Tracheal intubation remains one of the most common life-saving procedures provided to critically ill children (1–3) and is often required to stabilize a patient prior to transport to a tertiary care center (4, 5). Large registries, such as the National Emergency Airway Registry for Children (NEAR4KIDS), have provided detailed information on the safety of advanced airway management in the PICU setting, where it has been shown that adverse events associated with intubation are common. Multicenter studies have demonstrated in this setting that approximately 20% of intubations are complicated by adverse events, with severe tracheal intubation-associated events (TIAEs) occurring in 3–6.5% (1, 3, 6–10). Critically ill children are at high risk of complications due to their decreased physiologic reserve and potential for hemodynamic and respiratory compromise (3, 11). Adverse TIAEs have been linked with adverse outcomes (1); in particular, oxygen desaturation has been associated with longer duration of mechanical ventilation and hemodynamic adverse events such as cardiac arrest, dysrhythmia, and hypotension (1, 6). In pediatric patients with acute respiratory compromise, failure of intubation at the first attempt has been associated with progression to cardiac arrest (12).
Although TIAEs in tertiary care settings have been widely studied in the literature, relatively little is known about complication rates in children requiring airway management outside of these centers. The majority of critically ill children often first present to nonspecialist centers, where local nonspecialist teams must provide initial resuscitation and stabilization, including advanced airway management. In the United Kingdom, since centralization of PICUs, nearly 5,000 children require transport from local hospitals to tertiary centers each year, the majority after intubation at the nonspecialist center. Tracheal intubation is much less frequent in community hospitals and usually the responsibility of a general adult anesthetist rather than a specialist pediatric anesthetist (13–16). From the available data, the rate of TIAEs in children before admission to PICU is thought to be between 19% and 54% (13, 17, 18).
The aims of this study were to: 1) describe the frequency and types of adverse TIAEs during emergency intubations at nonspecialist centers, 2) describe the frequency of severe TIAEs, and 3) explore any associations between patient factors, hospital factors, operator factors, and TIAEs. We hypothesized that the local hospitals in our region would have a higher rate of TIAEs and severe TIAEs than currently described in the literature for TIAEs in patients intubated in the PICU setting.
MATERIALS AND METHODS
We conducted a prospective multicenter observational study from June 1, 2016, to May 31, 2018, at the referring hospitals for the Children’s Acute Transport Service (CATS). The study was registered with the Great Ormond Street Hospital audit department who waived the requirement for formal ethical approval.
The CATS team is an intensive care transport team serving critically ill children from local hospitals in the North Thames, Essex, Herts, Beds, and East Anglia regions of England. It is one of the largest transport services in Europe, receiving over 2,500 referrals a year and transporting over 1,200 critically ill patients a year.
Our study cohort included all patients 0–16 years old who underwent emergency intubation at nonspecialist centers within our catchment area and were transported to an ICU by the CATS team. Therefore, children with tracheostomy tubes, those intubated in the prehospital setting and those intubated at a specialist center by an intensive care team (neonatal or pediatric) were excluded. In addition, as the CATS team are a specialist intensive care team and the focus of our study was stabilization and airway management at nonspecialist centers by local teams, we chose to exclude the few intubations done by the CATS team at the referring hospital prior to transport (Fig. 1). Data were prospectively collected at the referral centers by the CATS team at the time of patient transport on a data collection form that was included as part of the team’s standard transport documentation. Initially, a feasibility audit was conducted over a 6-week period (October 2015 to December 2015), which included 115 patients. The data collection form and format were revised based on user feedback and the form underwent internal review with senior CATS team members prior to its adoption into the clinical paper record. The CATS team collected the following data from the intubating physician at the time of handover: location of patient, specialty and grade of final intubator, induction drugs and doses, laryngoscopy attempts, intubation attempts, Cormack-Lehane grade of airway, endotracheal tube size, depth, type (oral vs nasal, cuffed vs uncuffed), chest radiograph confirmation of tube position, and complications associated with intubation. In addition, at the time of referral, information was collected about preexisting comorbidities, presenting diagnosis, and demographic details including age, weight, gender, gestational age, and referral center details.
