Pediatric Application of Cuffed Endotracheal Tube.

A young child's larynx was formerly believed to be narrowest at the cricoid level, circular in section, and funnel shaped. This supported the routine use of uncuffed endotracheal tubes (ETTs) in young children despite the benefits of cuffed ETTs, such as lower risk for air leakage and aspiration. In the late 1990s, evidence supporting the pediatric use of cuffed tubes emerged largely from anesthesiology studies, while some technical flaws of the tubes remained a concern. Since the 2000s, imaging-based studies have clarified laryngeal anatomy, revealing that it is narrowest at the glottis, elliptical in section, and cylindrical in shape. The update was contemporaneous with technical advances in the design, size, and material of cuffed tubes. The American Heart Association currently recommends the pediatric use of cuffed tubes. In this review, we present the rationale for using cuffed ETTs in young children based on our updated knowledge of pediatric anatomy and technical advances.

Plain Radiographic Analysis of Laryngeal Dimensions in Young Children: Normal versus Croup.

(1) Background: Contrary to a tenet of the funnel-shaped pediatric larynx with the cricoid level being narrowest, recent studies show the glottis and subglottis as the narrowest levels. To locate the functionally narrowest level of the larynx, we reported normal laryngeal dimensions and their croup-related changes in young children. (2) Methods: We reviewed normal plain neck radiographs recorded for the evaluation of minor trauma or foreign bodies in 504 children aged ≤4 years who visited the emergency department from 2016 through 2021. Using computed tomography-based localization of the glottis, we radiographically defined the subglottis and cricoid. At these levels, we measured diameters and calculated cross-sectional areas (CSAs) on the radiographs. The values were compared to the equivalent values of a 1:1 age-matched population with croup. (3) Results: In the study population (n = 401), the narrowest diameter and CSA were observed in the glottis. In detail, the mean anteroposterior/transverse diameters were 9.8/3.4 mm at the glottis, 8.5/5.6 mm at the subglottis, and 7.4/6.8 mm at the cricoid (p < 0.001), respectively. In the same order, the mean CSAs were 26.5, 38.1, and 40.5 mm2 (p < 0.001). All dimensions were narrower in the croup population (p < 0.001). We found croup-related narrowing, namely reductions in the transverse diameter and CSA that were more severe closer to the glottis (p < 0.001), without differences per level in the anteroposterior diameter. (4) Conclusions: This study confirms the glottis as the narrowest level of the larynx in young children. In addition, level-based differences in croup-related narrowing suggest some point between the glottis and subglottis as the functionally narrowest level.

Factors Associated with the Underuse of Sedatives and Neuromuscular Blocking Agents for Pediatric Emergency Endotracheal Intubation in Korea.

PURPOSE: Rapid sequence intubation (RSI) using sedatives and neuromuscular blocking agents (NMBAs) is recommended for pediatric emergency endotracheal intubation (ETI), but is not frequently performed in Korea. This study aimed to verify factors associated with the underuse of RSI medications. MATERIALS AND METHODS: This multicenter retrospective study reviewed patients aged under 18 years who underwent an ETI within 24 hours of arrival at the emergency department between 2016 and 2019. Any cases of ETI during cardiopulmonary resuscitation were excluded. We investigated the characteristics of the patients, intubators, RSI medications, and outcomes. The study cases were classified into no-medication, sedative-only, and sedative-with-NMBA groups. Multivariable logistic regression analysis of RSI medication use was conducted. RESULTS: A total of 334 cases with a median age of 3.4 years were included in this study. Sedatives and NMBAs were used in 63.8% and 32.9%, respectively. In comparing the no-medication (n=121), sedative-only (n=103), and sedative-with-NMBA (n=110) groups, patient age (median; 1.0 year vs. 2.8 years vs. 11.3 years; p<0.001), underlying medical conditions (77.7% vs. 56.3% vs. 36.4%; p<0.001), and pediatricians as intubators (76.9% vs. 54.4% vs. 17.3%; p<0.001) were different. The factors that influenced sedatives with NMBA use were patient age [for a year increment; adjusted odds ratio (aOR), 1.182; 95% confidence interval (CI), 1.120-1.249], no underlying medical conditions (aOR, 2.109; 95% CI, 1.093-4.070), and intubators other than pediatricians (aOR, 5.123; 95% CI, 2.257-11.626). CONCLUSION: RSI accounted for 32.9% of pediatric emergency ETI in Korea. The underuse of RSI medications is associated with younger patient age, underlying medical conditions, and pediatricians as intubators.

