Ericka L. Fink

Part 13: Pediatric Basic Life Support 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

In contrast to adults, cardiac arrest in infants and children does not usually result from a primary cardiac cause. More often it is the terminal result of progressive respiratory failure or shock, also called an asphyxial arrest. Asphyxia begins with a variable period of systemic hypoxemia, hypercapnea, and acidosis, progresses to bradycardia and hypotension, and culminates with cardiac arrest.1 Another mechanism of cardiac arrest, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), is the initial cardiac rhythm in approximately 5% to 15% of pediatric in-hospital and out-of-hospital cardiac arrests;2,–,9 it is reported in up to 27% of pediatric in-hospital arrests at some point during the resuscitation.6 The incidence of VF/pulseless VT cardiac arrest rises with age.2,4 Increasing evidence suggests that sudden unexpected death in young people can be associated with genetic abnormalities in myocyte ion channels resulting in abnormalities in ion flow (see “Sudden Unexplained Deaths,” below). Since 2010 marks the 50th anniversary of the introduction of cardiopulmonary resuscitation (CPR),10 it seems appropriate to review the progressive improvement in outcome of pediatric resuscitation from cardiac arrest. Survival from in-hospital cardiac arrest in infants and children in the 1980s was around 9%.11,12 Approximately 20 years later, that figure had increased to 17%,13,14 and by 2006, to 27%.15,–,17 In contrast to those favorable results from in-hospital cardiac arrest, overall survival to discharge from out-of-hospital cardiac arrest in infants and children has not changed substantially in 20 years and remains at about 6% (3% for infants and 9% for children and adolescents).7,9 It is unclear why the improvement in outcome from in-hospital cardiac arrest has occurred, although earlier recognition and management of at-risk patients on general inpatient units …

Part 8: Post-cardiac arrest care: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care

The recommendations in this 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) after the publication of the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 1,2 and was completed in February 2015.3,4 In this in-depth evidence review process, ILCOR examined topics and then generated a prioritized list of questions for systematic review. Questions were first formulated in PICO (population, intervention, comparator, outcome) format,5 and then search strategies and inclusion and exclusion criteria were defined and a search for relevant articles was performed. The evidence was evaluated by the ILCOR task forces by using the standardized methodological approach proposed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.6 The quality of the evidence was categorized based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias). Then, where possible, consensus-based treatment recommendations were created. To create this 2015 Guidelines Update, the AHA formed 15 writing groups, with careful attention to manage conflicts of interest, to assess the ILCOR treatment recommendations and to write AHA treatment recommendations by using the AHA Class of Recommendation (COR) and Level of Evidence (LOE) system. The recommendations made in the Guidelines are informed by the ILCOR recommendations and GRADE classification, in the context of the delivery of medical care in North America. The AHA writing group made new recommendations only on topics specifically reviewed by ILCOR in 2015. This chapter delineates instances where the AHA writing group developed recommendations that are significantly stronger or weaker than the ILCOR statements. In the online …

Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

For best survival and quality of life, pediatric basic life support (BLS) should be part of a community effort that includes prevention, early cardiopulmonary resuscitation (CPR), prompt access to the emergency response system, and rapid pediatric advanced life support (PALS), followed by integrated post–cardiac arrest care. These 5 links form the American Heart Association (AHA) pediatric Chain of Survival (Figure 1), the first 3 links of which constitute pediatric BLS. FIGURE 1. Pediatric Chain of Survival. Rapid and effective bystander CPR can be associated with successful return of spontaneous circulation (ROSC) and neurologically intact survival in children following out-of-hospital cardiac arrest.1,–,3 Bystander resuscitation may have the greatest impact for out-of-hospital respiratory arrest,4 because survival rates >70% have been reported with good neurologic outcome.5,6 Bystander resuscitation may also have substantial impact on survival from primary ventricular fibrillation (VF), because survival rates of 20% to 30% have been documented in children with sudden out-of-hospital witnessed VF.7 Overall about 6%8 of children who suffer an out-of-hospital cardiac arrest and 8% of those who receive prehospital emergency response resuscitation survive, but many suffer serious permanent brain injury as a result of their arrest.7,9,–,14 Out-of-hospital survival rates and neurological outcome can be improved with prompt bystander CPR,3,6,15,–,17 but only about one third to one half of infants and children who suffer cardiac arrest receive bystander CPR.3,9,12,18 Infants are less likely to survive out-of-hospital cardiac arrest (4%) than children (10%) or adolescents (13%), presumably because many infants included in the arrest figure are found dead after a substantial period of time, most from sudden infant death syndrome (SIDS).8 As in adults, survival is …

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.).