The complication list was derived from a review of the literature and was reviewed by all CATS consultants during the audit sheet development (19–21). Complications were categorized as severe TIAEs (esophageal intubation, hypoxia, cardiac arrest, aspiration of gastric contents, pneumothorax, hypotension, surgical airway, “Can’t intubate; CAN ventilate” and “Can’t intubate; CANNOT ventilate”) and nonsevere TIAEs (endobronchial intubation, airway trauma, bradycardia, hypertension, tachycardia, unanticipated difficult airway) (Table 1). Once collected, data were then reviewed by members of the research team, anonymized, and entered into a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA).
Categorical data are reported as numbers and proportions, continuous data are reported as means and sd (or median and interquartile range for skewed data). We performed univariate analysis to test for associations between the occurrence of TIAE and severe TIAE and patient factors such as age group (0–3 mo, 4–11 mo, 1–4 yr, 5–10 yr, 11–15 yr), presence of comorbidities, diagnostic category (upper airway problem, lung disease, other respiratory condition, congenital heart disease, arrhythmia, other cardiac condition, seizures, coma, other neurologic condition, sepsis, accidents, or other), Cormack-Lehane airway grade, gender, and weight-for-age z scores; systems factors such as hospital type (categorized by the volume of annual inpatient pediatric admissions according to the Royal College of Paediatrics and Child Health Facing the Future standards into small [1,501–2,500]; medium [2,501–5,000]; large [5,001–6,000]; and very large [> 6,000]) (22), patient care area where intubation was performed (emergency department, operating theaters, ward, or other), and time of procedure (07:00–19:00 hr or 19:00–07:00 hr); and provider factors such as main specialty of intubator (emergency physician, anesthetist, pediatrician, neonatologist, other), seniority (consultant, senior trainee, junior trainee, other), number of intubation attempts, and medications used during induction and intubation. The chi-square test was used to test for statistical significance. Significant variables from the univariate analyses (p < 0.1) were entered into multivariable models (simple logistic regression as well as mixed effects models with local hospitals as random effects to account for clustering) to explore independent associations between the occurrence of TIAE (outcome) and patient, system, and provider variables (exposure). Data analysis were done using Stata v14 (Stata Corp, College Station, TX).
A total of 2,383 patients were transported by the CATS team during the study period, of whom 1,625 (68.2%) were mechanically ventilated. Of the 1,625 ventilated patients, 388 were excluded based on predefined exclusion criteria and data were unavailable in 186, leaving 1,051 transports for analysis (85% of eligible patients; Fig. 1).
A greater proportion of our cohort comprised of male patients (n = 576, 54.8%). Nearly half (42.6%) of the cohort was under 12 months old (0–3 mo: n = 259, 24.6%; 4–12 mo: n = 189, 18%) and 74.3% were less than 5 years old. The most common diagnostic categories at presentation were respiratory disease (n = 540, 51.4%), followed by neurologic illness (n = 282, 26.8%), sepsis (n = 102, 9.7%), cardiac disease (n = 71, 6.8%), accidents (n = 16, 1.5%), and other (n = 40, 3.8%). Nearly half (45%) of the patients had preexisting comorbidities, of which neurologic, multisystem, and respiratory were the most common (13.7%; 11.2%; 10.9%, respectively). Multiple comorbidities were present in 47 patients (4.5%). The majority of patients (66.1%) were intubated at small and medium volume centers (defined as [1,501–2,500] and [2,501–5,000] annual pediatric inpatient admissions, respectively) by an anesthetist (87%) in either the emergency department (n = 425, 40.4%) or operating department (n = 286, 27.2%). The majority of patients were intubated by a consultant level physician (n = 582, 55.4%). Less than half (43.1%) were intubated out of hours (19:00–07:00 hr).
The most common induction agents used were fentanyl (44.3%), ketamine (39.6%), and propofol (24.6%); with 490 patients (46.6%) receiving multiple induction agents. Succinylcholine (49%), rocuronium (32.9%), and atracurium (14.7%) were most commonly used to achieve neuromuscular blockade (Table 2).
