Abstract
Background:
Beckwith-Wiedemann Syndrome is the most common congenital overgrowth disorder with an incidence of approximately 1 in 10,000 live births. The condition is characterized by lateralized overgrowth, abdominal wall defects, macroglossia, and predisposition to malignancy. Historically, children with Beckwith-Wiedemann Syndrome have been presumed to be difficult airways; however, most of the evidence to support this has been anecdotal and derived from case reports. Our study aimed to determine the prevalence of difficult airway in patients with Beckwith-Wiedemann Syndrome. We hypothesized that most patients with Beckwith-Wiedemann Syndrome would not have difficult airways.
Methods:
We retrospectively reviewed the electronic medical records of patients enrolled in our institution’s Beckwith-Wiedemann Syndrome registry. Patients with a molecular diagnosis of Beckwith-Wiedemann Syndrome who were anesthetized between January 2012 and July 2019 were included for analysis. The primary outcome was the presence of difficult airway, defined as difficult facemask ventilation, difficult intubation or both. We defined difficult intubation as the need for 3 or more tracheal intubation attempts, the need for advanced airway techniques (non-direct laryngoscopy) to perform tracheal intubation or a Cormack and Lehane grade ≥ 3 during direct laryngoscopy. Secondary objectives were to define predictors of difficult intubation and difficult facemask ventilation, and the prevalence of adverse airway events. Generalized linear-mixed effect models were used to account for multiple anesthesia events per patients.
Results:
Of 201 Beckwith-Wiedemann Syndrome patients enrolled in the registry, 60% (n=122) had one or more documented anesthetics for a total of 310 anesthetics. A pre-existing airway was present in 22 anesthetics. The prevalence of difficult airway was 5.3% (95% confidence interval [CI] 3.0%-9.3%,18/288) of the cases. The prevalence of difficult intubation was 5.2% (95%CI 2.9%-9.4%,12/226). The prevalence of difficult facemask ventilation was 2.9% (95%CI 1.4%-6.2%, 12/277) and facemask ventilation was not attempted in 42 anesthetics. Age < 1 year, macroglossia, lower weight, endocrine comorbidities, plastics/craniofacial surgery, tongue reduction surgery, and obstructive sleep apnea were associated with difficult airways in cases without a pre-existing airway. 83.8% (95%CI 77.6%-88.5%) of the cases were intubated with a single attempt. Hypoxemia was the most common adverse event.
Conclusion:
The prevalence of difficult tracheal intubation and difficult facemask ventilation in children with Beckwith-Wiedemann Syndrome was 5.2% and 2.9% respectively. We identified factors associated with difficult airway which included age < 1 year, macroglossia, endocrine abnormalities, plastics/craniofacial surgery, tongue reduction surgery and obstructive sleep apnea. Clinicians should anticipate difficult airways in patients with these factors.
Keywords: Beckwith-Wiedemann syndrome, difficult airway, airway management, intubation pediatric, laryngoscopy, pediatric anesthesia
INTRODUCTION:
Beckwith-Wiedemann Syndrome (BWS) is a congenital disorder characterized by lateralized overgrowth, abdominal wall defects (e.g. omphalocele), hypoglycemia, macrosomia, macroglossia, and increased risk for embryonal tumors such as hepatoblastoma and Wilms tumor1. Although the alterations at the genetic level are complex, approximately 80% of patients have a molecularly confirmed abnormality involving the BWS imprinting regions on chromosome 11p15.5 2. Some authors estimate an incidence close to 1 in 10,000 live births with a further increased prevalence when assisted fertilization techniques are used3. BWS is considered the most common epigenetic overgrowth disorder, and patients may present with a wide spectrum of clinical features and severity4.
Traditionally, one of the main anesthetic concerns in patients with BWS is difficult airway due to macroglossia5, 6. Macroglossia results from overgrowth of the tongue muscle fibers and may lead to craniofacial abnormalities with maxillary and mandibular changes resulting in an anterior open bite and a prognathic appearance with an increased mandibular length7. Other anesthetic concerns include prematurity, tumor development, tracheal wall anomalies and the risk for hypoglycemia 6, 8, 9 Nonetheless, much of the literature describing the perioperative management of children with BWS comes from case reports and small case series.8, 10, 11. Determining the prevalence and risk factors for difficult airway is important to guide clinicians in preparing to anesthetize these patients.
