Ronald C. Sanders

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

BACKGROUND Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS We conducted this trial of two targeted temperature interventions at 38 childrens hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Critically ill children during the 2009-2010 influenza pandemic in the United States.

BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1–20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors.

Level of Trainee and Tracheal Intubation Outcomes

BACKGROUND: Tracheal intubation is an important intervention to stabilize critically ill and injured children. Provider training level has been associated with procedural safety and outcomes in the neonatal intensive care settings. We hypothesized that tracheal intubation success and adverse tracheal intubation–associated events are correlated with provider training level in the PICU. METHODS: A prospective multicenter observational cohort study was performed across 15 PICUs to evaluate tracheal intubation between July 2010 to December 2011. All data were collected by using a standard National Emergency Airway Registry for Children reporting system endorsed as a Quality Improvement project of the Pediatric Acute Lung Injury and Sepsis Investigator network. Outcome measures included first attempt success, overall success, and adverse tracheal intubation–associated events. RESULTS: Reported were 1265 primary oral intubation encounters by pediatric providers. First and overall attempt success were residents (37%, 51%), fellows (70%, 89%), and attending physicians (72%, 94%). After adjustment for relevant patient factors, fellow provider was associated with a higher rate of first attempt success (odds ratio [OR], 4.29; 95% confidence interval [CI], 3.24–5.68) and overall success (OR, 9.27; 95% CI, 6.56–13.1) compared with residents. Fellow (versus resident) as first airway provider was associated with fewer tracheal intubation associated events (OR, 0.42; 95% CI, 0.31–0.57). CONCLUSIONS: Across a broad spectrum of PICUs, resident provider tracheal intubation success is low and adverse associated events are high, compared with fellows. More intensive pediatric resident procedural training is necessary before “live” tracheal intubations in the intensive care setting.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

Background Targeted temperature management is recommended for comatose adults and children after out‐of‐hospital cardiac arrest; however, data on temperature management after in‐hospital cardiac arrest are limited. Methods In a trial conducted at 37 childrens hospitals, we compared two temperature interventions in children who had had in‐hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS‐II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS‐II score of at least 70 before the cardiac arrest. Results The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS‐II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS‐II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1‐year survival, the rate of 1‐year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood‐product use, infection, and serious adverse events, as well as 28‐day mortality, did not differ significantly between groups. Conclusions Among comatose children who survived in‐hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA‐IH ClinicalTrials.gov number, NCT00880087.)

The Collaborative Pediatric Critical Care Research Network Critical Pertussis Study: collaborative research in pediatric critical care medicine.

Objective: To provide an updated overview of critical pertussis to the pediatric critical care community and describe a study of critical pertussis recently undertaken. Setting: The six sites, seven hospitals of the Collaborative Pediatric Critical Care Research Network, and 17 outside sites at academic medical centers with pediatric intensive care units. Results: Despite high coverage for childhood vaccination, pertussis causes substantial morbidity and mortality in US children, especially among infants. In pediatric intensive care units, Bordetella pertussis is a community-acquired pathogen associated with critical illness and death. The incidence of medical and developmental sequelae in critical pertussis survivors remains unknown, and the appropriate strategies for treatment and support remain unclear. The Collaborative Pediatric Critical Care Research Network Critical Pertussis Study has begun to evaluate critical pertussis in a prospective cohort. Conclusion: Research is urgently needed to provide an evidence base that might optimize management for critical pertussis, a serious, disabling, and too often fatal illness for U.S. children and those in the developing world.

Bactericidal effects of silver plus titanium dioxide-coated endotracheal tubes on Pseudomonas aeruginosa and Staphylococcus aureus

Purpose: Ventilator-associated pneumonia (VAP) is a nosocomial infection resulting in significant morbidity and mortality. Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) are pathogens associated with VAP. Silver (Ag) coating of endotracheal tubes (ETTs) reduces bacterial colonization, however titanium dioxide (TiO2) coating has not been studied. Methods: Five types of ETT coatings were applied over silica layer: Ag, solgel TiO2, solgel TiO2 with Ag, Degussa P25 TiO2 (Degussa TiO2), and Degussa TiO2 with Ag. After ETTs were incubated with P. aeruginosa or S. aureus; colonization was determined quantitatively. Results: Pseudomonas aeruginosa and S. aureus grew for 5 days on standard ETTs. Compared to standard ETTs, P. aeruginosa growth was significantly inhibited by solgel TiO2 with Ag at 24 hours, and by Degussa TiO2 with Ag at 24 and 48 hours after inoculation. No significant difference in S. aureus growth was observed between the control and any of the five coatings for 5 days. Conclusion: In vitro, solgel TiO2 with Ag and Degussa TiO2 with Ag both attenuated P. aeruginosa growth, but demonstrated no effect on S. aureus colonization. Further studies using alternative coating and incorporating UV light exposure are needed to identify their potential utility in reducing VAP.

Development of a Quality Improvement Bundle to Reduce Tracheal Intubation–Associated Events in Pediatric ICUs

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.

