Subglottic post-extubation upper airway obstruction is associated with long-term airway morbidity in children

Abstract

Objective:

Post-extubation upper airway obstruction (UAO) is the most common cause of extubation failure in children, but there are few data regarding long-term morbidity. We aim to describe the frequency of long-term airway sequelae in intubated children and determine the association with post-extubation UAO.

Design:

Retrospective, post hoc analysis of previously identified prospective cohort of children in the pediatric/cardiothoracic ICU at Children’s Hospital Los Angeles from July 2012-April 2015. A single provider blinded to the UAO classification reviewed the electronic medical records of all patients in the parent study, before and after the index extubation (extubation during parent study), to identify pre-index and post-index upper airway disease. Primary outcomes was prevalence of newly diagnosed airway anomalies following index extubation.

Setting:

Single center, tertiary, 391-bed children’s hospital

Patients:

From the parent study, 327 children younger than 18 years (intubated for at least 12 hours) were included if they received subsequent care (regardless of specialty) after the index extubation.

Interventions:

none

Measurements and main results:

New airway anomalies were identified in 40/327 (12.2%) children. Patients labeled with subglottic UAO at the index extubation were more likely to be diagnosed with new airway anomalies on subsequent follow-up, receive long-term ENT follow-up, or receive airway surgery (all p≤0.006). In multivariable modeling, UAO as the primary reason for initial intubation [OR 3.71, CI 1.50-9.19], re-intubation during the index ICU admission [OR 4.44, CI 1.67-11.80], pre-index airway anomaly [OR 3.31, CI 1.36-8.01], and post-extubation subglottic UAO [OR 3.50, CI 1.46-8.34] remained independently associated with the diagnosis of new airway anomalies.

Conclusions:

Post-extubation subglottic upper airway obstruction is associated with a three-fold greater odds of long-term airway morbidity. These patients may represent an at-risk population that should be monitored closely after leaving the ICU.

I. Introduction

Post-extubation upper airway obstruction (UAO) is the most common cause of extubation failure in children (1). While recent data highlight that UAO is also common after extubation in adults (2–6), children have always been considered to be higher risk for short-term complications like re-intubation, prolonged mechanical ventilation, longer hospital/intensive care unit (ICU) stay, and higher health care costs and resource utilization (7–9). Long-term sequelae of post-extubation UAO are not well characterized in children, and the limited published literature has not consistently found that post-extubation UAO is a risk factor for longer term complications (10–11).

Using a physiologic tool with esophageal manometry and respiratory inductance plethysmography (RIP), we have shown that nearly half of the cases of post-extubation UAO in children are supraglottic in nature, although many are labeled by treating clinicians as “stridor” and are treated with corticosteroids and racemic epinephrine (12). Furthermore, we showed that the risk factors for developing subglottic versus supraglottic post-extubation airway obstruction differ. We believe that subjectivity in the assessment of UAO after extubation, and imprecise differentiation of supraglottic from subglottic causes of the obstruction, may contribute to uncertainty regarding the long-term effects of post-extubation UAO (13). We sought to describe the frequency of long-term airway sequelae in a cohort of endotracheally intubated children, and determine whether they were associated with acute post-extubation upper airway obstruction (either subglottic or supraglottic). We hypothesized that patients with subglottic post-extubation UAO would require more airway sub-specialty follow-up, would be at risk for developing new airway anomalies, and would require more surgical airway interventions.