The aim of our study was to describe airway management techniques in a large cohort of patients with BWS at a single children’s hospital. Our primary objective was to determine the prevalence of difficult mask ventilation and difficult intubation, in this cohort. Secondary objectives were to define predictors of difficult intubation and difficult facemask ventilation (FMV), and the prevalence of adverse airway events during the perioperative period.
METHODS:
This study adhered to strengthening the reporting of observational studies in epidemiology (STROBE) guidelines.12 Using an established Institutional Review Board approved study (IRB#13-010658) with written parental consent, we conducted a retrospective analysis of electronical medical records of children with a confirmed molecular diagnosis of BWS enrolled in the BWS Registry at the Children’s Hospital of Philadelphia. Patients who had one or more general anesthetics documented between January 2012 to July 2019 were included. We excluded anesthetics with incomplete airway documentation. Patients who had a secured airway (endotracheal tube (ETT) or tracheostomy tube) prior to their anesthetic were excluded from additional analysis beyond frequencies.
We collected perioperative data using the electronic heath record system (Epic Systems Corporation, Verana, USA). We reviewed the electronic health records for preoperative and intraoperative anesthetic management details. Preoperative data included the following: patient demographics, type of surgery or procedure, history of prior difficult laryngoscopy, history of prior tongue reduction surgery, recent upper respiratory infection, anemia, obstructive sleep apnea (OSA), eczema, exposure to second hand smoking, current cardiac, pulmonary, renal or endocrine comorbidities, and clinical diagnosis of macroglossia as part of the problem list or as part of the physical exam.
Intraoperative data included type of anesthetic used for induction, medications used for tracheal intubation, details about airway management such as difficulty with FMV, number of attempts to successful tracheal intubation, and hypoxemia (defined as an oxygen saturation below 90% with pulse oximetry for more than 30 seconds), bradycardia or hypotension during the procedure.
The primary outcome was the presence of difficult airway, defined as difficult facemask ventilation, difficult intubation or both. Difficult mask ventilation was defined as the inability to provide adequate FMV after placement of an oral airway, the need for two-hand FMV or the inability to bag-mask ventilate requiring the use of a supraglottic airway device (SGA). Difficult intubation was defined as a Cormack and Lehane grade 3 or 4 during direct laryngoscopy (DL) or video laryngoscopy (VL), three or more intubation attempts by a pediatric anesthesiologist using DL and two or more attempts using VL, the need for advanced airway techniques such as a flexible fiberoptic scope (FOS) or combined techniques (VL+FOS or FOS+ SGA) to successfully intubate the trachea.
Secondary outcomes included the ease of facemask ventilation, number of tracheal intubation attempts, use of advance airway techniques for airway management, to determine predictors of difficult intubation and difficult facemask ventilation, and the occurrence of adverse airway events during the perioperative period or the need for an emergent surgical airway.
Patients who received multiple anesthetics had all the available anesthetics included in the study. We separately analyzed patients with macroglossia as we thought this was the most significant clinical feature associated with difficult airway.
Statistical analysis
All the collected data was entered into a Microsoft Excel (Redmond, WA, USA) database and analyzed using the statistical software SPSS version 26 (IBM Corporation, Chicago, USA), as well as SAS software version 9.4 (SAS Institute Inc., Cary, NC). Demographic characteristics, preoperative characteristics, airway management techniques and intraoperative variables were summarized as medians and interquartile ranges (IQR) for continuous variables, while frequencies and percentages for categorical variables. To account for multiple anesthesia events per patient, unconditional generalized linear mixed-effect models (GLMM) with patient ID as random effect were used to estimate the prevalence of primary and secondary outcomes. Binary distribution and logit link function were specified for dichotomous outcomes (i.e. difficult airway status, difficult facemask ventilation, difficult intubation), while multinomial distribution with cumulative logit link function were specified for the ordinal outcome (i.e. number of attempts to successful intubation). Difficult intubation and number of attempts to successful intubation were only analyzed for those anesthesia encounters in which tracheal intubation was attempted (n=226).
To explore the association of difficult airway with demographic factors and preoperative characteristics, separate GLMM with binary distribution, logit link function, difficult airway status as response variable, and random intercept with patient ID as random variable was fitted for each variable. We also compared differences in secondary outcomes (including first-attempt intubation success rate, perioperative medication usage and complications) between cases with and without difficult airway using similar GLMMs with difficult airway status as a fixed effect in the model. Additionally, we compared secondary outcomes between patients with and without macroglossia, and conducted a subgroup analysis to explore the association between difficult airway with demographics factors and perioperative characteristics for patients with documented macroglossia using similar GLMMs as full sample analysis above. A subgroup analysis was planned. Statistical significance was set at p <0.05. The sample size was based on all available patients in the registry during the study period, we did not perform an a priori sample size calculation.
