Kathleen L. Meert

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.).

Multicenter cohort study of in-hospital pediatric cardiac arrest.

Objectives: 1) To describe clinical characteristics, hospital courses, and outcomes of a cohort of children cared for within the Pediatric Emergency Care Applied Research Network who experienced in-hospital cardiac arrest with sustained return of circulation between July 1, 2003 and December 31, 2004, and 2) to identify factors associated with hospital mortality in this population. These data are required to prepare a randomized trial of therapeutic hypothermia on neurobehavioral outcomes in children after in-hospital cardiac arrest. Design: Retrospective cohort study. Setting: Fifteen children’s hospitals associated with Pediatric Emergency Care Applied Research Network. Patients: Patients between 1 day and 18 years of age who had cardiopulmonary resuscitation and received chest compressions for >1 min, and had a return of circulation for >20 mins. Interventions: None. Measurements and Main Results: A total of 353 patients met entry criteria; 172 (48.7%) survived to hospital discharge. Among survivors, 132 (76.7%) had good neurologic outcome documented by Pediatric Cerebral Performance Category scores. After adjustment for age, gender, and first documented cardiac arrest rhythm, variables available before and during the arrest that were independently associated with increased mortality included pre-existing hematologic, oncologic, or immunologic disorders, genetic or metabolic disorders, presence of an endotracheal tube before the arrest, and use of sodium bicarbonate during the arrest. Variables associated with decreased mortality included postoperative cardiopulmonary resuscitation. Extending the time frame to include variables available before, during, and within 12 hours following arrest, variables independently associated with increased mortality included the use of calcium during the arrest. Variables associated with decreased mortality included higher minimum blood pH and pupillary responsiveness. Conclusions: Many factors are associated with hospital mortality among children after in-hospital cardiac arrest and return of circulation. Such factors must be considered when designing a trial of therapeutic hypothermia after cardiac arrest in pediatric patients.

The spiritual needs of parents at the time of their child's death in the pediatric intensive care unit and during bereavement: a qualitative study.

Objective: Death is common in pediatric intensive care units. A child’s death can shatter parents’ personal identities, disrupt their relationships, and challenge their worldviews. Spirituality is a human characteristic that engenders transcendence; seeks meaning, purpose, and connection to others; and helps to construct a coherent worldview. Greater attention to spiritual needs may help parents cope with their loss. Our objective is to gain a deeper understanding of parents’ spiritual needs during their child’s death and bereavement. Design: Prospective, qualitative study. Setting: University-affiliated children’s hospital. Participants: Thirty-three parents of 26 children who died in the pediatric intensive care unit between January 1, 1999, and August 31, 2000. Interventions: Semistructured, in-depth, videotaped interviews with parents 2 yrs after their child’s death. Measurements and Main Results: The main spiritual need described by parents was that of maintaining connection with their child. Parents maintained connection at the time of death by physical presence. Parents maintained connection after the death through memories, mementos, memorials, and altruistic acts such as organ donation, volunteer work, charitable fund raising, support group development, and adoption. Other spiritual needs included the need for truth; compassion; prayer, ritual, and sacred texts; connection with others; bereavement support; gratitude; meaning and purpose; trust; anger and blame; and dignity. Conclusions: Bereaved parents have intense spiritual needs. Health care providers can help to support parents’ spiritual needs through words and actions that demonstrate a caring presence, impart truth, and foster trust; by providing opportunity to stay connected with the child at the time of death; and by creating memories that will bring comfort in the future.