II. Methods

This was a retrospective, post hoc analysis of a previously identified prospective cohort of endotracheally intubated children in the pediatric ICU or cardiothoracic ICU at Children’s Hospital Los Angeles (CHLA) from July 2012 to April 2015. For the original study, patients were eligible if they were between 37 weeks gestational age and 18 years and intubated for at least 12 hours with planned extubation between 7:00 AM and 5:00 PM on weekdays. This was a convenience sample because limited funding precluded having research staff available for night and weekend coverage. Children were excluded if there were contraindications to esophageal catheter or respiratory inductance plethysmography (RIP) bands. Informed consent was obtained from the parent or guardian. In the original study, inspiratory flow limitation after extubation was characterized from RIP/esophageal manometry and used to label the patient with tool-assessed post-extubation UAO. UAO was further categorized as supraglottic if inspiratory flow limitation and effort of breathing (pressure-rate product from esophageal manometry) improved by at least 50% with an Esmarch’s (jaw thrust) maneuver. The pressure-rate product is calculated as the respiratory rate/min * peak-to-trough change in esophageal pressure with inspiratory effort. All other cases of UAO were labeled as subglottic. Further details about study methodology have been previously published (12).

For the current study, which the CHLA Institutional Review Board (IRB) reviewed and approved (# CCI-11-00210-AM009), a single provider blinded to the UAO classification reviewed the electronic medical records of all enrolled patients in the parent study during the academic 2017-2018 year, before and after the index extubation, to identify any evaluation of the upper airway. The term “index extubation” describes the first extubation while enrolled in the parent study when the patient had esophageal pressure and RIP monitoring. We defined the term “new airway anomaly” as any abnormal evaluation of the upper airway noted following the parent study, not previously diagnosed (see limitations in Discussion section). Classifications of newly diagnosed airway anomalies were recorded based on laryngoscopy/bronchoscopy reports. If a prior airway anomaly was noted in the patient record before the index extubation, subsequent findings were termed “new airway anomaly” if they were anatomically different than those diagnosed prior to the index extubation (e.g.: mild subglottic stenosis progressing to severe subglottic stenosis would not be classified as a newly diagnosed airway anomaly, whereas subglottic stenosis found after laryngomalacia would be classified as a newly diagnosed airway anomaly). Patients were included in this follow-up cohort if they received any subsequent care (regardless of specialty) after the index extubation at CHLA. All inpatient and outpatient Otolaryngology (ENT), Pulmonology and operating room (OR) visits were reviewed to determine whether the patient was diagnosed with pre-existing upper airway or pulmonary anomalies (before the index extubation), whether they were subsequently diagnosed with new anomalies after the index extubation, whether they received long-term ENT or Pulmonology sub-specialty follow-up, and whether they received subsequent operative interventions such as tracheal dilations or tracheostomy. Additional data included patient demographics, co-morbidities, reason for intubation, intubation data, extubation data and post-extubation interventions such as need for heliox or racemic epinephrine.

Our primary outcome was pre-specified as the diagnosis of a new airway anomaly (categorical yes/no) found on bronchoscopy by ENT or Pulmonology, or in the OR by Anesthesiology, that was identified for the first time after the index extubation. This outcome was chosen as the reference standard given that laryngoscopy/bronchoscopy is the accepted standard to diagnose such lesions. Secondary outcomes included ENT follow-up, Pulmonology follow-up, and airway surgery.

We sought to (1) describe the frequency of new airway anomalies after intubation in the PICU or cardiac ICU, (2) identify if they were independently associated with post-extubation UAO following the index extubation (subglottic and supraglottic, pre-specified yes/no categorical outcome) and (3) determine if we could identify patients who may be at high risk for anomalies which would warrant routine ENT follow-up.

We report descriptive statistics for the entire cohort, stratified by the primary outcome as well as by the presence of UAO following the index extubation. Categorical variables are reported as count and percentage and were analyzed with the Pearson’s χ² or Fisher Exact Test. Continuous variables were reported as median (interquartile range) and analyzed with a Mann-Whitney U test or Kruskall Wallis ANOVA for multiple groups. Univariate odds ratios and likelihood ratios were also reported. Finally, we created a multivariable logistic regression model using variables which had a univariate association with new airway anomaly or post-extubation UAO (p<0.2), retaining those with an independent relationship (p<0.05) in the final model. Variables could also be retained if they had a significant confounding effect on the relationship (changed the parameter estimate by at least 20%) between the main variable of interest, subglottic UAO, and newly diagnosed airway anomaly. Multiplicative interaction terms were also considered for model inclusion. When variables were highly correlated, we retained the variable with the strongest univariate association with outcome in the final model and created a correlation matrix evaluating variables which were strongly associated with one another. Model performance was assessed with the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) plot and the Hosmer-Lemeshow test, although the primary goal was not to create a predictive model, but rather to determine whether subglottic UAO following the primary intubation was independently associated with post-ICU airway morbidity. We restricted the number of variables included in the final multivariable model to approximately 1 variable per 10 cases of the outcome of interest. Analysis was performed in Statistica (TIBCO Software Inc, Palo Alto CA) version 13.1 and Stata (Statacorp, College Station, Texas) version 15.1. The Standards for Reporting Diagnostic Accuracy Studies (STARD) checklist was used for transparency in reporting and is attached in the supplementary materials (14–16).

