Dennis W. Simon

Rates of Medical Errors and Preventable Adverse Events Among Hospitalized Children Following Implementation of a Resident Handoff Bundle

IMPORTANCE Handoff miscommunications are a leading cause of medical errors. Studies comprehensively assessing handoff improvement programs are lacking. OBJECTIVE To determine whether introduction of a multifaceted handoff program was associated with reduced rates of medical errors and preventable adverse events, fewer omissions of key data in written handoffs, improved verbal handoffs, and changes in resident-physician workflow. DESIGN, SETTING, AND PARTICIPANTS Prospective intervention study of 1255 patient admissions (642 before and 613 after the intervention) involving 84 resident physicians (42 before and 42 after the intervention) from July-September 2009 and November 2009-January 2010 on 2 inpatient units at Boston Childrens Hospital. INTERVENTIONS Resident handoff bundle, consisting of standardized communication and handoff training, a verbal mnemonic, and a new team handoff structure. On one unit, a computerized handoff tool linked to the electronic medical record was introduced. MAIN OUTCOMES AND MEASURES The primary outcomes were the rates of medical errors and preventable adverse events measured by daily systematic surveillance. The secondary outcomes were omissions in the printed handoff document and resident time-motion activity. RESULTS Medical errors decreased from 33.8 per 100 admissions (95% CI, 27.3-40.3) to 18.3 per 100 admissions (95% CI, 14.7-21.9; P < .001), and preventable adverse events decreased from 3.3 per 100 admissions (95% CI, 1.7-4.8) to 1.5 (95% CI, 0.51-2.4) per 100 admissions (P = .04) following the intervention. There were fewer omissions of key handoff elements on printed handoff documents, especially on the unit that received the computerized handoff tool (significant reductions of omissions in 11 of 14 categories with computerized tool; significant reductions in 2 of 14 categories without computerized tool). Physicians spent a greater percentage of time in a 24-hour period at the patient bedside after the intervention (8.3%; 95% CI 7.1%-9.8%) vs 10.6% (95% CI, 9.2%-12.2%; P = .03). The average duration of verbal handoffs per patient did not change. Verbal handoffs were more likely to occur in a quiet location (33.3%; 95% CI, 14.5%-52.2% vs 67.9%; 95% CI, 50.6%-85.2%; P = .03) and private location (50.0%; 95% CI, 30%-70% vs 85.7%; 95% CI, 72.8%-98.7%; P = .007) after the intervention. CONCLUSIONS AND RELEVANCE Implementation of a handoff bundle was associated with a significant reduction in medical errors and preventable adverse events among hospitalized children. Improvements in verbal and written handoff processes occurred, and resident workflow did not change adversely.

Emerging Therapies in Traumatic Brain Injury

Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. Using a mechanism-based approach the authors define the targets and emerging therapies for TBI. They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discussTBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field.

Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation after Traumatic Brain Injury in Children

Objectives: The magnitude and role of the cellular immune response following pediatric traumatic brain injury remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric traumatic brain injury by measuring cerebrospinal fluid levels of soluble cluster of differentiation 163 and ferritin and soluble interleukin-2 receptor &agr;, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome. Design: Retrospective analysis of samples from an established, single-center cerebrospinal fluid bank. Setting: PICU in a tertiary children’s hospital. Patients: Sixty-six pediatric patients after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1 month to 16 years old and 17 control patients who were 1 month to 14 years old. Interventions: None. Measurements and Main Results: Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor &agr; were determined by enzyme-linked immunosorbent assay at two time points (t1 = 17 ± 10 hr; t2 = 72 ± 15 hr) for each traumatic brain injury patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor &agr; after traumatic brain injury were compared with controls and analyzed for associations with age, patient sex, initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid level of soluble cluster of differentiation 163 was increased in traumatic brain injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile range, 21.8–134.0 ng/mL] vs 31.0 ng/mL [5.7–77.7 ng/mL] and 27.8 ng/mL [19.1–43.1 ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was increased in traumatic brain injury patients at t2 and t1 versus controls (8.3 ng/mL [<7.5–19.8 ng/mL] and 8.9 ng/mL [<7.5–26.7 ng/mL] vs <7.5 ng/mL below lower limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of soluble interleukin-2 receptor &agr; in traumatic brain injury patients at t2 and t1 were not different versus controls. Multivariate regression revealed associations between high ferritin and age 4 years or younger, lower Glasgow Coma Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score. Conclusions: Children with traumatic brain injury demonstrate evidence for macrophage activation after traumatic brain injury, and in terms of cerebrospinal fluid ferritin, this appears more prominent with young age, initial injury severity, abusive head trauma, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses and whether inflammation represents a therapeutic target after traumatic brain injury.

