Publications

Phospholipases A2 are enzymes that liberate membrane-bound lipids in a tissue and cell-specific fashion. Group V secretory phospholipase A2 is necessary for the development of M2 macrophages and their effector functions in a mouse model of the T-helper-2 allergic airway inflammation. However, the function of group V phospholipase A2 in human M2 activation and T-helper-2 inflammation is ill-defined. Transglutaminase-2, a protein cross-linking enzyme, is a newly identified marker of both human and mouse interleukin-4-activated M2 macrophages and is also found in the lungs of patients with asthma. We report that group V phospholipase A2 and transglutaminase-2 colocalized in macrophages of human nasal polyp tissue obtained from patients with T-helper-2 eosinophilic inflammation, and their coexpression positively correlated with the number of eosinophils in each tissue specimen. We demonstrate that in human monocyte-derived macrophages activated by interleukin-4, group V phospholipase A2 translocated and colocalized with transglutaminase-2 in the cytoplasm and on the membrane of macrophages. Moreover, knocking down group V phospholipase A2 with small interfering ribonucleic acid reduced macrophage transglutaminase activity, whereas mass spectrometry analysis of lipids also showed reduced prostaglandin E2 production. Finally, exogenous prostaglandin E2 restored transglutaminase activity of group V phospholipase A2-small interfering ribonucleic acid-treated macrophages. Thus, our study shows a novel function of group V phospholipase A2 in regulating the transglutaminase activity of human interleukin-4-activated M2 macrophages through prostaglandin E2 generation and suggests that group V phospholipase A2 is a functionally relevant enzyme that may have therapeutic value for the treatment of human T-helper-2 inflammatory disorders.

INTRODUCTION: The objective of this study was to investigate the factors associated with first-pass success in pediatric intubation in the emergency department (ED).

METHODS: We analyzed the data from two multicenter prospective studies of ED intubation in 17 EDs between April 2010 and September 2014. The studies prospectively measured patient's age, sex, principal indication for intubation, methods (e.g., rapid sequence intubation [RSI]), devices, and intubator's level of training and specialty. To evaluate independent predictors of first-pass success, we fit logistic regression model with generalized estimating equations. In the sensitivity analysis, we repeated the analysis in children <10 years.

RESULTS: A total of 293 children aged ≤18 years who underwent ED intubation were eligible for the analysis. The overall first-pass success rate was 60% (95%CI [54%-66%]). In the multivariable model, age ≥10 years (adjusted odds ratio [aOR], 2.45; 95% CI [1.23-4.87]), use of RSI (aOR, 2.17; 95% CI [1.31-3.57]), and intubation attempt by an emergency physician (aOR, 3.21; 95% CI [1.78-5.83]) were significantly associated with a higher chance of first-pass success. Likewise, in the sensitivity analysis, the use of RSI (aOR, 3.05; 95% CI [1.63-5.70]), and intubation attempt by an emergency physician (aOR, 4.08; 95% CI [1.92-8.63]) were significantly associated with a higher chance of first-pass success.

CONCLUSION: Based on two large multicenter prospective studies of ED airway management, we found that older age, use of RSI, and intubation by emergency physicians were the independent predictors of a higher chance of first-pass success in children. Our findings should facilitate investigations to develop optimal airway management strategies in critically-ill children in the ED.

Advanced airway management in the pediatric intensive care unit (PICU) is hazardous, with associated adverse outcomes. This report describes a methodology to develop a bundle to improve quality and safety of tracheal intubations. A prospective observational cohort study was performed with expert consensus opinion of 1715 children undergoing tracheal intubation at 15 PICUs. Baseline process and outcomes data in tracheal intubation were collected using the National Emergency Airway Registry for Children reporting system. Univariate analysis was performed to identify risk factors associated with adverse tracheal intubation-associated events. A multidisciplinary quality improvement committee was formed. Workflow analysis of tracheal intubation and pilot testing were performed to develop the Airway Bundle Checklist with 4 parts: (1) risk factor assessment, (2) plan generation, (3) preprocedure time-out to ensure that providers, equipment, and plans are prepared, (4) postprocedure huddle to identify improvement opportunities. The Airway Bundle Checklist developed may lead to improvement in airway management.

STUDY OBJECTIVE: We describe emergency department (ED) intubation practices for children younger than 16 years through multicenter prospective surveillance.

METHODS: Academic and community EDs in the United States, Canada, and Australia recorded data electronically, from 2002 to 2012, with verified greater than or equal to 90% reporting.