Our data captured 312 adverse events in 239 patients (22.7%). Of these, 53 patients (22.2%) experienced more than one adverse event. Severe TIAEs occurred in 145 patients (13.8%) and accounted for 54.5% of all complications, with the most common being hypotension (5.4%), hypoxia (4.1%), esophageal intubation (2.9%), and cardiac arrest (1.6%). As shown in Table 3, the most common nonsevere TIAEs included endobronchial intubation (6.2%), bradycardia (4.2%), unanticipated difficult airway (1.5%), and airway trauma (1.1%).
Analysis of patient factors showed that age, weight, and airway grade were significantly associated with the occurrence of TIAEs. Patients less than 5 years old had a higher rate of complications than those over 5 years (26.6% vs 10.1%; p = 0.009). Median weight for those with TIAEs was 8.96 kg and those without TIAEs was 10.35 kg (p = 0.003). Mean z scores for weight for patients who suffered TIAEs was –1.21 compared with –0.88 for those who did not (p = 0.01). Patients with complications were less likely to have a grade 1 airway (74.5% vs 83.0%; p = 0.001). Patient factors that were not statistically significant included gender and primary diagnosis (Table 4). Patients with comorbidities were more likely to suffer severe TIAEs during intubation than those without (53.1% vs 43.8%; p = 0.037). Those with more difficult airways were also more likely to experience severe TIAEs (p = 0.037). Other patient factors (age, gender, weight, and diagnosis) were not associated with a higher rate of severe TIAEs (Table 4).
System factors (hospital type, location, time of procedure) analysis showed that none of the factors studied were associated with a risk of TIAEs, both severe and nonsevere (Table 5). Among operator factors, specialty, grade of specialist, and number of intubation attempts were all associated with higher rate of TIAEs. For nonsevere TIAEs, specialists from emergency medicine, pediatrics, and neonatal backgrounds had higher rates of TIAEs (p = 0.025) as did consultant level practitioners compared with senior trainees (64.9% vs 35.1%; p = 0.023). Patients who required more than one attempt at intubation were more likely to experience an adverse event, with 45.2% of patients with TIAEs being intubated on the first attempt compared with 70.0% in the group who did not have complications (p ≤ 0.001). This was also true for severe TIAEs where 53.9% of those with severe TIAEs required more than one attempt at intubation compared with 25.9% in the group that did not have a severe adverse event (p ≤ 0.001).
Similar results were obtained in simple logistic regression and mixed effects models (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/PCC/A948). Variables independently associated with TIAEs were the 4–11 month age group (compared with 0–3 mo age group odds ratio [OR], 1.77; 95% CI, 1.02–3.08), greater number of intubation attempts (OR for > 4 attempts compared with a single attempt 19.06; 95% CI, 5.91–61.46), and specialty of the intubator (emergency medicine compared with anesthesiologists OR, 6.86; 95% CI, 1.14–41.39). Variables independently associated with the occurrence of severe TIAEs were the other respiratory diagnoses group (compared with upper airway obstruction OR, 3.61; 95% CI, 1.07–12.16) and the number of intubation attempts (OR for > 4 attempts compared with a single attempt 10.80; 95% CI, 4.06–28.77).
Our study provides a valuable snapshot of the frequency and nature of adverse TIAEs occurring in infants and children requiring emergency intubation across 47 district general hospitals in the United Kingdom. We hypothesized that nonspecialist centers within our catchment area would have a higher rate of TIAEs than reported values in the literature for children intubated at tertiary center PICUs. Although the overall rate of complications was similar (22.7% vs 20%), the rate of severe TIAEs was much higher in our cohort (13.8% vs 3–6.5%). We identified a number of risk factors for adverse events in emergency intubations at referral centers such as younger age group, low weight-for-age z score, and those with a Cormack-Lehane airway grade of greater than 1. Children with comorbidities and known difficult airways were more likely to sustain a severe TIAE, and a higher number of attempts at intubation was associated with both severe and nonsevere TIAEs. Although we did not collect specific data on the individual laryngoscopy attempts, the use of videolaryngoscopy was documented in 11 cases (1%), only five (0.5%) of which did not have a documented airway grade from an attempt with direct laryngoscopy. We suspect that the number of missed cases where videolaryngoscopy was used is small, as the majority of our nonspecialist centers do not have access to videolaryngoscopy for pediatric patients.
