Preoperative Evaluation

The preoperative evaluation should include measurements of the hematocrit, electrolyte levels, and glucose levels. A hemoglobin (Hb) A1c level (i.e., glycosylated Hb assay), although a useful index of long-term glucose control, is unlikely to affect the anesthetic plan and is not a necessary preoperative test (Nathan et al., 1984). If glycohemoglobin results are available, it is important to remember that different laboratories have different ranges for Hb A1c in normal subjects. Even in the same laboratory, the normal range may change from time to time. It is therefore important to know the laboratory’s normal range to interpret results in patients with diabetes. The normal range of Hb A1c is 4.5% to 6.1%, but the normal range also varies with age (Rhodes et al., 2005; Custer and Rau, 2009).

Several systemic abnormalities may be present in the child with diabetes. Nineteen percent of children with diabetes have a vital capacity two standard deviations below the predicted mean value, suggesting the presence of restrictive lung disease (Buckingham et al., 1986). No apparent association exists between decreased vital capacity and duration of diabetes or presence of other diabetic complications. Abnormal lung elasticity and thickening of the alveolar basal laminae have been reported in children with diabetes (Schuyler et al., 1976; Vracko et al., 1980). Routine preoperative pulmonary function tests are not indicated in the asymptomatic child who has diabetes.

Decreased atlantooccipital joint mobility, resulting in difficult intubation, may be present in a subset of adolescents with a syndrome of diabetes mellitus, short stature, and tightness of small joints of the fingers, wrists, ankles, and elbows (Salzarulo and Taylor, 1986). Abnormal cross-linking of collagen by nonenzymatic glycosylation is the postulated cause of this syndrome (Chang et al., 1980).

Perioperative Management

Various regimens for managing insulin therapy perioperatively have been proposed, three of which are discussed in the following sections and in Table 36-2: a classic regimen, the subcutaneous infusion insulin pump, and intravenous (IV) insulin infusion. Essential to optimal management, regardless of regimen, is the scheduling of elective surgery for the child with diabetes as early as possible in the day (first case) to minimize time that the patient must fast. The fasting interval should be the same as that recommended for patients who do not have diabetes: no solid food or milk for 8 hours, and clear liquids are permissible until 2 hours before the scheduled time of surgery (Schreiner et al., 1990). Children with diabetes should be encouraged to continue taking clear liquids until 2 hours before surgery. If this is not possible, an IV fluid infusion should be started (described later). As recommended in adult patients with type 2 diabetes, metformin should be stopped 48 hours before surgery, based on reports of lactic acidosis in patients who remain on the drug and are in a fasting state perioperatively. Other orally administered medications (e.g., thiazolidinediones or sulfonylureas) may be continued through the day before surgery.

TABLE 36-2 Protocols for Perioperative Insulin Therapy

Although some investigators have recommended the withholding of preoperative sedation from patients with diabetes to better monitor for signs of hypoglycemia, premedication is recommended in children. The use of agents such as benzodiazepines, opioids, or barbiturates does not alter glucose metabolism, and the failure to use such agents may elevate the blood sugar level as a result of anxiety, which causes a stress response with catecholamine release.

Based on the blood-glucose level determined on arrival to the preoperative facility and before implementation of the regimens discussed in the following sections, glucose or insulin should be administered according to the scheme outlined in Table 36-3.

TABLE 36-3 Preoperative Glucose and Insulin Management for Diabetic Patients

NS, Normal saline; SC, subcutaneously.

Anesthetic Management

Regional or general anesthesia is appropriate for the child with diabetes mellitus. If tolerated with minimal sedation, regional anesthesia might be argued to offer the advantage of allowing for observation of the level of consciousness as a monitor of hypoglycemia. Practically speaking, most children require general anesthesia, even when regional techniques are employed. The ease and availability of point-of-care glucose determination from venous or finger-stick specimens obviate the need for monitoring of cerebral function.

Perioperative Management of Diabetic Ketoacidosis

Occasionally, patients with diabetes require surgery for trauma or infection while they are in a state of ketoacidosis. Diabetic ketoacidosis includes hyperglycemia (plasma-glucose concentration greater than 300 mg/dL) with glucosuria, ketonemia (ketones strongly positive at greater than 1:2 dilution of serum), ketonuria, and acidemia (pH lower than 7.30, serum bicarbonate lower than 15 mEq/L, or both). It is common for intraabdominal catastrophes with infection (e.g., appendicitis) to precipitate ketoacidosis. Foster and McGarry (1983) have succinctly summarized the pathophysiology of diabetic ketoacidosis. The initiating event is usually cessation of insulin therapy or onset of stress that renders the usual dose of insulin inadequate. Glucagon, catecholamines, cortisol, and growth hormone levels increase. A catabolic state is produced as substrates are mobilized, resulting in hepatic production of glucose and ketone bodies, which causes hyperglycemia and ketoacidosis. Subclinical brain swelling nearly always occurs during diabetic ketoacidosis therapy, although most patients remain asymptomatic (Krane et al., 1985). Fatalities from cerebral edema do occur, and some studies suggest that high rates of fluid administration early in treatment (more than 50 mL/kg in the first 4 hours) greatly increase the risk of herniation (Mahoney et al., 1999). Studies using 4 L/m² for the first 24 hours followed by 1 to 1.5 times maintenance resulted in clearance of ketoacidosis equal to that in patients who were given more fluid, but a low but persistent incidence (0.35% to 0.5%) of symptomatic cerebral edema remained (Felner and White, 2001). The best methods to prevent the development of this devastating complication are administration of isotonic fluid only and frequent monitoring of serum osmolality (by direct measurement or calculation) to ensure that elevated osmolality is reduced gradually. Insulin therapy should be tailored to decrease the blood glucose concentration at a rate not greater than 100 mg/dL per hour. To prevent a more rapid decrease in blood glucose concentration, 5% dextrose and if necessary, 10% dextrose, should be added to the rehydration solution to slow the rate of fall, rather than decreasing the rate of insulin infusion (Arslanian et al., 1994). Fortunately, the anesthesiologist is rarely called on to administer anesthesia during this severe metabolic derangement. If an anesthetic is required during diabetic ketoacidosis, preoperative attention should be directed toward the correction of hypovolemia and hypokalemia, along with beginning an insulin infusion. Invasive hemodynamic monitoring may be indicated preoperatively to optimize the patient’s fluid and electrolyte balance and to monitor the patient’s hemodynamic status accurately. Surgery should not be delayed inordinately because it may be impossible to correct the metabolic derangements before the underlying source of infection or organ dysfunction is corrected. For patients with signs of cerebral edema, monitoring of intracranial pressure may be necessary.

Adrenal Insufficiency as a Result of Primary Abnormalities of the Hypothalamic-Pituitary-Adrenal Axis

Adrenal insufficiency is an uncommon disease in children, but when it occurs it is associated with significant implications for the anesthesiologist. The causes of adrenal insufficiency are listed in Box 36-3. Adrenal insufficiency may include glucocorticoid deficiency with or without mineralocorticoid deficiency (Box 36-4). Isolated hypoaldosteronism is rare. In the perioperative period, children with congenital adrenal insufficiency require glucocorticoid and mineralocorticoid replacement.

Chronic deficits in adrenal function result in the classic findings of Addison disease, including hyperpigmentation, weakness, and hyponatremia. The hyperpigmentation results from high levels of adrenocorticotropic hormone (ACTH) and unopposed melanophore-stimulating hormone caused by cortisol insufficiency. The additional presence of aldosterone insufficiency may produce hyponatremia, hyperkalemia, hypotension, and a small cardiac silhouette that results from hypovolemia (Keon and Templeton, 1993).

Perioperative Steroid Management

The preoperative recognition of adrenal insufficiency and appropriate preoperative therapy minimize the likelihood of significant perioperative complications. Ninety percent of patients with congenital adrenal hyperplasia with adrenal insufficiency have 21-hydroxylase deficiency (Migeon and Donohoue, 1994). Virilization of the external genitalia occurs in female patients, and they often require surgical revision of their external genitalia. An abnormal genital pigmentation occurs in male patients, but this finding may be subtle. Infants with undiagnosed congenital adrenal hyperplasia may undergo exploratory laparotomy for acute abdomen because of nausea and vomiting. It is important to be attuned to the signs and symptoms in the history, physical examination, and laboratory evaluation that point to this diagnosis to prevent or treat shock, which may occur because of failure to administer steroid replacement.

Mineralocorticoid deficiency can be managed by administering saline solution and avoiding potassium in IV fluids. Mineralocorticoid secretion rates in children are similar to those in adults, and the replacement dose is independent of age and weight. Desoxycorticosterone acetate may be administered intramuscularly in a dose of 1 mg/day. The intramuscular injection may be replaced by a single daily oral dose of 9-fluorocortisol (Florinef, 0.05 to 0.1 mg) when it is clear that an oral medication can be tolerated and absorbed. When cortisol is administered perioperatively, it has sufficient mineralocorticoid activity to obviate the need for any other replacement; 20 mg of hydrocortisone has mineralocorticoid activity equivalent to 0.1 mg 9a-fluorocortisol (Miller et al., 2008).

Glucocorticoid deficiency is treated with cortisol (hydrocortisone) replacement. The importance of cortisol replacement for patients with known adrenal insufficiency should not be underestimated, although vastly excessive doses are unwarranted. In the normal individual, the adrenal gland secretes 12 ± 2 mg of cortisol per square meter of body surface area every 24 hours (Kenny and Preeyasombat, 1966). The normal replacement dose prescribed for unstressed children is 25 mg/m² per day; the dose is double the normal production because of factors of bioavailability and half-life (Migeon and Donohoue, 1994). In response to stress (e.g., fever, acute illness, surgery, and anesthesia), the normal adrenal gland secretes 3 to 15 times this amount. Consequently, in the past, the recommendations for “stress” steroid coverage in the perioperative period ranged from 36 to 180 mg/m² per day.