RESULTS:
Demographic Characteristics
A total of 201 patients at our institution were part of the registry during the study period. One hundred twenty-two patients (60%) had a total of 316 anesthetics. Six anesthesia events were excluded due to incomplete documentation. The final analysis included 310 anesthetics. Demographics and other characteristics of the cohort are shown in Table 1. Approximately half of the anesthetics occurred in infants, and approximately 40% of patients were premature. Various molecular causes of BWS were observed in the group. Figure 1 presents a flow chart of the patients meeting inclusion criteria for the study. A pre-existing airway (ETT or tracheostomy tube) was present in 22 anesthetics prior to arrival to the operating room and these cases were excluded from the difficult airway analyses. Sixty-two other anesthetics had an SGA as the primary airway device. A total of 226 anesthetics documented endotracheal intubation in the operating room.
Table 1.
Demographic data of the cohort. Generalized linear mixed-effect model analysis of factors associated with difficult airway and not difficult airway events.
| Total | Airway Complexitya (n=288) |
Generalized Linear Mixed-effect modela | |||
|---|---|---|---|---|---|
|
|
|||||
| (n=310) | Difficult (n=18) |
Not Difficult (n=270) |
Odds Ratio (95%CI) |
p value | |
|
| |||||
| Ageb (months), median [IQR] | 9.0 [2.0-31.0] | 4.0 [1.0-6.0] | 12.0 [2.0-36.0] | N/Ac | N/Ac |
|
| |||||
| Infants d , n (%) | 172 (55.5%) | 15 (83.3%) | 139 (51.5%) | 5.4 (1.3, 23.5) | 0.024 |
|
| |||||
| Sex (male), n (%) | 189 (61%) | 10 (55.6%) | 169 (62.6%) | 1.1 (0.3, 3.9) | 0.865 |
|
| |||||
| Weighte (kg), median [IQR] | 9.3 [5.7-15.9] | 5.5 [4.8-8.3] | 10.0 [6.0-16.1] | 0.84 (0.72, 0.98) | 0.027 |
|
| |||||
| Gestational age at birth | |||||
| < 28 weeks | 12 (3.9%) | 1 (5.6%) | 6 (2.2%) | ||
| 28 to 32 weeks | 22 (7.1%) | - | 13 (4.8%) | N/Ac | N/Ac |
| 32 – 37 weeks | 87 (28.0%) | 11 (61.1%) | 72 (26.6%) | ||
| > 37 weeks | 189 (61.0%) | 6 (33.3%) | 179 (66.3%) | ||
|
| |||||
| Prematurity (≤37 weeks) | 121 (39.0%) | 12 (66.7%) | 91 (33.7%) | 3.0 (0.9, 9.8) | 0.076 |
|
| |||||
| BWS Genetic Subtype f | |||||
| IC1 GOM | 48 (15.5%) | 2 (11.1%) | 46 (17.0%) | Reference | Reference |
| IC2 LOM | 100 (32.3%) | 6 (33.3%) | 88 (32.6%) | 1.4 (0.2, 11.0) | 0.739 |
| pUPD11 | 134 (43.2%) | 10 (55.6%) | 116 (43.0%) | 1.6 (0.2, 11.8) | 0.633 |
| CDKN1C mutation | 7 (2.3%) | -- | 5 (1.9%) | N/A | N/A |
| 11p15.5 anomalies | 21 (6.8%) | -- | 15 (5.6%) | N/A | N/A |
Analysis performed in events from patients without a pre-existing airway (endotracheal tube or tracheostomy) on arrival to the operating room.
Age reported is chronological age not gestationally corrected age.
Not applicable since Generalized linear mixed-effect model did not converge for age in month and gestational age groups.
Infants defined as <1 year of age (not corrected for gestational age).
Weight measured prior to surgery and not corrected for gestational age.
BWS Genetic Subtypes: IC1 GOM (gain of methylation at imprinting control region 1); IC2 LOM (loss of methylation at imprinting control region 2); pUPD11 (paternal uniparental isodisomy of chromosome 11p15); 11p15.5 anomalies (chromosomal abnormalities involving translocations, deletions and duplications, etc); CDKN1C mutation and 11p15.5 anomalies were not included in generalized linear-mixed effect model because they have 0 difficult airway.