A tertiary care center's experience with therapeutic hypothermia after pediatric cardiac arrest*

Objective: To describe the use and feasibility of therapeutic hypothermia after pediatric cardiac arrest. Design: Retrospective cohort study. Setting: Pediatric tertiary care university hospital. Patients: Infants and children (age 1 wk to 21 yrs) without complex congenital heart disease with return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest from 2000 to 2006. Intervention: None. Measurements and Main Results: We studied 181 patients after cardiac arrest, of which 91% were asphyxial in etiology (vs. cardiac) and 52% occurred in-hospital. Overall survival to hospital discharge was 45%. Forty patients received therapeutic hypothermia; all were admitted during or after 2002. Sixty percent of patients in the therapeutic hypothermia group had an initial temperature <35°C. The median therapeutic hypothermia target temperature was 34.0°C (33.5–34.8°C), was reached by 7 hrs (5–8 hrs) after admission in patients who were not hypothermic on admission, and was maintained for 24 hrs (16–48 hrs). Re-warming lasted 6 hrs (5–8 hrs). In the therapeutic hypothermia group, temperature <32°C occurred in 15% of patients and was associated with higher hospital mortality (29% vs. 11%; p = .02). Patients treated with therapeutic hypothermia differed from those treated with standard therapy, with more un-witnessed cardiac arrest (p = .04), more doses of epinephrine to achieve return of spontaneous circulation (p = .03), and a trend toward more out-of-hospital cardiac arrests (p = .11). After arrest, therapeutic hypothermia patients received more frequent electrolyte supplementation (p < .05). Standard therapy patients were twice as likely as therapeutic hypothermia patients to have a fever (>38°C) after arrest (37% vs. 18%; p = .02) and trended toward a higher rate of re-arrest (26% vs. 13%; p = .09). Rates of red blood cell transfusions, infection, and arrhythmias were similar between groups. There was no difference in hospital mortality (55.0% therapeutic hypothermia vs. 55.3% standard therapy; p = 1.0), and 78% of the therapeutic hypothermia survivors were discharged home (vs. 68% of the standard therapy survivors; p = .46). In multivariate analysis, mortality was independently associated with initial hypoglycemia or hyperglycemia, number of doses of epinephrine during resuscitation, asphyxial etiology, and longer duration of cardiopulmonary resuscitation, but not treatment group (odds ratio for mortality in the therapeutic hypothermia group, 0.47; p = .2). Conclusions: This is the largest study reported on the use of therapeutic mild hypothermia in pediatric cardiac arrest to date. We found that therapeutic hypothermia was feasible, with target temperature achieved in <3 hrs overall. Temperature below target range was associated with increased mortality. Prospective study is urgently needed to determine the efficacy of therapeutic hypothermia in pediatric patients after cardiac arrest.

Part 6: Pediatric basic life support and pediatric advanced life support. 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

The Pediatric Task Force reviewed all questions submitted by the International Liaison Committee on Resuscitation (ILCOR) member councils in 2010, reviewed all council training materials and resuscitation guidelines and algorithms, and conferred on recent areas of interest and controversy. We identified a few areas where there were key differences in council-specific guidelines based on historical recommendations, such as the A-B-C (Airway, Breathing, Circulation) versus C-A-B (Circulation, Airway, Breathing) sequence of provision of cardiopulmonary resuscitation (CPR), initial back blows versus abdominal thrusts for foreign-body airway obstruction, an upper limit for recommended chest compression rate, and initial defibrillation dose for shockable rhythms (2 versus 4 J/kg). We produced a working list of prioritized questions and topics, which was adjusted with the advent of new research evidence. This led to a prioritized palate of 21 PICO (population, intervention, comparator, outcome) questions for ILCOR task force focus. The 2015 process was supported by information specialists who performed in-depth systematic searches, liaising with pediatric content experts so that the most appropriate terms and outcomes and the most relevant publications were identified. Relevant adult literature was considered (extrapolated) in those PICO questions that overlapped with other task forces, or when there were insufficient pediatric data. In rare circumstances (in the absence of sufficient human data), appropriate animal studies were incorporated into reviews of the literature. However, these data were considered only when higher levels of evidence were not available and the topic was deemed critical. When formulating the PICO questions, the task force felt it important to evaluate patient outcomes that extend beyond return of spontaneous circulation (ROSC) or discharge from the pediatric intensive care unit (PICU). In recognition that the measures must have meaning, not only to clinicians but also to parents and caregivers, longer-term outcomes at 30 …

Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse.

Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis. To resolve this issue, cytochrome c concentration was determined in 167 ventricular cerebrospinal fluid (CSF) samples from 67 infants and children with TBI (including 15 patients diagnosed with child abuse) by ELISA. Controls included lumbar CSF from 19 infants and children without trauma or meningitis. A multivariate model adjusted for multiple within-subject observations was used to identify clinical variables associated with CSF cytochrome c. Other apoptosis-related proteins were also examined in a subset of TBI patients. Increased CSF cytochrome c was independently associated with inflicted TBI (P = 0.0001) and female gender (P = 0.04), but not age, Glasgow coma scale score, or survival. Other apoptosis-related proteins including Fas and caspase-1 were increased in CSF after TBI, but did not independently discriminate between accidental and inflicted TBI. These data suggest that apoptosis, as detected by the presence of cytochrome c in CSF, is uniquely prominent among the subset of TBI patients diagnosed with child abuse. The degree of apoptosis after TBI also appears to be gender-dependent. Development of strategies targeting apoptosis after TBI, particularly in victims of child abuse and in girls, appears justified.

