Supplemental Material

Fetal and Neonatal Medicine

The heart of a healthy neonate is quite different from that of an adult. The thickness of the right ventricle exceeds that of the left, as seen by the normal right-axis deviation on the neonatal electrocardiogram (ECG). Shortly after birth, with closure of the fetal circulation, the left ventricle enlarges disproportionately. By the age of 6 months, the adult right/left ventricular size ratio is established. The newborn myocardium is also significantly different from that of the adult. Cardiac output is rate dependent in the neonatal heart, which has reduced compliance and contractility. The low compliance of the relaxed ventricle limits the size of the stroke volume; therefore increases in preload are not as important in neonatal physiology as the heart rate. Bradycardia invariably equates with reduced cardiac output because the infant heart cannot achieve the increased contractility needed to maintain cardiac output. It is extremely important to recognize this distinction during surgical and anesthetic procedures that may induce bradycardia. Autonomic innervation is also incomplete in the neonatal heart, with its relative lack of sympathetic elements; this relative underdevelopment may further compromise the ability of the less contractile neonatal myocardium to respond to stress.

Heart rate is crucially important in the very young. The normal range for the newborn is 100 to 170 beats/min, and the rhythm is regular. As the child grows, the heart rate decreases. Sinus arrhythmia is common in children, but all other irregular rhythms should be considered abnormal. The average newborn systolic blood pressure is 60 mm Hg and the diastolic pressure is 35 mm Hg.

Because the total blood volume of an infant is small, relatively minor surgical blood loss may be hemodynamically significant. It has been observed during exchange transfusions that withdrawal of blood parallels a decline in systolic blood pressure and cardiac output. Replacement of the same blood volume that was removed can reverse this decline to restore normal parameters. When the heart rate is normal, changes in arterial blood pressure are thus proportional to the degree of hypovolemia. A newborn’s ability to adapt the intravascular volume to the available blood volume is limited because of less efficient control of capacitance vessels and immature or ineffective baroreceptors.

Neonatal blood volume is approximately 80 mL/kg at term and is notably 20% higher in preterm infants. The hematocrit is 60%, and the hemoglobin content is 18 g/100 mL, although these values vary by infant and depend on when the umbilical cord is clamped. After remaining stable during the first week of life, the hemoglobin level declines, with the change occurring more rapidly in preterm infants. Approximately 70% to 90% of the hemoglobin in a full-term infant is of the fetal type. Fetal hemoglobin has a higher affinity for oxygen than that of an adult. It combines with oxygen more readily but also releases oxygen less efficiently at the tissue level compared with adult hemoglobin. The increase in hemoglobin content in neonates is required to overcome this higher affinity of fetal hemoglobin for oxygen. A concentration less than 12 g/100 mL constitutes anemia. Correction of anemia by blood transfusion is indicated if the infant requires oxygen or experiences apnea.

During the first weeks of life, the hematocrit drops as a result of early suppression of erythropoiesis; the fetal type of hemoglobin is replaced with the adult type of hemoglobin with more optimal oxygen-carrying capacity. This physiologic anemia reaches its nadir at 2 to 3 months, with a hemoglobin content of 9 to 11 g/100 mL. Provided that nutrition is adequate, the hemoglobin level will then gradually rise over several weeks to 12 to 13 g/100 mL, which is maintained throughout childhood.

Because neonates have a relatively high metabolic rate and low reserve for gas exchange, hypoxemia develops rapidly, first manifesting as bradycardia. During surgery, any unexplained episode of bradycardia should initially be treated with oxygen and increased ventilation. Pulmonary vasoconstriction and hypertension occur more dramatically in response to hypoxemia in the neonate than in the adult. With a patent foramen ovale and/or a persistent patent ductus arteriosus (PDA), the increase in pulmonary vascular resistance (PVR) may favor a shift into fetal circulation with right-to-left shunting, which compounds the problem. Changes in cardiac output and systemic vascular resistance also differ in neonates compared with older children and adults. During hypoxemia in adults, the principal response is systemic vasodilation; this, together with an increase in cardiac output, helps to maintain oxygen transport to the tissues. Fetuses and some neonates respond to hypoxemia with systemic vasoconstriction. In the fetus, hypoxemia shifts blood to the placenta to improve gas exchange and oxygenation. After birth, however, hypoxemia may lead to decreased cardiac output, further limiting oxygen delivery and increasing cardiac work. In infants, early and pronounced bradycardia may result from myocardial hypoxia and acidosis. Neonates exposed to hypoxemia suffer pulmonary and systemic vasoconstriction, decreased cardiac output, and bradycardia. Rapid recognition and intervention are necessary to prevent cardiopulmonary collapse, cardiac arrest, and death.

Short- and Long-Term Consequences of Prematurity

Prematurity affects virtually every organ system. The cardiovascular system has immature calcium homeostasis and relatively noncompliant cardiac fibers, which result in impaired contractility and limited ability to augment cardiac output. Ex-premature infants have a higher incidence of respiratory complications after surgery, including postanesthetic apnea. Postanesthetic apnea is defined as cessation of breathing for at least 15 seconds or any pause in breathing associated with a heart rate of less than 80 beats/min. Apnea may be central (e.g., caused by an underdeveloped brainstem), obstructive (e.g., caused by an upper or lower airway obstruction), or mixed. It may also be influenced by pharmacologic and metabolic factors (i.e., metabolic alkalosis). The incidence of apnea after anesthesia is highest in the first 4 to 6 hours after the procedure but can persist up to 12 hours after an anesthetic, often requiring overnight observation. The additional cost associated with a prolonged stay in a postanesthesia care unit (PACU) and often an overnight hospital stay must be considered versus the risk of postponing elective surgical procedures until the chance of apnea is minimal. This risk decreases with increasing gestational age and age at the time of surgical intervention, with a risk reduction to 1% at approximately 56 weeks postconceptual age (PCA). A conservative approach is to admit all premature infants with PCA less than 60 weeks for at least 12 hours; however, policies will vary across institutions.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly associated with prematurity. However, BPD can also occur in full-term infants with a history of prolonged mechanical ventilator support, chorioamnionitis, or persistent PDA. BPD is caused by an arrest in lung development and is characterized by formation of fewer, larger alveoli with smaller capillary beds and associated interstitial fibrosis. These abnormalities lead to hypoxemia, bronchial hyperreactivity, ventilation/perfusion mismatch, pulmonary hypertension, and a propensity for tracheobronchomalacia secondary to inadequate cartilaginous support. Management strategies include using optimal peak end-expiratory pressure (PEEP) to prevent large airway collapse and atelectasis, diuresis, avoiding increases in PVR, using smaller tidal volumes to prevent volutrauma and barotrauma, and close monitoring of electrolyte abnormalities. Although controversial, several studies advocate maintaining lower oxygen saturation to prevent the sequelae of hyperoxia. Most studies support a goal oxygen saturation of 91% to 95% because of the potential for increased mortality with saturations lower than 90%.

Immature thermoregulatory centers and increased surface-area-to-volume ratio predispose premature infants to hypothermia. In addition, premature, and term, infants rely on nonshivering thermogenesis via brown fat cells for heat generation, although this capability is not fully developed until 26 to 30 weeks of gestation. As a result, premature patients require aggressive maneuvers to prevent cooling, including increasing the temperature in the operating suite, convective warmers, infrared lights, humidified anesthetic gases, and warmed intravenous (IV) and irrigation fluids.

Development of electrolyte abnormalities, such as hypoglycemia, hypocalcemia, and hyponatremia, is common in premature infants. Hypoglycemia results from a combination of increased glucose requirements and decreased glycogen stores; therefore premature infants undergoing surgical procedures will generally require glucose-containing fluids. Hypocalcemia is often a result of parathyroid hormone resistance or insufficiency, decreased maternal transfer of calcium, renal losses, and increased calcitonin production. Premature infants have an immature renal tubular collecting system that can lead to the development of hyponatremia. Pharmacokinetic differences with regard to anesthetic medications must also be considered because of a larger volume of distribution (increased total body water) and immature renal and hepatic function.

Children born prematurely continue to be at risk for sedation- and anesthesia-related adverse events, usually related to the airway and pulmonary system. One study demonstrated that preterm patients are nearly twice as likely to experience sedation- or anesthesia-related adverse events compared with term-born children, with adverse consequences extending into adulthood as well.

Additional Reading

• Bailey NA, Diaz-Barbosa M. Effect of maternal substance abuse on the fetus, neonate, and child. Pediatr Rev . 2018;39(11):550–559. doi:10.1542/pir.2017-0201

• CDC’s Developmental Milestones. Centers for Disease Control and Prevention. https//www.cdc.gov/ncbddd/ActEarly/milestones/index.html . Published June 10, 2020.

• Corkins MR, Daniels SR, de Ferranti SD, et al. Nutrition in children and adolescents. Med Clin North Am . 2016;100(6):1217–1235. doi:10.1016/j.mcna.2016.06.005 (See full article)

• Grunauer M, Jorge AAL. Genetic short stature. Growth Horm IGF Res 2018;38:29–33. (See full article)

• Homan GJ. Failure to thrive: a practical guide. Am Fam Physician . 2016;94(4):295–299.

• Lauer BJ, Spector ND. Hyperbilirubinemia in the newborn. Pediatr Rev . 2011;32(8):341–348.

• Pomeranz ES. Child abuse and conditions that mimic it. Pediatr Clin N Am . 2018;65:1135–1150. doi:10.1016/j.pcl.2018.07.009 (See full article)

• Szakmar E, Jermendy A, El-Dib M. Respiratory management during therapeutic hypothermia for hypoxic-ischemic encephalopathy [published correction appears in J Perinatol . 2019 Apr 8]. J Perinatol . 2019;39(6):763–773. doi:10.1038/s41372-019-0349-2

Intensive Care Considerations in Pediatric Otolaryngology

• Breuer RK, Taicher B, Turner DA, Cheifetz IM, Rehder KJ. Standardizing postoperative PICU handovers improves handover metrics and patient outcomes. Pediatr Crit Care Med . 2015;16(3):256–263. doi:10.1097/PCC.0000000000000343

• Shapiro MC, Donohue PK, Kudchadkar SR, Hutton N, Boss RD. Professional responsibility, consensus, and conflict: a survey of physician decisions for the chronically critically ill in neonatal and pediatric intensive care units. Pediatr Crit Care Med . 2017;18(9):e415–e422. doi:10.1097/PCC.0000000000001247

• Walker T, Kudchadkar SR. Pain and sedation management: 2018 update for the Rogers’ Textbook of Pediatric Intensive Care. Pediatr Crit Care Med . 2019;20(1):54–61. doi:10.1097/PCC.0000000000001765

Ethical Considerations in Treating Vulnerable Populations (see Chapter 1 , Chapter 17 )

The current era is notable for pluralistic values, such that individuals hold a wide range of beliefs and values that are important to them. Widespread immigration and the effect of global communication via the Internet, social media, and television allow these diverse values to be distributed widely. The Western tradition of philosophical thought, which originated with Plato and Aristotle, has traditionally guided moral decision making in providing the principles of autonomy, nonmaleficence, beneficence, and justice. It offers moral insight into the patient’s illness and the realities of his or her life situation.