Impact of Intubator's Training Level on First-Pass Success of Endotracheal Intubation in Acute Care Settings: A Four-Center Retrospective Study.

(1) Background: First-pass success (FPS) of endotracheal intubation is more challenging in children than in adults. We aimed to identify factors associated with FPS of intubation in acute care settings. (2) Methods: We analyzed data of children aged <10 years who underwent intubation within ≤24 h of arrival at four Korean emergency departments (2016−2019). Variables were compared according to FPS. A logistic regression was performed to quantify the association of factors with FPS. An experienced intubator was defined as a senior resident or a specialist. (3) Results: Of 280 children, 169 (60.4%) had FPS. The children with FPS were older (median age, 23.0 vs. 11.0 months; p = 0.018), were less frequently in their infancy (36.1% vs. 50.5%; p = 0.017), and were less likely to have respiratory compromise (41.4% vs. 55.0%; p = 0.030). The children with FPS tended to be more often intubated by experienced intubators than those without FPS (87.0% vs. 78.4%; p = 0.057). Desaturation was rarer in those with FPS. Factors associated with FPS were experienced intubators (aOR, 1.93; 95% CI, 1.01−3.67) and children's age ≥12 months (1.84; 1.13−3.02). (4) Conclusion: FPS of intubation can be facilitated by deploying or developing clinically competent intubators, particularly for infants, in acute care settings.

Comparison of Base Deficit and Vital Signs as Criteria for Hemorrhagic Shock Classification in Children with Trauma.

PURPOSE: Base deficit (BD) is superior to vital signs in predicting trauma outcomes in adults. The authors aimed to compare BD and vital signs as criteria for the four-tiered hemorrhagic shock classification in children with trauma. MATERIALS AND METHODS: We retrospectively reviewed the data of 1046 injured children who visited a Korean academic hospital from 2010 through 2018. These children were classified separately based on BD (class I, BD ≤2.0 mmol/L; II, 2.1-6.0 mmol/L; III, 6.1-10 mmol/L; and IV, ≥10.1 mmol/L) and vital signs (<13 years: age-adjusted hypotension and tachycardia, and Glasgow Coma Scale; 13-17 years: the 2012 Advanced Trauma Life Support classification). The two methods were compared on a class-by-class basis regarding the outcomes: mortality, early transfusion (overall and massive), and early surgical interventions for the torso or major vessels. RESULTS: In total, 603 children were enrolled, of whom 6.6% died. With the worsening of BD and vital signs, the outcome rates increased stepwise (most p<0.001; only between surgical interventions and vital signs, p=0.035). Mortality more commonly occurred in BD-based class IV than in vital signs-based class IV (58.8% vs. 32.7%, p=0.008). Early transfusion was more commonly performed in BD-based class III than in vital signs-based class III (overall, 73.8% vs. 53.7%, p=0.007; massive, 37.5% vs. 15.8%, p=0.001). No significant differences were found in the rates of early surgical interventions between the two methods. CONCLUSION: BD can be a better predictor of outcomes than vital signs in children with severe hemorrhagic shock.

Performance of the BIG Score in Predicting Mortality in Normotensive Children With Trauma.

