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 children's 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 .).

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 children's 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.).

Strategies to Maximize Enrollment in a Prospective Study of Comatose Children in the PICU.

OBJECTIVES: To analyze barriers to recruitment encountered during a prospective study in the PICU and evaluate strategies implemented to improve recruitment. DESIGN: Prospective observational study of continuous electroencephalogram monitoring in comatose children. SETTING: PICUs at four North American institutions. PATIENTS: Patients with a Glasgow Coma Scale score of less than or equal to 8 for at least an hour. INTERVENTIONS: Four strategies to increase recruitment were sequentially implemented. MEASUREMENTS AND MAIN RESULTS: The baseline enrollment rate was 2.1 subjects/mo, which increased following the single-site introduction of real-time patient screening using an online dashboard (4.5 subjects/mo), deferred consenting (5.2 subjects/mo), and weekend screening (6.1 subjects/mo). However, the subsequent addition of three new study sites was the greatest accelerator of enrollment (21 subjects/mo), representing a 10-fold increase from baseline (p < 0.0001). CONCLUSIONS: Identifying barriers to recruitment and implementing creative strategies to increase recruitment can successfully increase enrollment rates in the challenging ICU environment.

Serum Biomarkers Help Predict Attention Problems in Critically Ill Children With Traumatic Brain Injury.

OBJECTIVE: To evaluate the association between acute serum biomarkers, and the changes in attention at 1 year following traumatic brain injury. DESIGN AND SETTING: A prospective observational and laboratory study conducted in PICUs at five Canadian children's hospitals. STUDY POPULATION AND MEASUREMENTS: Fifty-eight patients aged 5 to 17 years with traumatic brain injury were enrolled in the study. Nine brain-specific and inflammatory serum protein biomarkers were measured multiple times over the first week following injury. Attention was measured at "baseline" to represent pre-injury function and at 1 year following injury using the Conners Third Parent Rating Scale. RESULTS: Compared with baseline, there were significantly more clinical symptoms of inattention at 1 year post injury. The Glasgow Coma Scale score, age at injury, baseline levels of inattention, and highest levels of serum biomarkers were used to estimate the probability of developing inattention. These independent variables were first evaluated individually followed by combinations of the best predictors using area under the receiver operating characteristic curve analyses. A combination of high baseline levels of inattention and high serum levels of the biomarker neuron-specific enolase was the best predictor for inattention. Glasgow Coma Scale and age at injury were not associated with inattention at 1 year post injury. CONCLUSIONS: Combining baseline assessment of attention with measurement of serum biomarkers shows promise as reliable, early predictors of long-term attention after childhood traumatic brain injury.

Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications.

OBJECTIVE: To describe outcomes and complications in the drowning subgroup from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial. DESIGN: Exploratory post hoc cohort analysis. SETTING: Twenty-four PICUs. PATIENTS: Pediatric drowning cases. INTERVENTIONS: Therapeutic hypothermia versus therapeutic normothermia. MEASUREMENTS AND MAIN RESULTS: An exploratory study of pediatric drowning from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial was conducted. Comatose patients aged more than 2 days and less than 18 years were randomized up to 6 hours following return-of-circulation to hypothermia (n = 46) or normothermia (n = 28). Outcomes assessed included 12-month survival with a Vineland Adaptive Behavior Scale score of greater than or equal to 70, 1-year survival rate, change in Vineland Adaptive Behavior Scale-II score from prearrest to 12 months, and select safety measures. Seventy-four drowning cases were randomized. In patients with prearrest Vineland Adaptive Behavior Scale-II greater than or equal to 70 (n = 65), there was no difference in 12-month survival with Vineland Adaptive Behavior Scale-II score of greater than or equal to 70 between hypothermia and normothermia groups (29% vs 17%; relative risk, 1.74; 95% CI, 0.61-4.95; p = 0.27). Among all evaluable patients (n = 68), the Vineland Adaptive Behavior Scale-II score change from baseline to 12 months did not differ (p = 0.46), and 1-year survival was similar (49% hypothermia vs 42%, normothermia; relative risk, 1.16; 95% CI, 0.68-1.99; p = 0.58). Hypothermia was associated with a higher prevalence of positive bacterial culture (any blood, urine, or respiratory sample; 67% vs 43%; p = 0.04); however, the rate per 100 days at risk did not differ (11.1 vs 8.4; p = 0.46). Cumulative incidence of blood product use, serious arrhythmias, and 28-day mortality were not different. Among patients with cardiopulmonary resuscitation durations more than 30 minutes or epinephrine doses greater than 4, none had favorable Pediatric Cerebral Performance Category outcomes (≤ 3). CONCLUSIONS: In comatose survivors of out-of-hospital pediatric cardiac arrest due to drowning, hypothermia did not result in a statistically significant benefit in survival with good functional outcome or mortality at 1 year, as compared with normothermia. High risk of culture-proven bacterial infection was observed in both groups.