A collaborative family meeting with open disclosure and discussion prior to decision making will enable a noncoercive consensus-seeking dialogue. This dialogue/consensus approach, also referred to as the shared decision-making model, currently drives the case conferences among clinicians, the family, and other stakeholders in determining what will best contribute to the welfare of the ill child. The purpose of the family case conference is to explain the facts of the medical condition, convey any uncertainty about the exact diagnosis and prognosis, and allow the various participants to speak truthfully and noncoercively in a way that does not aim to direct or influence other participants in the discussion. The ultimate aim is to achieve consensus, ensuring all involved understand the reality of the situation along with the values held by the patient’s caregivers and the clinicians. Habermas refers to the truth in the dialogue, the data collection, and explanation, which is aimed at maximizing the “good.” Emphasizing a forthright and honest approach to the truth of the situation helps to achieve a level of consensual dialogue that is meaningful.

Families and medical professionals alike face competing values. The joy of the expectant parents is acknowledged along with the personhood and dignity of the child. At the same time, the possibility of no intervention and its consequences may also be discussed. Children with congenital anomalies may require long-term care and multistage surgeries to improve their well-being in terms of respiration, feeding, and swallowing. Normal speech and swallowing cannot be assumed, and the family must be prepared for the possibility of other comorbidities not yet diagnosed, such as hearing loss and central neurologic dysfunction. A child who needs specialized care may be ineligible for day care or an untrained babysitter, which will affect the parents’ ability to work, with potential financial implications. The family’s dynamics are affected, even to the point of divorce from the stress involved in caring for a child with a disability. The pediatric otolaryngologist must have the medical training to care for critically ill children and to use new technology to perform complex procedures while exhibiting professionalism and expertise in patient- and family-centered care. On the basis of the consensus gained via dialogue, parents are supported in their decision making, which is all the more important when outcomes may be painful.

Despite the large percentage of families pursuing a listening and spoken language approach, professionals need to be aware of other modes of communication. Hearing parents are unlikely to be familiar with signed communication or other options; therefore professionals should ensure that families are aware of their options and assist the family on deciding what is best for them. Professionals must be sensitive and knowledgeable when sharing this information, while explaining how their decisions on using visual and/or signed language may affect the development of spoken language.

Source for the following text: Cummings Otolaryngology-Head and Neck Surgery , 7th edition, Chapter 149.

Recent advances in genetics have raised a host of ethical issues. From the physician’s perspective, one issue relates to a physician’s “duty” to inform patients who are at risk for genetic disorders. If a woman is found to carry breast cancer liability alleles on the BRCA1 gene, is it the physician’s responsibility to make sure that this patient communicates the possibility of risk to her female relatives? Clearly, a conflict exists here between the patient’s right to privacy and the responsibility to “do good” by informing women for whom this extra diligence just might be lifesaving. Any genetic diagnosis carries with it the potential that a person other than the primary patient could be involved. The diagnosis of GJB2 -related hearing loss identifies siblings, cousins, and other relatives as potential heterozygotes who have an increased risk of having a child with profound deafness. It is not always the case that family members want the information, either. Although the issue is still argued, the general consensus is that the flow of information must come from the patient or, in the case of a minor, from an immediate family member.

Fluids and Electrolytes

As in adults, preoperative, intraoperative, and postoperative fluid management is extremely important in children; extreme vigilance, early recognition, and tight control are required. Some of the physiologic differences outlined earlier make fluid administration even more critical. Because of their small intravascular volume (70 to 80 mL/kg), infants who experience small changes in fluid balance can easily become either dehydrated or overloaded with fluid. The compartmentalization of total body water changes with age, but intracellular and extracellular electrolyte composition remains stable ( Table A.1 ). Maintenance fluid requirements for a child can be calculated by relatively simple formulas that vary according to metabolic and physical activity. The calculation of water loss per calorie is described in Table A.2 . The correspondence of necessary fluid intake proportional to weight is described in Table A.3 . Complex fluid and electrolyte deficits are beyond the scope of this discussion. In most cases, consultation with pediatric medical specialists is advised.

Medications

Midazolam is a benzodiazepine with a rapid onset and short duration of action. It induces anterograde amnesia and anxiolysis without significant effects on heart rate, systolic blood pressure, arterial oxygen saturation, or respiratory rate. Midazolam-mediated dose efficacy is inversely correlated to age, with younger patients often requiring higher doses. It is the most commonly used pediatric anxiolytic medication and is often given orally (PO). The dose recommended for PO midazolam is 0.5 to 1 mg/kg (up to a maximum dose of 20 mg). Time to onset of effect is 10 to 15 minutes with a peak of 30 minutes. At increased doses (1 mg/kg), side effects can include blurred vision, dysphoric reactions, and loss of balance and head control. The taste of midazolam is bitter, and patients occasionally refuse to take the medication or take only a partial dose, affecting onset and quality of effect. Midazolam administered via the intranasal (IN) route at a dose of 0.2 to 0.3 mg/kg has a peak onset of 10 minutes, but it can cause nasal mucosal irritation. IV administration of midazolam is preferred when available, at a dose of 0.025 to 0.1 mg/kg.

Dexmedetomidine and clonidine are α-2 adrenoreceptor agonists commonly used as premedication agents. Compared with clonidine, dexmedetomidine has significantly increased α-2 to α-1 receptor specificity and a shorter half-life. These medications provide analgesic benefit, decrease the incidence of emergence delirium, treat withdrawal symptoms, and may provide a neuroprotective benefit to the developing brain. A 2015 meta-analysis demonstrated better sedation with use of dexmedetomidine premedication during separation from parents compared with midazolam. Dexmedetomidine is also used in the pediatric intensive care unit (PICU) for sedation and in the operating suite as an adjunct to general anesthesia. It can be administered PO (1 to 4 μg/kg), buccally (3 to 4 μg/kg), IN (0.5 to 1 μg/kg), intramuscularly (IM; 2 to 4 μg/kg), or IV (loading dose of 0.5 to 1 μg/kg over 10 minutes, followed by an infusion of 0.5 to 1.0 μg/kg/h). Reported adverse outcomes include, but are not limited to, hemodynamic changes including hypotension and biphasic blood pressure responses, decreased respiratory rate, and dose-dependent bradycardia.

Other premedication agents that may be encountered in pediatric practice include ketamine (see later), opioids, barbiturates (i.e., pentobarbital), antihistamines (i.e., diphenhydramine and hydroxyzine), and chlorohydrate.

Application of a topical mixture of lidocaine and prilocaine, also known as EMLA (eutectic mixture of local anesthetics) cream, to the potential IV site approximately 60 minutes prior to insertion has been shown to significantly decrease pain with placement. Topical 4% lidocaine is equally effective for IV cannulation if applied 30 minutes prior to insertion. A side effect of topical local anesthetic use is blanching at the site of application; for EMLA, specifically, there is a small risk of methemoglobinemia caused by the use of prilocaine. Additional techniques include cold sprays and needleless lidocaine application.

Drug-induced sleep endoscopy (DISE) is used to identify causes of upper airway obstruction and ultimately guide surgical therapy, which may be performed at the time of endoscopy or deferred for a later date. Anesthetic induction of a sleeplike state reproduces dynamic airway changes not visible during studies performed in awake patients. There is currently no consensus regarding the choice of anesthetic medication for DISE. It may be beneficial to discontinue inhalational agents after obtaining IV access, as volatile anesthetics decrease upper airway muscle tone. Propofol also causes dose-dependent respiratory depression with similar decreases in muscle tone. Ketamine and dexmedetomidine offer the advantage of preserving ventilation; however, ketamine can result in an increase in genioglossus activity. Rapid emergence from anesthesia is desirable, and prolonged PACU observation or hospital admission should be considered for patients showing signs of severe obstruction or respiratory difficulty after the procedure.

Postoperative Nausea Prophylaxis

Postoperative nausea and vomiting (PONV) is one of the most common adverse side effects of anesthetic and pain medications. Risk factors for PONV include age 3 years and older, procedure length longer than 30 minutes, specific surgical procedures including strabismus correction and adenotonsillectomy, and previous history or family history of PONV. Patients with four or more of the aforementioned risk factors were found to have a 70% incidence of PONV. Strategies to reduce the risk of PONV include prophylactic preventative medications, minimizing the use of volatile anesthetics and considering propofol for induction and maintenance, avoidance of nitrous oxide for procedures longer than 30 minutes, utilization of regional anesthesia, maximization of nonopioid analgesics to decrease opioid use, and ensuring adequate hydration.

Dexamethasone is an agent routinely used for PONV prophylaxis and has been shown to reduce the morbidity in children undergoing tonsillectomy. A Cochrane review showed that for pediatric patients undergoing tonsillectomy or adenotonsillectomy, a single IV corticosteroid dose administered intraoperatively resulted in reduced PONV, earlier advancement of diet on postoperative day 1, and improved postoperative pain measures without adverse outcomes. Optimal dosing is debatable. Several studies demonstrate increased efficacy of PONV prophylaxis with increased doses; however, other studies demonstrate no difference.

Serotonin antagonists, such as ondansetron, are also commonly used in PONV prophylaxis. Serotonin antagonists, metoclopramide, phenothiazines, and butyrophenones target the chemoreceptor trigger zone. Cannabinoids and benzodiazepines affect the cerebral cortical regions. Antihistamines and anticholinergics act on the vomiting center, and metoclopramide and serotonin antagonists affect the visceral afferents.

The most common side effects of opioids are vomiting, pruritus, and constipation; however, respiratory depression may occur and is the most serious and life-threatening consequence of opioid administration. An understanding of opioid pharmacokinetics and pharmacodynamics, including developmental effects on clearance and elimination, is essential for safe use. Common opioids used in anesthetic practice are discussed later.

Morphine is the standard to which all other opioids are compared, as it is the most frequently administered agent for treatment of acute pain. Its analgesic effect is via activation of supraspinal mu receptors. Morphine is highly water soluble, resulting in a delayed onset of action compared with other lipid-soluble opioids. Metabolism is via the liver, and its metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), have pharmacologic activity. Impaired renal function may lead to accumulation of active metabolites leading to respiratory depression.

