E REVIEW ARTICLE CME
Pierre Robin Sequence: A Perioperative Review Franklyn Cladis, MD, FAAP,* Anand Kumar, MD,† Lorelei Grunwaldt, MD,† Todd Otteson, MD,‡ Matthew Ford, MS, CCC-SLP,† and Joseph E. Losee, MD, FAAP† The clinical triad of micrognathia (small mandible), glossoptosis (backward, downward displacement of the tongue), and airway obstruction defines the Pierre Robin sequence (PRS). Airway obstruction and respiratory distress are clinical hallmarks. Patients may present with stridor, retractions, and cyanosis. Severe obstruction results in feeding difficulty, reflux, and failure to thrive. Treatment options depend on the severity of airway obstruction and include prone positioning, nasopharyngeal airways, tongue lip adhesion, mandibular distraction osteogenesis, and tracheostomy. The neonate and infant with PRS require care from multiple specialists including anesthesiology, plastic surgery, otolaryngology, speech pathology, gastroenterology, radiology, and neonatology. The anesthesiologist involved in the care of patients with PRS will interface with a multidisciplinary team in a variety of clinical settings. This perioperative review is a collaborative effort from multiple specialties including anesthesiology, plastic surgery, otolaryngology, and speech pathology. We will discuss the background and clinical presentation of patients with PRS, as well as some of the controversies regarding their care. (Anesth Analg 2014;119:400–12)
I
n 1923, Pierre Robin, a stomatologist from France, coined the term “glossoptosis” to describe the “obstruction of the oral pharynx by the tongue” in the setting of a small mandible. Although others have previously described patients with small mandibles, airway obstruction, and cleft palate, Dr. Robin has been credited with defining the criteria for the Pierre Robin sequence (PRS).1,2 The clinical triad of micrognathia (small mandible), glossoptosis (backward, downward displacement of the base of the tongue; Fig. 1), and airway obstruction defines PRS. Some authors have described PRS as micrognathia, glossoptosis, and cleft palate.3,4 Although clefting of the palate is common, it does not occur in all infants with PRS. However, all patients with PRS have airway obstruction,5 and this is a requirement for the clinical diagnosis. There is ongoing debate regarding the biologic etiology of PRS. There does not appear to be a clear genetic abnormality, although the etiology of the micrognathia may be different for syndromic and nonsyndromic PRS.6 Some authors have suggested a genetic cause for syndromic PRS and an external mechanism like in utero compression secondary to oligohydramnios for nonsyndromic PRS.6 It is suspected that micrognathia keeps the tongue superiorly positioned between the naturally clefted palatal shelves and prevents normal palatal closure during the first trimester of pregnancy. Although micrognathia appears to be an isolated event for most patients with PRS, there is
From the Departments of *Anesthesiology and †Plastic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; and ‡Pediatric Otolaryngology, UH Rainbow Babies and Children’s Hospital CWRU School of Medicine, Cleveland, Ohio. Accepted for publication March 28, 2014. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Franklyn Cladis, MD, Department of Anesthesiology, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave., 5th Floor, Pittsburgh, PA 15224. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000301
400 www.anesthesia-analgesia.org
an association with certain syndromes. The most common syndromes are Stickler, velocardiofacial (22q, 11.2 deletion), fetal alcohol syndrome, and Treacher-Collins syndrome (Table 1).5,7,8 The incidence of PRS varies from 1:5000 to 1:85,000.3,6,9,10 The large variation in the incidence of PRS may be dependent on the variability of clinical presentation. The patient with mild symptoms may go unrecognized. Infants with PRS present with respiratory and feeding difficulties. As many as half of these infants will also have associated malformations. Airway obstruction and respiratory distress are the primary respiratory signs. Patients may present with stridor, retractions, and cyanosis. Severe obstruction results in feeding difficulty, reflux, and failure to thrive. Treatment options depend on the severity of airway obstruction. Obstruction that is mild when supine or relieved completely when prone may be observed without a procedural intervention. Prone positioning may relieve airway obstruction in as many as 70% of these subjects.6 The therapeutic options for more severe obstruction include nasopharyngeal airways (NPA), tongue lip adhesion (TLA), mandibular distraction osteogenesis (MDO), and tracheostomy. Clinical intervention is frequently dependent on the experience of the institution. Centers with larger patient volumes may have a multidisciplinary protocol that defines the clinical course of these patients. The neonate and infant with PRS require care from multiple specialists including plastic surgery, otolaryngology, speech pathology, gastroenterology, radiology, and neonatology. The anesthesiologist involved in the care of patients with PRS will interface with this multidisciplinary team in a variety of clinical settings. This perioperative review is intended to discuss the background and clinical presentation of patients with PRS and some of the controversies regarding their care.
FEEDING
Feeding and swallowing are complex biologic functions. In the newborn period, suckling is quite reflexive and likely is controlled at a subcortical level. Nutritive suckling is accomplished by compression of a nipple against the palate. Most August 2014 • Volume 119 • Number 2
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Figure 1. An infant with Pierre Robin sequence (PRS) and glossoptosis. Note the small and posteriorly displaced tongue (Courtesy of Joseph Losee, MD).