Abbreviations: BWS=Beckwith-Wiedemann syndrome; IQR=Interquartile range; kg=kilogram, N/A=not applicable.
Figure 1.
Flow chart illustrating patient selection.
Preoperative Characteristics
Preoperative characteristics for the group are presented in Table 2. Almost three-quarters of patients were ASA physical status III and approximately half had macroglossia documented on physical examination. The most common procedure types were general surgery, radiologic, and plastics/craniofacial. Associated comorbidities were common.
Table 2.
Preoperative characteristics of the cohort. Generalized linear mixed-effect model analysis of factors associated with difficult airway and not difficult airway events.
| Total | Airway Complexitya (n=288) |
Generalized Linear Mixed-effect modela | |||
|---|---|---|---|---|---|
|
|
|||||
| (n=310) | Difficult (n=18) |
Not Difficult (n=270) |
Odds Ratio (95%CI) |
p value | |
|
| |||||
| ASA physical status | |||||
| I | - | - | - | ||
| II | 57 (18.4 %) | 2 (11.1%) | 55 (20.5%) | Reference | Reference |
| III | 229 (73.9%) | 13 (72.7%) | 203 (75.7%) | 1.3 (0.3, 6.8) | 0.728 |
| IV | 22 (7.1%) | 3 (16.7%) | 10 (3.7%) | 5.5 (0.6, 48.8) | 0.124 |
| Eb | 9 (2.8%) | - | 8 (3.0%) | ||
|
| |||||
| Type of procedure, n (%) c | |||||
| General surgery | 101 (32.6%) | 3 (16.7%) | 90 (33.3%) | Reference | Reference |
| Medical/Line placement | 29 (9.4%) | 2 (11.1%) | 27 (10.0%) | 2.6 (0.4, 19.4) | 0.341 |
| Plastics/Craniofacial | 50 (16.1%) | 8 (44.4%) | 36 (13.3%) | 6.3 (1.4, 29.0) | 0.017 |
| Radiologic | 83 (26.8%) | 5 (27.8%) | 74 (27.4%) | 2.3 (0.5, 10.9) | 0.311 |
| ENT | 23 (7.4%) | - | 20 (7.4%) | N/A | N/A |
| Neurosurgery | 3 (1.0%) | - | 2 (0.7%) | N/A | N/A |
| Ophthalmologic | 2 (0.6%) | - | 2 (0.7%) | N/A | N/A |
| Orthopedic | 3 (1.0%) | - | 3 (1.1%) | N/A | N/A |
| Urologic | 16 (5.2%) | - | 16 (5.9%) | N/A | N/A |
|
| |||||
| Tongue reduction procedure, n (%) | 41 (13.2%) | 7 (38.9%) | 29 (10.7%) | 5.1 (1.6, 16.4) | 0.0071 |
|
| |||||
| History of prior difficult laryngoscopy, n (%) | 12 (3.9%) | 2 (11.1%) | 7 (2.6%) | 2.0 (0.3, 14.1) | 0.473 |
|
| |||||
| History of prior tongue reduction surgery, n (%) | 29 (9.4%) | 6 (33.3%) | 23 (8.5%) | 2.9 (0.7, 12.2) | 0.140 |
|
| |||||
| Preoperative History | |||||
| Anemia | 58 (18.7%) | 6 (33.3%) | 44 (16.4%) | 3.0 (0.8, 10.7) | 0.099 |
| Obstructive sleep apnead | 50 (16.1%) | 11 (61.1%) | 33 (12.3%) | 9.6 (3.0, 31.0) | 0.002 |
| Recent URI | 23 (7.4%) | - | 20 (7.4%) | N/Ae | N/Ae |
| Eczema | 1 (0.3%) | - | 1 (0.4%) | N/Ae | N/Ae |
| Second hand smoking | 2 (0.6%) | - | 2 (0.7%) | N/Ae | N/Ae |
| Associated comorbidities: | |||||
| Cardiac | 87 (28.0%) | 6 (33.3%) | 66 (24.6%) | 1.9 (0.5, 6.8) | 0.313 |
| Pulmonary | 92 (29.6%) | 6 (33.3%) | 67 (25.0%) | 1.6 (0.5, 5.5) | 0.470 |
| Renal | 98 (31.6%) | 4 (22.2%) | 89 (33.2%) | 0.8 (0.2, 3.1) | 0.765 |
| Endocrine | 141 (45.5%) | 15 (83.3%) | 109 (40.7%) | 6.0 (1.5, 23.9) | 0.012 |
|
| |||||
| Macroglossia on physical examination, n (%), missing=2 | 165 (53.2%) | 18 (100%) | 133 (49.3%) | N/Ae | N/Ae |
|
| |||||
| Omphalocele, n (%) | 74 (23.9%) | 5 (27.8%) | 61 (22.6%) | 1.4 (0.4, 5.3) | 0.651 |
|
| |||||
| Pre-medication administered, n (%), missing=6 | 104 (33.5%) | 1 (5.6%) | 97 (36.3%) | 0.14 (0.02, 1.14) | 0.065 |
Analysis performed in events from patients without a pre-existing airway (endotracheal tube or tracheostomy) on arrival to the operating room.