Codeine is an opioid with 1/10 the potency of morphine. Historically, it was commonly used in the outpatient setting for treatment of acute pain and as a cough suppressant. The use of codeine has significantly declined because of genetic variations in metabolism leading to prolongation of analgesic effect and severe respiratory depression. In 2013 the U.S. Food and Drug Administration (FDA) issued a black-box warning recommending against the use of codeine after adenotonsillectomy secondary to an increasing number of mortalities attributed to overdose resulting from genetic polymorphism (often gene duplication of CYP2D6) and ultrarapid metabolism. In 2015 the FDA issued a warning detailing the risk of serious respiratory complications with the use of codeine in children, and in 2017, the FDA updated this warning to a relative contraindication. The American Academy of Pediatrics (AAP) has recommended using alternative analgesics, especially in pediatric patients with obesity and obstructive sleep apnea (OSA).

Hydromorphone is a semisynthetic opioid approximately 5 to 7.5 times more potent than morphine. It is metabolized by the liver into hydromorphone-3-glucuronide, a clinically inactive metabolite.

Oxycodone is an oral semisynthetic opioid that undergoes metabolism via cytochrome pathways (CYP3A and CYP2D6) into oxymorphone and noroxymorphone. Oxymorphone is 14 times more potent than oxycodone because of its increased affinity for the mu receptor. Clearance is decreased in patients with liver dysfunction.

Hydrocodone is an oral agent that is metabolized by the CYP2D6 pathway to its active metabolite, hydromorphone. Individual genetic variation in metabolism can significantly affect its analgesic efficacy. Hydrocodone is frequently used in combination preparations with acetaminophen and can lead to acetaminophen overdose if inappropriately administered.

Meperidine is a weak mu-opioid receptor agonist that is 1/10 as potent as morphine. Its use in the treatment of acute pain has fallen out of favor because of increased incidence of seizures secondary to its active metabolite, normeperidine. Meperidine is used in the immediate postoperative period for treatment of shivering and/or pain relief in patients who are not at risk for developing seizures.

Fentanyl is a potent synthetic mu-opioid receptor agonist that is approximately 75 to 125 times more potent than morphine. It is highly lipid soluble and has a quick onset of action and short duration of action. Fentanyl undergoes hepatic metabolism via CYP3A4 to inactive metabolites excreted via the kidneys.

Additionally, synthetic analogs of fentanyl, such as sufentanil, alfentanil, and remifentanil, may be encountered in the operating suite. Remifentanil is an analog of fentanyl commonly used in total intravenous anesthesia (TIVA). It is unique in that it is characterized by a very short elimination half-life of 3 to 6 minutes with metabolism via blood and tissue esterases. Use of remifentanil is unaffected by liver and renal dysfunction. Its use may be limited by cost.

Acetaminophen is one of many nonopioid analgesics used in anesthetic practice. Its antipyretic and analgesic mechanisms of action are still not clearly understood even after decades of use. Acetaminophen blocks prostaglandin synthesis through COX-3 inhibition. It may also have cannabinoid agonist and N -methyl-D-aspartate (NMDA) receptor antagonist properties. Onset of action for PO administration is approximately 30 minutes with duration of action of 4 to 6 hours. Rectal administration requires use of a higher dose because of variability in absorption and a longer onset of action. The onset time for IV dosing is 5 to 10 minutes with duration of action similar to PO dosing. Compared with rectal acetaminophen, the IV form has a shorter duration of action and shorter time to requiring rescue analgesic. Intraoperative opioid requirement has been shown to decrease with IV compared with PO administration of acetaminophen; however, there was no significant difference in postoperative opioid consumption. IV acetaminophen may be of limited use because of cost.

Acetaminophen undergoes hepatic metabolism to N -acetyl- p -benzoquinone imine (NAPQI), a highly reactive and hepatotoxic metabolite. NAPQI is then inactivated by glutathione to cysteine and mercapturic acid. Large doses of acetaminophen may lead to glutathione store depletion, resulting in NAPQI accumulation and subsequent hepatotoxicity. In addition, the half-life of acetaminophen decreases with age, with neonates having a half-life of 7 hours, infants 4 hours, children and adolescents 3 hours, and adults 2 hours. Thus reduced drug dosing regimens should be considered in young children and infants, and patients with liver dysfunction.

Nonsteroidal antiinflammatory drugs (NSAIDs) are effective analgesic medications commonly used in the pediatric population. Administration of both acetaminophen and NSAIDs results in an additive analgesic effect. NSAIDs inhibit prostaglandin H2 synthase at peripheral COX sites resulting in reduced production of prostaglandin (PGE2) and subsequent decreased inflammation, smooth muscle contraction, and nociception. NSAIDs also act centrally by blocking spinal glutamate and substance P receptor activation. In addition, these medications inhibit thromboxane production and may theoretically result in platelet inhibition and increased risk of bleeding.

Ibuprofen, a commonly used NSAID, is an antipyretic and antiinflammatory medication with well-documented analgesic properties. It has been shown to be superior to acetaminophen and codeine in pediatric patients with musculoskeletal injury. Ketorolac is an IV NSAID with an onset time of 30 minutes and duration of action of 4 to 6 hours. It undergoes hepatic metabolism with excretion via the kidneys. Compared with opioids, use of ketorolac is associated with less respiratory depression, sedation, nausea, and pruritus. It is available in PO, intraocular, IV, and IM formulations. Ketorolac should be used with caution in patients with renal dysfunction and in patients less than 1 year of age because of immature renal function.

Possible adverse effects of NSAID administration include hypersensitivity reactions, bleeding, gastrointestinal (GI) ulcers, and renal dysfunction secondary to changes in renal vascular tone. The theoretical increased risk of bleeding with NSAID use is also controversial. A 2005 Cochrane meta-analysis found no increased risk of bleeding in pediatric tonsillectomy patients who received NSAIDs perioperatively; however, the incidence of PONV was decreased with the use of NSAIDs compared with alternative analgesic medications. The American Academy of Otolaryngology–Head and Neck Surgery recommends ibuprofen, but not ketorolac, as an option for postoperative pain control after adenotonsillectomy. In addition, the FDA recommends a 5-day limit on the use of NSAIDs to reduce the risk of potential side effects.

Gabapentin is a calcium-channel blocker traditionally employed as an anticonvulsant. It is often used as a nonopioid adjunct in multimodal analgesic regimens. In the adult population, gabapentin has been used with success in treating chronic neuropathic pain, and evidence supports its use in the treatment of acute pain as well. In the pediatric population, gabapentin has been shown to reduce opioid consumption in posterior spinal fusion surgery. In addition, its administration in healthy children undergoing adenotonsillectomy has resulted in a decrease in total analgesic medication requirement postoperatively. Common side effects include sedation, dizziness, and nausea. Gabapentin should be used with caution in patients with impaired renal function.

Congenital Heart Disease (See Chapter 2 )

The presence of congenital (CHD) or acquired heart disease (AHD) poses a unique and serious risk for both elective and emergent surgical procedures. Pediatric patients with heart disease of any type have twofold higher rates of cardiac arrest and death during the perioperative period. The Pediatric Perioperative Cardiac Arrest (POCA) Registry found that children with CHD or AHD were on average sicker than those without heart disease and also had a higher mortality after arrest. For children with CHD or AHD undergoing noncardiac procedures, most cardiac arrests occurred in the intraoperative period and were caused by cardiovascular causes. Of note, otolaryngologic procedures, specifically myringotomy and tubes, bronchoscopy, and tracheostomy, were identified as having higher rates of complications in children with heart disease, as were GI procedures.

The care and triaging of children with heart disease is a controversial topic. Proposed high-risk criteria include complex lesions (single-ventricle physiology, aortic stenosis, Eisenmenger syndrome, or cardiomyopathy), poorly compensated physiology (cardiac failure, pulmonary hypertension, arrhythmias, or cyanosis), age less than 2 years, major surgery, emergency surgery, preprocedural hospital stay of greater than 10 days, and American Society of Anesthesiologists (ASA) class IV or V ( Box A.1 ). Low-risk characteristics include compensated or normal physiology, simple lesions, age greater than 2 years, minor surgery, elective surgery, and ASA class I to III.

In general, high-risk patients with CHD in need of surgery should be referred to a specialist center because of the high likelihood of need for specialized care (i.e., pediatric cardiac anesthesiologist, pediatric intensive care, and pediatric cardiology). Intermediate-risk children should be individually evaluated and considered for transfer if options are available. New evidence shows that low-risk children may undergo procedures safely in a local hospital setting.

CHD encompasses a wide spectrum of structural anomalies and, as a group, is considered the most common birth defect found in the pediatric population, with an incidence of 1 in 125 live births. Over the last several decades, improvements in medical innovation and care have led to the survival of 85% to 90% of these patients into adulthood; consequently, children and adults with CHD are increasingly likely to present for noncardiac surgery. Patients with CHD may have vastly different pathophysiology, and each lesion should be uniquely considered.

CHD patients can be classified based on their specific type of circulation: normal “series” circulation, parallel “balanced” circulation, and single-ventricle circulation. Normal or “series” circulation describes normal cardiac flow and physiology, which is typically observed in patients with isolated atrial septal defects and ventricular septal defects. Parallel or “balanced” circulation involves the mixing of systemic venous and pulmonary venous blood, often leading to variable degrees of cyanosis. Common lesions of this type include unrepaired atrioventricular septal defects; Blalock-Taussig, Glenn, or Sano (right ventricle to pulmonary artery) shunts; and truncus arteriosus. Single-ventricle circulation involves passive blood flow down a pressure gradient to the pulmonary system, usually via a shunt or palliated anatomic pathway, such as with Fontan physiology.

Pulmonary hypertension is defined as a mean pulmonary arterial pressure greater than 25 mm Hg. It is a common sequela of CHD but may also develop because of vascular anomalies, bronchopulmonary hypoplasia, or respiratory disease. Severe pulmonary hypertension is associated with high morbidity and mortality related to perturbations in baseline physiology in the perioperative period. Exacerbating factors include sedation-related hypercarbia and hypoxia, and hypothermia resulting from impaired thermoregulation under anesthesia and a cold operating environment. No single anesthetic technique has been shown to be superior in improving patient outcomes, thus an individualized approach to the patient with pulmonary hypertension is recommended. As with high-risk CHD, patients with pulmonary hypertension should undergo surgical procedures at a center with specialized expertise, including cardiac anesthesiologists, cardiologists, and pediatric intensivists. Inhaled and IV pulmonary vasodilators and postoperative ICU admission should be strongly considered in high-risk cases. Close monitoring, even after minor, low-risk procedures, is essential, as most perioperative deaths related to pulmonary hypertension occur in the postoperative period.

