Adam Schwarz

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.).

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.)

Accuracy of an Extubation Readiness Test in Predicting Successful Extubation in Children With Acute Respiratory Failure From Lower Respiratory Tract Disease

Objective: Identifying children ready for extubation is desirable to minimize morbidity and mortality associated with prolonged mechanical ventilation and extubation failure. We determined the accuracy of an extubation readiness test (Randomized Evaluation of Sedation Titration for Respiratory Failure extubation readiness test) in predicting successful extubation in children with acute respiratory failure from lower respiratory tract disease. Design: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial, a pediatric multicenter cluster randomized trial of sedation. Setting: Seventeen PICUs in the intervention arm. Patients: Children 2 weeks to 17 years receiving invasive mechanical ventilation for lower respiratory tract disease. Intervention: Extubation readiness test in which spontaneously breathing children with oxygenation index less than or equal to 6 were placed on FIO2 of 0.50, positive end-expiratory pressure of 5 cm H2O, and pressure support. Measurements and Main Results: Of 1,042 children, 444 (43%) passed their first extubation readiness test. Of these, 295 (66%) were extubated within 10 hours of starting the extubation readiness test, including 272 who were successfully extubated, for a positive predictive value of 92%. Among 861 children who were extubated for the first time within 10 hours of performing an extubation readiness test, 788 passed their extubation readiness test and 736 were successfully extubated for a positive predictive value of 93%. The median time of day for extubation with an extubation readiness test was 12:15 hours compared with 14:54 hours for extubation without an extubation readiness test within 10 hours (p < 0.001). Conclusions: In children with acute respiratory failure from lower respiratory tract disease, an extubation readiness test, as described, should be considered at least daily if the oxygenation index is less than or equal to 6. If the child passes the extubation readiness test, there is a high likelihood of successful extubation.

Pediatric Ventilator-associated Infections: The Ventilator-associated Infection Study

Objective: Suspected ventilator-associated infection is the most common reason for antibiotics in the PICU. We sought to characterize the clinical variables associated with continuing antibiotics after initial evaluation for suspected ventilator-associated infection and to determine whether clinical variables or antibiotic treatment influenced outcomes. Design: Prospective, observational cohort study conducted in 47 PICUs in the United States, Canada, and Australia. Two hundred twenty-nine pediatric patients ventilated more than 48 hours undergoing respiratory secretion cultures were enrolled as “suspected ventilator-associated infection” in a prospective cohort study, those receiving antibiotics of less than or equal to 3 days were categorized as “evaluation only,” and greater than 3 days as “treated.” Demographics, diagnoses, comorbidities, culture results, and clinical data were compared between evaluation only and treated subjects and between subjects with positive versus negative cultures. Setting: PICUs in 47 hospitals in the United States, Canada, and Australia. Subjects: All patients undergoing respiratory secretion cultures during the 6 study periods. Interventions: None. Measurements and Main Results: Treated subjects differed from evaluation-only subjects only in frequency of positive cultures (79% vs 36%; p < 0.0001). Subjects with positive cultures were more likely to have chronic lung disease, tracheostomy, and shorter PICU stay, but there were no differences in ventilator days or mortality. Outcomes were similar in subjects with positive or negative cultures irrespective of antibiotic treatment. Immunocompromise and higher Pediatric Logistic Organ Dysfunction scores were the only variables associated with mortality in the overall population, but treated subjects with endotracheal tubes had significantly lower mortality. Conclusions: Positive respiratory cultures were the primary determinant of continued antibiotic treatment in children with suspected ventilator-associated infection. Positive cultures were not associated with worse outcomes irrespective of antibiotic treatment although the lower mortality in treated subjects with endotracheal tubes is notable. The necessity of continuing antibiotics for a positive respiratory culture in suspected ventilator-associated infection requires further study.