Multicenter cohort study of out-of-hospital pediatric cardiac arrest*

Objectives:To describe a large cohort of children with out-of-hospital cardiac arrest with return of circulation and to identify factors in the early postarrest period associated with survival. These objectives were for planning an interventional trial of therapeutic hypothermia after pediatric cardiac arrest. Methods:A retrospective cohort study was conducted at 15 Pediatric Emergency Care Applied Research Network clinical sites over an 18-month study period. All children from 1 day (24 hrs) to 18 yrs of age with out-of-hospital cardiac arrest and a history of at least 1 min of chest compressions with return of circulation for at least 20 mins were eligible. Measurements and Main Results:One hundred thirty-eight cases met study entry criteria; the overall mortality was 62% (85 of 138 cases). The event characteristics associated with increased survival were as follows: weekend arrests, cardiopulmonary resuscitation not ongoing at hospital arrival, arrest rhythm not asystole, no atropine or NaHCO3, fewer epinephrine doses, shorter duration of cardiopulmonary resuscitation, and drowning or asphyxial arrest event. For the 0- to 12-hr postarrest return-of-circulation period, absence of any vasopressor or inotropic agent (dopamine, epinephrine) use, higher lowest temperature recorded, greater lowest pH, lower lactate, lower maximum glucose, and normal pupillary responses were all associated with survival. A multivariate logistic model of variables available at the time of arrest, which controlled for gender, age, race, and asystole or ventricular fibrillation/ventricular tachycardia anytime during the arrest, found the administration of atropine and epinephrine to be associated with mortality. A second model using additional information available up to 12 hrs after return of circulation found 1) preexisting lung or airway disease; 2) an etiology of arrest drowning or asphyxia; 3) higher pH, and 4) bilateral reactive pupils to be associated with lower mortality. Receiving more than three doses of epinephrine was associated with poor outcome in 96% (44 of 46) of cases. Conclusions:Multiple factors were identified as associated with survival after out-of-hospital pediatric cardiac arrest with the return of circulation. Additional information available within a few hours after the return of circulation may diminish outcome associations of factors available at earlier times in regression models. These factors should be considered in the design of future interventional trials aimed to improve outcome after pediatric cardiac arrest.

Tolerance and Withdrawal From Prolonged Opioid Use in Critically Ill Children

OBJECTIVE: After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS: Relevant manuscripts published in the English language were searched in Medline by using search terms “opioid,” “opiate,” “sedation,” “analgesia,” “child,” “infant-newborn,” “tolerance,” “dependency,” “withdrawal,” “analgesic,” “receptor,” and “individual opioid drugs.” Clinical and preclinical studies were reviewed for data synthesis. RESULTS: Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS: Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

Weaning and extubation readiness in pediatric patients.

Objective: A systematic review of weaning and extubation for pediatric patients on mechanical ventilation. Data Selection: Pediatric and adult literature, English language. Study Selection: Invited review. Data Sources: Literature review using National Library of Medicine PubMed from January 1972 until April 2008, earlier cross-referenced article citations, the Cochrane Database of Systematic Reviews, and the Internet. Conclusions: Despite the importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are even less clear, although a trial of spontaneous breathing would seem a prerequisite. Several indices have been developed in an attempt to predict weaning and extubation success but the available literature would suggest they offer no improvement over clinical judgment. Extubation failure rates range from 2% to 20% and bear little relationship to the duration of mechanical ventilation. Upper airway obstruction is the single most common cause of extubation failure. A reliable method of assessing readiness for weaning and predicting extubation success is not evident from the pediatric literature.

In-hospital versus out-of-hospital pediatric cardiac arrest: A multicenter cohort study

Objectives: To describe a large multicenter cohort of pediatric cardiac arrest (CA) with return of circulation (ROC) from either the in-hospital (IH) or the out-of-hospital (OH) setting and to determine whether significant differences related to pre-event, arrest event, early postarrest event characteristics, and outcomes exist that would be critical in planning a clinical trial of therapeutic hypothermia (TH). Design: Retrospective cohort study. Setting: Fifteen Pediatric Emergency Care Applied Research Network sites. Patients: Patients aged 24 hours to 18 years with either IH or OH CA who had a history of at least 1 minute of chest compressions and ROC for at least 20 minutes were eligible. Interventions: None. Measurements and Main Results: A total of 491 patients met study entry criteria with 353 IH cases and 138 OH cases. Major differences between the IH and OH cohorts were observed for patient prearrest characteristics, arrest event initial rhythm described, and arrest medication use. Several postarrest interventions were used differently, however, the use of TH was similar (<5%) in both cohorts. During the 0–12-hour interval following ROC, OH cases had lower minimum temperature and pH, and higher maximum serum glucose recorded. Mortality was greater in the OH cohort (62% vs. 51%, p = 0.04) with the cause attributed to a neurologic indication much more frequent in the OH than in the IH cohort (69% vs. 20%; p < 0.01). Conclusions: For pediatric CA with ROC, several major differences exist between IH and OH cohorts. The finding that the etiology of death was attributed to neurologic indications much more frequently in OH arrests has important implications for future research. Investigators planning to evaluate the efficacy of new interventions, such as TH, should be aware that the IH and OH populations differ greatly and require independent clinical trials.