Another consideration in the CHD population is the need for antibiotic prophylaxis against infective endocarditis (IE). In 2007 the American Heart Association (AHA) published updated guidelines for the prevention of IE in patients with specific cardiac defects who are undergoing procedures disrupting the normal mucosal barrier, including those near the teeth and oropharynx. Antibiotics should be administered to patients with (1) prosthetic cardiac valve/prosthetic material used for valve repair; (2) previous IE; (3) unrepaired cyanotic CHD, including palliative shunts and conduits; (4) CHD completely repaired with prosthetic material or device, whether placed by surgery or catheter intervention, during the first 6 months after the procedure; and (5) repaired CHD with residual defects at or adjacent to the site of prosthetic patch or device. The antibiotic agent should cover streptococcal and staphylococcal species, the most common flora present on mucosal surfaces. Recommended agents include amoxicillin, ampicillin, cefazolin, ceftriaxone, or cephalexin; for those severely allergic to these medications, clindamycin, azithromycin, or clarithromycin are acceptable alternatives.

Duchenne Muscular Dystrophy (See Chapter 2 )

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy. The two best known X-linked traits are hemophilia and DMD. Patients with DMD lack the dystrophin protein. DMD is characterized by a painless degeneration of muscle fibers and subsequent fatty hypertrophy of muscle tissue. Progressive respiratory weakness, difficulty with handling secretions, and ineffective cough and airway clearance may lead to recurrent pneumonias, and most patients generally suffer respiratory-related morbidity and mortality. Severe scoliosis may lead to development of restrictive lung disease. Cardiac disease may manifest as conduction defects or progressive cardiomyopathy. Patients may suffer from gastric hypomotility and delayed gastric emptying, which increase the risk for aspiration during induction.

There is no standardized anesthetic technique for patients with muscular dystrophies, although some specific considerations apply to each of the various types. Pulmonary function testing should be considered for symptomatic patients, and perioperative optimization of patients with muscular dystrophy may warrant initiation of noninvasive positive-pressure ventilation. Preoperative echocardiogram should be considered to assess for cardiac dysfunction. Long-term steroid usage may necessitate “stress doses” in the perioperative period. Succinylcholine has been implicated in several cases of hyperkalemic cardiac arrest in previously healthy children who were subsequently found to have an underlying myopathy; as a result, the FDA placed a black-box warning on the use of succinylcholine in pediatric patients, recommending its use for emergency situations only.

Muscular dystrophy is not independently associated with an increased risk of malignant hyperthermia (MH) unless the patient is known to have a mutation of the ryanodine receptor 1 gene (RYR1). Despite this lack of evidence, use of volatile anesthetics in patients with muscular dystrophy remains controversial. Volatile anesthetics are considered relatively contraindicated as a result of reports of rhabdomyolysis attributed to muscle membrane fragility. Most anesthesiologists favor performing a total IV anesthetic when feasible.

Sickle Cell Anemia (See Chapter 2 )

Sickle cell disease (SCD) is an inherited group of hemoglobinopathies prevalent in the African American and Hispanic population. The pathophysiology of SCD is extremely complex but can be broadly described as accumulation of sickled erythrocytes in the microvasculature, leading to decreased peripheral perfusion. Children diagnosed with SCD have a higher degree of perioperative morbidity and mortality, with the rate of complications estimated to be 30% to 50% higher than in patients without SCD.

Preoperative evaluation should include a detailed history and physical focusing on prior vaso-occlusive crises (e.g., acute chest syndrome, cerebrovascular accidents, and pulmonary hypertension), prior transfusions, current analgesic regimen, neurologic assessment, and oxygen saturation. Important laboratory tests include baseline hematocrit and type and crossmatch. Preoperative methods to decrease the risk of sickling include aggressive IV hydration, bronchodilators, hydroxyurea, and transfusion. The current recommendation is to transfuse to a hemoglobin goal of 10 g/dL in children with SCD to decrease the risk of vaso-occlusive crises and cerebrovascular accidents. Exchange transfusion should be used in patients with more severe sickle cell phenotypes who are still experiencing frequent pain crises or other complications related to the disease despite hemoglobin levels greater than 10 g/dL.

Goals of intraoperative anesthetic care should focus on maintaining normal physiology and avoiding factors that may precipitate sickling crises. Postoperative considerations include consultation with a hematology service, monitoring for complications such as acute chest syndrome and cerebrovascular accidents, oxygen supplementation, appropriate antibiotics, adequate hydration status, and early mobilization. Aggressive pain management is essential, but achieving adequate pain control may be difficult because of high rates of chronic analgesic use to treat chronic pain. Consultation with an acute pain service is often desirable and effective.

Diabetes Mellitus (See Chapter 2 )

Successful management of patients with diabetes mellitus requires interdisciplinary communication between the perioperative team and the patient’s endocrinologist to optimize oral medication and insulin dosing. Near-normoglycemia is the goal, and dose reduction of intermediate- and long-acting insulin formulations is often required to avoid hypoglycemia. Metformin should be held for 24 hours preoperatively to decrease the risk of lactic acidosis. Diabetic patients should also be scheduled as the first case of the day to limit nil per os (NPO) times and facilitate optimal perioperative glucose values. Typically, preoperative correction of hyperglycemia is not necessary unless glucose values are greater than 250 mg/dL. Intraoperatively, frequent blood glucose monitoring is recommended, and in major procedures of 2 hours or more where operative stress can lead to an increase in blood glucose levels, an insulin infusion is preferred over subcutaneous correction. Postoperatively, diabetic patients should resume their home medication regimen as soon as they are able to tolerate a normal diet.

Mitochondrial Myopathies (See Chapter 2 )

Mitochondrial myopathies describe a group of disorders of variable genetic penetrance, which affect tissues with high-energy consumption, most notably neurologic and musculoskeletal systems. Common symptoms at presentation include hypotonia, respiratory muscle weakness, seizures, and encephalopathy. Patients with mitochondrial myopathies may be exquisitely sensitive to hypoglycemia and metabolic stress, and many have the propensity to develop lactic acidosis. Therefore fasting periods should be minimized, IV glucose supplementation should be provided when indicated, and avoiding exogenous lactate-containing fluids may be necessary. The risk of lactic acidosis may be mitigated by preventing shivering, maintaining normothermia, and optimizing perioperative analgesia. All general anesthetic medications depress mitochondrial function to some degree; thus careful anesthetic titration is of utmost importance.

The potential for a difficult airway should be anticipated in children with genetic conditions, including but not limited to Down syndrome, Beckwith-Wiedemann syndrome, Pierre Robin sequence, Treacher Collins syndrome, hemifacial microsomia (HFM), Apert syndrome, Klippel-Feil anomaly, muscular dystrophies, and mucopolysaccharidoses. Factors evaluated by anesthesiologists to determine the potential for a difficult airway include Mallampati score, thyromental distance, mouth opening, tongue size, presence of loose teeth, cervical flexibility, and previous intubation history. In 2014 a review of airway management at a tertiary care pediatric hospital demonstrated that patient history identified 98% of patients with difficult airways. The most common etiologies identified were mandibular hypoplasia, micrognathia, limited neck extension, poor temporomandibular joint mobility, macroglossia, severe glottic or subglottic stenosis, and tracheal anomalies or stenosis. Thus a careful history and physical examination should identify the majority of difficult or potentially difficult airway situations, allowing for thorough planning and care coordination between the anesthesiologist and otolaryngologist for both otolaryngologic and nonotolaryngologic procedures.

Direct Laryngoscopy and Bronchoscopy

Anesthesia for rigid bronchoscopy presents a significant challenge for the anesthesiologist. Patients requiring rigid bronchoscopy often present with some degree of airway abnormality, with or without compromised oxygenation and ventilation. In addition, the anesthesiologist and otolaryngologist must “share” the surgical field, with the patient turned away from the anesthesia machine and provider. Thus clear and concise communication between members of the operative team is imperative.

The anesthetic goals for bronchoscopy are to maintain spontaneous ventilation, minimize the patient’s response to airway stimulation, and to ensure expeditious return of airway reflexes prior to leaving the operating suite by using anesthetic agents with a quick onset and fast resolution. No difference in outcomes exists between controlled versus spontaneous ventilation; however, maintenance of spontaneous ventilation allows for dynamic assessment of airway pathophysiology and provides a potential pathway to awaken the patient should he or she be impossible to mask ventilate or intubate. Associated respiratory pathology should be considered prior to administering a premedication, as airway obstruction, respiratory depression, apnea, hypoxia, and prolonged recovery times can occur with even standard doses.

Induction of anesthesia can occur via inhalational or IV techniques. If nitrous oxide is administered to speed an inhalational induction, it should be discontinued to increase the fraction of inspired oxygen prior to airway evaluation. Studies show no difference in outcomes with the use of either inhalational or IV agents for maintenance of anesthesia. A TIVA technique using propofol is commonly used and may be supplemented with dexmedetomidine, ketamine, and/or opioids. Additionally, IV, as opposed to inhalational, anesthetic administration minimizes interruptions in drug delivery and exposure of the operating room (OR) staff to escaped anesthetic gases. Muscle relaxants are generally avoided in favor of spontaneous ventilation. Topicalization of the vocal cords, glottis, and trachea with lidocaine during direct laryngoscopy decreases coughing and bucking during subsequent instrumentation. Lidocaine doses should be weight based, with a maximum dose of 5 mg/kg for lidocaine without epinephrine and 7 mg/kg for lidocaine with epinephrine. Dexamethasone may be administered to decrease mucosal swelling and postoperative stridor. An antisialagogue, such as atropine or glycopyrrolate, can decrease oral secretions and improve bronchoscopic visualization of airway structures. Standard monitors should be used for all bronchoscopic procedures; however, continuous capnography may not be accurate or possible. Use of a precordial stethoscope and visualization or palpation of chest wall movement during respirations is a common method to assess ventilation in these cases. CO ₂ retention is generally well tolerated in the pediatric population and resolves quickly as the anesthetic level is decreased . 259 Hypoxia is not well tolerated and should be recognized and treated immediately, as untreated hypoxemia can quickly lead to bradycardia and cardiac arrest. Supplemental oxygen may be delivered through the bronchoscope sidearm attachment, a small, uncuffed endotracheal tube (ETT) placed in the hypopharynx, or by using high-flow nasal cannula; however, use of high oxygen concentrations in the presence of certain therapeutic interventions (i.e., laser) is contraindicated because of the risks of airway fire. If maintenance of spontaneous ventilation is not possible, high fresh gas flows and hand ventilation with increased inspiratory pressures and respiratory rates may be required to compensate for increased resistance through and/or a large leak present around the bronchoscope .