Association of early postresuscitation hypotension with survival to discharge after targeted temperature management for pediatric out-of-hospital cardiac arrest secondary analysis of a randomized clinical trial

Importance Out-of-hospital cardiac arrest (OHCA) occurs in more than 6000 children each year in the United States, with survival rates of less than 10% and severe neurologic morbidity in many survivors. Post–cardiac arrest hypotension can occur, but its frequency and association with survival have not been well described during targeted temperature management. Objective To determine whether hypotension is associated with survival to discharge in children and adolescents after resuscitation from OHCA. Design, Setting, and Participants This post hoc secondary analysis of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial included 292 pediatric patients older than 48 hours and younger than 18 years treated in 36 pediatric intensive care units from September 1, 2009, through December 31, 2012. Participants underwent therapeutic hypothermia (33.0°C) vs therapeutic normothermia (36.8°C) for 48 hours. All participants had hourly systolic blood pressure measurements documented during the initial 6 hours of temperature intervention. Hourly blood pressures beginning at the time of temperature intervention (time 0) were normalized for age, sex, and height. Early hypotension was defined as a systolic blood pressure less than the fifth percentile during the first 6 hours after temperature intervention. With use of forward stepwise logistic regression, covariates of interest (age, sex, initial cardiac rhythm, any preexisting condition, estimated duration of cardiopulmonary resuscitation [CPR], primary cause of cardiac arrest, temperature intervention group, night or weekend cardiac arrest, witnessed status, and bystander CPR) were evaluated in the final model. Data were analyzed from February 5, 2016, through June 13, 2017. Exposures Hypotension. Main Outcomes and Measure Survival to hospital discharge. Results Of 292 children (194 boys [66.4%] and 98 girls [33.6%]; median age, 23.0 months [interquartile range, 5.0-105.0 months]), 78 (26.7%) had at least 1 episode of early hypotension. No difference was observed between the therapeutic hypothermia and therapeutic normothermia groups in the prevalence of hypotension during induction and maintenance (73 of 153 [47.7%] vs 72 of 139 [51.8%]; P = .50) or rewarming (35 of 118 [29.7%] vs 19 of 95 [20.0%]; P = .10) during the first 72 hours. Participants who had early hypotension were less likely to survive to hospital discharge (20 of 78 [25.6%] vs 93 of 214 [43.5%]; adjusted odds ratio, 0.39; 95% CI, 0.20-0.74). Conclusions and Relevance In this post hoc secondary analysis of the THAPCA trial, 26.7% of participants had hypotension within 6 hours after temperature intervention. Early post–cardiac arrest hypotension was associated with lower odds of discharge survival, even after adjusting for covariates of interest.

Racial and Ethnic Disparities in Parental Refusal of Consent in a Large, Multisite Pediatric Critical Care Clinical Trial

Objective To evaluate whether race or ethnicity was independently associated with parental refusal of consent for their childs participation in a multisite pediatric critical care clinical trial. Study design We performed a secondary analyses of data from Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), a 31‐center cluster randomized trial of sedation management in critically ill children with acute respiratory failure supported on mechanical ventilation. Multivariable logistic regression modeling estimated associations between patient race and ethnicity and parental refusal of study consent. Result Among the 3438 children meeting enrollment criteria and approached for consent, 2954 had documented race/ethnicity of non‐Hispanic White (White), non‐Hispanic Black (Black), or Hispanic of any race. Inability to approach for consent was more common for parents of Black (19.5%) compared with White (11.7%) or Hispanic children (13.2%). Among those offered consent, parents of Black (29.5%) and Hispanic children (25.9%) more frequently refused consent than parents of White children (18.2%, P < .0167 for each). Compared with parents of White children, parents of Black (OR 2.15, 95% CI 1.56‐2.95, P < .001) and Hispanic (OR 1.44, 95% CI 1.10‐1.88, P = .01) children were more likely to refuse consent. Parents of children offered participation in the intervention arm were more likely to refuse consent than parents in the control arm (OR 2.15, 95% CI 1.37‐3.36, P < .001). Conclusions Parents of Black and Hispanic children were less likely to be approached for, and more frequently declined consent for, their childs participation in a multisite critical care clinical trial. Ameliorating this racial disparity may improve the validity and generalizability of study findings. Trial registration ClinicalTrials.gov: NCT00814099.

Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness

Abstract Background Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza–MRSA pneumonia and evaluated antibiotic use. Methods We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008–5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. Results We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza–MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza–MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤ .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8–22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL. Conclusions Influenza–MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.