Specialty and number of intubation attempts appeared to be independent predictors of TIAEs. We only captured final airway data and not the data for initial attempts at laryngoscopy and intubation if there was more than one attempt. Being intubated by an Emergency Medicine Specialist was also independently associated with a higher risk of TIAEs, although the number of these intubations was very small.
Little is known about the rates and types of adverse events associated with tracheal intubation of children in nonspecialist centers and the literature provide conflicting data. Easley et al (17) conducted an 18-month prospective study of 250 children intubated in community hospitals, emergency departments, and children’s hospital emergency departments and found that major and minor variances occurred in 54% of patients, 60% of which were major variances. Adverse events were more common in younger children (< 1 yr) and those not receiving neuromuscular blockade. In a retrospective chart review from 2011, Nishisaki et al (13) studied 253 pediatric intubations at referring hospitals and found that self-reported adverse TIAEs were common but not higher when compared with PICU intubations. Long et al (18) conducted a prospective observational study of pediatric intubations in a large tertiary pediatric emergency department in Australia and reported an adverse event rate of 39%, with hypotension and desaturation being the most common adverse events. Hypotension was also more common in our cohort than in the published PICU cohorts. We suspect this may be due to the frequent use of induction agents with a propensity to cause hypotension, such as thiopentone, propofol, and inhalational agents (Table 2).
The body of literature examining the rate and nature of TIAEs in the PICU population is growing and provides data on large cohorts of patients across many centers. Factors consistently associated with adverse TIAEs include multiple attempts, desaturation, and time of procedure. Studies have shown that TIAEs appear to have a higher frequency during nights and weekends at specialized pediatric centers (11, 23). We found no difference in TIAE rate with time of procedure in our cohort. As demonstrated in our cohort, multiple attempts at tracheal intubation are associated with adverse events (2, 3, 24–26), including progression to cardiac arrest (12). Esophageal intubation with immediate recognition is frequently cited as the most common TIAE in children and infants (2, 7, 27), although in our study it was endobronchial intubation. This discrepancy may be due to under-reporting of esophageal intubations in our cohort or a difference in operator factors (the majority of intubators in our cohort were from an anesthesia background whereas it was pediatrics in other papers). In our cohort, hypoxia was common (4.1%); desaturation has been independently associated with hemodynamic adverse events (6) and longer durations of mechanical ventilation in PICU patients (1). Our rate of cardiac arrest (1.62%) is very similar to the PICU rate published previously (~1.7%) (6, 28), although our overall rate of severe complications was much higher, which is especially concerning as one would assume that the rate of TIAEs might be lower when performed by airway experts. Centralization of pediatric anesthesia in the United Kingdom has resulted in general adult anesthetists at nonspecialist hospitals having limited exposure to routine pediatric anesthesia. However, the airway management of critically ill children presenting to nonspecialist centers continues to remain their responsibility. Our data highlight the urgent need for a structured approach to ensuring the maintenance of competency for physicians working at nonspecialist centers. In addition, studies are needed to assess whether there is an association with overall PICU outcomes and adverse events during tracheal intubation in nonspecialist centers. Parker et al (1) recently demonstrated that severe TIAEs are independently associated with higher PICU mortality, but this association has not been studied outside of the tertiary care setting.
Our study has a number of important strengths. To the best of our knowledge, it is the largest study of adverse events associated with emergency tracheal intubation of pediatric patients at nonspecialist centers. In addition, a large number of centers (n = 47) across the United Kingdom were included in the study, and we collected data on a large proportion of eligible patients (85%). As the majority of documented intubations were done by providers with an anesthetic background, our findings can be generalized to pediatric intubations at other local hospitals in the United Kingdom and countries with a similar healthcare model.