More important than just the dose of steroid to be given, consideration should be devoted to the type of glucocorticoid administered, its half-life, the route of administration, and the timing of doses. The equivalencies for steroid preparations in terms of their relative glucocorticoid and mineralocorticoid effects are presented in Table 36-5. The most commonly cited recommendation for perioperative steroid coverage is hydrocortisone hemisuccinate (Solu-Cortef), given intravenously as 2 mg/kg immediately preoperatively and every 6 hours on the day of surgery, with reductions in the postoperative period depending on the degree of stress. Some practitioners feel that the half-life of hydrocortisone is so short that a 6-hour dosing interval may lead to periods of inadequate “coverage.” These practitioners recommend a preinduction dose of 25 mg/m² of hydrocortisone given intravenously, followed by a continuous infusion of 50 mg/m² administered during the estimated period of anesthesia. Postoperatively, 50 mg/m² by continuous infusion is administered over the remainder of the first 24 hours. The total dose for the first 24 hours is 125 mg/m², or 10 times normal physiologic production (Migeon and Donohoue, 1994). The first bolus dose must be administered before induction of anesthesia rather than waiting for an IV cannula to be placed after inhalational induction because of the stress associated with anesthetic induction itself. In the postoperative period, the steroid dose is tapered to a level commensurate with the residual stress. It is replaced with the child’s usual oral preparation when the child clearly can tolerate and absorb oral medication.

Hypothyroidism

Hypothyroidism occurs because of abnormally low production of thyroid hormone. It may be caused by primary thyroid dysfunction or result from pituitary failure with decreased production of thyroid-stimulating hormone (TSH). Normal values for routinely performed thyroid function tests are presented in Table 36-6, and the interpretation of these test results with regard to diagnosis is presented in Table 36-7.

TABLE 36-6 Thyroid Function Tests

RIA, Radioimmunoassay; RU, resin uptake; T₃, triiodothyronine; T₄, thyroxine; TBG, thyroid-binding globulin; TSH, thyroid-stimulating hormone.

* Measures thyroid hormone binding, not T₃.

† T₄ RIA × T₃ RU.

‡ Reverse T₃.

Modified from Johnson KB, editor: The Harriet Lane Handbook, St. Louis, 1993, Mosby.

Primary thyroid dysfunction may be congenital or acquired. Congenital hypothyroidism usually appears in infancy. Classic features in the infant include large fontanels, wide sutures, large tongue, umbilical hernia, and decreased deep tendon reflexes. In the older child, manifestations include slow heart rate, narrow pulse pressure, growth failure, hypothermia, and cold intolerance. Severe hypothyroidism is rare but may be associated with coma, cardiovascular collapse, hyponatremia, hypothermia, and respiratory failure. Keon and Templeton (1993) reviewed the anesthetic management of patients with hypothyroidism and stressed the importance of correcting hypothyroidism gradually over a 2-week period. Sudden death has been reported in children with myxedematous heart disease 2 to 3 weeks into therapy (LaFranchi, 1979). It is suggested that these children receive one fourth of the maintenance dose of thyroid hormone (6 to 8 mcg/kg per day for an infant), with gradual incremental increases over 2 to 4 weeks until a maintenance dose is reached (Custer and Rau, 2009). Patients who are adequately treated will have normal thyroid hormone and TSH levels. Patients who do not respond to oral thyroid replacement may be given IV triiodothyronine (T3; loading dose of 0.7 mcg/kg), followed by an infusion titrated to T3 and TSH levels. Severe cardiac dysfunction in such a patient improved with T3 therapy (Mason et al., 2001). Patients with incompletely restored thyroid hormone levels may require hemodynamic monitoring and support to maintain hemodynamic stability. Patients with severe hypothyroidism may have associated adrenal insufficiency, and if so, they should receive stress steroid coverage as outlined earlier.

The anesthetic care of the symptomatic patient with hypothyroidism can be problematic and requires caution when any depressant medications are given. Prolonged effects may result from decreased drug metabolism. Important considerations in the management of hypothyroidism as described by Keon and Templeton (1993) are outlined in Table 36-8. Invasive monitoring may be indicated when significant blood loss or fluid shifts occur. Care should be taken intraoperatively to minimize heat loss. Postoperative care should include monitoring of oxygen saturation, blood pressure, heart rate, and respiratory rate; postoperative ventilation may be necessary in the patient with delayed emergence from anesthesia.

TABLE 36-8 Anesthetic Implications of Hypothyroidism

MAC, Minimum alveolar concentration; PVR, peripheral vascular resistance; SIADH, syndrome of inappropriate antidiuretic hormone.

Hyperthyroidism

Hyperthyroidism is a syndrome produced by excess levels of circulating thyroid hormone. The most common causes are congenital hyperthyroidism and Graves disease (i.e., toxic goiter). Less commonly, acute suppurative thyroiditis, hyperfunctioning thyroid carcinoma, thyrotoxicosis factitia (i.e., exogenous administration of thyroid hormone), and toxic uninodular goiter (i.e., Plummer disease) may produce this syndrome. McCune-Albright syndrome (i.e., precocious puberty with polyostotic fibrous dysplasia) is also commonly associated with hyperthyroidism (Jones, 1988).

Laboratory Evaluation

Serum levels of thyroxine (T4) and T3 are usually elevated in hyperthyroidism. TSH secretion is suppressed and may be unmeasurable. T3 toxicosis (elevated T3 level with normal amounts of T4) is more common in adult patients and rarely seen in children. For borderline cases, thyrotropin-releasing hormone (TRH) stimulation tests may be needed. Many patients with Graves disease of recent onset may have elevated levels of thyroid-stimulating immunoglobulin. Radionuclide scans can also be helpful in making a diagnosis. If a large goiter is present, neck radiographs, computed tomography (CT) scans, or magnetic resonance imaging (MRI) may be used to evaluate the degree of tracheal compression and deviation.

Treatment

The management of hyperthyroidism is aimed at controlling the cardiovascular effects. β-adrenergic receptor blockade, usually with propranolol (1 to 2 mg/kg per day), is titrated to effect. Antithyroid medications include propylthiouracil and methimazole, both of which inhibit the incorporation of inorganic iodide into organic compounds. Propylthiouracil inhibits the conversion of T4 to T3. Although early studies suggested that these agents might inhibit the formation of thyroid antibodies, later studies that included careful histopathologic analysis have shown this to be false (Paschke et al., 1995). The Food and Drug Administration (FDA) has recently recommended that propylthiouracil not be administered to pediatric patients because of reports of liver failure associated with its use. Methimazole is the antithyroid medication recommended for use in infants, children, and adolescents (FDA, 2009). Saturated solutions of potassium iodide may be administered orally (1 drop every 8 hours) to suppress thyroid hormone secretion. The clinical response to therapy is evident in 1 to 3 weeks, and the patient may require up to 3 months for adequate control to be achieved. Patients must have appropriate, regular surveillance to ensure that the T3 and T4 levels are in the normal range and that TSH concentrations are normal. Clinically, the patient demonstrates a euthyroid state by return of the heart rate, blood pressure, and reflexes to normal.

Radioactive iodine is often used to treat hyperthyroidism in adults. However, such therapy is avoided in children because of side effects such as thyroid cancer, genetic damage to germ cells, and a higher incidence of hypothyroidism than occurs with pharmacologic therapy.

Anesthetic Management

Preoperatively, patients should be pharmacologically euthyroid. Any residual cardiovascular signs and symptoms should be well controlled through the use of a β-adrenergic receptor blocker. Esmolol is an excellent choice for intraoperative use. A large goiter may produce tracheal deviation or compression, and the possibility of airway compromise should be evaluated preoperatively with radiographic studies. Any commonly used sedative may be given for premedication. Atropine and other anticholinergics should be avoided or used with extreme caution, because they decrease sweating and may interfere with thermoregulation. Medications, including antithyroid drugs and β-adrenergic blockers, should be administered through the morning of surgery.

Postoperative Care

Children who have undergone thyroidectomy require close observation in the postoperative period (Fewins et al., 2003). They may develop postextubation croup or upper airway obstruction as a result of paralysis of the vocal cords, tetany (hypocalcemia), residual tracheomalacia, or tracheal compression resulting from a hematoma. Patients with postextubation croup may respond to supportive measures, including humidified supplemental oxygen, nebulized racemic epinephrine, and possibly, continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP). Occasionally, these patients require brief reintubation before they can be successfully extubated. Unilateral vocal cord paralysis may go unnoticed or be associated with only mild stridor. Bilateral vocal cord paralysis, on the other hand, may manifest as severe stridor and upper airway obstruction. The child with bilateral vocal cord paralysis requires reintubation for airway support. A muscle relaxant such as rocuronium should be used to facilitate reintubation to avoid damage to the abducted cords. If the paralysis is prolonged, the child may subsequently require tracheostomy. Compression of the trachea by a hematoma may occur immediately after the operation or over the course of several hours. The child requires reintubation and surgical evacuation of the hematoma to relieve tracheal compression. Opening the wound in the recovery room may be necessary and lifesaving. After the extrinsic obstruction has been relieved and the incision closed again (if necessary), the child may be safely extubated.