III. Results

A total of 409 patients were present in the parent study, and 327 were seen in follow-up at CHLA and included in the analysis. Approximately half of the children were post-operative from cardiac surgery. There were no significant differences in age, weight, endotracheal tube size, duration of mechanical ventilation, prevalence of post-extubation subglottic UAO, re-intubation rate, and PICU length of stay between the 327 patients with follow-up and the 82 patients who did not have follow-up at our institution (p>0.1) (Supplemental Table 1).

New airway anomalies were identified in 40/327 (12.2%) children after the index extubation. The most common lesions were vocal fold paralysis, laryngomalacia, and subglottic stenosis (Table 1, Figure 1). Several children had more than 1 newly diagnosed lesion (55 lesions identified amongst 40 patients). When stratifying by UAO following the index extubation, 43 (13.1%) children had subglottic UAO, 38 (11.6%) had supraglottic UAO, and 246 (75.2%) had no UAO. Patients with subglottic UAO had higher rates of new airway anomalies (15/43, 34.9%) compared to those with supraglottic disease (6/38, 15.8%) or no UAO (19/246, 7.7%) (Table 2, Table 4, Figure 2). On univariate analysis, subglottic UAO was associated with a five-fold increased risk (OR 5.55 [CI 2.62-11.74], p<0.001) of being diagnosed with a new airway anomaly than those without subglottic UAO. The presence of subglottic UAO was associated with a positive likelihood ratio of 3.97 for the diagnosis of a new airway anomaly.

Table 1.

Newly diagnosed airway anomalies observed after index extubation. Data are presented as number (percentage)

Airway Anomalies	Total # of patients (N = 40 discrete cases)	Cardiac cohort	Non-cardiac cohort
Vocal fold paralysis	17 (30.9%)	14 (82.4%)	3 (17.6%)
Laryngomalacia	16 (29.1%)	7 (42.8%)	9 (56.2%)
Subglottic stenosis	12 (21.8%)	7 (58.3%)	5 (41.7%)
Bronchomalacia	6 (10.9%)	4 (66.7%)	2 (33.3%)
Tracheomalacia	4 (7.3%)	1 (25%)	3 (75%)
Concurrent malacia + subglottic/vocal cord lesion	13 (23.6%)

Figure 1.

(a) Case of a one-month-old male with aortic arch hypoplasia and cleft lip post-cardiac surgery. He was found to have tool-assessed subglottic UAO after index study extubation and taken to the OR for bronchoscopy with findings showing a considerable amount of arytenoid edema with prolapse into the glottic airway causing obstruction. He ultimately required tracheostomy. (b) Case of a six-week-old female with hypoplastic left heart syndrome post-cardiac surgery, also found to have tool-assessed subglottic UAO after index study extubation. Initial workup for stridor included multiple bedside flexible laryngoscopies with no significant pathology. Eight months later, she was taken to the OR for formal bronchoscopy with findings showing glottic band at the inferior border of the posterior aspect of the true vocal folds, which is thick and narrowing the airway to about a 4 mm diameter, requiring band excision.

figure 1A – small arrow represents left vocal fold granuloma, large arrow represents arytenoid edema with prolapse; figure 1B – arrow represents very thick glottic band causing airway narrowing

Table 2.