OBJECTIVES: Children have a larger reserve for traumatic hemorrhagic shock, requiring a score that uses physiologic variables other than hypotension. Recently, the BIG score comprising admission base deficit, international normalized ratio, and the Glasgow Coma Scale has been reported to predict traumatic mortality. We aimed to validate the performance of the BIG score in mortality prediction of normotensive children with trauma. METHODS: We reviewed 1046 injured children (<18 years) who visited a Korean academic hospital from 2010 to 2018, excluding those with age-adjusted hypotension. In-hospital mortality, the BIG score and its predicted mortality, Revised Trauma Score, and Pediatric Trauma Score were calculated. We compared areas under the curve (AUCs) for in-hospital mortality of the 3 scores and did in-hospital and BIG-predicted mortalities. RESULTS: Of the 1046 children, 554 were enrolled with a 4.9% in-hospital mortality rate. The median BIG score was higher in the nonsurvivors (6.4 [interquartile range, 4.4-9.2] vs 20.1 [16.5-24.8]; P < 0.001). The AUC of the BIG score was 0.94 (95% confidence interval [CI], 0.92-0.96), which was higher than that of Pediatric Trauma Score (0.87 [95% CI, 0.84-0.90]; P < 0.001). The AUC of the BIG score tended to be higher than that of Revised Trauma Score without statistical significance (0.90 [95% CI, 0.87-0.92]; P = 0.130). We noted a parallel between in-hospital and BIG-predicted mortalities. The hemorrhage-related nonsurvivors showed higher median base deficit and BIG score than did the isolated traumatic brain injury-related ones. CONCLUSIONS: The BIG score can predict mortality with excellent accuracy in normotensive children with trauma.

Initial Characteristics and Clinical Severity of Hemophagocytic Lymphohistiocytosis in Pediatric Patients Admitted in the Emergency Department.

OBJECTIVES: The diagnosis and management of children with hemophagocytic lymphohistiocytosis (HLH) admitted in the emergency department (ED) are challenging. The present study aimed at describing the initial characteristics of pediatric patients with HLH upon admission in the ED. Moreover, the clinical severity of the condition was assessed. METHODS: We performed a retrospective study of patients who visited the pediatric ED and were newly diagnosed with HLH during hospitalization between February 2012 and January 2017. The patients were classified in the clinically unstable group if at least 1 of the following conditions was observed upon admission in the ED: hypoxia requiring oxygen supplementation, hypotension requiring inotropic support, coagulopathy with prothrombin time (international normalized ratio, ≥1.5), and seizures or altered consciousness. RESULTS: We enrolled 31 pediatric patients with HLH, with a median age of 6.53 years (interquartile range, 1.35-13.24 years). Abdominal discomfort along with fever (74.2%) was the most common presenting symptom in patients admitted in the ED. Based on the HLH-2004 diagnostic criteria, fever (96.8%), hyperferritinemia (96.8%), splenomegaly (74.2%), hypertriglyceridemia and/or hypofibrinogenemia (67.7%), and bicytopenia (41.9%) were observed in the patients. However, only 8 patients (25.8%) met the criteria. Nineteen patients (61.3%) were included in the clinically unstable group. This group had lower albumin (2.3 vs 3.3 g/dL, P = 0.002) and fibrinogen levels and higher ferritin level and neutrophil count than the clinically stable group. Meanwhile, the number of clinical findings that met the diagnostic criteria was not different between the 2 groups. Lower albumin level was a significant risk factor in the clinically unstable group (odds ratio, 0.040; P = 0.004). CONCLUSIONS: Pediatric patients with HLH often have clinically unstable conditions upon admission in the ED. However, only few patients meet the HLH-2004 diagnostic criteria. Lower albumin level may be useful in assessing clinically unstable patients and preparing for possible deterioration.

Admission Lactate and Base Deficit in Predicting Outcomes of Pediatric Trauma.