Inadvertent resection of the parathyroid glands during thyroidectomy may result in acute hypoparathyroidism after surgery. Clinical signs of hypocalcemia may become manifest within the first postoperative day or take as long as 72 hours to develop. A low serum-ionized calcium level and a low concentration of parathyroid hormone are diagnostic. Clinical hypocalcemia, including tetany, is treated with IV calcium therapy. Surgical manipulation of the trachea and neck tissues can also lead to subcutaneous emphysema and the more serious possibility of pneumomediastinum or pneumothorax. Postoperative evaluation should include radiologic examination of the chest if respiratory distress occurs.

Diagnosis

It is extremely important to establish the diagnosis of pheochromocytoma before induction of anesthesia and start of surgery. The significant cardiovascular effects of excess catecholamines can pose difficulties for the anesthesiologist and endanger the patient during the perioperative period if an appropriate diagnosis is not made preoperatively. These tumors can produce paroxysms of hypertension and other symptoms. Between paroxysms, the patient may be totally asymptomatic, making diagnosis extremely difficult. The demonstration of increased levels of catecholamines is the most specific diagnostic test. Although pheochromocytomas can produce norepinephrine and epinephrine, the predominant catecholamine produced in children is norepinephrine, which leads to chronic hypertension. Urine catecholamine concentrations are directly proportional to circulating levels, and determination of 24-hour urinary excretion of the primary catecholamines and their metabolites (i.e., 3-methoxy 4-hydroxy vanillyl-mandelic acid [VMA] and metanephrine) used to be the primary means of establishing the diagnosis. The plasma free metanephrine determination has better sensitivity (100%) and specificity (94%). Because normal values differ with age, it is important to use age-specific norms when interpreting results (Weise et al., 2002).

The differential diagnosis includes renal vascular disease, hyperthyroidism, Cushing syndrome, coarctation of the aorta, adrenal cortical tumors, and essential hypertension. Cerebral disorders, diabetes mellitus, and DI may produce similar symptoms. Neoplasms of neural origin (e.g., neuroblastoma or ganglioneuroma) may also secrete catecholamines.

Before any contemplated anesthesia and surgery, the patient must undergo a complete evaluation to localize the tumor, including CT and MRI scans. Magnetic resonance angiography (MRA) and venography (MRV) may be used to identify vascular supply. A radionuclide (I-131 metaiodobenzylguanidine [MIBG]) scan may also help to localize the tumor. Differential venous catheterization may be needed to obtain blood from various sites for catecholamine levels if multiple tumors are suspected. Sedation or anesthesia may be required to perform these studies in infants and children. Before sedation for these diagnostic studies, hemodynamic abnormalities must be normalized. Drugs that induce catecholamine secretion or histamine release should be avoided. General anesthesia for the diagnostic procedures must be conducted with the same extreme caution one would exercise for resection of the tumor itself.

Preoperative Preparation and Evaluation

Preoperative evaluation should include the measurement of serum electrolytes, determination of renal function, and fasting blood glucose. Excessive serum epinephrine levels may be associated with hyperglycemia and hypokalemia. An electrocardiogram and echocardiogram are important to evaluate cardiac rhythm, size, and function. Some patients with pheochromocytoma have a catecholamine-induced cardiomyopathy with decreased left ventricular contractility. The patient should be evaluated for associated endocrinopathies that may be present as part of MEN type II or III.

Symptomatic treatment includes the administration of phenoxybenzamine over a period of several days to weeks before surgery. Phenoxybenzamine is a long-acting, orally administered α-adrenergic blocking agent that attenuates the effects of catecholamines on the peripheral circulation by blocking excessive vasoconstriction (Hoffman and Lefkowitz, 1990). The starting dose of phenoxybenzamine is 0.2 mg/kg once daily (maximum adult dose, 10 mg) (Taketomo et al., 2008). Then both dose and frequency are gradually increased (up to 3 times a day) until a clinical effect is obtained; that is, the patient’s hematocrit decreases (because of vasodilation and increased blood volume), and the patient develops orthostatic changes in vital signs. Long-standing vasoconstriction produced by chronically high catecholamine levels causes decreased intravascular volume. Although the use of phenoxybenzamine restores vascular capacity to normal, increased oral fluid intake should accompany administration of phenoxybenzamine to avoid severe orthostatic changes. In some children, β-adrenergic blocking drugs such as propranolol may be needed to control heart rate and blood pressure. However, β-blocking agents should never be used without concurrent α-blockade therapy because of the deleterious effects of unopposed α-agonism, which may result in cardiac failure as a result of increased afterload. Labetalol may have a role in the management of pheochromocytoma, because it has α- and β-adrenergic blocking properties (Blom et al., 1987). It can be useful in minimizing the cardiovascular effects of excess catecholamines during the perioperative period, but it is not as potent an a blocker as is phenoxybenzamine for preoperative treatment.

In addition to pharmacologic preparation, children with pheochromocytoma benefit from preoperative sedation to reduce the release of catecholamines caused by anxiety. Oral or IV midazolam alone or in combination with an opioid provides a good level of sedation.

Anesthetic Induction

Induction of anesthesia is accomplished with IV anesthetics. Ketamine is specifically contraindicated, because it induces catecholamine release. Halothane should be avoided, because it may sensitize the myocardium to catecholamines and produce dysrhythmias. Mask induction with sevoflurane is well tolerated if hemodynamic parameters are well controlled, and IV cannula placement can be deferred until after induction. Intubation may proceed in the usual fashion, facilitated by a hemodynamically neutral nondepolarizing muscle relaxant such as vecuronium. Pancuronium, which causes muscarinic blockade and tachycardia, should be avoided. Despite the fact that atracurium causes histamine release and vasodilation, it has been used safely in adult patients with pheochromocytoma (Prys-Roberts, 2000). Before intubation, IV lidocaine (1 mg/kg), fentanyl (2 to 5 mcg/kg), or both are effective in minimizing the hemodynamic response to intubation.

Intraoperative Management

After induction of anesthesia, an intraarterial catheter is placed to monitor the blood pressure continuously. Before induction, a reliable automated blood pressure device can provide frequent, accurate blood pressure measurements. A central venous catheter provides direct and reliable access for the assessment of intravascular volume and for infusions of fluids and emergency medications.

Anesthesia may be maintained with isoflurane or sevoflurane, air, and oxygen. Both anesthetic agents have been used without exacerbation of hypertension, despite the fact that they do not blunt the production of norepinephrine in response to surgical stimulation (Suzukawa et al., 1983). Desflurane should be avoided because of its tendency to cause tachycardia and hypertension. The addition of moderately large doses of fentanyl (10 mcg/kg) or remifentanil (0.3 to 1 mcg/kg per minute) minimizes the stress response and provides stable hemodynamics. If remifentanil is chosen, it is important to give a longer-acting opioid before the end of surgery to avoid hypertension as a result of pain on awakening. Adjunctive use of epidural anesthesia (i.e., local anesthetic with or without a small dose of fentanyl) is an excellent method of reducing the stress response and catecholamine release caused by usual surgical stimulation. However, none of these anesthetic strategies blocks catecholamine release that results from direct surgical manipulation of tumor tissue.

Historically, controlling blood pressure during the induction and maintenance of anesthesia has been accomplished by an infusion of sodium nitroprusside or phentolamine. However, resection is increasingly being performed using a laparoscopic technique, and either nicardipine or magnesium sulfate infusions are used to maintain vasodilation and normotension during this type of surgery (Pretorius et al., 1998; Minami et al., 2002). In addition to propranolol use preoperatively, esmolol has been effective as a continuous infusion titrated to the level of surgical stimulation (Nicholas et al., 1988). Infusions of only short-acting vasodilators are recommended for control of hypertension before tumor resection, because with removal of the tumor, vasodilation caused by a persistent blockade and loss of excess catecholamines may lead to precipitous hypotension. Phenoxybenzamine has a long half-life; therefore, some physicians recommend discontinuing it 24 hours before surgery to decrease the likelihood that persistent vasodilation caused by a blockade will cause severe hypotension after the tumor is removed because of withdrawal of the catecholamines of tumor origin (Prys-Roberts, 2000). Hypotension is best treated with discontinuation of vasodilator infusions, titration of anesthetic agents, and administration of crystalloid or colloid and blood products, if it is indicated by the magnitude of blood loss. If these measures are ineffective, vasopressors may be necessary, but the patient may be relatively resistant to α-agonists as a result of persistent α-blockade. If this occurs, judicious use of small doses of more potent, direct-acting vasoconstrictors (e.g., norepinephrine or epinephrine) may be necessary. Recently, vasopressin infusion has been effective in this situation (Deutsch and Tobias, 2006).

During surgery, arterial blood gases, serum glucose, urine output, and body temperature should be closely monitored. Hyperglycemia may occur in response to high catecholamine levels. Hypoglycemia may occur when the tumor is removed and catecholamine levels decrease. Because of the potential for dysrhythmias, the electrocardiogram should also be vigilantly observed. At the end of surgery, the muscle paralysis is reversed. Extubation can be accomplished when the patient meets all normal extubation criteria.

Postoperative Care

Postoperatively, the patient should be observed in an intensive care unit, with continuous monitoring of the arterial blood pressure and electrocardiogram. Hypertension usually resolves within 24 to 48 hours after surgery. If symptoms persist beyond this period, further investigation for residual pheochromocytoma is warranted. Good postoperative analgesia is provided with epidural infusion (if an open procedure was performed) or IV patient- (parent- or nurse-) controlled analgesia.