Emergent status: includes 6 ASA III and 1 ASA IV. Not included for airway complexity analysis.
Type of procedure of ENT, neurosurgery, ophthalmologic, orthopedic and urologic were not included in the generalized linear mixed-effect model because they did not have difficult airways events.
Defined by polysomnography.
Not applicable since generalized linear mixed-effect model did not converge for preoperative history of recent URL, eczema, second-hand smoking and macroglossia due to the empty cell in the contingency table with airway complexity.
Abbreviations: ASA=American Society of Anesthesiologists; ENT=ear, nose, and throat; N/A=not applicable; URI=upper respiratory infection.
Facemask ventilation and number of intubation attempts
The majority of the anesthetics reported easy FMV. The prevalence of difficult FMV in the entire cohort was 2.9% (95% confidence interval [CI]: 1.4% to 6.2%; 12 cases out of 277 anesthesia encounters where FMV was attempted). The prevalence of difficult intubation was 5.2% (95%CI: 2.9% to 9.4%;12 cases of 226 attempts to intubate the trachea) and the first attempt success rate was 83.8% (95%CI:77.6% to 88.5%). The number of tracheal intubation attempts and type of airway device used are shown in Tables 3 and 4.
Table 3.
Ease of mask ventilation, type of airway device, and number of attempts to successful tracheal intubation.
| Total (n=310) | Prevalence (95%CI) (estimated from mixed-effect model) | |
|---|---|---|
|
| ||
| Ease of Mask Ventilation; n (%) | ||
| Easy | 256 (82.6%) | |
| Intermediate (required an adjunct) | 9 (2.9%) | N/Ae, f |
| Difficult | 12 (3.9%) | |
| Impossible | - | |
| Not attempted/Not feasible | 33 (10.6%) | |
|
| ||
| Difficult mask ventilation a ; n/N (%) | 12/277 (4.3%) | 2.9% (1.4% - 6.2%) |
|
| ||
| Type of airway device, n (%) | ||
| Pre-existing ETT or Tracheostomy tube on arrival to the operating room | 22 (7.1%) | N/Ae |
| SGA | 62 (20.0%) | |
| ETT | 226 (72.9%) | |
|
| ||
| Number of attempts to successful intubation a ; n (%) | ||
| 1 attempt | 189 (83.6%) | |
| 2 attempts | 28 (12.4%) | N/Ag, h |
| ≥3 attempts | 8 (3.5%) | |
| Intubation attempts abandoned | 1 (0.4%) | |
|
| ||
| Difficult intubation b, c ; n/N (%) | 12/226 (5.3%) | 5.2% (2.9% - 9.4%) |
Patients in whom bag-mask ventilation was attempted (n=277).
Patients in whom endotracheal intubation was attempted (n=226).
Difficult laryngoscopy as defined by the attending anesthesiologist, Cormack and Lehane view 3 or 4, ≥ 3 attempts to intubate or the need for an advance airway technique.
Generalized linear mixed-effect model with multinomial distribution and generalized logit link function did not converge.
Generalized linear mixed-effect model with multinomial distribution and cumulative logit link function did not converge either (not attempt/not feasible were not included).
Generalized linear mixed-effect model with multinomial distribution and cumulative logit link function was used (observations with failed intubation was not included in the model).
The model shows that the adjusted proportion of number of attempts to successful intubation=1 is 83.8% (77.6% - 88.5%); and the proportion of the number of attempts to successful intubation ≤2 is 96.6% (93.1- 98.4%).
Abbreviations: ETT=endotracheal tube; SGA=supraglottic airway device; N/A=not applicable.
Table 4.