Selected univariate risk factors for the development of newly diagnosed airway anomalies compared to those without. Data are presented as median (1^st, 3^rd Interquartile Range) or number (percentage).

Risk Factors	New Anomaly [n = 40 (12%)]	No New Anomaly [n = 287 (88%)]	Total [n = 327 (100%)]	p value
Demographics
Age, 1-6 months	25 (62.5%)	117 (40.8%)	142 (43.3%)	0.009
Age, 6-18 months	5 (12.5%)	41 (14.3%)	46 (14.1%)	0.76
Age, 18 months-5 years	3 (7.5%)	36 (12.5%)	39 (11.9%)	0.36
Age, > 5 years	3 (7.5%)	44 (15.3%)	47 (14.4%)	0.19
Weight, kg	4.3 (3.5 to 6.6)	6 (3.5 to 11.7)	5.6 (3.5 to 11.1)	0.11
Male gender	25 (62.5%)	167 (58.2%)	192 (58.7%)	0.60
Ethnicity (Hispanic vs. not)	21 (52.5%)	181 (63.3%)	202 (62%)	0.30
Genetic syndrome	10 (25%)	45 (15.7%)	55 (16.8%)	0.14
Pre-index airway   anomaly	15 (37.5%)	32 (11.1%)	47 (14.4%)	< 0.0001
Reason for primary intubation
UAO	15 (37.5%)	23 (8%)	38 (11.6%)	< 0.0001
Cardiac surgery	15 (37.5%)	149 (51.9%)	164 (50.2%)	0.09
Shock	2 (5%)	26 (9.2%)	28 (8.6%)	0.39
Neurologic	6 (15%)	51 (17.8%)	57 (17.4%)	0.67
Extrathoracic disease	0 (0%)	23 (8%)	23 (7%)	0.06
Lower airways disease	2 (5%)	7 (2.4%)	9 (2.75%)	0.35
Parenchymal lung disease	4 (10%)	26 (9.1%)	30 (9.2%)	0.85
Intubation data
No. intubation  attempts				0.70
1	30 (88.2%)	198 (84.6%)	228 (85.1%)
2	3 (8.8%)	22 (9.4%)	25 (9.3%)
3	0 (0%)	5 (2.1%)	5 (1.9%)
4	1 (2.9%)	3 (1.3%)	4 (1.5%)
5	0 (0%)	6 (2.6%)	6 (2.2%)
Traumatic intubation	3 (8.1%)	16 (6.1%)	19 (6.4%)	0.64
ETT size (mmID)	3.5 (3.5 to 4)	4 (3.5 to 4.5)	4 (3.5 to 4.5)	0.009
Cuffed ETT	11 (27.5%)	124 (43.2%)	135 (41.3%)	0.06
Leak at intubation	24 (82.8%)	144 (81.8%)	168 (82%)	0.90
Day of extubation data
Pre-extubation steroid use	11 (32.4%)	31 (13%)	42 (15.4%)	0.003
MV > 48 hours	32 (80%)	187 (65.2%)	219 (67%)	0.06
DMV, h	150 (60.5 to 220.5)	96 (29.5 to 186.5)	98 (32.5 to 192)	0.038
Outcomes
Re-intubation in ICU	12 (30%)	18 (6.3%)	30 (9.2%)	< 0.0001
NIV after extubation	23 (57.5%)	103 (35.9%)	126 (38.5%)	0.009
Post-extubation steroid   use	10 (25%)	32 (11.2%)	42 (12.8%)	0.01
Racemic epinephrine after   extubation	17 (42.5%)	49 (17.1%)	66 (20.2%)	< 0.0001
Post-extubation subglottic   UAO	15 (37.5%)	28 (9.8%)	43 (13.2%)	< 0.0001
PICU LOS, d	4.6 (2.6 to 13.3)	3.5 (2.5 to 5.6)	3.55 (2.5 to 6.4)	0.005
Overall LOS, d	15.7 (9.5 to 24)	8.8 (4.2 to 16.1)	9.1 (4.3 to 17)	0.0005

Abbreviations: UAO = upper airway obstruction, mmID = internal diameter in millimeters, ETT = endotracheal tube, MV = mechanical ventilation, DMV = duration of mechanical ventilation, NIV = non-invasive ventilation, LOS = length of stay

Table 4.