Pathophysiology of Upper Tract Respiratory Infection

Many investigators suggest that complications, including bronchospasm, intraoperative hypoxemia with an increased alveolar-arterial oxygen gradient, and postoperative hypoxemia, occur more often in children who undergo anesthesia while they have URIs (McGill et al., 1979; Olsson, 1987; DeSoto et al., 1988). The proclivity for these complications may be related to peripheral airway abnormalities, which have been demonstrated experimentally in adult humans and animals infected with viral respiratory pathogens (Johanson et al., 1969; Fridy et al., 1974; Dueck et al., 1991). These abnormalities include decreased diffusing capacity and increased closing volume—factors that can predispose patients to intrapulmonary shunting and hypoxemia, especially when they are combined with the effect of general anesthesia on lung volumes (decreased functional residual capacity) (see Chapter 3, Respiratory Physiology in Infants and Children) (Murat et al., 1985). These studies were done in adults who had infections involving their entire respiratory tracts rather than isolated URIs, and their results may support separation of treatment of patients with truly isolated URIs from those with any symptoms of more global airway or pulmonary parenchymal involvement (lower respiratory tract infection). Although the mechanisms by which viral respiratory infections lead to alterations in airway function are unclear, these experimental studies support the clinical impression that increased risk of perioperative hypoxemia occurs in patients with recent viral respiratory infection.

Empey et al. (1976) demonstrated in adult patients that acute viral respiratory tract infection (influenza) produced marked bronchial reactivity to experimental bronchoconstrictor challenge that may persist for 6 weeks. Mechanisms by which viral infections lead to increased airway reactivity include the release of immunologic and inflammatory mediators such as leukotrienes, bradykinin, and histamine, which cause bronchoconstriction. Vagal-mediated mechanisms may be involved, because viral infections have been associated with changes in muscarinic receptors on airway smooth muscle (Fryer et al., 1990). Tissue concentrations of important enzymes such as neutral endopeptidase, which break down the neuropeptides that cause bronchoconstriction, are also decreased in viral infections (Jacoby et al., 1988; Dusser et al., 1989). However, these patients and animals cannot be said to have only URIs, because the airways below the larynx are also clearly affected. Patients whose infections are truly uncomplicated URIs or those with noninfectious causes of runny nose should be differentiated from those who have evidence of lower respiratory involvement.

Perioperative Risk

Many case reports in the literature document that in the perioperative period children with URIs have respiratory complications, including bronchospasm, stridor caused by subglottic edema, hypoxia, and atelectasis (McGill et al., 1979; Konarzewski et al., 1992; Williams et al., 1992). Three prospective studies have shown that patients with an active or recent URI had a 2- to 10-fold higher risk of bronchospasm or laryngospasm (Olsson and Hallen, 1984; Olsson, 1987; Cohen and Cameron, 1991). The incidence was higher among younger children, especially those younger than 2 years and those whose tracheas were intubated (Cohen and Cameron, 1991). Retrospective studies of much larger numbers of patients show a higher risk of respiratory complications may actually exist in asymptomatic children with history of URI within the 2 to 4 weeks preceding surgery than in those with acute URI (Tait and Knight, 1987b; Tait et al., 2001). Other studies found that the factors that increase the risk of adverse events were history of prematurity or reactive airways disease (RAD), parental smoking, copious secretions, nasal congestion intubation, and airway surgery (Tait et al., 2000, 2001). Despite this increased risk of adverse events, complications usually were easily treated and were not associated with any significant prolonged morbidity (Rolf and Cote, 1992; Tait et al., 2000, 2001). However, some patients in one study developed atelectasis severe enough to require bronchoscopy and prolonged postoperative mechanical ventilation. Although most of these studies evaluated children undergoing relatively minor elective surgery, another study reported that children with URI symptoms at the time of cardiac surgery also had increased risks for respiratory and other complications, including nonrespiratory infection (Malviya et al., 2003). Despite these findings, patients’ hospital stays were not prolonged, and the incidence of long-term sequelae was not increased.

One study found that children with URIs who undergo mask halothane-nitrous oxide-oxygen anesthesia for myringotomy surgery had reduced severity and duration of URI symptoms in the postoperative period (Tait and Knight, 1987a). However, this reduction in symptoms may have resulted from the drainage and removal of infectious foci by the surgical procedure rather than from the beneficial effects of general anesthetics. Other investigators have reported no significant respiratory complications when children with URI were anesthetized (Hinkle, 1989; Jacoby and Hirshman, 1991). It is extraordinarily difficult to integrate the contradictory conclusions of these various series of patients to develop a logical algorithm for dealing with the child with a URI.

Anesthetic Decision Making

It is apparent that no consensus has been reached in the literature or in the general anesthesia community with regard to the wisdom and safety of anesthetizing children with active or recent URIs. The bulk of the literature, clinical and experimental, suggests that recent viral infection increases the perioperative risk for respiratory complications, albeit mild and treatable, when the surgical and anesthetic plans require intubation. In children with underlying RAD, the risk for pulmonary complications immediately after acute URI is much greater than in the normal patient population, making intraoperative bronchospasm much more likely. The threshold for postponing surgery in the asthmatic child with a recent URI who requires intubation is much lower. These risks must be weighed against the physiologic, psychological, and financial implications of delaying surgery.

The most conservative approach to the child with a URI or recent URI is to postpone elective procedures for 1 to 2 weeks for uncomplicated rhinorrhea, congestion, and nonproductive cough and for 4 to 6 weeks for patients with lower-airway involvement (e.g., wheezing or productive cough). However, this may be an overly cautious and somewhat unrealistic recommendation. Children without other health conditions have an average of 3 to 8 colds per year, and children whose mothers smoke, who live in crowded conditions, and who attend daycare centers have a 61% incidence of URIs over a 2-week period (Fig. 36-2) (Fleming et al., 1987). It may be nearly impossible to find a time when the child does not have a URI or is not recovering from one. The needs of the family must be considered. Often, parents have traveled significant distances, taken time off from work, and made alternative childcare arrangements for their other children. Because the available data do not clearly indicate a single best approach to these patients, each anesthesiologist should develop a consistent approach appropriate to the individual practice.

FIGURE 36-2 Probability of upper respiratory tract infection according to age, crowding, maternal smoking, and daycare status.

(From Fleming DW, et al.: Childhood upper respiratory tract infections: to what degree is incidence affected by daycare attendance? Pediatrics 79:55, 1987.)

The following is a summary of an approach to the child with symptoms of URI. First, many children undergo operations directed at ameliorating their chronic upper respiratory tract symptoms. In cases such as myringotomy with tube placement, tonsillectomy, adenoidectomy, and cleft palate repair, the procedures are not automatically canceled or postponed unless the child’s signs and symptoms are clearly “different from baseline” or clearly involve more than the upper respiratory tract. Children who undergo the procedures just listed have a high incidence of upper respiratory tract symptoms and may always have manifestations consistent with URI. Most parents can advise whether their child is more congested than usual.

Elective surgeries other than those cited previously are postponed if any of the following are present: “croupy” cough; rectal temperature higher than 38.3° C associated with any URI sign or symptom; malaise or decreased appetite; and any evidence or recent history of lower respiratory tract involvement such as rales, wheezes, productive cough, or abnormal chest radiograph (Box 36-5). Laboratory and radiographic tests are usually not helpful in the decision-making process, although some investigators recommend obtaining a chest radiograph and a white blood cell count to evaluate the child with a URI. The white blood cell count is neither sensitive nor specific in identifying a URI, and chest radiography associated with a normal auscultative examination is unlikely to identify abnormalities (Brill et al., 1973). The presence of rales or wheezes should lead to postponement of elective surgery, regardless of findings on the chest radiograph. A suggested algorithm for making decisions about proceeding with surgery is presented in Figure 36-3.

FIGURE 36-3 Algorithm for clinical decision making for a patient with upper respiratory tract infection.

(From Martin LD: Anesthetic implications of an upper respiratory tract infection in children, Pediatr Clin North Am 41:121, 1994.)

Anesthetic Management

Several major principles of anesthetic management can be suggested for dealing with children with acute or recent URIs (Tait and Malviya, 2005). These are especially important in anesthetizing children when surgery is urgent and cannot be delayed. In elective situations, it is best to avoid intubation if possible (if the surgical procedure allows), instead using regional anesthesia or general anesthesia by mask or laryngeal mask airway (LMA). A randomized, prospective study demonstrated a much lower incidence of bronchospasm in children with URI managed with LMA rather than ETT (0% vs. 12.2%) (Tait et al., 1998). The incidence of all respiratory complications was reduced by 50% for the LMA group (19% vs. 35%). LMA may be an excellent alternative for airway management for patients with URI if the planned surgical procedure and fasting status are compatible with its use. If intubation is indicated, it should be accomplished when the patient is at a deep plane of anesthesia using an ETT at least 1 size (0.5 cm) smaller than age would determine. Any IV induction agent is acceptable, with the most important guiding principle being that enough should be given to achieve a deep level of anesthesia. An alternative is mask induction of inhalation anesthesia with sevoflurane, with or without nitrous oxide, and oxygen. If the procedure is expected to be prolonged, heated humidification should be used, because use of dry gas may lead to inspissation of secretions.

Adjunctive agents, such as IV lidocaine (1 mg/kg), an opioid, or both, decrease airway reflexes (Hirshman, 1983). The preoperative use of anticholinergic agents (i.e., atropine and glycopyrrolate) theoretically may block muscarinic receptors, thereby interrupting the airway reflex arc (Jacoby and Hirshman, 1991). Their properties as antisialogogues may be helpful; however, these agents have not been shown to be beneficial in prospective studies (Tait et al., 2007). The use of glucocorticoids experimentally has decreased viral-associated, tachykinin-induced airway edema formation, although glucocorticoids are not routinely prescribed in this clinical situation—in contrast to their use in the patient with RAD (Piedimonte et al., 1990). Dexamethasone, however, has been used in an effort to prevent postextubation croup, but these studies have been performed in critically ill children who had undergone prolonged intubation and mechanical ventilation in the intensive care unit, rather than in children with respiratory infections who are undergoing surgery. In this high-risk population, dexamethasone may be effective (Markovitz and Randolph 2002; Lukkassen et al., 2006). If intubation is necessary, tracheal suction of URI-associated secretions after intubation and before extubation may decrease the chance of atelectasis and mucus plugging, although this hypothesis has not been studied.

