What’s Old and What’s New in Pediatric Anesthesiology

From the 47th Clinical Conference in Pediatric Anesthesiology, sponsored by the Pediatric Anesthesiology Foundation, Childrens Hospital Los Angeles

Educational Objectives

The goal of this program is to improve the management of anesthesia for children with sleep disorders and sickle cell

disease. After hearing and assimilating this program, the clinician will be better able to:

1.   Discuss the relationship between conceptual age and risk for apnea in preterm infants.

2.   Identify the risk factors for pediatric obstructive sleep apnea syndromes (OSAS), including obesity, large ton­sils, and craniofacial syndromes, and the sequelae of OSAS.

3.   Describe the best approach for anesthetizing a child with OSAS undergoing tonsillectomy and adenoidectomy.

4.   Explain the mechanisms of sickle cell disease and associated crises, such as ischemic events and acute chest syndrome.

5.   Manage intra- and postoperative concerns in anesthetizing a child with sickle cell disease.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and the planning committee re­ported nothing to disclose.

Acknowledgements

This conference was recorded at  47th Clinical Conference in Pediatric Anesthesiology, held February 6-8, 2009, in Ana­heim, CA, and sponsored by the Pediatric Anesthesiology Foundation, Childrens Hospital Los Angeles. The Audio-Digest Foundation thanks the speakers and the Pediatric Anesthesiology Foundation, Childrens Hospital Los Angeles for their co­operation in the production of this program.

Recognition and Management of Postoperative Apnea and Obstructive Sleep Apnea Syndrome

David J. Steward, MB, BS, Emeritus Professor of Anesthesiology, Keck School of Medicine, University of Southern California, and Childrens Hospital Los Angeles

Apnea in preterm infants: pause in breathing >20 sec or bradycardia <100 beats per minute (bpm) for 5 sec; rela­tionship unclear; some investigators define apnea as pause of >15 sec, especially if bradycardia also present

Lessons from various studies: risk for apnea highest in infants <44 wk postconceptual age (PCA); risk increases as PCA decreases; other risk factors include history of apnea and anemia; risk reduced by intravenous (IV) caffeine and regional analgesia; 1995 study by Coté et al suggests apnea risk persists as long as child remains anemic, al­though apnea rates vary widely among studies

Newer findings: 2006 study showed regional analgesia reduces apnea risk; underscores safety of regional analgesia for preterm infants and importance of adhering to strict protocol; 2008 study suggested incidence of apnea in pre­term infants lower than previously thought; risk factors included preoperative history of apnea or comorbidities (eg, intraventricular hemorrhage, patent ductus arteriosus); other predictive factors included intraoperative use of nar­cotics, muscle relaxants, or sevoflurane; apneas all occurred <12 hr postoperatively; recommendations for manag­ing apnea in preterm infants  —  data from combined analysis; postpone surgery until PCA >60 wk; refer patient to tertiary care center; determine level of postoperative monitoring based on assessment of comorbidities and anemia; if patient <46 wk PCA, perform surgery early in morning to allow 12 hr postoperative monitoring; for patients 46 to 60 wk PCA without comorbidities or anemia, 6 hr of monitoring sufficient; (12 hr if patient has comorbidities  [eg, chronic lung disease, continuing apnea, neurologic disease, or anemia]); spinal or general anesthetic recommended, with no narcotics or relaxants; administer caffeine in dose of 10 mg/kg

Speaker’s recommendations: assess each patient with preceding considerations in mind; manage each patient ac­cording to status and local practice

Pediatric obstructive sleep apnea syndromes (OSAS): absence or reduction in airflow over upper airway, despite ongoing respiratory effort; apnea  —  cessation of ventilation over >2 attempted respiratory cycles; hypopnea  —reduction in airflow over >2 attempted respiratory cycles, accompanied by 3% to 4% reduction in mixed venous oxygen saturation (SVO₂)