Multivariable logistic regression model for newly diagnosed airway anomalies

Factors	OR	95% CI	p value
Post-extubation subglottic UAO	3.50	1.46-8.34	0.005
Re-intubation during index ICU admission	4.44	1.67-11.80	0.006
Pre-index airway anomaly	3.31	1.36-8.01	0.008
Diagnosis UAO pre-intubation	3.71	1.50-9.19	0.008

OR = odds ratio, CI = confidence interval

AUC, ROC = 0.79, Hosmer-Lemeshow p=0.19

Other variables considered for inclusion in the final model but removed either because they did not retain an association with outcome or did not meet criteria for confounding: age (1-6 months); cardiac surgery; ETT size; pre-extubation steroid use; NIV after extubation; post-extubation steroid use; racemic epinephrine after extubation; MV > 48 hours; overall LOS

Figure 2.

STARD (Standards for Reporting of Diagnostic Accuracy Studies) flow diagram

In addition to subglottic UAO following the index extubation, other univariate risk factors for new airway anomaly included: age 1-6 months (OR 2.42 [CI 1.22-4.79], p=0.009), pre-index airway anomaly (OR 4.78 [CI 2.29-10.00], p<0.0001), primary intubation for UAO (OR 6.9 [CI 3.19-14.87], p<0.0001), smaller ETT size (3.5 mmID [IQR 3.5, 4; range 3.0, 6.0] vs. 4 mmID [IQR 3.5, 4.5; range 2.5, 7.5], p=0.009), use of pre-extubation steroids [OR 3.13 [CI 1.42-6.88], p=0.003), re-intubation during index ICU stay (OR 6.40 [2.80-14.64], p<0.0001), post-extubation steroids (OR 2.66 [CI 1.19-5.95], p=0.01), racemic epinephrine after extubation (OR 3.59 [CI 1.79-7.22], p<0.0001), and longer overall length of stay (15.7 days [IQR 9.5, 24] vs. 8.8 days [IQR 4.2, 16.1], p=0.0005). The presence of supraglottic UAO, number of intubation attempts, leak at intubation or extubation, the use of a cuffed ETT, duration of mechanical ventilation, cardiac surgery and co-morbidities were not associated with the diagnosis of new airway anomalies (all p>0.05, Table 2).

On multivariable analysis, UAO as the primary reason for initial intubation (OR 3.71 [CI 1.50-9.19], p=0.008), re-intubation during the index ICU admission (OR 4.44 [CI 1.67-11.80], p=0.006), post-extubation subglottic UAO (OR 3.50 [1.46-8.34], p=0.005), and pre-index airway anomaly (OR 3.31 [1.36-8.01], p=0.008] remained independently associated with the diagnosis of new airway anomalies (Table 4).

Outcomes are presented in Table 3, stratified by UAO type following the index extubation. The presence of subglottic UAO was associated with higher likelihood of long-term ENT follow-up (OR 4.36 [CI 2.13-8.90], positive likelihood ratio 3.10) and airway surgery such as tracheostomy or tracheal dilation (OR 3.59 [CI 1.44-8.92], positive likelihood ratio 3.33). The most common airway surgeries included tracheostomy, tracheal dilation, granuloma debridement, and supraglottoplasty. Patients with subglottic UAO (6/43, 14%) were more than 3 times more likely (OR 3.68 [CI 1.30-10.40]) to receive tracheostomy compared to those with supraglottic UAO (2/38, 5.3%) or no UAO (10/246, 4.1%), with a positive likelihood ratio of 3.33. Pulmonology follow-up did not differ substantially based on UAO following the index extubation.