Relationship Between Adverse Tracheal Intubation Associated Events and PICU Outcomes

Objective: Tracheal intubation in PICUs is a common procedure often associated with adverse events. The aim of this study is to evaluate the association between immediate events such as tracheal intubation associated events or desaturation and ICU outcomes: length of stay, duration of mechanical ventilation, and mortality. Study Design: Prospective cohort study with 35 PICUs using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from January 2013 to June 2015. Desaturation defined as Spo2 less than 80%. Setting: PICUs participating in NEAR4KIDS. Patients: All patients less than18 years of age undergoing primary tracheal intubations with ICU outcome data were analyzed. Measurements and Main Results: Five thousand five hundred four tracheal intubation encounters with median 108 (interquartile range, 58–229) tracheal intubations per site. At least one tracheal intubation associated event was reported in 892 (16%), with 364 (6.6%) severe tracheal intubation associated events. Infants had a higher frequency of tracheal intubation associated event or desaturation than older patients (48% infants vs 34% for 1–7 yr and 18% for 8–17 yr). In univariate analysis, the occurrence of tracheal intubation associated event or desaturation was associated with a longer mechanical ventilation (5 vs 3 d; p < 0.001) and longer PICU stay (14 vs 11 d; p < 0.001) but not with PICU mortality. The occurrence of severe tracheal intubation associated events was associated with longer mechanical ventilation (5 vs 4 d; p < 0.003), longer PICU stay (15 vs 12 d; p < 0.035), and PICU mortality (19.9% vs 9.6%; p < 0.0001). In multivariable analyses, the occurrence of tracheal intubation associated event or desaturation was significantly associated with longer mechanical ventilation (+12%; 95% CI, 4–21%; p = 0.004), and severe tracheal intubation associated events were independently associated with increased PICU mortality (OR = 1.80; 95% CI, 1.24–2.60; p = 0.002), after adjusted for patient confounders. Conclusions: Adverse tracheal intubation associated events and desaturations are common and associated with longer mechanical ventilation in critically ill children. Severe tracheal intubation associated events are associated with higher ICU mortality. Potential interventions to decrease tracheal intubation associated events and oxygen desaturation, such as tracheal intubation checklist, use of apneic oxygenation, and video laryngoscopy, may need to be considered to improve ICU outcomes.

Goal-Directed Resuscitative Interventions During Pediatric Interfacility Transport.

Objectives:This article reports results of the first National Institutes of Health-funded prospective interfacility transport study to determine the effect of goal-directed therapy administered by a specialized pediatric team to critically ill children with the systemic inflammatory response syndrome. We hypothesized that goal-directed therapy during interfacility transport would decrease hospital length of stay, prevent multiple organ dysfunction, and reduce subsequent ICU interventions. Design:Before-and-after intervention trial. Setting:During interfacility transport of critically ill patients by a specialized pediatric transport team, back to a tertiary care children’s hospital. Patients:Before-and-after intervention trial. Design:Interfacility pediatric transport patients, age 1 month to 17 years, with systemic inflammatory response syndrome. Interventions:Prospective data were collected on all pediatric interfacility transport patients with systemic inflammatory response syndrome transported by the Angel One Transport team at Arkansas Children’s Hospital. A 10-month data collection period was followed by institution of a goal-directed resuscitation protocol. Data were subsequently collected for 10 additional months followed by comparison of pre- and postintervention groups. All transport personnel underwent training with didactics and high-fidelity simulation until mastery with goal-directed resuscitation was achieved. Measurements and Main Results:All transport patients were screened for systemic inflammatory response syndrome using established variables and 235 (123 preintervention and 112 postintervention) were enrolled. Univariate analysis revealed shorter hospital stay (11 ± 15 d vs 7 ± 10 d; p = 0.02) and fewer required therapeutic ICU interventions in the postintervention group (Therapeutic Intervention Scoring System-28 Scores, 19.4 ± 6.8 vs 17.3 ± 6.6; p = 0.04). ICU stay and prevalence of organ dysfunction were not statistically different. Multivariable analysis showed a 1.6-day (95% CI, 1.3–2.03; p = 0.02) decrease in hospital stay in the postintervention group. Conclusions:This study suggests that goal-directed therapy administered by a specialized pediatric transport team has the potential to impact the outcomes of critically ill children. Findings from this study should be confirmed across multiple institutions, but have the potential to impact the clinical outcomes of critically ill children with systemic inflammatory response syndrome.

Comparison of work of breathing between two neonatal ventilators utilizing a neonatal pig model.

Objective The purpose of this study was to determine whether variations in the delivery systems of continuous positive airway pressure between two ventilators would lead to differences in patient work of breathing (WOBp). Design Comparison of two neonatal ventilators with a neonatal pig model. Setting Animal laboratory. Subjects Thirty healthy, intubated, sedated, spontaneously breathing neonatal piglets weighing 1.0–2.0 kg. Interventions Patient work of breathing (WOBp) (gm cm/kg) was measured by using measurements based on an esophageal balloon and a flow transducer. Each breath was analyzed for ventilator response times (in msecs) and negative deflection of pressure. Each animal was studied with the Siemens SV300 and Drager Babylog 8000, on continuous positive airway pressure settings of 0, 3, and 5 cm H2O. Data were analyzed by using Wilcoxon’s Signed Rank Test with significance of p ≤ .05. Measurements and Main Results Comparing ventilators, WOBp was on average 29% higher in the Babylog. Analysis of individual breaths showed that disparity in WOBp was probably related to the automatic availability of 2 cm H2O pressure support ventilation in the SV300. This may also explain the differences in delay time during the start of the inspiratory phase before initiation of gas flow. The mean duration of inspiratory effort was 394 (± 157) msecs in the Babylog and 138 (± 35) msecs in the SV300, a 174% increase in time delay for the Babylog (p = .005). During inspiratory effort, there was >1 cm H2O negative pressure before flow was available with the Babylog. Conclusions In intubated patients, maximum energy expenditure occurs at the initiation of ventilator breaths. WOBp in neonatal pigs was significantly increased. The response time of the ventilators may explain the differences in initiation of flow times and patient work. These differences may have important implications for energy kinetics, weight gain, and duration of mechanical ventilation in preterm neonates.