Management of children with URI requires a logical approach. When this issue arises in the preoperative period, the patient, parents, surgeon, and anesthesiologist must participate in an informed fashion in the decision-making process; however, “in the final analysis, the name of the game is clinical judgment and a degree of good fortune” (Berry, 1990).

Etiologic Factors and Pathophysiology

Asthma is a chronic inflammatory disorder of medium and small airways in which many cell types play a role, including mast cells and eosinophils. These cells release mediators of inflammation that, in susceptible individuals, cause symptoms associated with variable airway obstruction and airway hyperreactivity that is partially or completely reversible spontaneously or with appropriate treatment. Understanding the important role of inflammation in the immunopathogenesis of asthma in recent years has changed the focus to a newer therapeutic approach using antiinflammatory agents. Among the immune regulatory pathways involved in the pathogenesis of asthma, 2 cytokines—interleukin-4 and interferon-γ—appear to be important in controlling immunoglobin E (IgE) production, which is critical in the allergic inflammatory process. In individuals with asthma, mast cells and eosinophils are attracted to airways and release cytokines and lipid mediators that cause inflammation (Goldstein et al., 1994). The interplay of allergens and irritants, mast cells, eosinophils and their mediators, and the end effects on pulmonary vessels and airways is depicted in Figure 36-4. These mediators include histamines, leukotrienes, prostaglandins, kinins, and cytokines. Airway obstruction in asthma results from a combination of several factors, including airway smooth muscle spasm, airway mucosal edema, hypersecretion, and mucus plugging of small bronchi and bronchioles (Djukanovic et al., 1990). These changes result in airway obstruction, increased work of breathing, uneven distribution of ventilation, and in severe disease, air trapping, hyperinflation, and ventilation-perfusion imbalance, which leads to hypoxemia, diaphragmatic fatigue, hypercapnia, and respiratory failure. In longstanding RAD, mast cells infiltrate airway smooth muscle and in combination with chronic inflammation may result in airway remodeling, potentiating bronchoconstriction and airway hyperreactivity (Brightling et al., 2002).

FIGURE 36-4 Pathophysiology of asthma.

A strong association exists between asthma and allergy. Up to 90% of children with recurrent wheezing respond positively to bronchoconstrictor challenge, especially when associated with atopy (Clough et al., 1991). An increased prevalence of asthma is reported among first-degree relatives of asthmatic subjects; over two thirds of children with asthma appear to have a familial predisposition (Clifford et al., 1989). Various environmental factors precipitate airway hyperreactivity and trigger asthma. Recent evidence has shown that obesity is associated with a proinflammatory state and is an independent risk factor for the development of asthma (Visser et al., 2001; Guerra et al., 2004).

The onset of asthmatic symptoms is often associated with viral infection of the lower respiratory tract, particularly respiratory syncytial virus (RSV) infection in infants and children (Rooney and Williams, 1971). Severe viral bronchiolitis in infancy is significantly associated with the subsequent development of airway hyperreactivity and asthma, although familial factors cannot be ruled out (Gurwitz et al., 1981; Gern et al., 2005; Lemanske et al., 2005). The development of IgE antibody to RSV may have an important role in inducing an allergic response to the virus (Welliver et al., 1989; Rakes et al., 1999). Children who experience respiratory failure and mechanical ventilation during infancy and early childhood, such as those with bronchopulmonary dysplasia (BPD), neonatal repair of congenital diaphragmatic hernia, or severe viral bronchiolitis, develop and sustain airway hyperreactivity even without a family history of asthma (Mallory et al., 1989; Nakayama et al., 1991). Prematurity alone may be associated with a higher incidence of asthma in preadolescent children (von Mutius et al., 1993). The primary site of airway obstruction and hyperreactivity in children with a history of neonatal respiratory failure appears to be in relatively small airways—in contrast to relatively large central airway obstruction and hyperreactivity in those with typical allergic (i.e., IgE antibody-mediated) asthma (Mallory et al., 1991). In these patients, airway spasm is characterized by a rapid drop in oxygen saturation of Hb (SpO₂) without audible wheezing by auscultation.

In children with RAD, parental smoking (passive smoking) increases the severity of symptoms and exacerbates airway hyperreactivity (Soussan et al., 2003). Intrauterine exposure to maternal smoking also increases the incidence of airway hyperresponsiveness in infants (Singh et al., 2003). Infants with gastroesophageal reflux and chronic esophagitis often develop airway hyperresponsiveness with or without chronic aspiration and resultant tracheobronchial inflammation (Sheikh et al., 1999). Contributing factors responsible for the development of airway hyperreactivity and asthma are listed in Figure 36-5.

FIGURE 36-5 Contributing factors to the development of RAD. ARF, Acute renal failure; LRI, lower respiratory tract infection; RSV, respiratory syncytial virus.

Precipitating Factors for Reactive Airways Disease

Viral lower respiratory infections, particularly those caused by RSV and influenza, sensitize airways and provoke airway hyperreactivity even in individuals who are nonasthmatic and nonallergic for as long as 6 weeks (Empey et al., 1976). Exposure to dry, cold air can precipitate tracheobronchial constriction in subjects with asthma, presumably in response to reduced tracheal temperature caused by evaporative heat loss (Gilbert et al., 1988). The same mechanism appears to be responsible for exercise-induced bronchospasm and precipitation of asthma with excitement, anxiety, and hyperventilation (McFadden and Gilbert, 1994).

The time before and during the induction of anesthesia is uniquely suited to trigger bronchospasm in susceptible individuals because of the patient’s emotional stress, fear, and excitement. Hyperventilation results, with mouth breathing of dry anesthetic gas mixtures, airway irritation by volatile anesthetics, and mechanical stimulation of the pharyngeal and laryngeal mucosa by laryngoscopy and endotracheal intubation (Box 36-6).

Pharmacologic Agents for Asthma

The pharmacologic management of asthma consists of bronchodilators and antiinflammatory drugs and includes six different classes of drugs: corticosteroids, leukotriene inhibitors, β-adrenergic agonists, theophylline, cromolyn (or nedocromil), and anticholinergics. Recently published guidelines for treatment of asthma in children include a useful algorithm (Fig. 36-6) (Bacharier et al., 2008). Initial treatment for asthma most commonly consists of inhaled corticosteroids (ICSs) and leukotriene-receptor antagonists, with ICSs usually being the first-line drugs. Montelukast has been used widely in children. Other first-line alternatives are cromolyn (or nedocromil). Because of safety concerns, long-acting β₂-agonists such as salmeterol are now reserved for patients with poor control despite use of an ICS and leukotriene-receptor antagonists (Martinez, 2005). Theophylline has reentered the treatment algorithm if patients have exacerbations despite ICS and β-adrenergic agonists. Oral corticosteroids in brief high-dose pulses are reserved for patients with moderate to severe asthma that is unresponsive to combinations of the other drugs (Stempel, 2003). Drugs commonly used in children are listed in Table 36-10.

FIGURE 36-6 Algorithm for treatment of RAD. Once control is achieved, therapy may be stepped down to previous level. ICS, Inhaled corticosteroid; BDP, beclomethasone equivalent; LTRA, leukotriene receptor antagonist, for dose, see Table 36-10.

(Modified from Bacharier LB, et al: Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report, Allergy 63:5, 2008.)

TABLE 36-10 Drugs Used for Asthma

DPI, Dry powder inhaler; MDI, metered-dose inhaler; prn, as needed

* Recommended only for use in combination with inhaled corticosteroid for children >4-5 years of age. Data from Bacharier LB et al.: Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report, Allergy 63:5, 2008; modified from Treatment guidelines from the medical letter 6:86, 2008.

† Zorc JJ et al.: Ipratroprium bromide added to asthma treatment in the pediatric emergency department, Pediatrics 103:748, 1999.

Anesthetic Management

The anesthesiologist must get to know the child with asthma and his or her parents and gain their confidence to minimize the child’s anxiety before anesthesia induction. The child should be well sedated to avoid struggle and hyperventilation, which can provoke exercise-induced asthma. Midazolam, which may be administered transmucosally (i.e., orally, nasally, or rectally) in infants and young children and orally or intravenously (if IV access is present) in older children, works well for sedation. A β₂-adrenergic agonist may be given prophylactically using a metered-dose inhaler or nebulizer before induction (Table 36-10). Otherwise, the drug can be given after the induction of anesthesia through the ETT using the metered-dose inhaler and an aerosol chamber inserted in between the ETT adapter and the anesthesia circuit.

The anesthetic approach is similar to that for children with URIs. After applying standard monitors (a minimum of a pulse oximeter and precordial stethoscope if the child is uncooperative), the inhalation induction should be smooth and progress swiftly with sevoflurane and nitrous oxide (see Chapter 11, Monitoring). For infants and young children, heated humidification should be used if available; the dry gas mixture from the anesthesia machine is a perfect environment for provocation of bronchospasm secondary to irritation and reduced tracheal temperature from evaporative heat loss of the tracheal mucosa in a child with asthma (McFadden and Gilbert, 1994).