Table 3.

Outcomes comparing post-extubation UAO to those without UAO. Data are presented as number (percentage)

Outcomes	Subglottic UAO [n = 43]	Supraglottic UAO [n = 38]	No UAO [n = 246]	Total [n = 327]	p value
Newly diagnosed airway anomalies	15 (34.9%)	6 (15.8%)	19 (7.7%)	40 (12.2%)	< 0.001
Long term ENT follow-up	16 (37.2%)	6 (15.8%)	28 (11.4%)	50 (15.3%)	< 0.001
Need for airway surgery	6 (14%)	2 (5.3%)	10 (4.1%)	18 (5.5%)	0.006
Tracheostomy	6 (14%)	2 (5.3%)	10 (4.1%)	18 (5.5%)
Tracheal dilation	3 (7%)	0 (0%)	1 (0.4%)	4 (1.2%)
Glottic/subglottic granuloma debridement	6 (14%)	1 (2.6%)	5 (2%)	9 (2.8%)
Supraglottoplasty	0 (0%)	2 (5.3%)	5 (2%)	7 (2.1%)
Long term Pulmonology follow-up	7 (16.3%)	6 (15.8%)	22 (8.9%)	35 (10.7%)	0.22

IV. Discussion

We have found that approximately 12% of children who are intubated in the PICU are later diagnosed with an airway anomaly, and close to 5% go on to receive an airway specific surgery. A large proportion of these lesions occur at the level of the glottis/subglottis, although a significant proportion of patients had concurrent supra- and subglottic pathology. We found that subglottic post-extubation UAO, re-intubation, pre-index airway anomaly, and pre-intubation UAO are independently associated with subsequent diagnosis of airway anomalies, each associated with a roughly three-fold greater odds of airway anomaly.

Endotracheal intubation remains one of the most common supportive therapies in critically ill children. While short-term complications from intubation are well described, longer term sequelae have been incompletely characterized, including identifying children who may be at high risk for long-term airway abnormalities. We have shown that being intubated for UAO, the presence of an already existing airway anomaly, and the presence of post-extubation subglottic UAO is associated with a much higher risk of long-term airway sequelae, with a positive likelihood ratio of close to 4. Nearly 35% of patients who had subglottic UAO after extubation went on to receive ENT follow-up, and 14% had an airway surgery. Interestingly, many patients with known airway anomalies had additional, distinct airway anomalies after endotracheal intubation. While this is an observational study and we cannot conclude this is a causal relationship, the magnitude of this association is high and warrants further study. Furthermore, it also suggests that the diagnosis of post-extubation subglottic UAO should be communicated with primary care physicians, so that appropriate follow-up and potential referral to ENT can be made in a timely fashion, given these patients are at high risk.

We also found that children who had supraglottic causes of post-extubation UAO were not at higher risk for long-term airway anomalies. For this study, we have objective criteria to define UAO and label it as subglottic versus supraglottic, based on esophageal manometry and respiratory inductance plethysmography. In particular, supraglottic UAO was differentiated from subglottic UAO based on response to an airway maneuver (jaw thrust). While there may be merits to implementation of this UAO tool routinely, this is not the reality for most clinicians. However, based on our findings it is important to clinically differentiate subglottic from supraglottic disease, as both short- and long-term outcomes are worse for those with subglottic disease. Gauging clinical response to a jaw thrust maneuver should therefore be a routine procedure in anyone with suspected post-extubation UAO.

Infants have long been believed to be at highest risk for both supraglottic and subglottic airway obstruction due to a relatively larger tongue and occiput, and a long-held belief that the pediatric airway is conical and narrowest at the level of the cricoid (17). While recent data highlight that other parts of the subglottis may be more narrow (18–19), the cricoid cartilage is more immobile and rigid than other parts of the subglottic space, making it relevant for endotracheal tube selection and post-extubation UAO (20). We found that infants less than 6 months of age had a 21% absolute risk for being diagnosed with new airway anomalies, although age was not an independent risk factor in multivariable modeling. Approximately half of the infants in our study were post-operative cardiac patients, which may explain higher rates of vocal fold pathology due to risk of recurrent laryngeal nerve injury during congenital heart surgery (21). Cardiac surgery itself was also not a specific risk factor for either UAO or new airway anomaly.