There are several limitations to consider when interpreting the findings of our study. Firstly, the data were obtained by the transport team on handover from the local hospital care team; thus, the data are self-reported by the local teams and under-reporting cannot therefore be excluded. This may be especially true for nonsevere TIAEs such as esophageal intubation with immediate recognition. Secondly, the definitions used in this study are slightly different from the definitions used in the NEAR4KIDS registry, from which the baseline numbers for complications within a PICU originate. Specifically, hypoxia is not included in the registry but is included in our complication list. We did not document the occurrence rate of laryngospasm, malignant hyperthermia, medication errors, or arrhythmias. The most common severe TIAE in our cohort was hypotension, although we did not specify that it required intervention in contrast to the NEAR4Kids definition. This could have contributed to the higher rate of severe TIAEs in our cohort. Furthermore, we did not differentiate between esophageal intubation with immediate versus delayed recognition and counted all as a severe TIAE. Thirdly, although the generalizability of our results to other U.K. centers may be good, this may not apply to countries where nonanesthetists (emergency medicine or pediatric specialists) do the majority of the emergency pediatric intubations at nonspecialist centers. It is possible that the rate of complications would be higher with predominantly nonairway specialist intubators, as the literature suggests that the rate may be higher in this group (16, 29). Last, we only collected data on the intubator specialty and grade for the final airway (successful) attempt and are unable to determine which attempt had the complications and which operator experienced the complication if there were multiple operators.
Adverse TIAEs are common during the intubation of critically ill children at nonspecialist centers, occurring at a rate similar to tertiary center PICUs, although the rate of severe TIAEs was much higher in the nonspecialist setting. Patient factors as well as operator factors were associated with a higher rate of TIAEs. The findings of our study could inform future strategies for quality improvement efforts to reduce the risk of severe TIAEs and improve PICU outcomes in this vulnerable cohort.
We would like to thank Deborah Farrell for doing data collection during the feasibility audit and the Children’s Acute Transport Service team for collecting the data during the transports throughout the feasibility audit and subsequent study period.
1. Parker MM, Nuthall G, Brown C 3rd, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Relationship between adverse tracheal intubation
associated events and PICU outcomes. Pediatr Crit Care Med 2017; 18:310–318
2. Lee JH, Turner DA, Kamat P, et al. Pediatric Acute Lung Injury and Sepsis Investigators (PALISI); National Emergency Airway Registry for Children (NEAR4KIDS): The number of tracheal intubation
attempts matters! A prospective multi-institutional pediatric observational study. BMC Pediatr 2016; 16:58
3. Nishisaki A, Ferry S, Colborn S, et al.; National Emergency Airway Registry (NEAR); National Emergency Airway Registry for kids (NEAR4KIDS) Investigators: Characterization of tracheal intubation
process of care and safety outcomes in a tertiary pediatric intensive care unit. Pediatr Crit Care Med 2012; 13:e5–10
4. Warren J, Fromm RE Jr, Orr RA, et al.; American College of Critical Care
Medicine: Guidelines for the inter- and intrahospital transport of critically ill patients. Crit Care Med 2004; 32:256–262
5. Kronick JB, Kissoon N, Frewen TC. Guidelines for stabilizing the critically ill child before transfer to a tertiary care facility. CMAJ 1988; 139:213–20
6. Li S, Hsieh TC, Rehder KJ, et al.; for National Emergency Airway Registry for Children (NEAR4KIDS) and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Frequency of desaturation and association with hemodynamic adverse events during tracheal intubations in PICUs. Pediatr Crit Care Med 2018; 19:e41–e50
7. Nishisaki A, Turner DA, Brown CA 3rd, et al.; National Emergency Airway Registry for Children (NEAR4KIDS); Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: A national emergency airway registry for children: Landscape of tracheal intubation
in 15 PICUs. Crit Care Med 2013; 41:874–885
8. Nett S, Emeriaud G, Jarvis JD, et al.; NEAR4KIDS Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Site-level variance for adverse tracheal intubation