infants will have multiple suckles, which fills the vallecular space before swallowing. During deglutition, the tongue expresses and propels the milk/formula posteriorly, while the soft palate rises to separate the mouth from the nose. The bolus travels to the vallecular space before swallowing. The larynx then is pulled upward and mildly forward resulting in epiglottic closure. Simultaneously, respiration ceases momentarily and the vocal folds close. The presence of a cleft palate decreases the infant’s ability to establish negative intraoral air pressure required to suck milk from a normal bottle or breast. This results in decreased organization of bolus formation and transit. The palatal defect creates the infant’s inability to separate the mouth from the nose.11 The prevalence of feeding and swallowing disorders in patients with PRS has been estimated at 25% to 45%.12 These difficulties are linked to their respiratory issues.13–15 However, correcting the airway obstruction will not always improve feeding and swallowing issues. Positioning an infant prone with PRS may be adequate to manage minor upper airway obstruction by minimizing glossoptosis, but this will not obviate the infants’ feeding challenges. Infants cannot be successfully fed in the prone position, and many cannot safely or adequately swallow once positioned upright for feeding. Some PRS infants need long-term nasogastric or gastrostomy tube feeds. Temporary NPAs have been used for airway management
and frequently will manage the airway obstruction but again may not obviate the need for nasogastric or gastrostomy feeds for adequate nutrition and growth.16,17 Surgical interventions have been described to successfully manage glossoptosis and upper airway obstruction.18–20 While this has been associated with improvement in feeding, it is not a guarantee of successful oral feeding. Smith and Senders21 noted a prevalence of nasogastric or gastrostomy tube feedings of 53% in isolated PRS patients, 67% in syndromic patients, and 83% in “unique” (abnormalities that did not satisfy the criteria for a named syndrome) PRS patients. MDO is a technique frequently used for the management of more severe PRS patients. In 2004, Monasterio et al.20 found a trend toward resolution of feeding difficulties in most patients in their cohort with MDO. Despite correction of the airway obstruction, many infants with PRS will have persistent feeding and swallowing challenges. The causes of these challenges are multifactorial. Baudon et al.22 in 2002 and Baujat et al.23 in 2001 documented, by electromyography and esophageal manometry, an increased prevalence of esophageal motility disorders. Gastroesophageal reflux (GER) is a known comorbidity with PRS and is thought to be due to altered intrathoracic pressures secondary to airway obstruction.24,25 The clinical consequences of GER include aspiration, and pharyngeal and laryngeal edema. Laryngeal edema increases airway obstruction. Because of the incidence and consequences of reflux, most practitioners advocate prophylactic medical treatment. Infants with PRS require additional feeding support to deal with altered suction abilities13 and formula delivery.26,27 Specialized bottles, nursers, and nipples are typically required for an adequate volume of milk delivery to infants with cleft palate. These feeders allow milk to be actively dispensed into the infant’s mouth during suckling maneuvers. This may include the Mead Johnson Cleft Nurser, Pigeon Cleft Bottle, or Haberman Special Needs Feeder (Fig. 2, A–C). Although respiratory distress frequently results in an acute life-threatening event and morbidity in infants with PRS, swallowing and feeding issues can also contribute to infant morbidity and mortality. Untreated aspiration can lead to significant pulmonary morbidity. Inadequate nutrition similarly can result in failure to thrive and associated morbidity. This underscores the critical importance of an
Table 1. Syndromes Associated with Pierre Robin Sequence Syndrome Fetal alcohol syndromea
Sticklerb Treacher Collinsb
Velocardiofacialb
Associated anomalies Microcephaly, maxillary hypoplasia, micrognathia, short neck, ventricular septal defect, cognitive developmental delay, hyperactivity Marfanoid appearance, airway obstruction, micrognathia, joint laxity, mitral valve prolapse. Craniofacial clefting, mandibular hypoplasia. May have obstructive sleep apnea. May have congenital heart disease Microdeletion of chromosome 22, microcephaly, micrognathia, congenital cardiac disease. May have developmental delay, neonatal hypocalcemia, T-cell immune deficiency
Anesthetic concerns May be difficult to ventilate and intubate. Preoperative echo may be indicated. Consider subacute bacterial endocarditis prophylaxis. May be uncooperative May be difficult to ventilate and intubate. Care with positioning May be difficult or impossible to intubate. Preoperative echo may be indicated. Consider subacute bacterial endocarditis prophylaxis May be difficult to intubate. Preoperative echo may be indicated. Consider subacute bacterial endocarditis prophylaxis. Blood products need to be irradiated
Frost et al.8 Adapted from Losee, Kirschner, Comprehensive Cleft Care, McGraw Hill, 2008, chapter 13, Table 13–1, p. 214–5.67
a
b
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Figure 2. Feeders for infants with cleft palates. (A) Mead Johnson bottle; (B) Pigeon nipple; and (C) Haberman bottle (Courtesy of Matthew Ford).
in-depth feeding and swallowing evaluation in the PRS infant. Assessment of swallowing safety and aspiration risk is primary for developing an appropriate feeding plan. Some infants can be fed safely with alterations of feeding with specialized feeding equipment, altered formula/milk consistency, or modified feeding schedules. However, many require time to transition from nonoral feeding to oral feeding as their respiratory status improves with interventions and general growth and development. Nasogastric or gastrostomy feeds do not preclude oral feeding attempts and should be considered in any infant with significant nutritional or aspiration risks. Feeding facilitation techniques have also been advocated to improve oral feeding. This includes oral stimulation and tongue massage techniques with a pacifier and gloved fingers.28 Depending on the institution, the PRS infant with feeding difficulties is typically managed by either a speech pathologist and/or an occupational therapist. Given the complex interaction between feeding and airway difficulties in the infant with PRS, early input from both speech pathology and occupational therapy is critical to the success of these patients. Feeding and swallowing evaluations typically take place in the neonatal intensive care unit at the bedside once the infant is medically stable. Oral trials should not be considered until the infant demonstrates baseline stable respiratory status, adequate oropharyngeal secretion control, and adequate level of alertness. Fatigue with oral stimulation should be documented. When aspiration risk is identified, it is critical to obtain further direct swallowing assessment before initiation of ad lib oral feeds. Comprehensive swallowing evaluation should be performed using direct assessments, and these are typically performed as part of PRS treatment protocols in most centers. Assessments may be done before and after surgical
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or nonsurgical interventions such as MDO, TLA, or placement of an NPA. The “gold standard” for assessing swallow and aspiration risk is the modified barium swallow study, referred to as a cookie swallow study.29 This is completed in the radiology department. Swallowing is assessed under lateral fluoroscopy. The infant is positioned semi-upright in a fluoroscopic infant seating device. Silent aspiration can be identified, which refers to tracheal aspiration in the absence of coughing or choking. Endoscopic assessment of swallowing has also been described and is frequently used in the PRS population to assess aspiration risk. This type of assessment is referred to as fiberoptic endoscopic evaluation of swallowing (Video 1, Supplemental Digital Content 1, http://links.lww.com/ AA/A915).30,31 This can be performed at the bedside. This assessment is typically completed in conjunction with an otolaryngologist and speech pathologist. If milk/formula is seen on the vocal folds or in the larynx proper, the child should be considered an aspiration risk. The other benefit of fiberoptic endoscopic evaluation of swallowing is that it allows direct visualization of multiple components of the upper airway including nose, pharynx, and larynx to the level of the true vocal folds. It does not allow for evaluation of extraction ability (ability to extract milk or formula from a bottle), swallowing organization, bolus control, degree of laryngeal penetration, or direct visualization of tracheal aspiration. Instrumental evaluation provides information necessary to establish successful oral feeding. Once swallowing safety can be assured, the child can then begin therapeutic feedings at bedside. The speech pathologist, occupational therapist, or critical care nursing team will initiate a program of feeding intervention with the goal of safe and efficient oral nutrition. Multiple techniques may be used during feeding such as chin or cheek support, pacing (altering bottle presentation or pressure and providing breaks), or physical stimulation to facilitate swallowing.