RESULTS: Ten of 18 participating centers provided qualifying data, reporting 1,053 encounters. Emergency physicians initiated 85% of intubations. Trainees initiated 83% (95% confidence interval [CI] 81% to 85%). Premedication became uncommon, reaching less than 30% by the last year. Etomidate was used in 78% of rapid sequence intubations. Rocuronium use increased during the period of study, whereas succinylcholine use declined. Video laryngoscopy increased, whereas direct laryngoscopy declined. The first attempt was successful in 83% of patients (95% CI 81% to 85%) overall. The risk of first-attempt failure was highest for infants (relative risk versus all others 2.3; 95% CI 1.8 to 3.0). Odds of first-attempt success for girls relative to boys were 0.57. The odds were 3.4 times greater for rapid sequence intubation than sedation without paralysis. The ultimate success rate was 99.5%.

CONCLUSION: Because we sampled only 10 centers and most of the intubations were by trainees, our results may not be generalizable to the typical ED setting. We found that premedication is now uncommon, etomidate is the predominant induction agent, and rocuronium and video laryngoscopy are used increasingly. First-attempt failure is most common in infants.

INTRODUCTION: Video laryngoscopy (VL) has been advocated for several aspects of emergency airway management; however, there are still concerns over its use in select patient populations such as those with large volume hematemesis secondary to gastrointestinal (GI) bleeds. Given the relatively infrequent nature of this disease process, we sought to compare intubation outcomes between VL and traditional direct laryngoscopy (DL) in patients intubated with GI bleeding, using the third iteration of the National Emergency Airway Registry (NEARIII).

METHODS: We performed a retrospective analysis of a prospectively collected national database (NEARIII) of intubations performed in United States emergency departments (EDs) from July 1, 2002, through December 31, 2012. All cases where the indication for intubation was "GI bleed" were analyzed. We included patient, provider and intubation characteristics. We compared data between intubation attempts initiated as DL and VL using parametric and non-parametric tests when appropriate.

RESULTS: We identified 325 intubations, 295 DL and 30 VL. DL and VL cases were similar in terms of age, sex, weight, difficult airway predictors, operator specialty (emergency medicine, anesthesia or other) and level of operator training (post-graduate year 1, 2, etc). Proportion of successful first attempts (DL 261/295 (88.5%) vs. VL 28/30 (93.3%) p=0.58) and Cormack-Lehane grade views (p=0.89) were similar between devices. The need for device change was similar between DL [2/295 (0.7%) and VL 1/30 (3.3%); p=0.15].

CONCLUSION: In this national registry of intubations performed in the ED for patients with GI bleeds, both DL and VL had similar rates of success, glottic views and need to change devices.

BACKGROUND: Although the international guidelines emphasize early and systematic use of rescue intubation techniques, there is little evidence to support this notion. We aimed to test the hypothesis that preceding multiple failed intubation attempts are associated with a decreased success rate on the first rescue intubation in emergency departments (EDs).

METHODS: We analysed data from two multicentre prospective registries designed to characterize current ED airway management in Japan between April 2010 and June 2013. All patients who underwent a rescue intubation after a failed attempt or a series of failed attempts were included for the analysis. Multiple failed intubation attempts were defined as ≥2 consecutive failed intubation attempts before a rescue intubation. Primary outcome measure was success rate on the first rescue intubation attempt.

RESULTS: Of 6,273 consecutive patients, 1,151 underwent a rescue intubation. The success rate on the first rescue intubation attempt declined as the number of preceding failed intubation attempts increased (81% [95% CI, 79%-84%] after one failed attempt; 71% [95% CI, 66%-76%] after two failed attempts; 67% [95% CI, 55%-78%] after three or more failed attempts; P(trend) <0.001). In the multivariable analysis adjusting for age, sex, principal indication, change in methods, devices, and intubator specialty, and clustering of patients within EDs, success rate on the first rescue intubation after two failed attempts was significantly lower (OR, 0.56; 95% CI, 0.41-0.77) compared to that after one failed attempt. Similarly, success rate on the first rescue intubation attempt after three or more failed attempts was significantly lower (OR, 0.49; 95% CI, 0.25-0.94) compared to that after one failed attempt.

CONCLUSION: Preceding multiple failed intubation attempts was independently associated with a decreased success rate on the first rescue intubation in the ED.

OBJECTIVE: To determine whether the success rate of repeated attempts at tracheal intubation by a single intubator was lower than those by alternate intubators in the emergency department (ED).

METHODS: An analysis of data from a multicentre prospective registry (Japanese Emergency Airway Network Registry) of 13 academic and community EDs in Japan between April 2010 and August 2012. We included all adult and paediatric patients who underwent repeated attempts at tracheal intubation in the ED. We compared the intubation success rates at the second and third attempts between attempts at intubation by a single intubator who performed the previous attempts, and the attempts by alternate intubators.