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

Objectives: We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Design: Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Setting: Tertiary children’s hospital PICU. Patients: One hundred consecutive severe sepsis admissions. Interventions: Clinical data were recorded daily, and blood was collected twice weekly. Measurements and Main Results: Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Conclusions: Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

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.

Trend and Outcomes of Video Laryngoscope Use Across Picus.

Objective: Video (indirect) laryngoscopy is used as a primary tracheal intubation device for difficult airways in emergency departments and in adult ICUs. The use and outcomes of video laryngoscopy compared with direct laryngoscopy has not been quantified in PICUs or cardiac ICUs. Design: Retrospective review of prospectively collected observational data from a multicenter tracheal intubation database (National Emergency Airway Registry for Children) from July 2010 to June 2015. Setting: Thirty-six PICUs/cardiac ICUs across the United States, Canada, Japan, New Zealand, and Singapore. Patients: Any patient admitted to a PICU or a pediatric cardiac ICU and undergoing tracheal intubation. Interventions: Use of direct laryngoscopy versus video laryngoscopy for tracheal intubation. Measurements and Main Results: There were 8,875 tracheal intubations reported in the National Emergency Airway Registry for Children database, including 7,947 (89.5%) tracheal intubations performed using direct laryngoscopy and 928 (10.5%) tracheal intubations performed using video laryngoscopy. Wide variability in video laryngoscopy use exists across PICUs (median, 2.6%; range, 0–55%). Video laryngoscopy was more often used in older children (p < 0.001), in children with history of a difficult airway (p = 0.01), in children intubated for ventilatory failure (p < 0.001), and to facilitate the completion of an elective procedure (p = 0.048). After adjusting for patient-level covariates, a secular trend, and site-level variance, the use of video laryngoscopy significantly increased over a 5-year period compared with fiscal year 2011 (odds ratio, 6.7; 95% CI, 1.7–26.8 for fiscal year 2014 and odds ratio, 11.2; 95% CI, 3.2–38.9 for fiscal year 2015). The use of video laryngoscopy was independently associated with a lower occurrence of tracheal intubation adverse events (adjusted odds ratio, 0.57; 95% CI, 0.42–0.77; p < 0.001) but not with a lower occurrence of severe tracheal intubation adverse events (adjusted odds ratio, 0.86; 95% CI, 0.56–1.32; p = 0.49) or fewer multiple attempts at endotracheal intubation (adjusted odds ratio, 0.93; 95% CI, 0.71–1.22; p = 0.59). Conclusions: Using National Emergency Airway Registry for Children data, we described patient-centered adverse outcomes associated with video laryngoscopy compared with direct laryngoscopy for tracheal intubation in the largest reported international cohort of children to date. Data from this study may be used to design sufficiently powered prospective studies comparing patient-centered outcomes for video laryngoscopy versus direct laryngoscopy during endotracheal intubation.

How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis.

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A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis.

