Heidi J. Dalton

Pediatric critical care medicine: Planning for our research future

Objective To introduce to the pediatric critical care medicine community a new program in pediatric critical care medicine at the National Institutes of Health. Data Source Summary of literature review and conference proceedings. Data Synthesis At the National Institute of Child Health and Human Development (NICHD), a new program in pediatric critical care and rehabilitation research has been established in the National Center for Medical Rehabilitation Research. The program is directed by a pediatric intensivist and is focused on developing research directed toward improving long-term outcomes in pediatric critical care and on incorporating pediatric rehabilitation medicine as a partner in this goal. To provide strategic direction for the new program, the NICHD sponsored a planning conference May 3–4, 2002, at the NICHD in Bethesda, MD. The conference invitees represented a broad range of pediatric critical care medicine clinical and research interests, expertise, and career stages. It also included individuals with expertise in rehabilitation research. Conclusion The composition of the new program, including its link to physical medicine and rehabilitation, is discussed. In addition, recommendations by the conference participants and program director are provided to foster the development of more randomized, controlled clinical trials and to develop successful clinician scientists in pediatric critical care medicine.

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.

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.

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

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.

Instillation of calf lung surfactant extract (calfactant) is beneficial in pediatric acute hypoxemic respiratory failure

OBJECTIVE Prospective study of the efficacy of calf lung surfactant extract in pediatric respiratory failure. DESIGN Multi-institutional, prospective, randomized, controlled, unblinded trial. SETTING Eight pediatric intensive care units (ICU) of tertiary medical centers. PATIENTS Forty-two children with acute hypoxemic respiratory failure characterized by diffuse, bilateral pulmonary infiltrates, need for ventilatory support, and an oxygenation index of >7. INTERVENTION Instillation of intratracheal surfactant (80 mL/m2). MEASUREMENTS AND MAIN RESULTS Ventilator parameters, arterial blood gases, and derived oxygenation and ventilation indices were recorded before and at intervals after surfactant administration. Complications and outcome measures, including mortality, duration of mechanical ventilation, and length of pediatric ICU and hospital stay, were also examined. Patients who received surfactant demonstrated rapid improvement in oxygenation and, on average, were extubated 4.2 days (32%) sooner and spent 5 fewer days (30%) in pediatric intensive care than control patients. There was no difference in mortality or overall hospital stay. Surfactant administration was associated with no serious adverse effects. CONCLUSIONS Administration of calf lung surfactant extract, calfactant, appears to be safe and is associated with rapid improvement in oxygenation, earlier extubation, and decreased requirement for intensive care in children with acute hypoxemic respiratory failure. Further study is needed, however, before widespread use in pediatric respiratory failure can be recommended.

Extracorporeal membrane oxygenation in postcardiotomy patients: factors influencing outcome.

OBJECTIVE Our objective was to assess the morbidity and mortality in children requiring extracorporeal membrane oxygenator support after cardiac surgery and to determine factors influencing outcome. METHODS Between January 2003 and June 2008, 58 patients required extracorporeal membrane oxygenator support after cardiac surgery. A retrospective study was performed and factors influencing outcome were determined by logistic regression modeling with the probability of outcome based on a combination of multivariate predictors. RESULTS Median age and weight were 12 days and 3.3 kg, respectively. Thirty-one patients had single ventricle repair and 27 had biventricular repair. Median duration of support with the oxygenator was 6 days. Thirty-nine (67%) patients were successfully weaned off the support, but only 24 (41%) survived to hospital discharge. Chief complications were renal failure (31%), neurologic complications (29%), and sepsis (16%). Multivariable logistic regression analysis identified 10 days or more of extracorporeal membrane oxygenation (odds ratio = 6.1), urine output less than 2 mL x kg(-1) x h(-1) in first 24 hours (odds ratio = 15), renal failure (odds ratio = 9.4), and pH less than 7.35 after 24 hours of extracorporeal membrane oxygenation (odds ratio = 82) as significant independent factors associated with failure to wean off extracorporeal membrane oxygenation. Factors associated with failure of hospital discharge despite successful decannulation were as follows: extracorporeal membrane oxygenator support time of 10 days or more, red blood cell transfusion of greater than 1000 mL/kg during the entire period of oxygenator support, and sepsis. Patients with single ventricle repair were at higher risk of hospital mortality. CONCLUSION Longer duration of extracorporeal membrane oxygenator support, low pH and urine output in the first 24 hours, and renal failure are significant factors associated with mortality during extracorporeal membrane oxygenator support. Exposure to high amounts of blood transfusion during extracorporeal oxygenation, extended extracorporeal membrane oxygenator support, and sepsis increase risk of death after successful decannulation.