Sleep-disordered breathing: continuum ranging from snoring to obstructive hypoventilation to severe OSAS; 3.2% to 12.1% of children snore; severe OSAS found to affect 1% to 10% of children (depending on study)

Effects of OSAS: nocturnal  —  hypercarbia and hypoxemia, disrupted sleep, and enuresis; diurnal  —  somnolence or hyperactivity; possible learning and behavior problems; occur in all age groups, but most common among pre­schoolers; seen in children of all body types (not only obese); equally common in both sexes; common risk factors  —  obesity, large tonsils and adenoids, and craniofacial syndromes

Obesity: associated OSAS may differ from other types; study conducted in United States showed increased levels of C-reactive protein and other inflammatory markers in children with OSAS (not seen in similar study of Greek children); may be related to higher rate of obesity among American children

Mechanism: normally, when diaphragm descends during inspiration, other muscles dilate upper respiratory pas­sages; as negative pressure in upper airway increases, muscle activity also increases to maintain airway patency; makes system vulnerable; risk factors for obstruction  —NSinadequate muscle activity during sleep; excessive adipose tissue (obstructs airway and compromises action of muscles); lymphoid tissue (obstructs airway and in­creases inspiratory effort, thus raising negative pressure and increasing risk for airway collapse); craniofacial anomalies (can create anatomic obstruction)

Implications for anesthesia: in 2002 study of children with OSAS, higher negative pressure under mask associated with higher risk for airway collapse than in controls; muscular control of airway compromised in patients with OSAS; severity of OSAS correlated with pressure at which airway collapsed; 1999 study showed that children with OSAS have impaired response to hypercapnia, compared to controls; ventilation decreases more than nor­mal with anesthetics or narcotics; children with OSAS have decreased requirement for opioids for analgesia; study attributed this to chronic, repeated episodes of hypoxemia; younger age also increases sensitivity to nar­cotic analgesia; pediatric OSAS associated with increased variability in blood pressure while awake and during sleep (probably catecholamine response to repeated episodes of hypoxemia)

Diagnosis: overnight polysomnography (gold standard); history, physical examination, and questionnaires unreli­able; no standardization of polysomnography between laboratories; relationship to incidence of complications unclear; expensive; not always available; interpretation of findings  —  apnea-hypopnea index >1 suggests mild OSAS; >5 apneic episodes per hour indicates severe OSAS; very severe  —  >15 episodes per hour or evidence of cardiac changes related to right ventricular stress dysfunction

Alternatives to overnight: daytime nap  —  positive results have good predictive value, but negative results not use­ful; overnight oximetry  —  positive predictive value 97% to 100%; negative results less reliable

Risk for complications after tonsillectomy and adenoidectomy (T and A): on preoperative assessment, apnea-hy­popnea index >5 or O₂ saturation <80% on overnight oximetry predictive of complications; need for admission and postoperative monitoring highest among children younger than 3 yr of age or for child with severe OSAS on polysomnography, cardiac complications, or failure to thrive; other candidates include very obese children, preterm children, or those with recent respiratory infection or craniofacial or neuromuscular anomalies

Optimal anesthesia for children with OSAS undergoing T and A: if OSAS severe, schedule surgery for early morning and follow with overnight monitoring; exercise caution and monitor carefully if premedicating; in­duce with inhalational sevoflurane and IV propofol; dexamethasone, analgesia, antinausea medication, and small doses of ketamine also considered useful; intubation preferred over mask ventilation; allow spontaneous ventilation; extubate with lidocaine to reduce risk of coughing; no-touch extubation  —  turn off anesthetic; keep tubes and monitoring equipment in place; extubate when patient opens eyes; titrate narcotics carefully; start at 0.05 mg/kg and titrate until desired effect reached; SVO₂ monitoring recommended; patients with severe OSAS candidates for intensive care; some children may require continuous positive airway pressure or assisted ventilation