Airway management techniques and complications.
| Techniques and Complications | Total intubation attempts (n=226) |
|---|---|
| Ease of Mask Ventilation | |
| Easy without adjunct | 142 (62.8 %) |
| Easy mask ventilation with airway adjunct | 53 (23.5 %) |
| Intermediate | 8 (3.5 %) |
| Difficult | 11 (4.9 %) |
| Impossible | - |
| Not attempted | 12 (5.3 %) |
|
| |
| Intubation route | |
| Oral | 189 (83.6 %) |
| Nasal | 36 (15.9 %) |
| Abandoned intubation attempts | 1 (0.4 %) |
|
| |
| First attempt technique for intubation, n (%) | |
| Direct laryngoscopy | 161 (71.2 %) |
| Videolaryngoscopy | 43 (19.0 %) |
| Flexible fiberoptic bronchoscopy | 21 (9.3 %) |
| Combined (FOS/SGA) | 1 (0.4 %) |
|
| |
| Successful technique for tracheal intubation, n (%) | |
| Direct laryngoscopy | 160 (70.8 %) |
| Videolaryngoscopy | 45 (19.9 %) |
| Flexible fiberoptic bronchoscopy | 18 (8.0 %) |
| Combined (FOS/SGA; FOS/VL) | 2 (0.9 %) |
| Failed intubation | 1 (0.4 %) |
|
| |
| Laryngeal view a | |
| Grade 1 | 187 (82.7 %) |
| Grade 2 | 17 (7.5 %) |
| Grade 3 | 2 (0.9 %) |
| Grade 4 | 1 (0.4 %) |
| Not documented | 19 (8.4 %) |
|
| |
| Provider, n (%) | |
| Attending anesthesiologist | 33 (14.6 %) |
| Trainee | 107 (47.34 %) |
| CRNA | 80 (35.4 %) |
| ENT surgeon/other | 6 (2.6 %) |
|
| |
| Change of provider needed to intubate, n (%) | 8 (2.6 %) |
|
| |
| Duration of induction (mins), median [IQR] | 7.0 [5.0-10.0] |
|
| |
| Neuromuscular blockade use, n (%) | 152 (67.2 %) |
|
| |
| Use of apneic oxygenation | 14 (6.2 %) |
|
| |
| Complications, n (%) | |
| Hypoxemia | 34 (15.0 %) |
| Laryngospasm | - |
| Bronchospasm | 1 (0.4 %) |
| Esophageal intubation with immediate recognition | 1 (0.4 %) |
| Emergent surgical airway | - |
Modified Cormack and Lehane classification. All reported direct laryngoscopy views were included.
Abbreviations: FOS/SGA= Fiberoptic scope intubation through a supraglottic airway; FOS/VL=fiberoptic scope and videolaryngoscopy; CRNA=certified nurse anesthetist; ENT=ear, nose, and throat.
Difficult Airway
The prevalence of difficult airways was 5.3 % (95%CI 3.0% to 9.3%; 18 of 288 events). These events occurred in 13 different patients, representing 10.7% of the total 122 patients in the cohort. In the cases with difficult airway (n=18), one of the patients experiencing difficult FMV was successfully rescued with an SGA that was kept as the primary airway device. Techniques for tracheal intubation included DL (27.8%; 5/18), VL (33.3%; 6/18) and FOS alone or in combination with VL or an SGA (33.3%; 6/18). Nasal ETT was more commonly used in the difficult airway group than in the non-difficult group (27.8% vs 11.5%). No patient in the study needed an emergent surgical airway. Three patients underwent ETT exchange in the operating room.
Demographic and preoperative variables associated with difficult airway were age less than 1 year, lower weight (measured on the day of surgery and not corrected for gestational age), plastics/craniofacial surgery, patients undergoing tongue reduction surgery, obstructive sleep apnea, and endocrine comorbidities (e.g. hyperinsulinism, hypoglycemia, etc.) (Table 1 and 2). One patient had Pierre Robin Sequence in addition to BWS and was included in the difficult airway group. Macroglossia was reported in the pre-operative evaluation of all the cases in which the airway was difficult.
Airway Management and Intubation Techniques
A total of 226 anesthetics documented endotracheal intubation in the operating room. Table 4 presents different variables related to airway management, intubation techniques and complications. The majority of the anesthetics reported easy FMV. The most common intubation route was oral and the most successful technique was DL. Neuromuscular blockade was used in more than half of the anesthetics, and apneic oxygenation was rarely used. Complications were infrequent with the exception of hypoxemia, which occurred in 15% (34/226) of intubations.