-associated events across 15 North American PICUs: A report from the national emergency airway registry for children*. Pediatr Crit Care Med 2014; 15:306–313
9. Fiadjoe JE, Nishisaki A, Jagannathan N, et al. Airway management complications in children with difficult tracheal intubation
from the Pediatric Difficult Intubation (PeDI) registry: A prospective cohort analysis. Lancet Respir Med 2016; 4:37–48
10. Sanders RC Jr, Giuliano JS Jr, Sullivan JE, et al.; National Emergency Airway Registry for Children Investigators and Pediatric Acute Lung Injury and Sepsis Investigators Network: Level of trainee and tracheal intubation
11. Carroll CL, Spinella PC, Corsi JM, et al. Emergent endotracheal intubations in children: Be careful if it’s late when you intubate. Pediatr Crit Care Med 2010; 11:343–348
12. Stinson HR, Srinivasan V, Topjian AA, et al.; American Heart Association Get With the Guidelines-Resuscitation Investigators: Failure of invasive airway placement on the first attempt is associated with progression to cardiac arrest in pediatric acute respiratory compromise. Pediatr Crit Care Med 2018; 19:9–16
13. Nishisaki A, Marwaha N, Kasinathan V, et al. Airway management in pediatric patients at referring hospitals compared to a receiving tertiary pediatric ICU. Resuscitation 2011; 82:386–390
14. Ramnarayan P, Britto J, Tanna A, et al. Does the use of a specialised paediatric retrieval service result in the loss of vital stabilisation skills among referring hospital staff? Arch Dis Child 2003; 88:851–854
15. Simon HK, Sullivan F. Confidence in performance of pediatric emergency medicine procedures by community emergency practitioners. Pediatr Emerg Care 1996; 12:336–339
16. Sagarin MJ, Chiang V, Sakles JC, et al.; National Emergency Airway Registry (NEAR) Investigators: Rapid sequence intubation for pediatric emergency airway management. Pediatr Emerg Care 2002; 18:417–423
17. Easley RB, Segeleon JE, Haun SE, et al. Prospective study of airway management of children requiring endotracheal intubation before admission to a pediatric intensive care unit. Crit Care Med 2000; 28:2058–2063
18. Long E, Sabato S, Babl FE. Endotracheal intubation in the pediatric emergency department. Paediatr Anaesth 2014; 24:1204–1211
19. Griesdale DE, Bosma TL, Kurth T, et al. Complications of endotracheal intubation in the critically ill. Intensive Care Med 2008; 34:1835–1842
20. Schwartz DE, Matthay MA, Cohen NH. Death and other complications of emergency airway management in critically ill adults. A prospective investigation of 297 tracheal intubations. Anesthesiology 1995; 82:367–376
21. Cook TM, Woodall N, Frerk C; Fourth National Audit Project: Major complications of airway management in the UK: Results of the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1: Anaesthesia. Br J Anaesth 2011; 106:617–631
23. Rehder KJ, Giuliano JS Jr, Napolitano N, et al.; National Emergency Airway Registry for Children and Pediatric Acute Lung Injury and Sepsis Investigators: Increased occurrence of tracheal intubation
-associated events during nights and weekends in the PICU. Crit Care Med 2015; 43:2668–2674
24. Mort TC. Emergency tracheal intubation
: Complications associated with repeated laryngoscopic attempts. Anesth Analg 2004; 99:607–613, table of contents
25. Sakles JC, Chiu S, Mosier J, et al. The importance of first pass success when performing orotracheal intubation in the emergency department. Acad Emerg Med 2013; 20:71–78
26. Hasegawa K, Shigemitsu K, Hagiwara Y, et al.; Japanese Emergency Medicine Research Alliance Investigators: Association between repeated intubation attempts and adverse events in emergency departments: An analysis of a multicenter prospective observational study. Ann Emerg Med 2012; 60:749–754.e2
27. Pallin DJ, Dwyer RC, Walls RM, et al.; NEAR III Investigators: Techniques and trends, success rates, and adverse events in emergency department pediatric intubations: A report from the National Emergency Airway Registry. Ann Emerg Med 2016; 67:610–615.e1
28. Shiima Y, Berg RA, Bogner HR, et al.; National Emergency Airway Registry for Children Investigators: Cardiac arrests associated with tracheal intubations in PICUs: A multicenter cohort study. Crit Care Med 2016; 44:1675–1682
29. Choi HJ, Je SM, Kim JH, et al.; Korean Emergency Airway Registry Investigators: The factors associated with successful paediatric endotracheal intubation on the first attempt in emergency departments: A 13-emergency-department registry study. Resuscitation 2012; 83:1363–1368