Video 1. Fiberoptic endoscopic evaluation of swallowing study (FEES). This video is viewed at half normal speed to allow visualization of the airway and the formula in the glottic opening. The view of the hypopharynx is notable for laryngomalacia. Immediately after swallowing, milk can be seen pooling in both the vallecular space and pyriform sinuses with overflow to the vocal cords. This is referred to as laryngeal penetration and is concerning for aspiration.
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Figure 3. Grading of epiglottis and base of tongue collapse. (A) Grade 0-Normal airway, no collapse; (B) Grade 1-prolapse of epiglottis against postpharynx; (C) Grade 2-prolapse of epiglottis and base of tongue—the tip of epiglottis visible—the vallecular is not visible. (D) Grade 3-complete prolapse of base of tongue. The epiglottis is not visible.66
SURGICAL MANAGEMENT Otolaryngology
Airway obstruction in the patient with PRS may exist at multiple levels from oropharyngeal obstruction due to glossoptosis to hypopharyngeal obstruction due to collapse of the epiglottis and base of tongue (EBT) (Fig. 3, A–D). Children with PRS are especially prone to this type of hypopharyngeal collapse as a sequelae of the micrognathia. In general, the more severe the micrognathia, the more severe the EBT collapse and symptoms of airway obstruction. Other airway anomalies such as laryngomalacia (LM) or subglottic or tracheal pathology may also be present. The airway evaluation begins with a careful history, including details of the delivery, initial Apgar scores, and any apnea or cyanotic episodes in the early neonatal period. Observations regarding the neonate’s ability to feed are important since feeding difficulties and airway abnormalities are inextricably linked, as previously outlined. The physical examination should include a complete head and neck examination documenting any stigmata that would suggest syndromic PRS. The infant should be examined in a variety of positions, including seated, prone, and supine, evaluating for exacerbation of airway symptoms. If the infant is stable, a flexible nasolaryngoscopy is performed in a seated position, on a caregiver’s lap, and then immediately in a supine position to assess differences in the severity of any airway obstruction based on position. The flexible nasolaryngoscopy examination confirms patent choanae, determines the degree of any oropharyngeal obstruction due to glossoptosis, documents any degree of EBT collapse, and evaluates August 2014 • Volume 119 • Number 2
any laryngeal abnormalities, including LM and any sequelae of acid reflux. Additional information gathered from computerized tomography (CT) imaging studies, cine-magnetic resonance imaging (MRI), and polysomnography (PSG) may help determine the severity of the airway obstruction and add information to the anatomic location of the obstruction. Mild airway obstruction at birth may prompt only conservative measures such as prone positioning or a nasal or oral airway. A lower threshold to perform airway endoscopy should be used in children with a syndrome. More severe airway obstruction that does not improve with conservative measures warrants a diagnostic endoscopy in the operating room consisting of at least a flexible nasolaryngoscopy and a direct rigid laryngo-bronchoscopy (DLB). The exact anatomic location of the airway obstruction may be determined. If the severity of the obstruction warrants it, or if multiple levels of obstruction are present, surgical intervention to improve the safety of the airway is indicated. The DLB also provides an assessment of the difficulty of orotracheal intubation. If additional intervention is required, the patient may be intubated as part of the endoscopic procedure. A DLB in an infant with PRS is more difficult technically because of the retrognathia and the position of the mandible relative to the anteriorly placed larynx. Definitive airway management in infants with PRS is challenging and has been the topic of much debate. In general, infants with nonsyndromic PRS improve with conservative measures such as prone positioning or an NPA.32,33 They are also more likely to have symptomatic improvement after surgical interventions such as TLA or MDO. Children
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with syndromic PRS are more likely to fail TLA or MDO21 and may need tracheostomy tube placement and/or gastrostomy tube placement. Tracheostomy is indicated in children with multilevel airway obstruction and those who fail other surgical interventions to alleviate airway obstruction. Some advocate for tracheostomy in children with airway obstruction and PRS associated with a syndrome and neurologic comorbidities. Tracheostomy may be the required airway intervention if the infant is 6 4. No significant central apnea 5. No neurologic comorbidities or syndromes 6. Medically stable reflux
TLA VS MDO
Severe
1. Fail prone positioning or NPA 2. Multilevel obstruction on flexible scope & DLB 3. Apnea-hypopnea index > 6 4. Central apnea 5. Neurologic comorbidities and/or syndromes 6. Medically refractory reflux
Tracheostomy +/- delayed MDO
Figure 4. Clinical care algorithm for the surgical management of Pierre Robin sequence.