Adjuncts for tracheal intubation included oral airways, nasopharyngeal airways and in one case a SGA that was used as a conduit for FOS tracheal intubation. Other assistive maneuvers for tracheal intubation included jaw thrust and placement of a shoulder roll. Supplemental Table 1 presents the types of blade used for DL and VL attempts. The majority of events used a Miller or Wis-Hipple blade for DL attempts and a Miller type VL or Glidescope Cobalt for VL attempts.
Images in Supplemental Figure 1 (included in supplemental material) were obtained from an infant scheduled for hemiglossectomy. The patient presented with right lateralized overgrowth of the entire body. Supplemental Figure 1B shows the laryngeal view obtained during rigid bronchoscopy. Mask ventilation was easy and the patient was intubated on the first attempt.
Intraoperative Management
Supplemental Table 2 shows intraoperative anesthetic management and complications. In half of the cases, inhalational induction and neuromuscular blockade were used. Apneic oxygenation was infrequent and administration of opioids during the procedure was common. Hypoxemia during induction occurred in 35 anesthetics but intraoperative complications were uncommon (Supplemental Table 2).
The use of apneic oxygenation and anticholinergic agents was significantly more common in the difficult airway patients (33.3% vs. 3.4%, odds ratio [OR] 16.2, 95%CI 4.0 to 65.0, p<0.001; and 50% vs. 8.1%, OR 11.4, 95%CI 3.5 to 36.9, p<0.001; respectively). Hypoxemia during induction was also significantly more common in difficult airway patients, occurring in more than half of the anesthetics (61.1% vs. 8.9%, OR 16.9, 95%CI 5.0 to 57.1, p<0.001). Intraoperative hypoxemia also occurred more often when difficult airway was encountered.
Macroglossia (Sub-group analysis)
Macroglossia was reported on preoperative physical examination in 53.2% of the patients and was present in all cases of difficult airway. Patients with macroglossia also required multiple intubation attempts (23.0% vs. 7.1%, OR 3.9, 95%CI 1.6 to 9.6, p=0.0033), and experienced higher frequencies of hypoxemia during intubation (19.7% vs. 9.1%, OR 2.5, 95%CI 1.0 to 6.2, p=0.046), but did not differ in other complications such as bradycardia and hypotension, or intraoperative hypoxemia.
Airway complexity analysis in events with macroglossia
In patients with macroglossia without a pre-existing airway (n=151), the prevalence of difficult FMV was 6.0% (95%CI 2.7% to 12.7%) and difficult intubation was 9.4% (95%CI 5.2% to 16.5%). Demographic and preoperative variables associated with difficult airway were lower weight on the day of surgery, higher frequencies of OSA, endocrine comorbidities, and anemia (Supplemental Table 3A and 3B. No other analyzed factors were significant, including factors that were identified as significant in the larger cohort (infant, plastic/craniofacial surgery and tongue reduction procedure).
DISCUSSION:
We discovered that although most patients with BWS can be ventilated using a face mask and intubated using conventional laryngoscopy by pediatric anesthesiologists there remains a subset of patients that have an increased risk of difficult FMV and difficult laryngoscopy. Patients with macroglossia experienced a higher prevalence of difficult FMV, difficult intubation, multiple intubation attempts and hypoxemia; reinforcing the notion that macroglossia might be a contributing factor to difficulty with airway management.
Several case reports have associated BWS with difficult airway. Kim et al13 described the management of 2 patients with BWS, in both cases direct laryngoscopy was described as easy, but mask ventilation was difficult in one of the patients. Nargozian10 described that the large tongue in patients with BWS makes laryngeal visualization difficult and recommended avoiding mask ventilation as well as keeping the patient intubated post-procedure. In our study the prevalence of difficult FMV was 2.9% (95% CI: 1.4% to 6.2%), which is similar to the prevalence of difficult FMV reported in the general pediatric population (of 5-6%) 14, 15.
The prevalence of difficult intubation in our cohort was 5.2% (95%CI:2.9% to 9.4%) which seems higher than the prevalence in the general pediatric population of 2% 16. Interestingly, most patients in our cohort were easy to intubate. Factors associated with a difficult airway included macroglossia, age less than 1 year, lower weight, plastic/craniofacial surgery, tongue reduction surgery, history of OSA, and endocrine comorbidities. Analysis of patients with macroglossia showed that anemia, history of OSA, and endocrine comorbidities were associated with difficult airway. Patients with BWS have been reported to have a higher incidence of sleep disordered breathing (SDB) with an increased risk in premature infants17. Additionally, the prevalence of macroglossia was not previously found to significantly differ in the presence of SDB within the BWS population, and it has been suggested that airway obstruction is not caused solely by macroglossia (17). Higher BWS clinical diagnostic scores in infants with BWS appear to correlate with the severity of OSA, more than to other characteristics such as macroglossia or genetic subtype, suggesting a multifactorial basis for airway obstruction in this population18–20. Sleep studies prior to anesthetics would likely be useful in patients to assess for OSA. Further research is needed to determine whether these associations are influenced by other confounding factors.
