This multicenter study investigated the association between number of TI attempts and clinical outcomes in the PICU, accounting for patient characteristics previously associated with adverse events. We demonstrated that an increasing number of TI attempts in children with acute respiratory failure were associated with increased occurrence of desaturations, adverse TIAEs, and severe TIAEs. Desaturation (<80 %) was commonly observed in a quarter of the patients during TIs. The odds of desaturations increased approximately 3- and 6-fold with 2 attempts and ≥3 attempts of TIs, respectively. Adverse TIAEs were also observed in 19 % of patients undergoing TIs. The occurrences of any TIAE and severe TIAE were directly associated with increased number of attempts.
Our study adds strength to the current evidence in the medical literature that multiple TI attempts in critically ill children are associated with adverse clinical outcomes, even after accounting for patient characteristics such as age, history of difficult airway, and upper airway obstruction. In particular, our study focused on a unique cohort of children at high risk for desaturation during TIs. Patients with acute respiratory failure often have limited tolerance to apneic time (i.e., the time span without spontaneous ventilation, or positive pressure ventilation provided by an airway provider) which is required for the TI procedure. Therefore those children are perceived as particularly high risk for acute desaturation and physiological instability (hypotension, bradycardia) during a TI procedure. Our study was the first multi-center effort to quantify the impact of multiple attempts on this high risk pediatric population.
In critically ill adults, repeated TI attempts are associated with increased complications. In a seminal study of 2833 adults, ≥3 attempts in TI was associated with a 14-fold increased risk of severe desaturation (SpO2 < 70 %) and seven-fold increased risk for cardiac arrest . Similar to these findings in adults, our findings add to the growing evidence that in critically ill children, multiple TI attempts are associated with worse clinical outcomes, including cardiac arrest (Table 4). In a previous single-center study of 137 TIs performed outside the operating room over a two-year period in a tertiary pediatric hospital, investigators reported complications in 56 (41 %) TI encounters . Complications that were recorded in this study included desaturations, hypotension, bradycardia, vomiting and esophageal intubation. In that investigation, it was demonstrated that ≥3 attempts at intubation was an independent risk factor for complications (OR 2.3, 95 % CI: 1.3–4.3). Of note, the proportion requiring ≥3 attempts [20/137(15 %)] was similar to the proportion requiring ≥3 attempts [321/2080 (15 %)] in our investigation. While this study provided preliminary data on the risks associated with multiple TI attempts at a single center, our investigation of a large, multi-center cohort of patients (n = 2080) allowed us to precisely quantify the association of immediate clinical outcomes with number of TI attempts. In another prospective study conducted in a tertiary pediatric emergency department involving 71 TIs, >1 attempt was demonstrated to be associated with higher risk of adverse events (OR 7.7. 95 % CI: 2.0–26.5) . In addition, a study that specifically examined TI in 105 pediatric trauma patients (with 151 TI attempts) reported that the risk of airway complication was 2.5-fold higher in children who required >1 attempt at TI . The investigators demonstrated that multiple TIs were also associated with increased transport time, longer hospital length of stay and lower discharge Glasgow Coma Scale scores. However, not all studies involving TIs in children have reported increased risk with increasing TI attempts. A separate study that reported a similar proportion of TIs involving ≥3 attempts [36/281 (13 %)] did not demonstrate a significant association in the frequency of TIAEs between 1 attempt and >1 attempt groups [11/190 (6 %) vs. 10/91(11 %) respectively, p = 0.146]. This investigation was performed in a very different setting of a mixed adult-pediatric population in 13 emergency departments in Korea , which may suggest that different clinical areas with different spectrums of patient population may have an impact on the risk of TIAEs with increased number of attempts.
Another interesting finding in this investigation was the difference in the median age of patients across the three groups of TI attempts (Table 1). Patients that required ≥3 attempts were younger compared to the other two groups. This association between age of patient and number of TI attempts indicates that younger patients will be more likely to require multiple TI attempts. Our finding is congruent with findings from other studies that focused specifically on infants. In a study involving 203 infants in five tertiary neonatal intensive care units, investigators examined the characteristics of TIs over a one year period . In contrast to our data where more than half of our patients required only 1 attempt, their study reported a higher number of attempts to establish a secure airway; 60/203 (30 %) required two attempts and 69/203 (34 %) required ≥3 attempts . Unfortunately, this study did not report the incidence of desaturation or TIAEs with increasing number of TI attempts. Our findings in conjunction with the existing literature focusing on the younger age spectrum in pediatrics suggest that younger age is associated with higher risk of requiring multiple attempts in TIs and as such, higher risk for desaturation and adverse TIAEs.