“taken down” before the first year of life. The reversal of the TLA can be combined with repair of the cleft palate if present. Concerns regarding TLA include dehiscence and subsequent airway obstruction. Patients also require sedation and paralysis during the postoperative period, necessitating meticulous intensive care unit care. Opponents to the TLA argue that it does not correct the underlying pathology (micrognathia).6,46 Reasonable results using TLA have been
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reported.42,43 Preoperative predictors of TLA success can be determined by clinical features. Rogers et al.42 created the GILLS score to help predict which patients with PRS might fail TLA. The clinical features they evaluated included GER (G), preoperative intubation (I), later operation (>2 weeks of age) (L), low birth weight (2 kg and is older than 34 weeks gestational age. Proper laryngoscopy skills are essential when intubating patients with micrognathia. Using a paraglossal approach may be more effective than standard laryngoscopy. This technique was described by Henderson58 in 1997 and then applied by Semjen et al.59 in 2008 in 6 patients with PRS. They successfully intubated 5 of the 6 PRS patients. The laryngoscope blade is placed in the right corner of the mouth and passed along the groove between the tongue and the right tonsil, using leftward and anterior pressure. The tongue is displaced to the left, and there should be no tongue hanging over the blade at any time. This technique reduces the distance to the glottic opening (Fig. 8). The space along the right side of the mouth is also reduced, and this makes passing an endotracheal tube more challenging. The authors used a gum elastic bougie to facilitate endotracheal intubation. If a fiberoptic scope is used, it can be placed orally through an LMA or nasally to visualize the glottic opening. When used nasally, an NPA can be placed in the opposite nares and used as a conduit to introduce volatile anesthetic and oxygen into the posterior pharynx of the spontaneously breathing patient. In smaller patients, the fiberoptic scope may be too large to allow the endotracheal tube to be loaded onto it. In these patients, the scope can be placed nasally to visualize the glottis while an orally placed endotracheal
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Pierre Robin Sequence: A Perioperative Review
tube is passed into the glottic opening under direct fiberoptic visualization.60 There are other techniques that have been described to facilitate intubation in pediatric patients and they may prove to be useful in the patient with PRS. These techniques include video laryngoscopes (Storz videolaryngoscope, Glidescope) and ultrasound. There is 1 case report of an intubation with the Storz video laryngoscope in a 9-kg infant with PRS.61
The Glidescope Cobalt (Verathon), while it has not been described in the airway management of PRS, can be used in infants and neonates. Fiadjoe et al.62 recently compared the Glidescope with direct laryngoscopy in infants and neonates. Although none of these patients had craniofacial anomalies, the Glidescope was effective in patients younger than 1 year. Time to obtain best laryngoscopic view was faster with the Glidescope compared with direct laryngoscopy with a
Guidelines for Anesthesia Management of Neonates with Pierre Robin Sequence (PRS) or Severe Micrognathia for TLA, MDO or Tracheostomy Preoperative 1. 2. 3.
History includes micrognathia, glossoptosis, and airway obstruction. Additionally, a cleft palate may be present, but is not a required feature of PRS. PRS can be seen as an isolated anomaly, as part of other syndromes (see Table 1), or as various unnamed or unassociated anomalies. Induction performed with pediatric otolaryngology present in the operating room with emergency bronchoscopy and tracheostomy equipment.
Induction (spontaneous ventilation maintained) 1. Inhalation with sevoflurane 2. Intravenous with propofol 3. LMA placed awake (if severe obstruction when awake) Can ventilate 1. maintain spont ventilation 2. prepare to intubate (paraglossal approach, videolaryngoscope, fiberoptic through nose or LMA)
Cannot ventilate 1. use OPA, NPA, two-handed jaw thrust, LMA
Can ventilate (Non-emergency) 1. prepare to intubate (paraglossal approach, videolaryngoscope, fiberoptic through nose or LMA)
1. 2. 3. 4.
Cannot ventilate (Emergency) Direct laryngoscopy x 1 Emergent rigid bronchoscopy placement by ENT LMA Tracheostomy
Maintenance 1. Volatile anesthetic:
sevoflurane vs isoflurane
2. Opioid infusion: sufentanil vs fentanyl
3. Alpha-2 agonist infusion: dexmedetomidine
4. Neuromuscular blockade 1. 2. 3.
Emergence
Planned postoperative intubation Neuromuscular blockade continued to PICU Sedation continued to PICU
Figure 9. An algorithm for the anesthesia management of Pierre Robin sequence (PRS) patients for tongue lip adhesion (TLA), mandibular distraction osteogenesis (MDO), or tracheostomy.
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Miller 1 blade. However, the time to pass an endotracheal tube was slower with the Glidescope. The Glidescope has different disposable adapters and per the manufacturer may be used in neonates as small as 1.5 kg. Patients presenting to the operating room after MDO may be significantly easier to mask ventilate and intubate. Frawley et al.63 described their experience with 51 PRS patients before and after MDO. Before distraction, the incidence of difficult intubation was 71%, and this decreased to 8.3% after distraction. A variety of techniques can be used for anesthesia maintenance for patients with PRS. There is little evidence to support one technique over another. Volatile anesthetic is ubiquitous and safe and is likely the primary anesthetic used in most centers. Sevoflurane is one of the most commonly used anesthetic drugs used for pediatric patients but isoflurane could be used as well. Desflurane may be advantageous regarding emergence but it has some limitations that may preclude its use in pediatric PRS patients. Desflurane increases airway reactivity and should not be used in pediatric patients with bronchial hyperreactivity (asthma, upper respiratory tract infection, or bronchopulmonary dysplasia).64 In addition, the package insert for desflurane has changed and now indicates that it should not be used with an LMA in 2to 6-year-old pediatric patients. There is an increased risk of laryngospasm, coughing, and secretions (suprane [desflurane] package insert). There is no information on patients younger than 2 years, but this population may also be at increased risk of airway complications if desflurane is used with an LMA. In addition to a volatile drug, anesthesia maintenance can be supplemented with an opioid and an α-2 agonist such as dexmedetomidine. If intubation is continued into the postoperative period (TLA, MDO), a longer-acting opioid may be preferred over remifentanil. If extubation is planned (cleft lip, cleft palate), an α-2 agonist provides analgesia and may reduce opioid requirements. Likewise, some practitioners may prefer an ultra-shortacting opioid like remifentanil in this setting. PRS patients should be extubated awake, and an NPA can be placed before extubation to minimize postoperative airway obstruction. Figure 9 outlines an algorithm for the anesthesia management of PRS patients for TLA, MDO, or tracheostomy.