Anesthetic Management of Sickle Cell Disease

Jerrold Lerman, MD, Clinical Professor of Anesthesia, Women and Children’s Hospital of Buffalo, State Uni­versity of New York at Buffalo, and Strong Memorial Hospital, University of Rochester, NY

Background: average adult has hemoglobin (Hb) AA; babies have Hb F for first 6 mo of life; sickle cell disease caused by single point mutation in b subunit (valine replaces glutamate and makes molecule hydrophobic; results in coalescence of b chains and accumulation of Hb at bottom of red blood cell [RBC], which causes cell to assume sickle shape)

Sickle cell crisis: sickle-shaped cells obstruct capillaries, with resulting ischemia, infarction, and pain; precipitating factors include hypoxia, hypothermia, acidosis and hypotension; sickling does not always lead to clinical symp­toms or crisis

Pathophysiology: in several small studies, individuals with sickle cell disease exposed to various degrees of hy­poxia did not develop crisis; death rarely caused by sickle cell crisis; tourniquets rarely elicit crises; evidence of inflammatory manifestations noted in vascular endothelium of affected individuals >50 yr ago; further re­search suggested inflammation and endothelial changes precede symptom onset; may predict sequelae; in 1980s, investigators observed that sickled cells may break down, release heme moieties or cell fragments and induce changes in small vessels, which leads to inflammation and release of adhesive compounds on endothe­lial surface; deformed RBCs also have adhesive properties, allowing them to adhere to endothelium and trigger inflammatory response; conclusion  —  unstable Hb triggers crisis, which elicits inflammatory response; crisis results from Hb S polymerization; therapeutic intervention; involve preventing Hb S concentration from be­coming too high (eg, prevention of cell dehydration), and preventing excess generation of Hb F, thus avoiding triggering of inflammatory response

RBC dehydration mechanisms: potassium chloride transport system  —  sensitive to acidification; hypoxia causes acidification which leads to chloride leakage; results in accumulation of Hb S and consequent exacerbation of cellular aggregation; Gardos (potassium-calcium) exchange channel  —  when Hb S aggregates, it allows cal­cium into cell; water leaves cell as calcium leaks out

Endothelium: adhesion of RBCs to endothelium causes spiraling of inflammatory response and blockage of arte­rioles by platelets, which leads to crisis

Vasoocclusive crises: in many cases, no antecedent event identified; may occur in long bones and be difficult to manage; may be painful and persist for days; probably explained by cascade of inflammatory responses

High-risk patients: spleen grows rapidly during first year of life; patient may experience splenic sequestration, lead­ing to auto-infarction of spleen, which necessitates splenectomy; patient may die of pneumococcal septicemia or meningitis; effects on central nervous system (CNS)  —  silent strokes detectable only on magnetic resonance imag­ing (MRI); proposed algorithm includes transcranial Doppler ultrasonography (TCD) starting at 2 yr of age and re­peated annually, to identify lesions in patients with no clinical manifestations; transfusion plus anti-inflammatory agents may help prevent serious neurologic problems; dactylitis  —harbinger of more serious vasoocclusive disease, especially in children <1 yr of age; leg ulcers and repeated bone infarcts may lead to aseptic necrosis and debilitat­ing chronic pain; acute chest syndrome  —  consists of respiratory symptoms, lung infiltrates, and fever; infection may cause local ischemia or precipitate inflammatory response, with resulting local deoxygenation and pulmonary vasoocclusive crisis; treatment consists of support and (rarely) exchange transfusion

Current management: diagnosis through state-mandated Hb electrophoresis for all neonates in United States, fol­lowed by regular blood tests; aggressive intervention including TCD up to 10 yr of age, transfusions (may atten­uate effects of stroke), pulmonary function studies, and echocardiography to monitor development of pulmonary hypertension; all infants vaccinated against pneumococcal infection up to 2 yr of age, followed by booster; vigor­ous treatment of all infections; standard management of vasoocclusive crises; blood transfusions indicated for acute chest syndrome, stroke, and grossly abnormal TCD