BACKGROUND: To compare admission lactate and base deficit (BD), which physiologically reflect early hemorrhagic shock, as outcome predictors of pediatric trauma. METHODS: We reviewed the data of children with trauma who visited a Korean academic hospital from 2010 through 2018. Admission lactate and BD were compared between children with and without primary outcomes. The outcomes included in-hospital mortality, early (≤24 h) transfusion, and early surgical interventions for the torso or major vessels. Subsequently, performances of lactate and BD in predicting the outcomes were compared using receiver operating characteristic curves. Logistic regressions were conducted to identify the independent associations of the two markers with each outcome. RESULTS: Of the 545 enrolled children, the mortality, transfusion, and surgical interventions occurred in 7.0%, 43.5%, and 14.9%, respectively. Cutoffs of lactate and BD for each outcome were as follows: mortality, 5.1 and 6.7 mmol/L; transfusion, 3.2 and 4.9 mmol/L; and surgical interventions, 2.9 and 5.2 mmol/L, respectively. No significant differences were found in the areas under the curve for each outcome. Of the two markers, a lactate of >5.1 mmol/L was associated with mortality (adjusted odds ratio, 6.43; 95% confidence interval, 2.61-15.84). A lactate of >3.2 mmol/L (2.82; 1.65-4.83) and a BD of >4.9 mmol/L (2.32; 1.32-4.10) were associated with transfusion, while only a BD of >5.2 mmol/L (2.17; 1.26-3.75) was done with surgical interventions. CONCLUSIONS: In pediatric trauma, lactate is more strongly associated with mortality. In contrast, BD may have a marginally stronger association with the need for hemorrhage-related procedures.

Human Cytomegalovirus-Induced Interleukin-10 Production Promotes the Proliferation of Mycobacterium massiliense in Macrophages.

Human cytomegalovirus (HCMV) exploits the interleukin-10 (IL-10) pathway as a part of its infection cycle through the manipulation of the host IL-10 signaling cascade. Based on its immunomodulatory nature, HCMV attenuates the host immune response and facilitates the progression of co-infection with other pathogens in an immune-competent host. To investigate the impact of HCMV infection on the burden of non-tuberculous mycobacteria (NTM), whose prevalence is growing rapidly worldwide, macrophages were infected with HCMV and further challenged with Mycobacterium massiliense in vitro. The results showed that HCMV infection significantly increased host IL-10 synthesis and promoted the proliferation of M. massiliense in an IL-10-dependent manner. Transcriptomic analysis revealed that HCMV infection dampened the regulatory pathways of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-1 (IL-1), consequently abrogating the immune responses to M. massiliense coinfection in macrophages. These findings provide a mechanistic basis of how HCMV infection may facilitate the development of pathogenic NTM co-infection by upregulating IL-10 expression.

HCMV-induced signaling through gB-EGFR engagement is required for viral trafficking and nuclear translocation in primary human monocytes.

Previous analysis of postentry events revealed that human cytomegalovirus (HCMV) displays a unique, extended nuclear translocation pattern in monocytes. We determined that c-Src signaling through pentamer engagement of integrins is required upon HCMV entry to avoid sorting of the virus into late endosomes and subsequent degradation. To follow up on this previous study, we designed experiments to investigate how HCMV-induced signaling through the other major axis-the epidermal growth factor receptor (EGFR) kinase-regulates viral postentry events. Here we show that HCMV induces chronic and functional EGFR signaling that is distinct to the virus as compared to the natural EGFR ligand: EGF. This chronic EGFR kinase activity in infected monocytes is required for the proper subcellular localization of the viral particle during trafficking events, as well as for promoting translocation of viral DNA into the host nucleus. Our data indicate that HCMV glycoprotein B (gB) binds to EGFR at the monocyte surface, the virus and EGFR are internalized together, and gB remains bound to EGFR throughout viral postentry events until de-envelopment to promote the chronic EGFR kinase activity required for viral trafficking and nuclear translocation. These data highlight how initial EGFR signaling via viral binding is necessary for entry, but not sufficient to promote each viral trafficking event. HCMV appears to manipulate the EGFR kinase postentry, via gB-EGFR interaction, to be active at the critical points throughout the trafficking process that leads to nuclear translocation and productive infection of peripheral blood monocytes.

Molecular and evolutionary analysis of dengue virus serotype 2 isolates from Korean travelers in 2015.