Postoperative Concerns
The primary concern in the postoperative management of the patient with PRS is airway obstruction. Acute postoperative airway obstruction may result in hypoxia, negative pressure pulmonary edema, and death. Patients with PRS are particularly prone to postoperative respiratory complications from airway obstruction for several reasons including previous airway obstruction, opioid sensitivity, and surgically induced airway edema. Chronic hypoxia from airway obstruction (OSA) increases opioid sensitivity if the obstruction is severe. Brown et al.50 have demonstrated that pediatric patients with severe OSA (oxygen saturation nadir
Pierre Robin Sequence: A Perioperative Review Franklyn Cladis, MD, FAAP,* Anand Kumar, MD,† Lorelei Grunwaldt, MD,† Todd Otteson, MD,‡ Matthew Ford, MS, CCC-SLP,† and Joseph E. Losee, MD, FAAP† The clinical triad of micrognathia (small mandible), glossoptosis (backward, downward displacement of the tongue), and airway obstruction defines the Pierre Robin sequence (PRS). Airway obstruction and respiratory distress are clinical hallmarks. Patients may present with stridor, retractions, and cyanosis. Severe obstruction results in feeding difficulty, reflux, and failure to thrive. Treatment options depend on the severity of airway obstruction and include prone positioning, nasopharyngeal airways, tongue lip adhesion, mandibular distraction osteogenesis, and tracheostomy. The neonate and infant with PRS require care from multiple specialists including anesthesiology, plastic surgery, otolaryngology, speech pathology, gastroenterology, radiology, and neonatology. The anesthesiologist involved in the care of patients with PRS will interface with a multidisciplinary team in a variety of clinical settings. This perioperative review is a collaborative effort from multiple specialties including anesthesiology, plastic surgery, otolaryngology, and speech pathology. We will discuss the background and clinical presentation of patients with PRS, as well as some of the controversies regarding their care. (Anesth Analg 2014;119:400–12)
I
n 1923, Pierre Robin, a stomatologist from France, coined the term “glossoptosis” to describe the “obstruction of the oral pharynx by the tongue” in the setting of a small mandible. Although others have previously described patients with small mandibles, airway obstruction, and cleft palate, Dr. Robin has been credited with defining the criteria for the Pierre Robin sequence (PRS).1,2 The clinical triad of micrognathia (small mandible), glossoptosis (backward, downward displacement of the base of the tongue; Fig. 1), and airway obstruction defines PRS. Some authors have described PRS as micrognathia, glossoptosis, and cleft palate.3,4 Although clefting of the palate is common, it does not occur in all infants with PRS. However, all patients with PRS have airway obstruction,5 and this is a requirement for the clinical diagnosis. There is ongoing debate regarding the biologic etiology of PRS. There does not appear to be a clear genetic abnormality, although the etiology of the micrognathia may be different for syndromic and nonsyndromic PRS.6 Some authors have suggested a genetic cause for syndromic PRS and an external mechanism like in utero compression secondary to oligohydramnios for nonsyndromic PRS.6 It is suspected that micrognathia keeps the tongue superiorly positioned between the naturally clefted palatal shelves and prevents normal palatal closure during the first trimester of pregnancy. Although micrognathia appears to be an isolated event for most patients with PRS, there is
From the Departments of *Anesthesiology and †Plastic Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; and ‡Pediatric Otolaryngology, UH Rainbow Babies and Children’s Hospital CWRU School of Medicine, Cleveland, Ohio. Accepted for publication March 28, 2014. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Franklyn Cladis, MD, Department of Anesthesiology, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave., 5th Floor, Pittsburgh, PA 15224. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000301
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an association with certain syndromes. The most common syndromes are Stickler, velocardiofacial (22q, 11.2 deletion), fetal alcohol syndrome, and Treacher-Collins syndrome (Table 1).5,7,8 The incidence of PRS varies from 1:5000 to 1:85,000.3,6,9,10 The large variation in the incidence of PRS may be dependent on the variability of clinical presentation. The patient with mild symptoms may go unrecognized. Infants with PRS present with respiratory and feeding difficulties. As many as half of these infants will also have associated malformations. Airway obstruction and respiratory distress are the primary respiratory signs. Patients may present with stridor, retractions, and cyanosis. Severe obstruction results in feeding difficulty, reflux, and failure to thrive. Treatment options depend on the severity of airway obstruction. Obstruction that is mild when supine or relieved completely when prone may be observed without a procedural intervention. Prone positioning may relieve airway obstruction in as many as 70% of these subjects.6 The therapeutic options for more severe obstruction include nasopharyngeal airways (NPA), tongue lip adhesion (TLA), mandibular distraction osteogenesis (MDO), and tracheostomy. Clinical intervention is frequently dependent on the experience of the institution. Centers with larger patient volumes may have a multidisciplinary protocol that defines the clinical course of these patients. The neonate and infant with PRS require care from multiple specialists including plastic surgery, otolaryngology, speech pathology, gastroenterology, radiology, and neonatology. The anesthesiologist involved in the care of patients with PRS will interface with this multidisciplinary team in a variety of clinical settings. This perioperative review is intended to discuss the background and clinical presentation of patients with PRS and some of the controversies regarding their care.
FEEDING
Feeding and swallowing are complex biologic functions. In the newborn period, suckling is quite reflexive and likely is controlled at a subcortical level. Nutritive suckling is accomplished by compression of a nipple against the palate. Most August 2014 • Volume 119 • Number 2
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Figure 1. An infant with Pierre Robin sequence (PRS) and glossoptosis. Note the small and posteriorly displaced tongue (Courtesy of Joseph Losee, MD).