In our study, pediatric residents were the first attempt provider more often in TIs requiring ≥3 attempts. This suggests the choice of first attempt provider may be an important modifiable factor to decrease number of TI attempts and related desaturation and adverse TIAEs [14, 16, 19]. To facilitate TI, sedation and neuromuscular blockade are often used. We did not find any association between the commonly used sedative drugs (e.g., fentanyl, midazolam) and number of TI attempts (Table 2). Neuromuscular blockade were used in a large majority [1920/2080 (92 %)] of the TI attempts in our study. We did not find any association between the use of neuromuscular blockade and number of TI attempts (Table 2). In an adult study involving 454 critically ill patients in two adult ICUs, the investigators reported a difference in the proportion of patients requiring “1 attempt” for successful TI with the use of neuromuscular blockade as compared to those without (85 % vs. 78 %, p = 0.047) . Furthermore, this study demonstrated that neuromuscular blockade was associated with reduced risk of hypoxemia (OR 0.52, 95 % CI: 0.28–0.97) and complications (OR 0.29, 95 % CI: 0.11–0.78) during TI attempts.
Our study must be interpreted in the context of the limitations. Our primary aim focused on investigating the association between number of TI attempts and adverse clinical outcomes, accounting for 3 important patient characteristics previously associated with desaturation and adverse events: age, history of difficult airway, and upper airway obstruction. We acknowledge that there are other factors, in addition to TI attempts, that predispose a critically ill child to adverse clinical outcomes during the process of TI. We attempted to control for known confounders, however, we were not able to control for other important clinical covariates such as severity scores, as these data were not collected consistently across all sites in the database. We also recognize that the definition of desaturation and severe desaturation is somewhat arbitrary, although we established the definition in this investigation a priori based on previously published literature [7, 16, 21, 22]. Using these definitions, our primary analysis, along with a more restrictive sensitivity analysis, demonstrated a clear and strong association between number of attempts and desaturation. We also recognize the definitions for our secondary outcomes: adverse TIAEs and severe TIAEs were a priori developed by the NEAR4KIDS expert consensus, and each component may not have equal impact on patient outcomes. Therefore the results reported in this study are sensitive to the definitions. For example, when esophageal intubations with immediate recognition were removed from TIAE definition, the odds ratio for adverse TIAEs events attenuated from 3.7 to 1.6 (Table 5, Additional file 2: Table S1). Another limitation is the self-reported nature of the NEAR4KIDs database. There is a possibility of underreporting in the occurrence and degree of desaturation and adverse TIAEs, even though we attempted to limit this by ensuring complete capture of data with site specific compliance plans. Future studies with monitor waveform analysis may be able to address this issue by providing further detailed information regarding apneic time during TI attempts and effectiveness of rescue breaths after failed attempts. Another potential limitation is that the centers included in this database are largely academic medical centers and despite the multi-center, collaborative effort, the sites involved are not necessarily representative of all PICUs in North America or Asia Pacific. It is possible that generalizability of our findings to other PICUs may be somewhat limited.
Building on results provided by other investigators and our study team, we recognize the following points regarding TI in critically ill children: 1. Provider experience and status (e.g., residents, fellows and attendings) have an impact on first attempt and overall TI success [10, 11, 14]; 2. Risk of TIAEs is reduced with increasing experience of the initial provider ; 3. An increasing number of TI attempts is associated with increased risk of desaturations and TIAEs ; and 4. Children with difficult airways have a higher incidence of TIAEs during TI attempts . Given these considerations, identification of which patients are safe and suitable for trainees to perform first TI attempt is of great importance to balance the need for training with patient safety. Currently several pediatric ICUs have implemented TI safety quality improvement bundle interventions to 1. Identify patients at risk for TIAEs and multiple attempts, 2. Generate a thoughtful airway management plan ahead of time, 3. Exercise a ‘timeout’ immediately before TI using a checklist, and 4. Conduct post TI procedure debriefing to identify strengths and room for improvement in technical skills and communication . This ongoing quality improvement intervention aims to reduce adverse TIAE rates and multiple attempts. Cumulative evidence to date also sets the stage for future interventions (e.g., passive oxygen administration during TI attempts,  effective bag-mask ventilation for pre-oxygenation using real-time feedback system) to prevent severe desaturation when multiple TI attempts are required or anticipated.