At the completion of the procedure, mask ventilation with supplemental oxygen should be initiated, or if the patient is spontaneously breathing and ventilation is adequate, supplemental oxygen should be provided via face mask. An ETT can be inserted prior to bronchoscope removal if apnea is present or if the airway is tenuous or deemed difficult. The patient should be transported by the anesthesia team to either the PACU or ICU, with destination depending on the extent of surgical intervention, underlying airway pathology, history of difficult airway, and associated comorbidities.

Obesity (See Chapter 12 )

According to the Centers for Disease Control and Prevention (CDC), childhood obesity affects more than 18% of the U.S. population between ages 2 and 19 years. Comorbidities related to obesity include impaired glucose tolerance, diabetes, hypertension, cardiovascular disease, asthma, and SDB. Obesity affects all aspects of anesthetic care. Monitoring of vital signs, such as blood pressure and ECG, and neuromuscular blockade, may be difficult because of body habitus and soft tissue impedance. Obtaining IV access, performing mask ventilation and intubation, patient positioning, and determining correct medication dosing in obese patients pose a serious challenge for the anesthesiologist.

Although obesity is a risk factor for pediatric SDB, most children with SDB are not obese. However, the prevalence of SDB in obese children is 25% to 40%. Obesity predisposes children to SDB by decreasing the cross-sectional area of the upper airway by the deposition of adipose tissue adjacent to the pharynx and also because of compression from subcutaneous fat deposits in the neck. Individual symptoms and polysomnogram (PSG) abnormalities do not correlate with the degree of obesity. Soultan and colleagues found that 10 of 17 children who were obese or morbidly obese with OSA had substantial weight gain after adenotonsillectomy, perhaps related to decreases in hyperactivity and restlessness. Therefore treatment of the SDB will not help and might worsen weight management in obese children. Diet, exercise, and behavior therapy are needed in addition to surgical therapy. OSA adversely affects several of the components associated with metabolic syndrome (insulin resistance, dyslipidemia, hypertension, and obesity), which is a known risk factor for cardiovascular disease in adults.

Repair Choanal Atresia (See Chapter 5 )

Treatment of unilateral atresia may be delayed for several months, allowing for growth of the nose, which enhances the ease of surgery and reduces the risk of postoperative complications and restenosis. Bilateral atresia requires initial intervention to establish an oropharyngeal or orotracheal airway and potentially gastrostomy tube feeding before definitive surgery. The timing of surgery is variable, and it may be preferable to wait several months until adequate facial growth has occurred (similar to the timing of cleft lip repair). In patients with multiple levels of airway obstruction or respiratory failure, a tracheotomy may be necessary and definitive atresia repair is often delayed. Currently, given advances in endoscopic instrumentation and the lower risk of dental and facial growth abnormalities, transnasal surgery is preferred over transpalatal approaches.

The repair begins with using a urethral sound or suction instrument to perforate the atretic plate at its thinnest portion. A 0-degree transnasal endoscope or a 120-degree nasopharyngoscope is used for visualization. Subsequently a backbiting forceps, a microsurgical debrider, a laser, and a drill are used as necessary to remove choanal soft tissue and bone. The posterior tip of the middle turbinate is a useful anatomic landmark. Restricting surgical maneuvers to remain inferior to this structure reduces the risk of intracranial injury. The use of stenting and/or fibroblast inhibitors (mitomycin C) and the importance of preserving mucosal flaps remain controversial. Regardless of the techniques used, most studies report significant recurrence rates necessitating revision surgery, although minimizing mucosal trauma is felt to lower the risk of restenosis. The lowest recurrence rates are seen in older children (with presumed unilateral atresia) and patients with nonsyndromic choanal atresia.

Syndromic and Nonsyndromic Craniosynostosis

Crouzon syndrome is a form of syndromic craniosynostosis associated with brachycephaly or brachyturricephaly. Usually bilateral coronal sutures are involved, but multiple sutures may be affected. Calvarial suture defects may occur prenatally or throughout the first 5 years of life. As the mandible is typically close to normal, hypoplasia of the midface (maxilla) leads to class III malocclusion. Exorbitism occurs as a result of decreased bony orbital volume (in contrast to exophthalmos, which results from greater intraorbital content). Intelligence is usually normal with appropriate management. Crouzon syndrome results from FGFR2 mutations, which are either sporadic or inherited in an autosomal dominant manner.

Most cases of Apert syndrome arise sporadically through new mutations, although some familial cases with autosomal dominant transmission have been reported. Apert syndrome resembles Crouzon syndrome in several ways. The disorder is characterized by brachycephaly (with resultant turricephaly) and midfacial hypoplasia (with associated orbital and dental issues). Unlike Crouzon syndrome, Apert syndrome is associated with symmetric syndactyly of the hands and feet and other axial skeletal abnormalities. The palate frequently has a high arch and may be cleft. The defects in Apert syndrome are present at birth, and intelligence may be affected.

Pfeiffer syndrome is an autosomal dominant disorder that features craniosynostosis. The coronal sutures are frequently involved, giving rise to brachycephaly, but the sagittal and lambdoid sutures may also be involved. Affected patients may have midface hypoplasia with associated orbital and dental issues, and enlarged thumbs and big toes.

Jackson-Weiss syndrome is an autosomal dominant disorder with high penetrance and variable expressivity with features similar to Pfeiffer syndrome. Brachycephaly is common. The big toes are abnormally wide, but the thumbs are typically normal. Midfacial hypoplasia is more common than in Pfeiffer syndrome. Jackson-Weiss syndrome was originally identified in the Amish population but may occur in other populations as well.

Saethre-Chotzen syndrome is an autosomal dominant disorder with full penetrance. Affected patients have craniosynostosis, often with brachycephaly, with a low hairline, ptosis, brachydactyly, and a high arched palate with occasional palatal clefting. Midface hypoplasia is not common.

Carpenter syndrome is a rare autosomal recessive syndrome. Craniosynostosis may involve the sagittal, lambdoid, and coronal sutures. Midfacial hypoplasia, if present, is usually mild. Other features include developmental delay, preaxial polysyndactyly of the feet, and other syndactyly.

Stickler syndrome is an autosomal dominant syndrome with variable expressivity, with an incidence of about 1 in 10,000. It is a connective tissue disorder with ocular, orofacial, skeletal, cardiac, and auditory manifestations, caused by mutations in genes that encode collagen.

The orofacial phenotype is characterized by occasional midface underdevelopment, mandibular hypoplasia, and cleft palate. About 30% to 40% of patients with Pierre Robin sequence (micrognathia, glossoptosis, and cleft palate) also have Stickler syndrome. It is thus the most common syndrome associated with Pierre Robin sequence but may often be unrecognized in its mild forms.

Velocardiofacial syndrome (see Chapter 11 ) or DiGeorge syndrome is an autosomal dominant syndrome with variable expressivity and penetrance, caused by deletions in chromosome 22q11. There are numerous associated anomalies aside from the well-documented craniofacial, cardiac, and vascular malformations. The craniofacial anomaly broadly consists of a more open angle of flexion in the basicranium, which affects the appearance of the midface and lower face (mandible). Clefting of the secondary palate may be overt, a submucous cleft, or an occult submucous cleft that is apparent only on nasopharyngoscopy (see Chapter 9 ). Velocardiofacial syndrome may be difficult to recognize, especially in patients with normal or mildly affected facial features. Patients with 22q11.2 deletion are at increased risk for velopharyngeal dysfunction (see Chapter 10 ), thus it is important to have a high index of suspicion when considering adenoidectomy.

First and Second Branchial Arch Syndromes

Treacher Collins syndrome (mandibulofacial dysostosis) is an autosomal dominant disorder with variable penetrance and expressivity. It involves numerous bilateral developmental abnormalities in structures derived from the first and second branchial arches. Clinical features include zygomatic hypoplasia, micrognathia, dysplastic ears, antimongoloid slants to the eyes, colobomas of the lower eyelids, and deficient eyelashes in the medial two thirds of the lower eyelids. Mandibulofacial dysostosis is associated with Pierre Robin sequence and palatal clefting in 35% of cases. Severe obstructive apnea secondary to the micrognathia and glossoptosis often requires intervention.

HFM, or more descriptively termed craniofacial macrosomia because it is sometimes bilateral, refers to a group of anomalies that originate from unilateral defects in the first and second branchial arches, with an incidence of 1 per 5600 births. It is also known as oculoauriculovertebral spectrum or Goldenhar syndrome. Most cases are sporadic, although familial cases have been reported. No specific molecular etiology has been identified, although it is hypothesized to result from a unilateral hemorrhagic event involving the stapedial artery during early craniofacial development. HFM often involves the soft and skeletal tissues of the face and external and middle ears. Patients with HFM may manifest temporal, zygomatic (malar), maxillary, and mandibular hypoplasia; hypoplastic facial musculature; and facial paresis or paralysis varying from mild, congenital unilateral lower lip paralysis to complete facial paralysis. Cleft lip and palate are not uncommon. HFM involves a wide variety of external and middle ear deformities, including atresia of the external auditory canals (EACs; see Chapter 19 ) and preauricular skin tags. Ocular involvement may present as colobomas, epibulbar choristomas, blepharophimosis, and/or strabismus. A variety of other, noncraniofacial abnormalities are associated with HFM, including fusion of vertebrae, spina bifida, and other vertebral anomalies.

Micrognathia

Mandibular distraction osteogenesis has been increasingly used in children with micrognathia and severe upper airway obstruction to eliminate the need for tracheotomy and gastrostomy tube placement or to assist with decannulation. Success is greater in nonsyndromic patients and in children without neurologic impairment. In the largest of the published series, 7 of 8 (88%) infants avoided tracheotomy, and 5 of 6 (83%) older micrognathic children were cured of OSA, but only 2 of 12 (17%) tracheotomized children with complex congenital syndromes were successfully decannulated. Midface advancement is the treatment of choice in children with craniosynostosis found in Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes. OSA is found in 50% to 70% of patients with syndromic craniosynostosis. These children may also present with elevated intracranial pressure, severe exorbitism, class III malocclusion, and aesthetic issues. Children with increased intracranial pressure are treated by posterior cranial vault expansion at about 9 months of age. Le Fort III midface distraction or monobloc distraction (simultaneous expansion of the anterior cranial vault with the midface) is typically performed at the age of 7 to 9 years but may be performed earlier for airway obstruction. Bannink and colleagues reported successful treatment of OSA in 6 of 11 patients, but 5 required long-term treatment with CPAP or tracheotomy; Nout and colleagues reported that 4 of 10 required long-term treatment with CPAP or tracheotomy.