infants will have multiple suckles, which fills the vallecular space before swallowing. During deglutition, the tongue expresses and propels the milk/formula posteriorly, while the soft palate rises to separate the mouth from the nose. The bolus travels to the vallecular space before swallowing. The larynx then is pulled upward and mildly forward resulting in epiglottic closure. Simultaneously, respiration ceases momentarily and the vocal folds close. The presence of a cleft palate decreases the infant’s ability to establish negative intraoral air pressure required to suck milk from a normal bottle or breast. This results in decreased organization of bolus formation and transit. The palatal defect creates the infant’s inability to separate the mouth from the nose.11 The prevalence of feeding and swallowing disorders in patients with PRS has been estimated at 25% to 45%.12 These difficulties are linked to their respiratory issues.13–15 However, correcting the airway obstruction will not always improve feeding and swallowing issues. Positioning an infant prone with PRS may be adequate to manage minor upper airway obstruction by minimizing glossoptosis, but this will not obviate the infants’ feeding challenges. Infants cannot be successfully fed in the prone position, and many cannot safely or adequately swallow once positioned upright for feeding. Some PRS infants need long-term nasogastric or gastrostomy tube feeds. Temporary NPAs have been used for airway management
and frequently will manage the airway obstruction but again may not obviate the need for nasogastric or gastrostomy feeds for adequate nutrition and growth.16,17 Surgical interventions have been described to successfully manage glossoptosis and upper airway obstruction.18–20 While this has been associated with improvement in feeding, it is not a guarantee of successful oral feeding. Smith and Senders21 noted a prevalence of nasogastric or gastrostomy tube feedings of 53% in isolated PRS patients, 67% in syndromic patients, and 83% in “unique” (abnormalities that did not satisfy the criteria for a named syndrome) PRS patients. MDO is a technique frequently used for the management of more severe PRS patients. In 2004, Monasterio et al.20 found a trend toward resolution of feeding difficulties in most patients in their cohort with MDO. Despite correction of the airway obstruction, many infants with PRS will have persistent feeding and swallowing challenges. The causes of these challenges are multifactorial. Baudon et al.22 in 2002 and Baujat et al.23 in 2001 documented, by electromyography and esophageal manometry, an increased prevalence of esophageal motility disorders. Gastroesophageal reflux (GER) is a known comorbidity with PRS and is thought to be due to altered intrathoracic pressures secondary to airway obstruction.24,25 The clinical consequences of GER include aspiration, and pharyngeal and laryngeal edema. Laryngeal edema increases airway obstruction. Because of the incidence and consequences of reflux, most practitioners advocate prophylactic medical treatment. Infants with PRS require additional feeding support to deal with altered suction abilities13 and formula delivery.26,27 Specialized bottles, nursers, and nipples are typically required for an adequate volume of milk delivery to infants with cleft palate. These feeders allow milk to be actively dispensed into the infant’s mouth during suckling maneuvers. This may include the Mead Johnson Cleft Nurser, Pigeon Cleft Bottle, or Haberman Special Needs Feeder (Fig. 2, A–C). Although respiratory distress frequently results in an acute life-threatening event and morbidity in infants with PRS, swallowing and feeding issues can also contribute to infant morbidity and mortality. Untreated aspiration can lead to significant pulmonary morbidity. Inadequate nutrition similarly can result in failure to thrive and associated morbidity. This underscores the critical importance of an
Table 1. Syndromes Associated with Pierre Robin Sequence Syndrome Fetal alcohol syndromea
Sticklerb Treacher Collinsb
Velocardiofacialb
Associated anomalies Microcephaly, maxillary hypoplasia, micrognathia, short neck, ventricular septal defect, cognitive developmental delay, hyperactivity Marfanoid appearance, airway obstruction, micrognathia, joint laxity, mitral valve prolapse. Craniofacial clefting, mandibular hypoplasia. May have obstructive sleep apnea. May have congenital heart disease Microdeletion of chromosome 22, microcephaly, micrognathia, congenital cardiac disease. May have developmental delay, neonatal hypocalcemia, T-cell immune deficiency
Anesthetic concerns May be difficult to ventilate and intubate. Preoperative echo may be indicated. Consider subacute bacterial endocarditis prophylaxis. May be uncooperative May be difficult to ventilate and intubate. Care with positioning May be difficult or impossible to intubate. Preoperative echo may be indicated. Consider subacute bacterial endocarditis prophylaxis May be difficult to intubate. Preoperative echo may be indicated. Consider subacute bacterial endocarditis prophylaxis. Blood products need to be irradiated
Frost et al.8 Adapted from Losee, Kirschner, Comprehensive Cleft Care, McGraw Hill, 2008, chapter 13, Table 13–1, p. 214–5.67
a
b
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Figure 2. Feeders for infants with cleft palates. (A) Mead Johnson bottle; (B) Pigeon nipple; and (C) Haberman bottle (Courtesy of Matthew Ford).
in-depth feeding and swallowing evaluation in the PRS infant. Assessment of swallowing safety and aspiration risk is primary for developing an appropriate feeding plan. Some infants can be fed safely with alterations of feeding with specialized feeding equipment, altered formula/milk consistency, or modified feeding schedules. However, many require time to transition from nonoral feeding to oral feeding as their respiratory status improves with interventions and general growth and development. Nasogastric or gastrostomy feeds do not preclude oral feeding attempts and should be considered in any infant with significant nutritional or aspiration risks. Feeding facilitation techniques have also been advocated to improve oral feeding. This includes oral stimulation and tongue massage techniques with a pacifier and gloved fingers.28 Depending on the institution, the PRS infant with feeding difficulties is typically managed by either a speech pathologist and/or an occupational therapist. Given the complex interaction between feeding and airway difficulties in the infant with PRS, early input from both speech pathology and occupational therapy is critical to the success of these patients. Feeding and swallowing evaluations typically take place in the neonatal intensive care unit at the bedside once the infant is medically stable. Oral trials should not be considered until the infant demonstrates baseline stable respiratory status, adequate oropharyngeal secretion control, and adequate level of alertness. Fatigue with oral stimulation should be documented. When aspiration risk is identified, it is critical to obtain further direct swallowing assessment before initiation of ad lib oral feeds. Comprehensive swallowing evaluation should be performed using direct assessments, and these are typically performed as part of PRS treatment protocols in most centers. Assessments may be done before and after surgical
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or nonsurgical interventions such as MDO, TLA, or placement of an NPA. The “gold standard” for assessing swallow and aspiration risk is the modified barium swallow study, referred to as a cookie swallow study.29 This is completed in the radiology department. Swallowing is assessed under lateral fluoroscopy. The infant is positioned semi-upright in a fluoroscopic infant seating device. Silent aspiration can be identified, which refers to tracheal aspiration in the absence of coughing or choking. Endoscopic assessment of swallowing has also been described and is frequently used in the PRS population to assess aspiration risk. This type of assessment is referred to as fiberoptic endoscopic evaluation of swallowing (Video 1, Supplemental Digital Content 1, http://links.lww.com/ AA/A915).30,31 This can be performed at the bedside. This assessment is typically completed in conjunction with an otolaryngologist and speech pathologist. If milk/formula is seen on the vocal folds or in the larynx proper, the child should be considered an aspiration risk. The other benefit of fiberoptic endoscopic evaluation of swallowing is that it allows direct visualization of multiple components of the upper airway including nose, pharynx, and larynx to the level of the true vocal folds. It does not allow for evaluation of extraction ability (ability to extract milk or formula from a bottle), swallowing organization, bolus control, degree of laryngeal penetration, or direct visualization of tracheal aspiration. Instrumental evaluation provides information necessary to establish successful oral feeding. Once swallowing safety can be assured, the child can then begin therapeutic feedings at bedside. The speech pathologist, occupational therapist, or critical care nursing team will initiate a program of feeding intervention with the goal of safe and efficient oral nutrition. Multiple techniques may be used during feeding such as chin or cheek support, pacing (altering bottle presentation or pressure and providing breaks), or physical stimulation to facilitate swallowing.