For IV induction, propofol may be a better agent of choice than thiopental because it suppresses airway reflexes as compared with barbiturates, although thiopental, despite risk of histamine release, is not necessarily contraindicated in patients with asthma (Brown et al., 1992; Gal, 1994). Propofol may also produce bronchodilation in patients with other types of airway disease (Conti et al., 1993). Regardless of the drug chosen, it is important to give sufficiently large IV doses to blunt the reflex response, and sevoflurane should be added before the peak effect of the IV agent is lost.

Whenever possible, endotracheal intubation should be avoided in patients with asthma, because the ETT stimulates large airway irritant receptors and can trigger bronchospasm (Hirshman, 1983). When no contraindications exist, an LMA is a good choice for patients with RAD, as its use avoids the laryngeal and tracheal stimulation of intubation (Groudine et al., 1995). It may also be prudent to avoid anesthetic agents that might release histamine (e.g., atracurium and morphine), although clinical evidence that such drugs actually cause intraoperative bronchospasm is limited.

An anesthetic technique using a volatile anesthetic may be preferable to a balanced technique (i.e., nitrous oxide, opioid, and muscle relaxant) for patients who have asthma because of the salutary bronchodilating properties of volatile agents. Regional anesthesia can be combined with inhalation anesthesia with sevoflurane or isoflurane. Desflurane may cause more airway irritation in patients with RAD and lead to bronchospasm and associated coughing, especially during emergence (von Ungern-Sternberg et al., 2008).

Pathogenesis

In the past, the development of BPD was associated with a condition that caused respiratory failure in the neonatal period (e.g., prematurity with respiratory distress syndrome, meconium aspiration syndrome, or congenital diaphragmatic hernia). Mechanical ventilation with high concentrations of oxygen (i.e., an acute insult to immature lungs) was employed, usually lasting longer than 1 week. Oxygen free radicals, which are not well handled by an immature antioxidant host-defense system in the neonatal lungs, can cause direct cellular injury (Ackerman, 1994). Although much lower concentrations of oxygen are now used than in the past, even room air (21% oxygen) is relatively hyperoxic for a premature infant whose in utero Po₂ is less than 30 mm Hg (Hazinski, 1990). Excessive hydration and patent ductus arteriosus with increased pulmonary fluid have been recognized as additional important factors contributing to the development of BPD (Gerhardt and Bancalari, 1980; van Marter et al., 1992). The current theory of the mechanism of injury in BPD also emphasizes the role of infection and inflammation (Gonzalez et al., 1996; Sadeghi et al., 1998). Recurrent bacterial or viral infections in these infants may cause persistent alveolitis, which worsens alveolar and airway damage (Rojas et al., 1995; Hannaford et al., 1999). Multiple markers of inflammation (e.g., lipid mediators, proteases, oxygen free radicals, and cytokines) are elevated (Bose et al., 2008; Ryan et al., 2008). Nutritional deficiencies may also play a role (Sosenko et al., 2000; Geary et al., 2008).

Immature, inflamed lungs with decreased compliance are most susceptible to high-volume (i.e., volutrauma) and low-volume (i.e., shear stress trauma) trauma with marked distortion and distention of terminal bronchioles at high positive pressures (Hazinski, 1990). In earlier pathologic examination of lungs of infants dying with BPD, peribronchiolar fibrosis and smooth muscle thickening were seen. They were also found in animal models exposed to prolonged positive pressure ventilation and hyperdistention (Coalson, 1999). The pathology now seen in extremely premature infants reflects the immature state of their pulmonary parenchyma, with enlarged and simplified alveolar structure and reduced numbers of capillaries that are dysmorphic in appearance. Therefore, the new BPD is now regarded primarily as a disorder of lung development with superimposition of mechanical factors. Fibroproliferation may still occur but is more variable. Changes in larger blood vessels are less prominent with less indication of pulmonary hypertension than seen in old BPD. Airway smooth muscle hyperplasia may still occur, but it is also more variable (Coalson, 2006). After this damage has occurred to immature lungs, infants may require prolonged mechanical ventilation and high oxygen concentration for weeks or months, despite having not required high oxygen concentrations in the first few weeks of life. Although less common than with old BPD, progressive respiratory failure with associated pulmonary hypertension, with or without cor pulmonale, may follow.

Even after the perinatal period, RAD persists in infants with BPD. Mallory et al. (1991) studied lung function longitudinally in infants with moderate to severe BPD during the first 4 years of life with the forced deflation technique and found that airway hyperresponsiveness or hyperreactivity continued to be present in all children studied. They postulated that airway hyperreactivity is an important etiologic factor for the pathogenesis of lower airway obstruction in BPD. Attributing the cause of RAD to BPD is confounded by the recent evidence that antenatal steroid therapy to hasten lung maturation is a risk factor for the development of RAD between the ages of 3 and 6, as well as by the fact that the rates of RAD-like symptoms occur more often in prematurely born children than in those born at term (Doyle, 2006; Pole et al., 2009). Most long-term studies of lung function are reports of infants who had the old form of BPD. Little information is available regarding long-term outcomes of infants with new BPD.

Preanesthetic Considerations

Most infants with moderate to severe BPD remain dependent on oxygen, with or without CPAP, or dependent on a ventilator beyond 4 weeks of age. They have persistent lower airway obstruction and airway hyperreactivity (Mallory et al., 1991). Tachypnea and dyspnea may be intermittently or chronically present. Growth failure because of chronic hypoxia despite oxygen therapy may occur, as well as cor pulmonale associated with pulmonary hypertension (Hazinski, 1990). Wheezing may or may not be present on auscultation, because the site of airway hyperreactivity is primarily in the periphery of the lungs as a result of increased thickness of the airway wall (Tiddens et al., 2008). In addition to lower airway obstruction primarily involving small airways, infants who have been intubated for prolonged periods sometimes develop large airway disease such as subglottic stenosis (that may or may not be recognized), tracheomalacia, and bronchomalacia (Miller et al., 1987; McCubbin et al., 1989). A later study also found a greater degree of upper airway obstruction in children with history of BPD, as compared with age-matched children with asthma (Sadeghi et al., 1998).

Infants with mild forms of BPD improve with age and may become asymptomatic, but airway hyperreactivity may persist. Parents of such an infant may not be aware of the history of BPD even when their child received prolonged mechanical ventilation as a neonate. It is appropriate, therefore, to assume that a child has or had BPD and has RAD if he or she was born prematurely and was mechanically ventilated for more than 1 week during the neonatal period. Inguinal hernia is often present in infants with BPD, probably owing to prematurity and continually increased abdominal pressure that results from airway obstruction and increased inspiratory effort. Prematurely born infants may require postoperative admission for monitoring, because they have an increased risk of postoperative apnea as discussed in Chapters 3, Respiratory Physiology in Infants and Children; 17, Neonatology for Anesthesiologists; and 18, Anesthesia for General Surgery in the Neonate.

As with asthmatic patients, careful history taking is of utmost importance before anesthetizing an infant with BPD or a history of BPD. These patients may have failure to thrive (a sign of chronic hypoxia). With lower respiratory tract infection, worsening of symptoms or even respiratory failure may occur. The patient may be taking SABAs or other treatments for asthma. Other medications may include diuretics. A family history of allergy and asthma is significant, because premature birth may be linked to smooth muscle hyperresponsiveness and asthma (Bertland et al., 1985). Relatively common surgical conditions in infants and children with BPD or a history of BPD include inguinal hernia, direct laryngoscopy and bronchoscopy for subglottic stenosis, and surgical procedures of the larynx for the complications of prolonged intubation or tracheostomy (e.g., excision of granuloma or laryngotracheoplasty).

Anesthetic Management

Anesthetic management of infants and children with BPD or a history of BPD is similar to that for those with asthma. Before anesthetizing a child in this population, it is imperative to obtain a baseline oxygen saturation measurement with a pulse oximeter (SpO₂), although a normal oxygen saturation level does not necessarily guarantee the absence of lung dysfunction. Many infants and young children with a history of BPD maintain remarkably good SpO₂ values, presumably because of hypoxic pulmonary vasoconstriction (HPV). The infant with BPD with near-normal SpO₂ in room air may develop marked desaturation after induction with sevoflurane, presumably because of a loss of HPV under general anesthesia, although HPV in healthy human volunteers may be insignificant (Benumof, 1994). In these patients, oxygen saturation may be maintained better with IV induction and maintenance techniques using opioids and propofol; however, no evidence supports this management protocol. Preoperative prophylactic treatment with a β₂-adrenergic agonist by a metered-dose inhaler or handheld nebulizer may be beneficial for patients with potential airway hyperreactivity to prevent perioperative bronchoconstriction. In intubating a child with a history of mechanical ventilation, it is prudent to start with an ETT one size (0.5 mm inner diameter) smaller than the appropriate size for the age in anticipation of subglottic narrowing, which may be the result of prolonged intubation. If rapid sequence intubation is required because of fasting violation or intestinal obstruction, desaturation may be rapid when apnea occurs, and gentle ventilation by mask with maintenance of cricoid pressure may be necessary to maintain saturation if intubation is not rapidly accomplished.

Pathogenesis

CF is characterized by exocrine gland dysfunction that results in chronic pulmonary disease, pancreatic dysfunction, and abnormalities in electrolyte reabsorption in the sweat duct, with increases in sweat sodium and chloride concentrations and electrolyte imbalance. The fact that CF patients have sweat chloride levels in excess of 60 mEq/L (normal is less than 40 mEq/L), as measured by pilocarpine iontophoresis, is the basis of the sweat chloride test, which is still the gold standard for making the diagnosis of CF. Increasingly, the diagnosis of CF is being made earlier because of newborn screening techniques that are designed to detect elevated serum levels of immunoreactive trypsinogen and the most common CFTR mutations (Comeau et al., 2007). Such screening accounted for 21.6% of the diagnoses of CF in the United States in 2006 (Cystic Fibrosis Foundation, 2007). Even if these screenings are found to be positive, two sweat chloride test results of greater than 60 mEq/L are necessary to make the diagnosis of CF. Significant clinical manifestations of CF, other than pulmonary disease, include those listed in Table 36-12.