Objectives: We tested the hypothesis that a C-reactive protein and ferritin-based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis. Design: Prospective cohort study. Setting: Tertiary PICU. Patients: Children with 100 separate admission episodes of severe sepsis were enrolled. Interventions: Blood samples were attained on day 2 of sepsis and bi-weekly for biomarker batch analysis. A 2 × 2 contingency table using C-reactive protein and ferritin thresholds was developed. Measurements and Main Results: A C-reactive protein of 4.08 mg/dL and a ferritin of 1,980 ng/mL were found to be optimal cutoffs for outcome prediction at first sampling (n = 100) using the Youden index. PICU mortality was increased in the “high-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL category (6/13 [46.15%]) compared with the “intermediate-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin less than 1,980 ng/mL or C-reactive protein less than 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL categories (2/43 [4.65%]), and the “low-risk” C-reactive protein less than 4.08 mg/dL and ferritin less than 1,980 ng/mL category (0/44 [0%]) (odds ratio, 36.43 [95% CI, 6.16–215.21]). The high-risk category was also associated with the development of immunoparalysis (odds ratio, 4.47 [95% CI, 1.34–14.96]) and macrophage activation syndrome (odds ratio, 24.20 [95% CI, 5.50–106.54]). Sixty-three children underwent sequential blood sampling; those who were initially in the low-risk category (n = 24) and those who subsequently migrated (n = 19) to the low-risk category all survived, whereas those who remained in the “at-risk” categories had increased mortality (7/20 [35%]; p < 0.05). Conclusions: A C-reactive protein- and ferritin-based contingency table effectively assessed mortality risk. Reduction in systemic inflammation below a combined threshold C-reactive protein of 4.08 mg/dL and ferritin of 1,980 ng/mL appeared to be a desired response in children with severe sepsis.

Clinical Impact of External Laryngeal Manipulation During Laryngoscopy on Tracheal Intubation Success in Critically Ill Children

Objectives: External laryngeal manipulation is a commonly used maneuver to improve visualization of the glottis during tracheal intubation in children. However, the effectiveness to improve tracheal intubation attempt success rate in the nonanesthesia setting is not clear. The study objective was to evaluate the association between external laryngeal manipulation use and initial tracheal intubation attempt success in PICUs. Design: A retrospective observational study using a multicenter emergency airway quality improvement registry. Setting: Thirty-five PICUs within general and children’s hospitals (29 in the United States, three in Canada, one in Japan, one in Singapore, and one in New Zealand). Patients: Critically ill children (< 18 years) undergoing initial tracheal intubation with direct laryngoscopy in PICUs between July 1, 2010, and December 31, 2015. Measurements and Main Results: Propensity score–matched analysis was performed to evaluate the association between external laryngeal manipulation and initial attempt success while adjusting for underlying differences in patient and clinical care factors: age, obesity, tracheal intubation indications, difficult airway features, provider training level, and neuromuscular blockade use. External laryngeal manipulation was defined as any external force to the neck during laryngoscopy. Of the 7,825 tracheal intubations, the initial tracheal intubation attempt was successful in 1,935/3,274 intubations (59%) with external laryngeal manipulation and 3,086/4,551 (68%) without external laryngeal manipulation (unadjusted odds ratio, 0.69; 95% CI, 0.62–0.75; p < 0.001). In propensity score–matched analysis, external laryngeal manipulation remained associated with lower initial tracheal intubation attempt success (adjusted odds ratio, 0.93; 95% CI, 0.90–0.95; p < 0.001). Conclusions: External laryngeal manipulation during direct laryngoscopy was associated with lower initial tracheal intubation attempt success in critically ill children, even after adjusting for underlying differences in patient factors and provider levels. The indiscriminate use of external laryngeal manipulation cannot be recommended.

Rationale for Adjunctive Therapies for Pediatric Sepsis Induced Multiple Organ Failure

Adjunctive therapies have been proposed for use in at least 5 inflammation pathobiology phenotypes in pediatric sepsis-induced multiple organ failure. This article discusses host-pathogen interaction prototypes to facilitate understanding of the rationale for personalized therapy in these phenotypes. The article discusses the literature on adjunctive antiinflammatory and immune modulation therapies that, in addition to traditional organ support and infection source control, might be part of a personalized precision medicine approach to the reversal of each of these inflammatory pathobiology phenotypes.