Video 1. Fiberoptic endoscopic evaluation of swallowing study (FEES). This video is viewed at half normal speed to allow visualization of the airway and the formula in the glottic opening. The view of the hypopharynx is notable for laryngomalacia. Immediately after swallowing, milk can be seen pooling in both the vallecular space and pyriform sinuses with overflow to the vocal cords. This is referred to as laryngeal penetration and is concerning for aspiration.
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Figure 3. Grading of epiglottis and base of tongue collapse. (A) Grade 0-Normal airway, no collapse; (B) Grade 1-prolapse of epiglottis against postpharynx; (C) Grade 2-prolapse of epiglottis and base of tongue—the tip of epiglottis visible—the vallecular is not visible. (D) Grade 3-complete prolapse of base of tongue. The epiglottis is not visible.66
SURGICAL MANAGEMENT Otolaryngology
Airway obstruction in the patient with PRS may exist at multiple levels from oropharyngeal obstruction due to glossoptosis to hypopharyngeal obstruction due to collapse of the epiglottis and base of tongue (EBT) (Fig. 3, A–D). Children with PRS are especially prone to this type of hypopharyngeal collapse as a sequelae of the micrognathia. In general, the more severe the micrognathia, the more severe the EBT collapse and symptoms of airway obstruction. Other airway anomalies such as laryngomalacia (LM) or subglottic or tracheal pathology may also be present. The airway evaluation begins with a careful history, including details of the delivery, initial Apgar scores, and any apnea or cyanotic episodes in the early neonatal period. Observations regarding the neonate’s ability to feed are important since feeding difficulties and airway abnormalities are inextricably linked, as previously outlined. The physical examination should include a complete head and neck examination documenting any stigmata that would suggest syndromic PRS. The infant should be examined in a variety of positions, including seated, prone, and supine, evaluating for exacerbation of airway symptoms. If the infant is stable, a flexible nasolaryngoscopy is performed in a seated position, on a caregiver’s lap, and then immediately in a supine position to assess differences in the severity of any airway obstruction based on position. The flexible nasolaryngoscopy examination confirms patent choanae, determines the degree of any oropharyngeal obstruction due to glossoptosis, documents any degree of EBT collapse, and evaluates August 2014 • Volume 119 • Number 2
any laryngeal abnormalities, including LM and any sequelae of acid reflux. Additional information gathered from computerized tomography (CT) imaging studies, cine-magnetic resonance imaging (MRI), and polysomnography (PSG) may help determine the severity of the airway obstruction and add information to the anatomic location of the obstruction. Mild airway obstruction at birth may prompt only conservative measures such as prone positioning or a nasal or oral airway. A lower threshold to perform airway endoscopy should be used in children with a syndrome. More severe airway obstruction that does not improve with conservative measures warrants a diagnostic endoscopy in the operating room consisting of at least a flexible nasolaryngoscopy and a direct rigid laryngo-bronchoscopy (DLB). The exact anatomic location of the airway obstruction may be determined. If the severity of the obstruction warrants it, or if multiple levels of obstruction are present, surgical intervention to improve the safety of the airway is indicated. The DLB also provides an assessment of the difficulty of orotracheal intubation. If additional intervention is required, the patient may be intubated as part of the endoscopic procedure. A DLB in an infant with PRS is more difficult technically because of the retrognathia and the position of the mandible relative to the anteriorly placed larynx. Definitive airway management in infants with PRS is challenging and has been the topic of much debate. In general, infants with nonsyndromic PRS improve with conservative measures such as prone positioning or an NPA.32,33 They are also more likely to have symptomatic improvement after surgical interventions such as TLA or MDO. Children
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with syndromic PRS are more likely to fail TLA or MDO21 and may need tracheostomy tube placement and/or gastrostomy tube placement. Tracheostomy is indicated in children with multilevel airway obstruction and those who fail other surgical interventions to alleviate airway obstruction. Some advocate for tracheostomy in children with airway obstruction and PRS associated with a syndrome and neurologic comorbidities. Tracheostomy may be the required airway intervention if the infant is 6 4. No significant central apnea 5. No neurologic comorbidities or syndromes 6. Medically stable reflux
TLA VS MDO
Severe
1. Fail prone positioning or NPA 2. Multilevel obstruction on flexible scope & DLB 3. Apnea-hypopnea index > 6 4. Central apnea 5. Neurologic comorbidities and/or syndromes 6. Medically refractory reflux
Tracheostomy +/- delayed MDO
Figure 4. Clinical care algorithm for the surgical management of Pierre Robin sequence.