TABLE 36-12 Organ System Involvement in Cystic Fibrosis

Pulmonary disease is the most common cause of morbidity and death. Enhanced absorption of sodium across the airway epithelium and failure to secrete chloride and fluid toward the airway lumen is thought to lead to dehydration and thickening of airway mucus and abnormal mucociliary clearance with subsequent bronchial inflammation and infection. Patients are initially colonized with Haemophilus influenzae and then by Staphylococcus aureus, and eventually by the mucoid variant of Pseudomonas aeruginosa. Colonization with Aspergillus and atypical mycobacteria may occur. The chronic infection in the periphery of the tracheobronchial tree results in bronchiolitis, which may lead to airway hyperresponsiveness, bronchiectasis, lobar or segmental atelectasis, and pneumothorax. Advanced disease is associated with destruction of airway architecture, fibrosis of lung parenchyma, and development of abscesses. Hemoptysis and eventually, cor pulmonale and respiratory failure ensue (Eckles and Anderson, 2003).

Small airway obstruction, hyperinflation, and ventilation- perfusion imbalance are the most common and important pulmonary changes in children with moderate-to-severe CF. The early signs of lung dysfunction include a reduction in maximum expiratory flow rates at low lung volumes (e.g., FEF_25-75, FEF₅₀, and FEF₇₅) and an increase in the ratio of residual volume to total lung capacity (RV/TLC) (see Chapter 3, Respiratory Physiology in Infants and Children). Airway hyperreactivity is often present, probably in response to airway inflammation. Some patients have a good response to bronchodilators, but others have inconsistent or even paradoxical responses, sometimes worsening airway function because of the relaxation of airway smooth muscles and resultant increases in airway collapsibility (Brand, 2000).

Treatment

Patients with CF take multiple medications. In 2007, a committee organized by the Cystic Fibrosis Foundation published guidelines for long-term medication used for optimal pulmonary symptom control in CF patients older than 6 years (Flume et al., 2007). Patients with a prominent bronchospastic component are on long acting β₂-agonist therapy (Hordvik et al., 2002). They often take inhaled or oral antibiotics for prophylaxis or treatment of pulmonary infection. Patients infected with P. aeruginosa often take aerosolized tobramycin, which when administered on a bimonthly basis has been shown to preserve pulmonary function and reduce hospitalization (Ramsey et al., 1999). Patients with infectious exacerbations are treated with IV antibiotics in a hospital or at home. Chest physiotherapy several times per day is a mainstay of CF treatment. Inhaled mucolytics (N-acetylcysteine) have long been used to decrease the viscosity of pulmonary secretions, but little is found in the literature documenting their efficacy (Duijvestijn and Brand, 1999). Inhaled hypertonic saline, which is thought to improve fluidity of pulmonary secretions, has been shown to decrease the frequency of pulmonary exacerbations (Flume et al., 2007). Dornase alfa (i.e., human recombinant DNase), which dissolves deoxyribonucleic acid (DNA) released from neutrophils, has improved pulmonary function and reduced the frequency of infection (Jones et al., 2003; Flume et al., 2007). High-dose ibuprofen therapy has been found to slow the decline of forced expiratory volume during the first second of measurement (FEV₁) in children and adolescents if started when the FEV₁ is greater than 60% of that predicted (Lands and Stanojevic, 2007). This effect is related to reduction in inflammation (Nichols et al., 2008). Doses between 20 and 30 mg/kg every 6 hours are administered to achieve plasma concentrations of 50 to 100 mcg/mL (Arranz et al., 2003). Ibuprofen treatment has been associated with a significant increase in gastrointestinal (GI) bleeding compared with patients who are not taking ibuprofen, although the absolute number of patients affected is small (Konstan et al., 2007). Patients with pancreatic impairment require pancreatic enzyme replacement.

Preanesthetic Considerations

Common surgical indications in infants and children with CF are listed in Table 36-13. Although some patients with CF require surgery in the neonatal period for meconium ileus, no special anesthetic considerations are necessary. Management of children with CF is a challenge to the anesthesiologist. These patients are often frail and malnourished. Decreased plasma albumin levels may affect anesthetic potency. Intravascular volume may be diminished because of chronic diarrhea, poor oral intake, and diuretic therapy. Electrolyte imbalance may result from excessive chloride and sodium losses. Pulmonary function ranges from near normal without airway obstruction to severe obstruction, air trapping, hypoxemia, and hypercapnia. Copious thick secretions and resultant ventilation-perfusion imbalance may prolong mask induction with volatile anesthetics. Secretions may irritate the larynx and precipitate laryngospasm. Nasal polyps may block the nasal airway completely during mask induction. Pathophysiologic considerations in patients with CF that may affect anesthetic management are listed in Table 36-14.

TABLE 36-13 Surgical Indications for Patients with Cystic Fibrosis

PICC, Peripherally inserted central catheter.

TABLE 36-14 Pathophysiology of Cystic Fibrosis: Effect on Anesthetic Management

The preoperative evaluation should include the assessment of pulmonary function by history, physical examination, and pulmonary-function testing. Pulmonary-function testing should include assessments of maximum expiratory flow-volume curves, lung volume measurements, and response to bronchodilators. An increase in TLC and the RV/TLC ratio with decreased vital capacity indicates the presence of hyperinflation and air trapping. Lower airway obstruction with small airway involvement is demonstrated when FEF_25-75, FEF₅₀, and especially FEF₇₅ are markedly decreased from predicted values. A recent preoperative chest radiograph is needed in patients with moderate to severe pulmonary disease. Preoperative oxygen saturation should be obtained by means of pulse oximetry in room air for postoperative comparison. Recent tracheal culture results should be reviewed as a guide to choice of perioperative antibiotic therapy. In patients with significant lower airway obstruction and air trapping, preoperative arterial blood gas measurement is recommended to assess the degree of hypoxemia more accurately and to evaluate the presence of hypercapnia and acid-base status. In those with long-standing hypoxemia, pulmonary hypertension and cor pulmonale should be suspected. These patients should have preoperative electrocardiography and echocardiography to evaluate myocardial function and reserve. Blood sugar, liver-function tests, and coagulation studies may be indicated. Eight percent of CF patients between the ages of 11 and 17 develop CF-related diabetes mellitus as a result of fibrosis and fatty infiltration of the pancreas (Cystic Fibrosis Foundation, 2007). Some, but not all, may require insulin, because some insulin continues to be produced. Malabsorption and liver disease may be associated with abnormal coagulation. Additional vitamin K supplementation may be necessary to correct coagulopathy. The patient’s pulmonary physician should be consulted to ensure that the patient’s condition is optimized as much as is possible before surgery. Ibuprofen should be stopped 2 days before surgery to allow its inhibitory effects on platelet aggregation to dissipate.

The child with CF and his or her family are exceedingly knowledgeable regarding the pathogenesis and treatment of the disease. A lack of knowledge of CF in general, and of the patient’s past history and present conditions in particular, at the time of the preoperative visit could quickly undermine the confidence of the family in the anesthesiologist. More importantly, the patient with CF is often petrified by the thought of death under anesthesia, in part because of a long-held belief in the pulmonary medicine community that general anesthesia leads to prolonged deterioration of pulmonary function (Price, 1986). It is therefore prudent for the anesthesiologist to gain the patient’s and the parents’ confidence and administer preoperative sedation such as oral midazolam (Della Rocca, 2002). Opioid premedication should be avoided in severe cases because of possible respiratory depression and hypoxemia.

Anesthetic Management

Because of copious secretions in affected patients, it is preferable to schedule surgery later in the day to allow enough time for ambulation and chest physiotherapy in the morning to facilitate expectoration of secretions retained overnight. The baseline oxygen saturation in room air is measured with a pulse oximeter before administering oxygen and anesthetics.

In patients with significant pulmonary involvement, IV access should be established before the induction of anesthesia because of prolonged mask induction and possible nasal obstruction from nasal polyps. An anticholinergic may be given during induction. Concern about excessive drying of secretions is unfounded, because atropine decreases secretions without changes in viscosity and has not been a significant problem in clinical practice (Lamberty and Rubin, 1985). IV propofol may be preferred to thiopental because it is less irritating to the upper airways and actually causes bronchodilation. Ketamine, despite its bronchodilating properties, is relatively contraindicated because it tends to increase secretions and may cause laryngospasm. Fifty percent of children with CF have gastroesophageal reflux disease and may require rapid-sequence intubation, although chronic treatment with H₂-blockers and or a proton-pump inhibitor along with an adequate fasting interval mitigates the risk of aspiration. Inhalation induction is usually satisfactory in young children with mild lung disease. Anesthetic gases should be heated and humidified to prevent irritation of the upper airways and laryngospasm and to avoid drying and inspissation of secretions. When trapped gas volume is suspected or proven by pulmonary function test, nitrous oxide should be avoided to prevent expansion of the emphysematous area and the potential danger of bleb rupture.