Additional reported issues that may complicate the anesthetic care of patients with BWS include smaller tracheal diameter than anticipated21, tracheomalacia8, and congenital cardiac disease9. In our study we did not find an association between the presence of cardiac comorbidities and difficult airway, but we did not stratify by severity of cardiac disease. Naujokat et al22 described a cohort of 44 children with severe macroglossia that underwent tongue reduction, respiratory complications occurred in 7% of the patients and no reintubations were reported. In our cohort the most common respiratory complication was hypoxemia. The prevalence of severe adverse events was low and there were no episodes of cardiac arrest during anesthetic management.
Our study has some limitations. First, all the data came from a single institution and our findings may reflect institutional biases. Secondly, the retrospective nature of our study increases the possibility of relative under or overreporting of findings. Furthermore, our study analyzes a rare disorder with a low occurrence of difficult airway, which limits the number of patients available for analysis, and our ability to control for confounding factors. Our finding of mostly favorable airway management should be interpreted with caution since we excluded 22 patients whose airways were secured prior to their anesthetic. This may have resulted in a selection bias as those patients may have been more severe and may have had very difficult airways. Finally, incomplete or erroneous documentation or omissions in the electronic medical records may have affected our results. We thought it was important to control the analysis for macroglossia as BWS is a spectrum and the extent of macroglossia can be variable. Clinicians may have only documented macroglossia when severe thereby introducing a recall bias in our data set.
Conclusion:
We determined the prevalence of difficult tracheal intubation and ventilation in patients with BWS and demographic and preoperative variables associated with difficult airway were identified. These factors included macroglossia, age less than 1 year, lower weight, history of OSA, endocrine comorbidities, and tongue reduction surgery. Clinicians should prepare for difficult airway management in BWS patients with these factors.
Supplementary Material
Supplemental Figure 1. Patient with Beckwith-Wiedemann syndrome affected by right lateralized overgrowth and macroglossia (A). Laryngeal view obtained during rigid bronchoscopy (B).
Key Points:
Question:
What is the prevalence of difficult airway in children with Beckwith-Wiedemann syndrome (BWS)?
Findings:
Of 310 anesthetic events, tracheal intubation was achieved on the first attempt in 83.8 % of the cases, the prevalence of difficult intubation was 5.2%, and the prevalence of difficult facemask ventilation was 2.9%.
Meaning:
There is a subset of patients with BWS that have difficult airway; however, the majority of patients were easy to mask ventilate and easily intubated in a tertiary children’s hospital.
Acknowledgement:
LSR and KAD are co-first authors. AP and JMK are co-senior authors. We would like to thank the patients and their families for participating in the BWS registry. We would like to acknowledge the Department of Anesthesiology and Critical Care Medicine at the Children’s Hospital of Philadelphia for its supporting efforts. We thank Dr. Murray Kalish for his critical reading of the manuscript.
Funding:
The study was supported by internal funding from the Department of Anesthesiology and Critical Care Medicine at CHOP, NIH K08 CA193915 (JMK), and the BWS registry (supported by the Victoria Fertitta Fund through the Turtle Chair for Beckwith-Wiedemann Syndrome Research).
GLOSSARY:
- BWS
Beckwith-Wiedemann syndrome
- FMV
facemask ventilation
- ETT
endotracheal tube
- OSA
obstructive sleep apnea
- SGA
supraglottic airway device
- DL
direct laryngoscopy
- VL
videolaryngoscopy
- FOS
flexible fiberoptic scope
- IQR
interquartile range
- GLMM
generalized linear mixed-effect models
- ASA
American Society of Anesthesiologists
- OR
odds ratio
- CI
confidence interval
- SDB
sleep disordered breathing
Footnotes
Financial Disclosures: None
Conflict of Interest Statement
The authors have no conflicts of interest to disclose.
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Supplementary Materials
Supplemental Figure 1. Patient with Beckwith-Wiedemann syndrome affected by right lateralized overgrowth and macroglossia (A). Laryngeal view obtained during rigid bronchoscopy (B).