In Korea, dengue infection has been frequently reported in travelers to tropical and subtropical countries. Global warming increases the probability of autochthonous dengue outbreaks in Korea. In this report, the molecular and evolutionary properties of four dengue virus (DENV) type 2 isolates from Korean overseas travelers were examined. Three of these isolates were classified as Cosmopolitan genotypes and further divided into sublineages 1 (43,253, 43,254) and 2 (43,248), while the other isolate (KBPV-VR29) was related to American genotypes. The variable amino acid motifs related to virulence and replication were identified in the structural and non-structural proteins. A negative selection mechanism was clearly verified in all of the DENV proteins. Potential recombination events were identified in the NS5 protein of the XSBN10 strain. The substitution rate (5.32 × 10-4 substitutions per site) and the time of the most recent common ancestor (TMRCA) for each evolutionary group were determined by the Bayesian skyline coalescent method. This study shows that DENV type 2 strains with distinct phylogenetic, evolutionary, and virulence characteristics have been introduced into Korea by overseas travelers and have the potential to trigger autochthonous dengue outbreaks.

Point-of-care ultrasound may be useful for detecting pediatric intussusception at an early stage.

BACKGROUND: This study aimed to verify the usefulness of point-of-care ultrasound (POCUS) performed by pediatric emergency physicians for detecting intussusception at an early stage. METHODS: This retrospective study included 1-month- to 6-year-old children with clinically suspected intussusception, who underwent POCUS in the pediatric emergency department between December 2016 and February 2018. The criteria for performing POCUS were set to broader standards: presenting any one of intermittent abdominal pain/irritability or bloody stool, or ≥ 2 symptoms among nonspecific abdominal pain/irritability, abdominal mass/distension, vomiting, or lethargy. POCUS results were interpreted and categorized as "negative" or "suspicious," and a radiologist performed confirmatory ultrasound in "suspicious" cases. RESULTS: We analyzed 575 POCUS scans from 549 patients (mean age, 25.5 months). Among the 92 "suspicious" cases (16.0%), 70 (12.2%) were confirmed to have intussusception. POCUS showed 100% sensitivity, 95.6% specificity, and 97.8% accuracy. Patients with confirmed intussusception were mainly diagnosed in the early stages, with a mean symptom duration of 11.7 h, and most patients (97.1%) were treated successfully via air enema reduction. Compared to the non-intussusception group, the intussusception group had more intermittent abdominal pain (P < 0.001), but less vomiting (P = 0.001); the other clinical features showed no intergroup differences. CONCLUSION: POCUS performed using the criteria set to broader standards by pediatric emergency physicians may be useful for detecting intussusception at an early stage, which may present with obscure clinical symptoms.

A case of ingested water beads diagnosed with point-of-care ultrasound.

A previously healthy 12-month-old girl presented to the emergency department with vomiting of water beads (superabsorbent polymer). The girl did not have clinical or radiographic signs of residual foreign bodies or intestinal obstruction. Point-of-care ultrasound showed well-demarcated, round, and hypoechoic materials in the stomach and first part of the duodenum, indicating ingested beads. Subsequently, the beads were retrieved by the esophagogastroduodenoscopy. Because water beads can be readily found with point-of-care ultrasound, the use of this imaging modality can expedite endoscopic intervention and avoid surgical removal of foreign bodies.

Point-of-Care Ultrasound Could Streamline the Emergency Department Workflow of Clinically Nonspecific Intussusception.