Endotracheal intubation with muscle relaxation is mandatory in patients with severe respiratory involvement, although the anesthesiologist should be exceedingly careful not to overdistend already air-trapped lungs. When a nondepolarizing muscle relaxant is chosen, the effect of aminoglycoside antibiotics to prolong the duration of action of such drugs must be kept in mind, and monitoring of train-of-four should be used to guide relaxant administration. It is also mandatory to carefully monitor end-tidal carbon dioxide to prevent hyperventilation and to maintain preoperative arterial partial pressure of carbon dioxide (Pco₂) levels, which may be elevated. Sudden hypocapnia in a chronically hypercapnic patient can disrupt the patient’s ventilatory control mechanisms, increasing the chance that the patient might require postoperative ventilation. After intubation, tracheobronchial suction should be performed and repeated at intervals throughout surgery and before extubation to improve pulmonary gas exchange. Although the use of an LMA might be an option for short cases, disadvantages include the inability to suction secretions, obstruction of the LMA by thick secretions, risk of laryngospasm, and risk of aspiration in patients with gastroesophageal reflux disease. For bronchoscopy for the purpose of removal of secretions for culture and bronchial lavage, the LMA has been safely used in patients with CF (Nussbaum and Zagnoev, 2001). Intraoperatively, glucose should be monitored in patients with glucose intolerance. Care should be taken to conserve heat in these patients with reduced body fat.

Regional anesthesia should be considered whenever applicable. Although regional anesthetic techniques without general anesthesia might be useful in some situations, these techniques should be carefully considered in children with severe pulmonary disease. Depression of abdominal and intercostal muscle function by thoracic levels of spinal or epidural anesthesia may not be tolerated. Pediatricians and pulmonologists often request regional anesthesia instead of general anesthesia because of fear that severely affected patients with CF will not tolerate general anesthesia or may become dependent on a ventilator after endotracheal intubation. However, most of these sick patients with CF, dyspneic or orthopneic with hypercapnia and oxygen dependence, may not tolerate even a short surgical intervention, such as insertion of a central venous catheter or MediPort, with local anesthesia and sedation. Instead, general endotracheal anesthesia with an inhaled agent, supplemented by caudal, lumbar, or thoracic epidural anesthesia for abdominal or thoracic procedures, is much better tolerated, safer, and provides good operative conditions, rapid emergence, and a pain-free postoperative state (Dalens et al., 1986). If epidural anesthesia is to be used, coagulopathy should be ruled out, and the appropriate concentration of local anesthetic drugs should be chosen to minimize motor block. Continuous caudal or epidural anesthesia with local anesthetic with or without carefully chosen doses of an opioid provides prolonged postoperative pain relief and facilitates coughing and deep breathing after upper abdominal or thoracic procedures. If regional anesthesia is not appropriate, judicious use of inhalation agents and short-acting opioids and wound infiltration with local anesthetic by the surgeon should facilitate early extubation, which is desirable in most cases. After surgeries without a high risk of postoperative bleeding, the use of NSAIDs may be effective in reducing the amount of opioid needed for analgesia.

Cystic Fibrosis and Hemoptysis

Hemoptysis may occur in older children with more severe lung disease. These children may come to the hospital for angiography and bronchial artery embolization. Preanesthetic considerations as described above should be evaluated, and the patient’s pulmonary status should be optimized to the greatest extent. Pulmonary hemorrhage has been reported after induction of general anesthesia, intubation, and institution of positive-pressure ventilation (McDougall and Sherrington, 1999). It is possible that airway and parenchymal distention associated with positive pressure ventilation results in the breach of relatively thin-walled vessels. These authors have recommended that sedation and local anesthesia may be safer in this situation (McDougall and Sherrington, 1999; Barben et al., 2002)

Cystic Fibrosis and Lung Transplantation

For patients with end-stage pulmonary disease, lung transplantation may be the final surgical option. Fifty percent of patients with CF and FEV₁ of less than 30%, partial pressure of oxygen (Pao₂) less than 55 mm Hg, or partial pressure of carbon dioxide (Paco₂) greater than 50 mm Hg will survive for 2 years and may be candidates for lung transplantation (i.e., double-lung or heart-lung procedure) (Belkin et al., 2006). Approximately 175 patients with CF per year undergo bilateral lung transplantation in the United States, of whom the minority are children (Cystic Fibrosis Foundation, 2007). The 3-year survival rate is 60%, which is similar to that seen in patients who do not have CF (Sweet et al., 1997). Some (27%) lung-transplant patients develop bronchiolitis obliterans, which is responsible for 40% of deaths that occur more than 1 year after transplantation (Boucek et al., 2004). Among the survivors of lung transplantation, no recurrence of CF in the transplanted lungs has been reported, as measured by the transepithelial potential differences (Alton et al., 1991). The management of end-stage CF patients for lung transplantation is described in Chapter 3, Respiratory Physiology, and Chapter 28, Anesthesia for Organ Transplantation.

Preoperative Period

Prolonged preoperative fasting should be avoided in children who have cyanotic heart disease with significant erythrocytosis to avoid dehydration and further increase of elevated hematocrit and blood viscosity. Small infants with significant heart failure and failure to thrive can have inadequate glycogen reserves and are at risk for hypoglycemia if they fast for many hours. Otherwise conventional age-appropriate preoperative sedation is in no way contraindicated in children with cyanotic or acyanotic heart disease unless the child is in profound heart failure.

Intraoperative Period

Although much discussion is appropriately devoted to the specifics of cardiac pathophysiology, most children with congenital heart disease who develop problems during anesthesia do so for primarily noncardiac reasons, particularly airway compromise (Strafford and Henderson, 1991). Infants who are cyanotic, in particular, begin with decreased oxygen saturation and can rapidly desaturate with transient interruption in ventilation, whether as a result of apnea or airway obstruction. Children with severe congestive failure or cyanosis have a decreased margin of safety and tolerate failures of respiratory or hemodynamic management poorly.

Much time is spent discussing the effects of left-to-right and right-to-left shunts on the onset time of IV and volatile anesthetics. Although differences exist, with currently available anesthetic gases of relatively low solubility, these differences are almost always so small as to be clinically irrelevant. In the absence of a complication such as loss of the airway or the development of a hypercyanotic “tet” spell in children with tetralogy of Fallot or variants, oxygen saturation in children with cyanotic disease almost invariably increases with induction of anesthesia (Laishley et al., 1986; Greeley et al., 1986). Several reasons are possible, one of the most likely being a decrease in oxygen consumption that causes an increase in mixed venous oxygen saturation and subsequently higher arterial oxygen saturation when some of this blood is shunted right to left.

Minimization of right-to-left shunting at the atrial level is addressed primarily by increasing intravascular volume. Minimization of shunting at the ventricular and great vessel levels is primarily modulated by changes in pulmonary vascular resistance (PVR) and systemic vascular resistance. Increasing systemic resistance or decreasing PVR increases left-to-right shunting (or decreases right-to-left shunting) and vice versa. Although α-adrenergic receptors are found in the pulmonary circulation (stimulation of which can increase PVR), they are denser in the systemic circulation, and α-agonists increase systemic vascular resistance significantly more than they increase PVR, with a decrease in right-to-left shunting.

Nitrous oxide is a mild myocardial depressant. In adult patients, it can increase PVR, particularly in patients in whom PVR is already elevated. However, in children, no significant increase in PVR has been observed with 50% nitrous oxide, regardless of the preexisting PVR (Hickey et al., 1986).

Patients who are cyanotic, and in particular patients with elevated central venous pressure, are at risk for increased perioperative blood loss and require adequate IV access. Not only do all patients with cyanotic disease need IV catheters to be kept clear of air bubbles to avoid systemic air emboli, but small amounts of transient right-to-left shunting can occur during the cardiac cycle, even with lesions thought of as left-to-right shunting lesions. Therefore, IV catheters must be cleared of air for all patients with shunt lesions, regardless of predominant direction of shunt flow. Stopcocks are common sites where air can be introduced inadvertently.

End-tidal Pco₂ correlates with arterial Pco₂ in acyanotic patients. However, in children and adults with cyanotic congenital heart disease, end-tidal Pco₂ tends to underestimate arterial Pco₂ (Burrows, 1989).

Postoperative Period

The specific length of observation in a postanesthesia care unit is dependent on the patient and the surgical procedure and cannot be generalized. Patients with good hemodynamic function may undergo relatively minor noncardiac surgery on an ambulatory basis and are not automatically excluded because of their cardiac disease.

When not under anesthesia, patients with cyanotic disease have relatively little increase in systemic oxygen saturation in response to supplemental oxygen. Similarly, oxygen saturation is not markedly decreased by removing supplemental oxygen (other causes for postoperative hypoxemia being absent). Knowledge of the patient’s normal preoperative range of oxygen saturation helps avoid unnecessary prolongation of the PACU stay for fear of removing supplemental oxygen.

Hypovolemia from continued surgical blood or fluid loss postoperatively can worsen right-to-left shunting in patients with cyanosis and should be rapidly corrected. The onset of hypovolemia can be insidious if it is as a result of gradual oozing from surgical drains. Patients with cyanotic disease should have repeated measurement of Hb after surgery, especially after significant blood loss. They may require a higher than normal hematocrit level to ensure adequate oxygen delivery. In general, a level similar to the preoperative hematocrit should be maintained.

Patients with labile pulmonary arterial hypertension particularly benefit from good postoperative analgesia, because pain increases pulmonary vascular tone. Even patients with cyanosis have a normal ventilatory response to hypercarbia and respond in a normal fashion to appropriate doses of parenteral, intrathecal, or epidural opiates; therefore, age- and weight-appropriate doses of analgesic drugs should be given. Patients who have had a Glenn or Fontan procedure are dependent on low PVR for maintenance of adequate pulmonary blood flow. If these patients should require postoperative ventilation, PVR should be minimized by limiting positive inspiratory pressure and using low levels of positive end-expiratory pressure to optimize functional residual capacity, which in turn, minimizes PVR.