Repair Complex Laceration

Source: Cummings Otolaryngology-Head and Neck Surgery , 7th edition, Chapter 19 .

Although the technical aspects of treating lacerations demand varied approaches to repair based on the complexity of the wound, some principles and techniques are nearly universal. The goals of treating any laceration should be the same as those for closure of a surgical incision: appropriate reapproximation of deep tissue, reapproximation of dermis with a tension-free closure, precise apposition of epidermal edges, and an everted skin closure.

The excellent blood supply in the face allows for conservative debridement; however, obviously devitalized tissue and significantly irregular wound edges must be excised. When an experienced surgeon recognizes that a wound edge will result in a wide, irregular scar likely to require revision later, that wound may be approached with conservative beveled excision to optimize closure. This is especially true in areas of soft tissue laxity or in lacerations along relaxed skin tension lines. Judicious undermining in subcutaneous or subfascial planes may be performed to decrease tension. This should be performed with proper attention to how redistributing tension may affect surrounding structures. For example, a periorbital laceration excessively undermined toward the eye, rather than away from it, may result in excessive lid tension with eventual distortion of the palpebral fissure.

Lacerations as a result of a severe contusion are caused by ripping, rather than cutting, of the tissues. Force is transmitted through the skin and soft tissues to the underlying bony prominences of the facial skeleton, resulting in a full-thickness crush injury, splitting open the skin and often the underlying soft tissue as well. In these cases the laceration is frequently within a larger crush injury with diffuse soft tissue hematoma. Closure of these lacerations where the surrounding tissue is partially compromised is best accomplished with the least amount of suture material capable of achieving adequate closure. Such lacerations commonly result in depressed, widened scars that require later revision for an optimal appearance. Stellate lacerations often occur in this setting. Small stellate lacerations can be excised in an elliptical fashion, converting the injury to a simple laceration that may then be closed primarily within a relaxed skin-tension line. Larger stellate lacerations should be closed under as little tension as possible, recognizing that a balance may need to be struck between optimal tension and optimal approximation. Although the characteristics of some complex lacerations may appear to lend themselves to additional manipulation and rearrangement with local flaps, such endeavors in a contaminated wound bed with extensively injured tissue are rarely indicated. Patients or family members should be counseled regarding the anticipated outcome and potential for improvement with scar revision in the future. This strategy allows for appropriate initial management with the creation of a clean, safe wound without exhausting future resources for local reconstruction or scar revision.

Lacerations rarely divide the skin at a 90-degree angle to the surface. Nearly all are tangential to some degree, and consideration should be given to converting a thin, beveled flap to a square edge while undermining the opposing side, such that deep and superficial sutures can be placed with equal eversion of skin edges. A good general rule is that any laceration with an angle too tangential to successfully evert both skin edges with simple sutures should be revised. This problem becomes more apparent in cases of a partial avulsion in which a U-shaped flap is elevated. If such a flap is sutured to the surrounding tissues without appropriate eversion of the excessively beveled component, a “pincushion” or “trapdoor” deformity often ensues with a bulky, raised appearance to the flap skin. However, it should be noted that even under ideal circumstances, lymphedema and scar contracture of a U-shaped laceration will also contribute to a pincushioned flap. Steroid injections in the postoperative period may make these contour irregularities less noticeable.

Soft Tissue Avulsions

Many partial avulsions with an apparently well-preserved pedicle can be treated as a complex laceration followed by close observation. Any resultant wounds from ischemia, venous congestion, or suture-line dehiscence may be treated as a secondary, rather than primary, defect. No evidence suggests that various interventions, such as topical nitroglycerin paste, anticoagulants, or vasodilatory agents, improve the outcome of partially devitalized or ischemic avulsion injuries and soft tissue flaps. Medicinal leeches may have a role in alleviating venous congestion in avulsion injuries with an intact arterial supply.

Partial avulsions with devitalized tissue and complete avulsions with full-thickness tissue loss represent some of the greatest challenges in managing facial trauma. Full-thickness loss of soft tissue in an area amenable to wide undermining may be suitable for primary closure, if surrounding structures are not distorted in the process; otherwise, resultant wounds may be managed with debridement and local wound care to allow healing by secondary intention, if no critical structures are exposed and a wound bed suitable for developing granulation tissue is observed. Depending on location, this process can be aided with negative-pressure wound therapy by placement of a wound vacuum-assisted closure device. Application of subatmospheric pressure to a wound has been shown to decrease bacterial counts, aid in the formation of granulation tissue, and increase the rate of wound contraction. Sequential management with conversion of a larger, contaminated wound to a smaller, clean wound followed by undermining or local flap closure may circumvent the need for more extensive reconstruction on presentation. In areas such as the forehead or non–hair-bearing scalp, such wounds may even be left to heal by secondary intention with results superior to split-thickness skin grafting or local flap reconstruction. In general, there are few areas in the face where split-thickness skin grafting is indicated as the optimal technique for final reconstruction. Usually, surrounding or even distant tissue is available for an aesthetically superior repair.

Perhaps the greatest dilemma comes from avulsion of specific structures with distinct anatomic features, such as the nose, ears, lips, eyelids, and scalp, where the avulsed portion appears relatively clean and viable. Small, composite segments from the ear or nose may be sutured in place as a graft. Depending on the nature of the defect, this strategy adds little to no additional morbidity and preserves future reconstructive options, if these should become necessary. In this situation, outside of routine suture line care, little adjunctive care has been demonstrated to be beneficial. Patients are typically appreciative of the effort made to salvage a particular structure, and no additional reconstructive efforts have been compromised.

Temporal Bone Trauma

• Waissbluth S, Ywakim R, Al Qassabi B, et al. Pediatric temporal bone fractures: a case series. Int J Pediatr Otorhinolaryngol. 2016;84:106–109. doi:10.1016/j.ijporl.2016.02.034 (See full article)

Source for the following text: Cummings Otolaryngology-Head and Neck Surge ry, 7th ed., Chapter 147.

Motor vehicle accidents result in head trauma in approximately 75% of incidents. Approximately 31% of these result in temporal bone fractures. Temporal bone fractures occur across all age groups; however, more than 70% occur among individuals in their second, third, or fourth decades. The temporal bone houses important structures such as the facial nerve, cranial nerves (CNs) IX through XI, cochlear, labyrinth, ossicles, tympanic membrane (TM), carotid artery, and the jugular vein. In addition, fracture of the temporal bone can cause cerebrospinal fluid (CSF) leak, meningitis, brain herniation, subdural hematoma, cerebral edema, posttraumatic encephalopathy, and elevated intracranial pressure. Temporal bone fractures can be divided into transverse and longitudinal fractures, and otic capsule sparing (OCS) or otic capsule disrupting fractures. Longitudinal fractures make up 70% to 90% of fractures. Otic capsule disrupting fractures have fourfold to fivefold higher risk of facial paralysis and a twofold to fourfold increased risk of CSF fistula. Facial paralysis complicates 7% of temporal bone fractures. The most important prognostic factor in facial paralysis is whether onset of complete paralysis is immediate or delayed. Delayed onset cases generally have an excellent recovery of function. Facial nerve exploration, decompression, and repair can be achieved via a middle cranial fossa or supra labyrinthine approach. The incidence of meningitis in temporal bone fractures is 1% and CSF fistula is 17%. In the setting of CSF fistula that persists less than 1 week, the incidence of meningitis is 5% to 11%; however, that incidence increases up to 88% if left to leak indefinitely.

Temporal bone fractures in the pediatric population differ somewhat from those in adults. In children, the incidence of intracranial complications is higher (58%), and the incidence of facial nerve paralysis is lower (3%).23 A retrospective review out of Montreal Children’s Hospital found motor vehicle accidents (53%), falls (21%), and bicycle accidents (10%) being the most common cause.24 Most of these fractures were mixed transverse and longitudinal (53%), with 14% being otic capsule involving. Nearly half developed conductive hearing loss (CHL), but only 8% had sensorineural hearing loss (SNHL), suspected to be from the innate flexibility of the pediatric temporal bone. Facial nerve injury only occurred in one patient.

Wexler and colleagues reviewed their 10-year experience of pediatric temporal bone trauma in 38 patients.25 Fifty percent of fractures were longitudinal and 12% transverse with the remaining 37% mixed; 80% were OCS and 5% otic capsule violating (OCV).

Dysphonia

Source for the following text: Cummings Otolaryngology-Head and Neck Surgery , 7th edition, Chapter 55.

Speech-language pathologists work with patients to use the most efficient and healthy voice-production mechanism possible to improve voice quality and loudness, minimize voice-related handicap, improve communicative effectiveness, and restore vocal identity and health. Voice therapy generally involves indirect and direct therapy to improve the patient’s voice-production technique. The number of voice therapy sessions and prognosis for improvement vary and depend on individual patients and their goals. Therapy is generally short term (one to eight sessions) and is more successful for those who demonstrate the capacity for improved voice early in the process. It is important to note that voice therapy requires behavioral changes, and patients only improve with therapy when they actively participate by incorporating the new skills into their daily lives. An overview of voice therapy for dysphonia is presented first, followed by therapy for laryngeal airway disorders.

The indirect component of voice therapy, counseling to optimize the laryngeal environment and voice use, is typically brief. It involves appropriate and relevant “vocal hygiene,” in which the speech-language pathologist reinforces physician recommendations regarding the internal laryngeal environment (e.g., hydration, reflux precautions, and compliance with prescribed medication regimen) and appropriate and relevant “phonotrauma reduction,” in which patients are guided to modify the amount and type of voice use. For some patients, the primary treatment recommendations are medical, surgical, or involve compensatory strategies (e.g., amplification). In this case one or two sessions of indirect voice therapy might be the only services they require from a speech-language pathologist. Typically, however, most voice therapy is devoted to direct work on voice-production technique, because direct voice therapy leads to greater improvement in voice quality and symptoms than vocal hygiene alone.

Attention/Deficit-Hyperactivity Disorder

Attention/deficit-hyperactivity disorder (ADHD) is defined by features of inattention, hyperactivity, and impulsivity. However, these same features are also among the most frequently associated symptoms of ASD.

Children with ADHD are more likely than normally developing children to display auditory, vestibular, visual, and tactile sensory processing problems. Although sensory processing differences are not technically considered a core feature of autism, abnormal sensory processing is found in over 90% of these children. In a study of children with ASD, ADHD, and children without disabilities, there were no major differences in sensory processing issues between children with ASD or ADHD. Thus ASD and ADHD have several similar core symptoms or traits that frequently co-occur, and this degree of overlap increases with age, severity of symptoms, and lower IQ. It is important to assess for other characteristics to distinguish ADHD from ASD in determining the most appropriate referrals ( Table A.4 ).

