92,93 Because the effect of perioperative red blood cell transfusion (versus no transfusion) in preventing ACS or other SCD complications has not been tested by an adequately controlled study, the efficacy of prophylactic erythrocyte transfusion is controversial. One guideline suggested that children in low-risk situations should not be transfused prophylactically, but children in high-risk situations may be transfused.⁹² A survey of North American pediatric anesthesiologists found that most tend not to transfuse children assessed as being at low risk undergoing minor procedures, whereas a greater number do transfuse those at greater risk (i.e., sicker children undergoing more invasive procedures).¹⁰⁹

If transfusion is undertaken, exchange transfusion aiming to decrease the concentration of hemoglobin S to 30% is no more efficacious than correction of anemia to a hematocrit of 30% in preventing SCD exacerbations but results in more transfusion-related complications.⁹⁸ Consequently, if a decision is made to transfuse in the hope of preventing ACS, the target should be a hematocrit of 30% rather than a specific dilution of hemoglobin S.

The one high-risk group that merits mention are children who have experienced or are at risk for a stroke. Risk factors for strokes include low hemoglobin, hypertension, and male gender as well as three single nucleotide polymorphisms.^110,111 Transcranial Doppler ultrasound and magnetic resonance imaging of the brain have been used serially to detect pathologic changes in blood flow or subclinical strokes, respectively, and in these children transfusion has been effective in reducing subsequent strokes.^112,113 Silent cerebral strokes have been detected in up to 30% of asymptomatic children with SCD.¹¹⁰ To reduce the risk of stroke, these children are transfused at regular intervals, based on the results of the serial investigations. However, this approach raises concern about iron overload and other complications associated with repeated blood transfusions. A recent study to limit the number of transfusions in those at risk for a stroke had to be stopped prematurely because two strokes occurred despite serial transcranial Doppler monitoring.¹¹⁴ Chronic hydroxyurea therapy has also been shown to be effective in reducing the risk of stroke.¹¹⁵

Children with SCD frequently develop postoperative atelectasis. It is unclear whether this relates to an underlying sickle lung disease, difficulty with analgesia, other causes, or a combination of factors. Pain management can be difficult in these children. Large doses of opioids can depress ventilation and cause atelectasis.¹¹⁶ ACS tends to involve the lower segments of the lung,⁹⁷ suggesting an association between atelectasis and ACS. Incentive spirometry can prevent the development of atelectasis and pulmonary infiltrates associated with ACS.¹¹⁷ Regional analgesia, supplemental nonopioid analgesics, prophylactic incentive spirometry, early mobilization, and good pulmonary toilet may decrease the incidence of atelectasis and ACS.

Treatment of ACS is focused on supporting gas exchange. Supplemental oxygen, noninvasive ventilatory support such as continuous positive airway pressure, or intubation and mechanical ventilation are indicated by the degree of dysfunction. Bronchodilators, incentive spirometry, and chest physiotherapy may be useful in preventing progression of the disease. In the presence of a significant ventilation/perfusion mismatch, correction of anemia can improve arterial oxygenation. Erythrocyte transfusion increases oxygen-carrying capacity, decreases fractional peripheral tissue extraction, and increases returning venous oxygen levels. Because the mean arterial oxygen content in the presence of a shunt is significantly affected by the oxygenation of blood returning from nonventilated parts of the lung, increasing venous oxygen levels can improve arterial oxygen content. Although transfusion has not been clearly shown to improve outcome, both exchange and simple transfusion can improve oxygenation.⁹⁷