Parents' perspectives on physician-parent communication near the time of a child's death in the pediatric intensive care unit

Objective: Communicating bad news about a child’s illness is a difficult task commonly faced by intensive care physicians. Greater understanding of parents’ scope of experiences with bad news during their child’s hospitalization will help physicians communicate more effectively. Our objective is to describe parents’ perceptions of their conversations with physicians regarding their child’s terminal illness and death in the pediatric intensive care unit (PICU). Design: A secondary analysis of a qualitative interview study. Setting: Six children’s hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Participants: Fifty-six parents of 48 children who died in the PICU 3–12 months before the study. Interventions: Parents participated in audio recorded semistructured telephone interviews. Interviews were analyzed using established qualitative methods. Measurements and Main Results: Of the 56 parents interviewed, 40 (71%) wanted to provide feedback on the way information about their child’s terminal illness and death was communicated by PICU physicians. The most common communication issue identified by parents was the physicians’ availability and attentiveness to their informational needs. Other communication issues included honesty and comprehensiveness of information, affect with which information was provided, withholding of information, provision of false hope, complexity of vocabulary, pace of providing information, contradictory information, and physicians’ body language. Conclusions: The way bad news is discussed by physicians is extremely important to most parents. Parents want physicians to be accessible and to provide honest and complete information with a caring affect, using lay language, and at a pace in accordance with their ability to comprehend. Withholding prognostic information from parents often leads to false hopes and feelings of anger, betrayal, and distrust. Future research is needed to investigate whether the way bad news is discussed influences psychological adjustment and family functioning among bereaved parents.

Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy.

ObjectiveTo study efficacy and safety of hypertonic saline administration in the management of hyponatremic seizures. DesignRetrospective, observational, cross-sectional study with factorial design. SettingIn-patient population in a university hospital. PatientsAll children admitted with serum sodium concentrations <125 mmol/L. Sixty-nine episodes of severe hyponatremia in 60 children were reviewed. Forty-one of these children presented with seizures. InterventionsTwenty-five of 41 seizure patients received an iv bolus of 4 to 6 mL/kg body weight of 3% saline. Twenty-eight patients were treated with a benzodiazepine and/or phenobarbital with or without the subsequent administration of hypertonic saline. Measurements and Main ResultsThirteen treatment failures and ten instances of apnea occurred among the 28 patients treated with benzodiazepine/phenobarbital. Administration of hypertonic saline resulted in resolution of seizures and apnea in all cases. Those patients receiving 3% saline had a higher serum sodium increase rate from 0 to 4 hrs than the remaining patients (3.1 ± 1.3 vs. 1.7 ± 1.2 mmol/L-hr, p < .01). None developed subsequent neurologic deterioration or clinical manifestations of osmotic demyelination syndrome. ConclusionTreatment of hyponatremic seizures with routine anticonvulsants may be ineffective and is associated with a considerable incidence of apnea. A rapid increase in the serum sodium concentration by 3 to 5 mmol/L with the use of hypertonic saline is safe and efficacious in managing acute symptomatic hyponatremia. (Crit Care Med 1991;19:758)

Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVE To determine whether dexamethasone prevents postextubation airway obstruction in young children. DESIGN Prospective, randomized, double-blind, placebo-controlled study. SETTING Pediatric intensive care unit of a university teaching hospital. PATIENTS Sixty-six children, < 5 yrs of age, intubated and mechanically ventilated for > 48 hrs. INTERVENTIONS Patients were randomized to receive intravenous dexamethasone (0.5 mg/kg, maximum dose 10 mg) or saline, every 6 hrs for six doses, beginning 6 to 12 hrs before elective extubation. MEASUREMENTS AND MAIN RESULTS Dependent variables included the presence of stridor, Croup Score, and pulsus paradoxus at 10 mins, 6, 12, and 24 hrs after extubation; need for aerosolized racemic epinephrine and reintubation. The dexamethasone and placebo groups were similar in age (median 3 months [range 1 to 57] vs. 4 months [range 1 to 59], p = .6), frequency of underlying airway anomalies (3/33 vs. 3/33, p = 1.0), and duration of mechanical ventilation (median 3.3 days [range 2.1 to 39] vs. 3.5 days [range 2.1 to 15], p = .7). The dexamethasone group had a lower frequency of stridor, Croup Score, and pulsus paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation. Fewer dexamethasone-treated patients required epinephrine aerosol (4/31 vs. 22/32, p < .0001) and reintubation (0/31 vs. 7/32, p < .01). Three patients exited the study early-one patient in the dexamethasone group had occult gastrointestinal hemorrhage and one patient in each group had hypertension. CONCLUSION Pretreatment with dexamethasone decreases the frequency of postextubation airway obstruction in children.