Autism (See Chapter 1 , Chapter 2 , Chapter 8 )

Autism has become a common condition faced by pediatric otolaryngologists, as these children display delayed speech and language development along with social isolation and unusual behavior. First described by Leo Kanner at the Johns Hopkins hospital in 1943, pervasive developmental disorders occur along a spectrum that includes Asperger syndrome, attention-deficit disorders, ADHD, learning disabilities, and autism. Autism affects 6 of every 1000 children and affects boys more commonly than girls by a ratio of 5:1. The conditions may present with some or all of the following features: (1) limited social interaction, (2) reduced imagination and unusual interests and activities, and (3) alteration of verbal and nonverbal communication.

Hearing impairment, speech delay, and suspected sleep apnea often manifest in this patient group, and involvement of the otolaryngology service is frequently requested. Autistic children also exhibit unusual responses to differing sensory stimuli, including a heightened or depressed response to hearing, sight, smell, taste, and touch, with reactions such as emotional instability. The otolaryngologist may often be the first physician to suggest the diagnosis of autism spectrum disorder, particularly once CHL and SNHL have been ruled out. The expertise of a pediatric audiologist may be required to assess hearing in these children. Snoring and chronic mouth breathing may be attributed to the presumed behavioral disorder without complete assessment of airway or sleep because of the difficulty of interacting with these children.

Children with autism may require extra time and patience to complete the clinic visit. Examination is facilitated by using play techniques to establish rapport, performing the examination on the floor of the office in the sector of toys, where the child feels most at ease and is most likely to allow a successful physical examination. It is important to prepare such a child for surgery appropriately, with the assistance of an anesthetist, to help the child get prepared in clothes of his or her own choosing, and to have a trusted caregiver with him or her at all times. Children with behavioral disorders will benefit from improved quality of life in terms of maintaining adequate hearing, good-quality sleep, and less frequent illnesses. The family unit often requires additional care, support, and predetermined management strategies during doctor and hospital visits and to prepare for surgical procedures, which then translates into better social integration over the long term.

Diagnostic criteria for autism spectrum disorders are based on deficits in multiple domains, including interpersonal relationships, nonverbal communication, and social-emotional reciprocity. The perioperative period is often an extremely stressful time for patients with autism, as they are exquisitely sensitive to light, sound, and touch. Wait times should be minimized if possible, and a dim, quiet preoperative room may be helpful in reducing undesirable stimulation. The preoperative interview requires both finesse and flexibility to accommodate behavioral needs. Limiting the number of providers in the area should be considered, and it may be prudent to have a single provider for the patient during induction.

The approach to induction of anesthesia should be individualized for each child. Some autistic patients will cooperate with preoperative IV placement, whereas others may need oral premedication or an IM injection prior to entry into the operative suite. Because primary caregivers are often aware of behavioral triggers and techniques to calm these patients, their presence at induction may be helpful. Child life specialists are also an invaluable resource. Postoperatively, actions should be taken to reduce emotional volatility on emergence from anesthesia, including keeping only essential monitors in place, early parental presence in the recovery room, and possible early IV removal.

Autism spectrum disorder (ASD) is defined by qualitative impairments in communication and social interaction and by restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The criteria for diagnosis (2013 Diagnostic Statistical Manual of Mental Disorders [DSM]-5) identify two core dimensions: social (social communication and social interaction) and nonsocial (restricted, repetitive patterns of behaviors, interests, or activities). The previous diagnostic subgroups of Asperger syndrome and Pervasive Developmental Disorder, Not Otherwise Specified (PDD-NOS) have been subsumed under the general diagnostic headings of autism (or Social Pragmatic Language Disorder for those not meeting criteria for ASD), with levels of severity based on the level of support a child requires to succeed. The prevalence of autism is currently 1/59, increased to 30% from the 2008 statistic of 1/88, and more than double the estimate of 1/150 in 2000. The incidence of autism in boys is 4.5 times more likely than girls (1:42, 1:189). In a 2016 CDC report, only 43% of the children diagnosed with autism had received comprehensive developmental evaluations by 3 years of age, even though many had evidence in their medical or educational records of developmental concerns prior to age 3.

Autism can now be diagnosed reliably by the age of 2 years, affording children the opportunity for earlier intervention, which increases the likelihood of an improved developmental trajectory. Early intervention is more cost and time efficient than a “wait and see” approach, which can have significant negative consequences for children with ASD. Promising interventions are available for infants within the first year of life, and early in the infant’s second year of life (12 to 18 months). Fewer than 10% of individuals with ASD will remain nonverbal with intervention. Moreover, children who are completely nonverbal who begin intervention in the early preschool years are far more likely to become verbal than children who begin intervention after the age of 5 years. It is currently well accepted that intervention must start at the earliest possible time for children with ASD so that parents can learn effective strategies to help their children improve socially and communicatively (thus also improving parental well-being), and to decrease the possibility of more severe secondary symptoms.

Neurodegenerative Disorders

Source: Cummings Otolaryngology-Head and Neck Surgery , 7th edition, Chapter 57.

Dystonia is a syndrome dominated by sustained contractions of skeletal muscles that frequently cause twisting and repetitive movements or abnormal postures that may be sustained or intermittent. Because the condition is rare, and the movements and resulting postures are often unusual, dystonia is among the most commonly misdiagnosed neurologic conditions. The prevalence is unknown, but an estimated 200,000 to 300,000 cases of idiopathic dystonia occur in the United States. Classification is important, because it can inform prognosis and the approach to management. The classification scheme is outlined in Table A.5 .

Dystonia can begin at nearly any age. Initial signs have occurred as early as 9 months and as late as 85 years. In general, onset has a bimodal distribution, with peaks at ages 8 and 42 years. As can be seen in Table A.5 , patients are partly categorized according to symptom distribution. Focal dystonia involves one isolated body region, segmental disease involves two or more contiguous regions, multifocal disease involves two or more noncontiguous regions, hemidystonia involves half the body, and generalized dystonia is 7, 13, 17, 21, 23, 24, 25, 27, and 28 phenotypes; dystonia plus, which can manifest with additional signs such as dopa-responsive parkinsonism or myoclonus ( DYT3, 5 [formerly 14 ], 11, 12, 15, 16, and 26 phenotypes); and paroxysmal forms of dystonia and dyskinesia ( DYT8, 9, 10, 18, 19, and 20 phenotypes).

Myopathies include dermatomyositis, muscular dystrophy, and metabolic myopathies. Dermatomyositis manifests as dermatitis in conjunction with muscle weakness. This disorder may be associated with lung cancer, systemic lupus erythematosus, or poliomyelitis. The muscular dystrophies vary in age at onset and anatomic distribution of involvement. The infantile variety often presents with oculopharyngeal weakness. Metabolic myopathies may result from abnormalities in acid maltase, glycogen branching enzyme, and cytochrome c-oxidase. Also, some episodic myopathies with periodic paralysis are drug induced or caused by fluctuating electrolyte abnormalities.

Neuromuscular junction disorders include myasthenia gravis and the less common Eaton-Lambert disease. In such disorders, muscles fatigue quickly with use. The incidence of myasthenia gravis is less than 10 per 100,000 people. Specific patient complaints may vary, depending on the distribution of the muscles involved. Many patients have ptosis or double vision because ocular muscles are most commonly affected. General fatigue is also a common complaint. Sometimes the disease is localized to the throat, and patients have difficulty speaking, breathing, or swallowing. Careful examination of the larynx and palate in such patients may reveal fatigue as a result of repetitive movements. For example, asking the patient to repeat “ee-ee-ee” can elicit laryngeal fatigue. Electromyography (EMG) and an edrophonium test are used for rapid diagnosis and treatment of myasthenia gravis. Blood testing is used to detect antibodies against acetylcholine. Early detection of this disorder is invaluable because medical treatment is effective and may be lifesaving.

Poliomyelitis is essentially eradicated today as a result of worldwide vaccination programs. However, some survivors of poliomyelitis experience postpolio syndrome with a recurrence of motor weakness. The exact cause of postpolio syndrome is unknown, but it is thought that the syndrome is derived from the natural loss of motor neurons during the aging process. Patients who have recovered from poliomyelitis function by virtue of a small pool of surviving neurons that sprout to supply expanded numbers of muscle fibers. Thus these patients are particularly susceptible to the loss of even a small additional number of neurons. Acute bulbar polio causes pharyngeal and laryngeal paresis but spares the cricopharyngeus muscle. The resulting symptoms are hoarseness, dysphagia, and aspiration. Because the cricopharyngeus muscle retains tone, cricopharyngeal myotomy is often helpful in the patient with recent onset of polio; however, in those with postpolio syndrome, the effectiveness of myotomy has not been established.

Examples of myopathies are dermatomyositis, muscular dystrophy, and metabolic myopathies. Dermatomyositis manifests as dermatitis in conjunction with muscle weakness. This disorder may be associated with lung cancer, systemic lupus erythematosus, or poliomyelitis. The muscular dystrophies vary in age at onset and anatomic distribution of involvement. The infantile variety often presents with oculopharyngeal weakness. Metabolic myopathies may result from abnormalities in acid maltase, glycogen branching enzyme, and cytochrome c-oxidase. Also, some episodic myopathies with periodic paralysis are drug induced or caused by fluctuating electrolyte abnormalities.

Medullary disorders that affect motor neurons include amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, postpolio syndrome, Arnold-Chiari malformations, and medullary strokes. ALS (also known as Lou Gehrig disease) is an idiopathic and progressive degeneration of upper and lower motor neurons that results in muscle wasting, fasciculations, and weakness. Incidence in the United States has been estimated at 1 to 2 per 100,000 people. Up to 25% of patients with ALS initially have complaints related to speech and swallowing. In many patients, limb symptoms predominate. The clinical course varies in its rate of progression but inevitably leads to deterioration. Approximately 25% of patients survive from 5 to 10 years after the onset of the disease. Death is most often related to respiratory insufficiency as a result of weak breathing muscles and aspiration pneumonia; therefore the prognosis for a more rapid demise is higher in patients with throat involvement.