Outcomes among neonates, infants, and children after extracorporeal cardiopulmonary resuscitation for refractory inhospital pediatric cardiac arrest: a report from the National Registry of Cardiopulmonary Resuscitation.

Objectives: Describe the use of extracorporeal cardiopulmonary resuscitation as rescue therapy in pediatric patients who experience cardiopulmonary arrest refractory to conventional resuscitation. We report on outcomes and factors associated with survival in children treated with extracorporeal cardiopulmonary resuscitation during cardiopulmonary arrest from the American Heart Association National Registry of CardioPulmonary Resuscitation. Design: Multicentered, national registry of in-hospital cardiopulmonary resuscitation. Setting: Two hundred eighty-five hospitals reporting to the registry from January 2000 to December 2007. Patients: Pediatric patients <18 yrs of age who received extracorporeal membrane oxygenation during cardiopulmonary resuscitation for in-hospital cardiopulmonary arrest. Interventions: None. Measurements and Outcomes: Prearrest and arrest variables were collected. The primary outcome variable was survival to hospital discharge. The secondary outcome was neurologic status after extracorporeal cardiopulmonary resuscitation at hospital discharge. Favorable neurologic outcome was defined as Pediatric Cerebral Performance Categories 1, 2, 3, or no change from admission Pediatric Cerebral Performance Category. Results: Of 6288 pediatric cardiopulmonary arrest events reported, 199 (3.2%) index extracorporeal cardiopulmonary resuscitation events were identified; 87 (43.7%) survived to hospital discharge. Fifty-nine survivors had Pediatric Cerebral Performance Category outcomes recorded, and of those, 56 (94.9%) had favorable outcomes. In a multivariable model, the prearrest factor of renal insufficiency and arrest factors of metabolic or electrolyte abnormality and the pharmacologic intervention of sodium bicarbonate/tromethamine were associated with decreased survival. After adjusting for confounding factors, cardiac illness category was associated with an increased survival to hospital discharge. Conclusions: Forty-four percent of pediatric patients who failed conventional cardiopulmonary resuscitation from in-hospital cardiopulmonary arrest and who were reported to the National Registry of CardioPulmonary Resuscitation database as treated with extracorporeal cardiopulmonary resuscitation survived to hospital discharge. The majority of survivors with recorded neurologic outcomes were favorable. Patients with cardiac illness category were more likely to survive to hospital discharge after treatment with extracorporeal cardiopulmonary resuscitation. Extracorporeal cardiopulmonary resuscitation should be considered for select pediatric patients refractory to conventional in-hospital resuscitation measures.

Pediatric intensive care outcomes: development of new morbidities during pediatric critical care.

Objective: To investigate significant new morbidities associated with pediatric critical care. Design: Randomly selected, prospective cohort. Setting: PICU patients from eight medical and cardiac PICUs. Patients: This was a randomly selected, prospective cohort of PICU patients from eight medical and cardiac PICUs. Measurements and Main Results: The main outcomes measures were hospital discharge functional status measured by Functional Status Scale scores and new morbidity defined as an increase in the Functional Status Scale of more than or equal to 3. Of the 5,017 patients, there were 242 new morbidities (4.8%), 99 PICU deaths (2.0%), and 120 hospital deaths (2.4%). Both morbidity and mortality rates differed (p < 0.001) among the sites. The worst functional status profile was on PICU discharge and improved on hospital discharge. On hospital discharge, the good category decreased from a baseline of 72% to 63%, mild abnormality increased from 10% to 15%, moderate abnormality status increased from 13% to 14%, severe status increased from 4% to 5%, and very severe was unchanged at 1%. The highest new morbidity rates were in the neurological diagnoses (7.3%), acquired cardiovascular disease (5.9%), cancer (5.3%), and congenital cardiovascular disease (4.9%). New morbidities occurred in all ages with more in those under 12 months. New morbidities involved all Functional Status Scale domains with the highest proportions involving respiratory, motor, and feeding dysfunction. Conclusions: The prevalence of new morbidity was 4.8%, twice the mortality rate, and occurred in essentially all types of patients, in relatively equal proportions, and involved all aspects of function. Compared with historical data, it is possible that pediatric critical care has exchanged improved mortality rates for increased morbidity rates.