Predictors of poor outcome: dactylitis before age 1 yr, severe anemia, or leukocytosis without evidence of infection (suggests inflammatory response)

Prognosis: in one study, acute chest syndrome before 3 yr of age predicted subsequent severe episodes of acute chest syndrome throughout childhood and need for close monitoring and intervention

Strategies for prevention of crises: no drugs currently available to prevent polymerization of Hb S; prevention of in­creased intracellular concentration of Hb S  —  clotrimazole (Gardos channel inhibitor); magnesium; hydroxyrea (increases Hb F expression, thus reducing Hb S concentration; infusion of mRNA into cell to disrupt Hb S produc­tion (animal studies only); bone marrow transplantation (not successful); antiadhesion therapy

Anesthesia management: determine severity of disease and stability of laboratory indices (any fluctuations in Hb, recent transfusions, or episodes of dehydration); consult with hematology team familiar with patient and knowl­edgeable about factors that might precipitate intra- or postoperative crisis; speaker recommends premedication to avoid undue anxiety about upcoming surgery (could trigger inflammation and crisis)

Predictors of postoperative complications: high-risk procedures (eg, cardiopulmonary bypass, transplantation); older age (complications more frequent and severe in adults); history of multiple or aggressive sickle cell crises (aggressive management indicated); in 1995 study, outcomes associated with simple transfusion to Hb A >10 g/dL no different from those associated with exchange transfusion; all transfusions associated with alloimmu­nization and hemolysis; many centers do not transfuse for minor surgery, but large randomized trial needed; other complications include delayed transfusion reaction and iron overload (heme moieties can accumulate in liver and heart and cause hemochromatosis)

Intraoperative management: aggressive management “totally unjustified and without any scientific basis whatso­ever”; aggressive pain management indicated to avoid crises (acute chest syndrome may occur £3 days postop­eratively and last for 1 wk); oxygen and transfusion necessary if patient hypoxic or anemic; may require nitric oxide and steroids; enlist aid of hematology service

Postoperative management: provide oxygen, fluids, and thermoneutral environment; avoid shivering, acidosis, and pain; discharge as per normal criteria, with extra observation and management before discharge

Suggested Reading

Brown KA et al: Recurrent hypoxemia in children is associated with increased analgesic sensivity to opiates. Anesthesiology 105:665, 2006; Coté CJ et al: Postoperative apnea in former preterm infants after inguinal herniorrhaphy. A combined analysis. An­esthesiology 82:809, 1995; Fu T et al Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without pre-operative blood transfusion. Pediatr Blood Cancer 45:43, 2005; Gold JI et al: Detection and assessment of stroke in pa­tients with sickle cell disease: neuropsychological functioning and magnetic resonance imaging. Pediatr Hematol Oncol 25:409, 2008; Kincaid MS: Transcranial Doppler ultrasonography: a diagnostic tool of increasing utility. Curr Opin Anaesthesiol 21:552, 2008; Mazumdar M et al: Preventing stroke among children with sickle cell anemia: an analysis of strategies that involve transcra­nial Doppler testing and chronic transfusion. Pediatrics 120:e1107, 2007; Murphy JJ et al: The frequency of apneas in premature in­fants after inguinal hernia repair: do they need overnight monitoring in the intensive care unit? J Pediatr Surg 43:865, 2008; Quinn CT et al: Prognostic significance of early vaso-occlusive complications in children with sickle cell anemia. Blood 109:40, 2007; Schwengel DA et al: Perioperative management of children with obstructive sleep apnea. Anesth Analg 109:60, 2009; Stinson J, Naser B: Pain management in children with sickle cell disease. Paediatr Drugs 5:229, 2003; Waters KA et al: Effects of OSA, inha­lational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol 92:1987, 2002; Williams RK et al: The safety and efficacy of spinal anesthesia for surgery in infants: the Vermont Infant Spinal Registry. Anesth Analg 102:67, 2006.