“taken down” before the first year of life. The reversal of the TLA can be combined with repair of the cleft palate if present. Concerns regarding TLA include dehiscence and subsequent airway obstruction. Patients also require sedation and paralysis during the postoperative period, necessitating meticulous intensive care unit care. Opponents to the TLA argue that it does not correct the underlying pathology (micrognathia).6,46 Reasonable results using TLA have been
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reported.42,43 Preoperative predictors of TLA success can be determined by clinical features. Rogers et al.42 created the GILLS score to help predict which patients with PRS might fail TLA. The clinical features they evaluated included GER (G), preoperative intubation (I), later operation (>2 weeks of age) (L), low birth weight (2 kg and is older than 34 weeks gestational age. Proper laryngoscopy skills are essential when intubating patients with micrognathia. Using a paraglossal approach may be more effective than standard laryngoscopy. This technique was described by Henderson58 in 1997 and then applied by Semjen et al.59 in 2008 in 6 patients with PRS. They successfully intubated 5 of the 6 PRS patients. The laryngoscope blade is placed in the right corner of the mouth and passed along the groove between the tongue and the right tonsil, using leftward and anterior pressure. The tongue is displaced to the left, and there should be no tongue hanging over the blade at any time. This technique reduces the distance to the glottic opening (Fig. 8). The space along the right side of the mouth is also reduced, and this makes passing an endotracheal tube more challenging. The authors used a gum elastic bougie to facilitate endotracheal intubation. If a fiberoptic scope is used, it can be placed orally through an LMA or nasally to visualize the glottic opening. When used nasally, an NPA can be placed in the opposite nares and used as a conduit to introduce volatile anesthetic and oxygen into the posterior pharynx of the spontaneously breathing patient. In smaller patients, the fiberoptic scope may be too large to allow the endotracheal tube to be loaded onto it. In these patients, the scope can be placed nasally to visualize the glottis while an orally placed endotracheal
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tube is passed into the glottic opening under direct fiberoptic visualization.60 There are other techniques that have been described to facilitate intubation in pediatric patients and they may prove to be useful in the patient with PRS. These techniques include video laryngoscopes (Storz videolaryngoscope, Glidescope) and ultrasound. There is 1 case report of an intubation with the Storz video laryngoscope in a 9-kg infant with PRS.61
The Glidescope Cobalt (Verathon), while it has not been described in the airway management of PRS, can be used in infants and neonates. Fiadjoe et al.62 recently compared the Glidescope with direct laryngoscopy in infants and neonates. Although none of these patients had craniofacial anomalies, the Glidescope was effective in patients younger than 1 year. Time to obtain best laryngoscopic view was faster with the Glidescope compared with direct laryngoscopy with a
Guidelines for Anesthesia Management of Neonates with Pierre Robin Sequence (PRS) or Severe Micrognathia for TLA, MDO or Tracheostomy Preoperative 1. 2. 3.
History includes micrognathia, glossoptosis, and airway obstruction. Additionally, a cleft palate may be present, but is not a required feature of PRS. PRS can be seen as an isolated anomaly, as part of other syndromes (see Table 1), or as various unnamed or unassociated anomalies. Induction performed with pediatric otolaryngology present in the operating room with emergency bronchoscopy and tracheostomy equipment.
Induction (spontaneous ventilation maintained) 1. Inhalation with sevoflurane 2. Intravenous with propofol 3. LMA placed awake (if severe obstruction when awake) Can ventilate 1. maintain spont ventilation 2. prepare to intubate (paraglossal approach, videolaryngoscope, fiberoptic through nose or LMA)
Cannot ventilate 1. use OPA, NPA, two-handed jaw thrust, LMA
Can ventilate (Non-emergency) 1. prepare to intubate (paraglossal approach, videolaryngoscope, fiberoptic through nose or LMA)
1. 2. 3. 4.
Cannot ventilate (Emergency) Direct laryngoscopy x 1 Emergent rigid bronchoscopy placement by ENT LMA Tracheostomy
Maintenance 1. Volatile anesthetic:
sevoflurane vs isoflurane
2. Opioid infusion: sufentanil vs fentanyl
3. Alpha-2 agonist infusion: dexmedetomidine
4. Neuromuscular blockade 1. 2. 3.
Emergence
Planned postoperative intubation Neuromuscular blockade continued to PICU Sedation continued to PICU
Figure 9. An algorithm for the anesthesia management of Pierre Robin sequence (PRS) patients for tongue lip adhesion (TLA), mandibular distraction osteogenesis (MDO), or tracheostomy.
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Miller 1 blade. However, the time to pass an endotracheal tube was slower with the Glidescope. The Glidescope has different disposable adapters and per the manufacturer may be used in neonates as small as 1.5 kg. Patients presenting to the operating room after MDO may be significantly easier to mask ventilate and intubate. Frawley et al.63 described their experience with 51 PRS patients before and after MDO. Before distraction, the incidence of difficult intubation was 71%, and this decreased to 8.3% after distraction. A variety of techniques can be used for anesthesia maintenance for patients with PRS. There is little evidence to support one technique over another. Volatile anesthetic is ubiquitous and safe and is likely the primary anesthetic used in most centers. Sevoflurane is one of the most commonly used anesthetic drugs used for pediatric patients but isoflurane could be used as well. Desflurane may be advantageous regarding emergence but it has some limitations that may preclude its use in pediatric PRS patients. Desflurane increases airway reactivity and should not be used in pediatric patients with bronchial hyperreactivity (asthma, upper respiratory tract infection, or bronchopulmonary dysplasia).64 In addition, the package insert for desflurane has changed and now indicates that it should not be used with an LMA in 2to 6-year-old pediatric patients. There is an increased risk of laryngospasm, coughing, and secretions (suprane [desflurane] package insert). There is no information on patients younger than 2 years, but this population may also be at increased risk of airway complications if desflurane is used with an LMA. In addition to a volatile drug, anesthesia maintenance can be supplemented with an opioid and an α-2 agonist such as dexmedetomidine. If intubation is continued into the postoperative period (TLA, MDO), a longer-acting opioid may be preferred over remifentanil. If extubation is planned (cleft lip, cleft palate), an α-2 agonist provides analgesia and may reduce opioid requirements. Likewise, some practitioners may prefer an ultra-shortacting opioid like remifentanil in this setting. PRS patients should be extubated awake, and an NPA can be placed before extubation to minimize postoperative airway obstruction. Figure 9 outlines an algorithm for the anesthesia management of PRS patients for TLA, MDO, or tracheostomy.
Postoperative Concerns
The primary concern in the postoperative management of the patient with PRS is airway obstruction. Acute postoperative airway obstruction may result in hypoxia, negative pressure pulmonary edema, and death. Patients with PRS are particularly prone to postoperative respiratory complications from airway obstruction for several reasons including previous airway obstruction, opioid sensitivity, and surgically induced airway edema. Chronic hypoxia from airway obstruction (OSA) increases opioid sensitivity if the obstruction is severe. Brown et al.50 have demonstrated that pediatric patients with severe OSA (oxygen saturation nadir