Re-intubation was independently associated with greater odds of long-term airway anomalies, although the number of intubation attempts was not, as some have previously reported (22–23). Re-intubation may reflect that the patient has developed an airway anomaly as part of the primary intubation, with the re-intubation being a surrogate for that anomaly. We also found no association between cuffed endotracheal tubes and higher risk of long-term airway anomalies. There is historical prejudice against cuffed tubes in infants and small children due to concerns for acute mucosal damage to the subglottic area (24). We (25–26) and others (27) have shown that with careful sizing, modern cuffed endotracheal tubes are safe in the short term and our current study highlights no increased risk of long-term sequelae.

Our study’s limitations include its partially retrospective design and single center nature. We included a convenience sample of patients extubated during daytime hours throughout the week, due to limitations in study funding. It is possible that patients with UAO are less likely to be extubated during night and weekend hours, which may over-estimate our prevalence of post-extubation UAO. While 80% of patients were captured for follow-up at CHLA, it is possible that patients received ENT, Pulmonology or other operative care at another institution. This would be unusual based on our geographic location and insurance models, and we found no difference between patients with and without routine follow-up. While we focused on newly diagnosed airway anomalies after the index extubation, we cannot definitively attribute the intubation to the new airway anomaly, as some of these lesions could have been present prior to the index extubation but never diagnosed (28). Further, there is a likelihood of residual confounding from events which may have occurred subsequent to the index extubation. The differentiation of subglottic from supraglottic UAO was based on an objective physiologic tool before and after a jaw thrust maneuver. As such, it is possible that there were discrepancies between the physiological (i.e. functional) characterization immediately post-extubation, compared to a visual (i.e. bronchoscopic) diagnosis at a later time. Time to diagnosis after the index extubation was also not quantified. Finally, patients likely had clinical symptoms prompting referral to ENT or Pulmonology specialists, so our study design is likely only detecting the most clinically significant lesions. We cannot quantify if there would be benefit to earlier identification and treatment with more routine follow-up post ICU discharge, although one could speculate that this is likely to be true. Moreover, we cannot determine whether routine follow-up would result in a high false positive rate. These should be areas of future investigation.

In conclusion, we demonstrated that post-extubation subglottic UAO is associated with a three-fold greater odds of long-term upper airway anomalies or new airway surgery. The presence of subglottic post-extubation UAO was associated with a positive likelihood ratio of almost 4 with regards to presence of a newly diagnosed airway anomaly, making it a potentially valuable diagnostic aid to identify an at-risk population that may benefit from longitudinal monitoring in the outpatient setting. A multi-disciplinary approach involving communication between ICU practitioners and general pediatricians and airway subspecialists may be valuable for these patients.

Report in Context.

• Long-term consequences of post-extubation upper airway obstruction (UAO) in children have not been well characterized.

• The subjective nature of the diagnosis of post-extubation UAO may contribute to imprecision in understanding long-term consequences.

• Using an objective physiologic tool to accurately label post-extubation UAO, we have found that post-extubation subglottic UAO in the ICU is independently associated with a 3-fold higher risk of long-term airway sequelae.

At the Bedside.

• A jaw thrust maneuver can be a clinically useful part of the physical examination to better delineate supraglottic vs. subglottic upper airway obstruction (UAO) in a child with UAO after extubation.

• The diagnosis of post-extubation subglottic UAO may signify the potential for persistent upper airway disease beyond the immediate post-extubation phase of a child’s illness.

• Clinicians who suspect post-extubation subglottic UAO, even only after 48 hours of mechanical ventilation, should communicate this information with primary care providers, and have a low threshold to consult ENT or pursue a diagnostic airways evaluation.