OBJECTIVES: The aim of this study was to evaluate whether point-of-care ultrasound (POCUS) for intussusception screening streamlines the workflow of clinically nonspecific intussusception (CNI), an intussusception presenting with only 1 manifestation of the classic triad, and/or vomiting. METHODS: We reviewed 274 consecutive children with intussusception, aged 6 years or younger, who visited a tertiary care hospital emergency department between May 2012 and April 2016. This period was dichotomized by May 2014 (the "PRE" and "POST" groups), starting point of implementation of the POCUS protocol for intussusception screening. All children with CNI who had positive results on or forwent POCUS underwent radiologist-performed ultrasound (US). We measured and compared emergency department length of stay (EDLOS), the sum of door-to-reduction and observation times, and the frequency of POCUS and positive US results between the 2 groups. RESULTS: Of 160 children with CNI, 93 visited the emergency department since May 2014. The POST group showed a shorter median EDLOS (856 vs 630 minutes, P < 0.001), door-to-reduction time (137 vs 111 minutes, P = 0.002), and observation time (700 vs 532 minutes, P < 0.001). The POST group had a higher frequency of POCUS (12% vs 60%, P < 0.001) with positive US results (33% vs 59%, P < 0.001). The PRE group had a higher frequency of severe bowel edema (16% vs 1%, P < 0.001). No significant differences were found in the severity, recurrence, admission, and surgery. One child had a false-negative result on POCUS. CONCLUSIONS: Point-of-care ultrasound could streamline the workflow of CNI via decrease in EDLOS and unnecessary referrals for US.

Implications of Increased Weight Status for the Occurrence of Fall-Induced Intracranial Hemorrhage in Children Aged 4 Years or Younger.

OBJECTIVES: The aim of this study was to investigate the association between increased weight status (IWS), a weight for age/sex at greater than the 95th percentile, and fall-induced intracranial hemorrhage (ICH) in children aged 4 years or younger. METHODS: In 7072 children aged 4 years or younger with head injury who visited a tertiary care hospital emergency department in Korea from 2013 through 2015, the presence of fall-induced ICH was reviewed. The association between IWS and ICH was investigated by multivariable logistic regression. We retrospectively validated the Pediatric Emergency Care Applied Research Network rule alone and in combination with IWS for predicting ICH. RESULTS: Of 7072 children, 547 (7.7%) underwent computed tomography, of whom 451 (6.4%) were enrolled. Of these, 41 (9.1%; estimated event rate, 0.6%) had ICHs, and 26 (5.8%) had IWS. Increased weight status was more common in the children with ICH (P = 0.023). The association between IWS and ICH remained significant after adjustment (odds ratio, 5.24; 95% confidence interval [CI], 1.49-18.46; P = 0.010). The validation of the rule in combination with IWS showed no significant increases in a sensitivity (92.7% [95% CI, 80.1%-98.5%] to 95.7% [95% CI, 83.5%-99.4%]) and negative predictive value (98.2% [95% CI, 94.7%-99.4%] to 98.8% [95% CI, 95.4%-99.8%]). CONCLUSIONS: Increased weight status is associated with fall-induced ICH in children aged 4 years or younger. Information on weight status could be potentially helpful in predicting ICH in young children with fall-induced head injury.

Delayed adenosine therapy is associated with the refractory supraventricular tachycardia in children.

OBJECTIVES: To study the association of time intervals on adenosine therapy with the occurrence of refractory supraventricular tachycardia (SVT) in children. METHODS: We reviewed 334 episodes of presumed SVT requiring adenosine in children (<18 years) who visited 4 academic hospital emergency departments (EDs) from July 2013 through June 2017. Refractory SVT was defined as an SVT episode persisting after 2 doses of adenosine. Clinical and electrocardiographic findings, and symptom-to-adenosine (symptom-to-ED plus ED-to-adenosine) time of refractory and responsive SVT episodes were compared. Multivariable logistic regression was performed to identify factors associated with the occurrence of refractory SVT. RESULTS: Of 211 SVT episodes, 42 episodes of refractory SVT (19.9%) were noted (overall sinus conversion rate, 79.6%). The refractory episodes were associated with a higher frequency of known structural heart diseases (9.5% vs. 1.8%; P = 0.030) and a longer median ED-to-adenosine time (15.5 vs. 11.0 min; P = 0.018). The association of the ED-to-adenosine time with refractory SVT remained significant after adjustment (for increment of 1 min; aOR, 1.02; 95% CI, 1.007-1.04). CONCLUSIONS: Delayed adenosine therapy is associated with the occurrence of refractory SVT in children, supporting the need for prompt adenosine therapy.