When ALS involves the upper airway, the voice is monotonous and raspy with abnormal hypernasal resonance. Speech is commonly dysarthric and labored and has velopharyngeal incompetence. The dysarthria is related to tongue involvement. Patients have slurred speech as a result of weakness and slowed activity of the tongue, and the tongue often has visible fasciculations. Weakness in the palate, pharynx, and larynx are evident, along with an inability to make rapid muscle adjustments or repetitive motions. Secretions pool in the hypopharynx, and aspiration often occurs during swallowing. Certain characteristics distinguish ALS from myasthenia gravis: symmetric facial weakness is common in patients with ALS, although extraocular motion is preserved; this characteristic contrasts with the proclivity of myasthenia gravis to involve the eyelids and extraocular muscles. ALS results in muscle wasting and fasciculations that are most easily observed in the tongue and the intrinsic muscles of the hand. Tongue fasciculations have a classic “bag of worms” appearance.

Therapeutic options for patients with ALS are essentially limited to supportive care. In some patients, a palatal lift prosthesis may improve speech intelligibility and reduce nasal regurgitation during speech. In most patients, no intervention can improve speech. Intractable aspiration eventually mandates enteral feeding, and tracheotomy is often necessary for airway protection, assisted ventilation, and pulmonary toilet.

Autosomal Trisomies and Other Aneuploidies

A trisomy is demonstrated when three copies of a whole chromosome occur in an offspring. This happens because of nondisjunction, which is the movement of a pair of chromosomes to the same pole during cell division; this results in one daughter cell lacking that chromosome and the other daughter cell possessing an extra copy of that chromosome. The three major autosomal trisomies are 13, 18, and 21.

Trisomies 13 and 18 are not compatible with long life, and the average life span of individuals with either of these conditions is less than 1 year. The majority of infants with trisomy 13 are profoundly deaf and have a cleft lip and palate in addition to multiple other congenital anomalies. Hearing loss is frequent in trisomy 18 as well. However, hearing and head and neck anomalies are unlikely to be a serious concern because of the limited survival.

Patients with trisomy 21 have ears that are smaller than normal. Approximately 75% have hearing loss, which can be sensorineural, conductive, or mixed. The prognosis of a child with trisomy 21 is generally good, and correction to normal hearing is important for helping such an individual achieve maximal abilities.

Common aneuploidies involving the sex chromosomes include 45,X (Turner syndrome, phenotypic female) and 47,XXY (Klinefelter syndrome, phenotypic male). Although profound hearing loss is infrequent, mild to moderate hearing loss is common in 45,X individuals. Turner syndrome patients are highly susceptible to otitis media, but whether this changes with hormone replacement therapy remains to be investigated. Approximately 20% of children with Klinefelter syndrome have a mild SNHL. Hearing losses in both Turner and Klinefelter syndromes often remain undetected unless specifically evaluated.

Chromosomal Rearrangements

Usually, aneuploidies are not heritable; however, rearrangements, translocations, and inversions can be. A heritable form of trisomy 21 exists that involves a translocation between chromosome 21 and another chromosome, usually chromosome 14. This is a so-called centric fusion translocation that results in the loss of both short arms and the fusion of the two long arms of chromosomes 21 and 14. A balanced chromosome complement would be 45 chromosomes. Because of the abnormal way in which the chromosomes need to be paired, this translocation sets the stage for an abnormal separation of chromosomes during meiosis. The result can be a balanced carrier, like the parent (normal), or a carrier who has three copies of chromosome 21 material. Both translocations and inversions can be heritable and could result in a family that has multiple instances of children with multiple anomalies. The heritable forms can be distinguished by a straightforward cytogenetic evaluation.

X-Linked Disorders

X-linked genes may also harbor recessive mutations. The molecular mechanisms are the same, but the pattern of inheritance is unique and remarkable. Females who have two X chromosomes are heterozygotes/carriers. Males, with only one X, are affected; they have only one copy of the abnormal gene because the Y chromosome carries little in the way of genetic information. Carrier females have a 50% chance of transmitting the abnormal gene, which means that half of a carrier female’s sons will be affected and that half of her daughters will also be carriers. An affected male cannot transmit the gene to his sons; however, all of his daughters would be carriers, which would mean that 25% of his grandsons could be affected. The two best known X-linked traits are hemophilia and DMD. X-linkage plays only a minor role in nonsyndromic hearing loss. To otolaryngologists, perhaps the most notable disorders are X-linked deafness with perilymphatic gusher, Alport syndrome, and Mohr-Tranebjaerg syndrome

Syndromes Associated With Imprinting

• Aygun D, Bjornsson HT. Clinical epigenetics: a primer for the practitioner. Dev Med Child Neurol . 2020;62(2):192–200. doi:10.1111/dmcn.14398

Children with Prader-Willi syndrome have severe infantile hypotonia, developmental delay, craniofacial abnormalities, and obesity, all of which contribute to the development of SDB. These children exhibit both central and obstructive apnea, likely as a result of hypothalamic dysfunction. Prader-Willi syndrome is associated with deletion of chromosome 15q11-13, specifically with the lack of expression of the paternally derived allele, whereas Angelman syndrome results from absent expression of the maternally derived allele. Children treated with growth hormone have been shown to have a higher risk of SDB, thus screening with PSG at initiation of therapy and with worsening of snoring is recommended. Adenotonsillectomy is effective in children with Prader-Willi syndrome with mild or moderate SDB, but less than half of children with severe OSA are cured. Iatrogenic causes of SDB are possible, such as pharyngoplasty to treat velopharyngeal dysfunction.

Mucopolysaccharidosis (See Chapter 3 )

The mucopolysaccharidoses (MPSs) are genetic disorders in which enzyme deficiencies lead to defective degradation of lysosomal glycosaminoglycans with accumulation of mucopolysaccharides in the soft tissues of the body, which includes the respiratory tract. The type of mucopolysaccharidosis is determined by the particular enzyme deficiency. Examples are Hurler and Scheie syndrome (α-L-iduronidase deficiency), Hunter syndrome (iduronate sulfatase deficiency), and Sly syndrome (β-glucuronidase deficiency). In addition to hypertrophy of the tonsils, adenoids, tongue, and oropharyngeal mucosa, deposits in the tracheobronchial tree often lead to chronic pulmonary disease. These children often develop scoliosis, spinal problems, and hepatosplenomegaly. OSA may be severe and may cause death. Treatment options include adenotonsillectomy, nasal CPAP, and tracheotomy. These patients require very complex airway management, and even tracheotomy may not ensure control of the airway.

Source for the following text: Cummings Otolaryngology-Head and Neck Surgery , 7th edition, Chapter 151.

The MPSs are a group of diseases caused by an inherited deficiency of one of several lysosomal enzymes that degrade mucopolysaccharides. As a result, undergraded mucopolysaccharides accumulate intracellularly, which gives rise to large cells with vacuolated cytoplasm. Ten enzyme deficiencies have been identified to date and are classified into seven types or syndromes. All are transmitted as autosomal recessive traits except for Hunter syndrome (MPS 2), which is X-linked recessive. Diagnosis is made either by an assay of the specific enzyme in plasma or serum or by tissue culture using fibroblasts or leukocytes. Management is mainly supportive and symptomatic; however, MPSs are potentially amenable to enzyme replacement therapy and to procedures such as bone marrow transplantation or gene transfer.

Hurler syndrome (MPS 1) is caused by a deficiency of L-iduronidase, leading to the accumulation of heparan sulfate and dermatan sulfate. Clinical manifestations include corneal clouding, abnormal facies, hepatosplenomegaly, mental retardation, dysostosis multiplex, joint stiffness, and hernias. Radiographic features include a broadening and shortening of the long bones; hypoplasia and fractures of the lumbar vertebrae, causing kyphosis; and enlargement of the sella turcica. Death usually occurs during the first decade of life.

Hunter syndrome (MPS 2) results from a deficiency of iduronate-2-sulfatase, which leads to an accumulation of heparan sulfate and dermatan sulfate. The syndrome is similar to Hurler syndrome, but corneal clouding is not seen. Survival to adulthood may occur.

Morquio syndrome (MPS 4) is attributable to a deficiency of N -acetylgalactosamine-6-sulfatase or of β-galactosidase, which results in excessive urinary excretion of keratan sulfate. Clinical manifestations include spondyloepiphyseal dysplasia. Spinal cord compression caused by hypoplasia of the odontoid process and cervical dislocation are common and may be the cause of death.

Usher syndrome

Usher syndrome consists of the combination of retinitis pigmentosa and SNHL, with or without vestibular deficits. Three distinct groups have been defined. Type 1 accounts for 85% of all cases and is characterized by profound congenital hearing loss, absent vestibular response, and the development of retinitis pigmentosa by the age of 10 years. Type 2 accounts for 10% of cases and is characterized by congenital, moderate-to-severe stable hearing loss, normal vestibular responses, and onset of retinitis pigmentosa in patients 17 to 23 years old. Type 3 is typified by progressive hearing loss with onset in childhood or late adolescence and variable onset of retinitis pigmentosa. Approximately 5% of patients have type 3 disease. The disease is transmitted in an autosomal-recessive fashion, and it is estimated that 1 of 100 people is a carrier of the trait.

Branchio-Oto-Renal Syndrome

Melnick coined the term branchio-oto-renal (BOR) syndrome in 1975 to describe the cosegregation of branchial, otic, and renal anomalies in deaf individuals. Inheritance is autosomal dominant, penetrance is nearly 100%, and prevalence is estimated at 1 in 40,000 newborns. BOR affects 2% of profoundly deaf children. Otologic findings can involve the external, middle, or inner ear. External ear anomalies include preauricular pits (82%) or tags, auricular malformations (32%), microtia, and EAC narrowing; middle ear anomalies include ossicular malformation (fusion, displacement, underdevelopment), facial nerve dehiscence, absence of the oval window, and reduction in the size of the middle ear cleft; and inner ear anomalies include cochlear hypoplasia and dysplasia. Enlargement of the cochlear or vestibular aqueducts may be seen, as may hypoplasia of the lateral semicircular canal.

Hearing impairment is the most common feature of BOR syndrome and is reported in almost 90% of affected individuals. The loss can be conductive (30%) or sensorineural (20%) but is most often mixed (50%). It is severe in one third of individuals and is progressive in one quarter. Branchial anomalies occur in the form of laterocervical fistulas, sinuses, and cysts; renal anomalies range from agenesis to dysplasia and are found in 25% of individuals. Less common phenotypic findings include lacrimal duct aplasia, short palate, and retrognathia.

One causative gene is EYA1, the human homologue of the Drosophila eyes absent gene. The gene contains 16 exons that encode for 559 amino acids. Pathogenic EYA1 variants are found in approximately 25% of patients with a BOR phenotype, and this phenotype is hypothesized to reflect a reduction in the amount of the EYA1 protein. Variants in two additional genes, SIX1 and SIX5, also have been shown more recently to cause BOR syndrome. Both genes act within the genetic network of the EYA and PAX genes to regulate organogenesis.