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.)

Experimental model of pediatric asphyxial cardiopulmonary arrest in rats.

Objective Develop a clinically relevant model of pediatric asphyxial cardiopulmonary arrest in rats. Design Prospective interventional study. Setting University research laboratory. Subjects Postnatal day 16–18 rats (n = 9/group). Interventions Anesthetized rats were endotracheally intubated and mechanically ventilated, and vascular catheters were inserted. Vecuronium was administered, and the ventilator was disconnected from the rats for 8 mins, whereupon rats were resuscitated with epinephrine, sodium bicarbonate, and chest compressions until spontaneous circulation returned. Shams underwent all procedures except asphyxia. Measurements and Main Results Asphyxial arrest typically occurred by 1 min after the ventilator was disconnected. Return of spontaneous circulation typically occurred <30 secs after resuscitation. An isoelectric electroencephalograph was observed for 30 mins after asphyxia, and rats remained comatose for 12–24 hrs. Overall survival rate was 85%. Motor function measured using beam balance and inclined plane tests was impaired on days 1 and 2, but recovered by day 3, in rats after asphyxia vs. sham injury (p < .05). Spatial memory acquisition measured using the Morris-water maze on days 7–14 and 28–35 was also impaired in rats after asphyxia vs. sham injury (total latency 379 ± 28 vs. 501 ± 40 secs, respectively, p < .05). DNA fragmentation was detected in CA1 hippocampal neurons bilaterally 3–7 days after asphyxia. Neurodegeneration detected using Fluorojade B was seen in bilateral CA1 hippocampi and layer V cortical neurons 3–7 days after asphyxia, with persistent neurodegeneration in CA1 hippocampus detected up to 5 wks after asphyxia. CA1 hippocampal neuron survival after asphyxia was 39–43% (p < .001 vs. sham). Evidence of DNA or cellular injury was not detected in sham rats. Conclusions This model of asphyxial cardiopulmonary arrest in postnatal day 17 rats produces many of the clinical manifestations of pediatric hypoxic-ischemic encephalopathy. This model may be useful for the preclinical testing of novel and currently available interventions aimed at improving neurologic outcome in infants and children after cardiopulmonary arrest.

Relationship Between Hyperglycemia and Outcome in Children with Severe Traumatic Brain Injury

Objective: To determine the relationship between hyperglycemia and outcome in infants and children after severe traumatic brain injury. Design: Retrospective review of a prospectively collected Pediatric Neurotrauma Registry. Setting and Patients: Children admitted after severe traumatic brain injury (postresuscitation Glasgow Coma Scale ⩽8) were studied (1999–2004). A subset of children (n = 28) were concurrently enrolled in a randomized, controlled clinical trial of early hypothermia for neuroprotection. Interventions: Demographic data, serum glucose concentrations, and outcome assessments were collected. Methods and Main Results: Children (n = 57) were treated with a standard traumatic brain injury protocol. Exogenous glucose was withheld for 48 hrs after injury unless hypoglycemia was observed (blood glucose <70 mg/dL). Early (first 48 hrs) and Late (49–168 hrs) time periods were defined and mean blood glucose concentrations were calculated. Additionally, children were categorized based on peak blood glucose concentrations during each time period (normal, blood glucose <150 mg/dL; mild hyperglycemia, blood glucose ⩽200 mg/dL; severe hyperglycemia, blood glucose >200 mg/dL). In the Late period, an association between elevated mean serum glucose concentration and outcome was observed (133.5 ± 5.6 mg/dL in the unfavorable group vs. 115.4 ± 4.1 mg/dL in favorable group, p = .02). This association continued to be significant after correcting for injury severity, age, and exposure to insulin (p = .03). Similarly, in the Late period, children within the severe hyperglycemia group had decreased incidence of good outcome compared to children within the other glycemic groups (% good outcome: normal, 61.9%; mild hyperglycemia, 73.7%; severe hyperglycemia, 33.3%; p = .05). However, when adjusted for exposure to insulin, this relationship was no longer statistically significant. Conclusions: In children with severe traumatic brain injury, hyperglycemia beyond the initial 48 hrs is associated with poor outcome. This relationship was observed in both our analysis of mean blood glucose concentrations as well as among the patients with episodic severe hyperglycemia. This observation suggests a relationship between hyperglycemia and outcome from traumatic brain injury. However, only a prospective study can answer the important question of whether manipulating serum glucose concentration can improve outcome after traumatic brain injury in children.