Adaptive behavior, functional outcomes, and quality of life outcomes of children requiring urgent ICU admission.

OBJECTIVE: To describe the adaptive behavior and functional outcomes, and health-related quality of life of children who were urgently admitted to the ICU. DESIGN: Prospective observational study. SETTING: Critical Care Medicine program at a University-affiliated pediatric institution. PATIENTS: Urgently admitted patients, aged 1 month to 18 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated children's adaptive behavior functioning with the Vineland Adaptive Behavior Scale-2, functional outcomes with the pediatric cerebral performance category and pediatric overall performance category, and health-related quality of life with the Pediatric Quality of Life Inventory 4 and Visual Analogue Scale. We enrolled 91 children and 65 (71%) completed the 1-month assessment. Patients had a mean (SD) Vineland Adaptive Behavior Scale-2 rating of 83.2 (± 24.8), considered to be moderate-low adaptive behavior functioning. From baseline to 1 month, pediatric cerebral performance category ratings did not significantly change (p = 0.59) and pediatric overall performance category ratings significantly improved (p = 0.03). Visual Analogue Scale ratings significantly worsened from baseline to 1 wk (p < 0.0001) and significantly improved from 1 wk to 1 month (p=0.002). At 1 month, patients had a mean (SD) Pediatric Quality of Life Inventory 4 rating of 52.8 (± 27.9) of 100, a poor quality of life rating. Circulatory admissions, worse pediatric cerebral performance category score at baseline, worse transcutaneous oxygen saturation, and longer cardiac compression duration were independently associated with worse adaptive behavior functioning. Neurological admissions, worse pediatric cerebral performance category score at baseline, longer ICU stay, and longer duration of extracorporeal membrane oxygenation were independently associated with worse functional outcome. Worse pediatric cerebral performance category score at baseline, longer ICU stay, and longer duration of extracorporeal membrane oxygenation were independently associated with worse health-related quality of life. CONCLUSIONS: Children surviving PICU have significant adaptive behavior functioning and functional morbidity and reduced health-related quality of life. Although neurologic morbidity following ICU was associated with baseline state, we found that resuscitation intensity and illness severity factors were independently associated with the development of acquired brain injury and reduced quality of life.

Abnormal fatty acid metabolism in spinal muscular atrophy may predispose to perioperative risks.

A 15 year old boy with SMA type II underwent spinal fusion and suffered a mitochondrial Reye-like catabolic crisis 4 days postop with hypoketotic hypoglycemia, lactic acidaemia, hyperammonemia and liver failure, with 90% coagulative necrosis and diffuse macro- and microvesicular steatosis, requiring orthotopic liver transplantation. This crisis responded in part to mitochondrial therapy and anabolic rescue. He made a dramatic sustained neurological recovery, though his post-transplant liver biopsies revealed micro- and macrosteatosis. We hypothesize that a combination of surgical stress-catecholamine induced lipolysis, prolonged general anaesthesia with propofol and sevoflurane, and perioperative fasting on a background of decreased ß-oxidation were potential risk factors for the mitochondrial decompensation.

A cross-sectional survey of levels of care and response mechanisms for evolving critical illness in hospitalized children.

OBJECTIVES: Recognition and treatment of evolving critical illness is a fundamental element of hospital care. Hospital systems should triage patients to receive appropriate levels of care. We describe here the levels of care, the frequency of near or actual cardiopulmonary arrest (code-blue events), identification mechanisms, and responses to evolving critical illness in hospitalized children. METHODS: A cross-sectional telephone survey of Canadian and American hospitals with > or = 50 pediatric acute care beds or > or = 2 pediatric wards was performed. Regression analysis identified factors associated with the frequency of code-blue events after adjustment for hospital volume. RESULTS: Responses from 388 (84%) hospitals identified the 181 eligible pediatric hospitals included in this survey. All had a PICU, 99 (55%) had high-dependency units, 101 (56%) had extracorporeal membrane oxygenation therapy, and 69 (38%) used extracorporeal membrane oxygenation therapy for refractory cardiopulmonary arrest. All of the hospitals had immediate-response teams. They were activated 4676 times in the previous 12 months. Twenty-four percent of hospitals had activation criteria for immediate-response teams. Urgent-response teams to treat children who were clinically deteriorating but not at immediate risk of cardiopulmonary arrest were available in 136 (75%) hospitals; 29 (17%) had formal medical emergency teams, and 92 (51%) consulted the PICU. Code-blue events were more common in hospitals with extracorporeal membrane oxygenation therapy, cardiopulmonary bypass, and larger PICU size. CONCLUSIONS: Currently, the organization of Canadian and American pediatric hospitals includes dedicated areas to match patient acuity and additional personnel to stabilize and facilitate transfer. The functioning of these systems of care results in calls for immediate medical assistance for ward patients approximately 5000 times annually.