RESULTS: We recorded 4094 patients (capture rate, 96%); 1289 patients with repeated attempts at tracheal intubation were eligible for this study. Among these, 871 patients (68%) had a second attempt at intubation by single intubators. At the second attempt, tracheal intubation by a single intubator was associated with a decreased success rate (adjusted odds ratio or AOR, 0.50; 95% CI 0.36 to 0.71), compared with alternate intubators. At the third attempt, intubation by a single intubator was also associated with a decreased success rate (58% vs 70%; unadjusted OR, 0.58; 95% CI 0.38 to 0.89). However, after adjustment for potential confounders, the association lost statistical significance (AOR, 0.89; 95% CI 0.52 to 1.56).

CONCLUSIONS: In this large multicentre study of ED patients undergoing tracheal intubation, second attempts at intubation by a single intubator, compared with those by alternate intubators, were independently associated with a decreased success rate.

OBJECTIVES: Tracheal intubation in PICUs is often associated with adverse tracheal intubation-associated events. There is a paucity of data regarding medication selection for safe tracheal intubations in PICUs. Our primary objective was to evaluate the association of medication selection on specific tracheal intubation-associated events across PICUs.

DESIGN: Prospective observational cohort study.

SETTING: Nineteen PICUs in North America.

SUBJECTS: Critically ill children requiring tracheal intubation.

INTERVENTIONS: None.

MEASUREMENT AND MAIN RESULTS: Using the National Emergency Airway Registry for Children, tracheal intubation quality improvement data were prospectively collected from July 2010 to March 2013. Patient, provider, and practice characteristics including medications and dosages were collected. Adverse tracheal intubation-associated events were defined a priori. A total of 3,366 primary tracheal intubations were reported. Adverse tracheal intubation-associated events occurred in 593 tracheal intubations (18%). Fentanyl and midazolam were the most commonly used induction medications (64% and 58%, respectively). Neuromuscular blockade was used in 92% of tracheal intubation with the majority using rocuronium (64%) followed by vecuronium (20%). Etomidate and succinylcholine were rarely used (1.6% and 0.7%, respectively). Vagolytics were administered in 37% of tracheal intubations (51% in infants; 28% in > 1 yr old; p < 0.001). Ketamine was used in 27% of tracheal intubations but more often for tracheal intubations in patients with unstable hemodynamics (39% vs 25%; p < 0.001). However, ketamine use was not associated with lower prevalence of new hypotension (ketamine 8% vs no ketamine 14%; p = 0.08).

CONCLUSIONS: In this large, pediatric multicenter registry, fentanyl, midazolam, and ketamine were the most commonly used induction agents, and the majority of tracheal intubations involved neuromuscular blockade. Ketamine use was not associated with lower prevalence of hypotension.

STUDY OBJECTIVE: We describe the operators, techniques, success, and adverse event rates of adult emergency department (ED) intubation through multicenter prospective surveillance.

METHODS: Eighteen EDs in the United States, Canada, and Australia recorded intubation data onto a Web-based data collection tool, with a greater than or equal to 90% reporting compliance requirement. We report proportions with binomial 95% confidence intervals (CIs) and regression, with year as the dependent variable, to model change over time.

RESULTS: Of 18 participating centers, 5 were excluded for failing to meet compliance standards. From the remaining 13 centers, we report data on 17,583 emergency intubations of patients aged 15 years or older from 2002 to 2012. Indications were medical in 65% of patients and trauma in 31%. Rapid sequence intubation was the first method attempted in 85% of encounters. Emergency physicians managed 95% of intubations and most (79%) were physician trainees. Direct laryngoscopy was used in 84% of first attempts. Video laryngoscopy use increased from less than 1% in the first 3 years to 27% in the last 3 years (risk difference 27%; 95% CI 25% to 28%; mean odds ratio increase per year [ie, slope] 1.7; 95% CI 1.6 to 1.8). Etomidate was used in 91% and succinylcholine in 75% of rapid sequence intubations. Among rapid sequence intubations, rocuronium use increased from 8.2% in the first 3 years to 42% in the last 3 years (mean odds ratio increase per year 1.3; 95% CI 1.3 to 1.3). The first-attempt intubation success rate was 83% (95% CI 83% to 84%) and was higher in the last 3 years than in the first 3 (86% versus 80%; risk difference 6.2%; 95% CI 4.2% to 7.8%). The airway was successfully secured in 99.4% of encounters (95% CI 99.3% to 99.6%).

CONCLUSION: In the EDs we studied, emergency intubation has a high and increasing success rate. Both drug and device selection evolved significantly during the study period.