Michael T. Meyer

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.).

The critical care air transport program.

Background:The critical care air transport team program is a component of the U.S. Air Force Aeromedical Evacuation system. A critical care air transport team consists of a critical care physician, critical care nurse, and respiratory therapist along with the supplies and equipment to operate a portable intensive care unit within a cargo aircraft. Discussion:This capability was developed to support rapidly mobile surgical teams with high capability for damage control resuscitation and limited capacity for postresuscitation care. The critical care air transport team permits rapid evacuation of stabilizing casualties to a higher level of care. The aeromedical environment presents important challenges for the delivery of critical care. All equipment must be tested for safety and effectiveness in this environment before use in flight. The team members must integrate the current standards of care with the limitation imposed by stresses of flight on their patient. Summary:The critical care air transport team capability has been used successfully in a range of settings from transport within the United States, to disaster response, to support of casualties in combat.

A prospective evaluation of opioid weaning in opioid-dependent pediatric critical care patients.

Critically ill children are treated with opioid medication in an attempt to decrease stress and alleviate pain during prolonged pediatric intensive care. This treatment plan places children at risk for opioid dependency. Once dependent, children need to be weaned or risk development of a withdrawal syndrome on abrupt cessation of medication. We enrolled opioid-dependent children into a prospective, randomized trial of 5- versus 10-day opioid weaning using oral methadone. Children exposed to opioids for an average of 3 wk showed no difference in the number of agitation events requiring opioid rescue (3 consecutive neonatal abstinence scores >8 every 2 h) in either wean group. Most of the events requiring rescue occurred on day 5 and 6 of the wean in both treatment groups. Patients may be able to be weaned successfully in 5 days once converted to oral methadone, with a follow-up period after medication wean to observe for a delayed withdrawal syndrome.

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.)

Efficacy of an enteral 10-day methadone wean to prevent opioid withdrawal in fentanyl-tolerant pediatric intensive care unit patients.

Objective To demonstrate the efficacy of a 10-day, single daily dose, enteral methadone weaning protocol for the prevention of opioid withdrawal symptoms in pediatric patients after prolonged fentanyl exposure. Design Prospective, observational study. Setting Twenty-four–bed medical-surgical intensive care unit within a 222-bed pediatric teaching hospital. Patients Twenty-nine children, aged 1 day to 19.8 yrs, who received methadone to prevent opioid withdrawal after prolonged continuous fentanyl infusion exposure. Interventions Institution of a standardized methadone weaning protocol. Measurements and Main Results All 29 patients had received a continuous fentanyl infusion; duration of exposure was 14.5 ± 9.2 days, cumulative fentanyl dose was 1.93 ± 1.53 mg/kg, and peak fentanyl infusion was 9.6 ± 4.3 &mgr;g/kg per hr. Twenty-five (86%) of 29 patients successfully completed the methadone wean in 10 days. Withdrawal complications that required a weaning delay were seen in three patients, and one patient expired before completion. Sixteen patients were discharged to complete their weaning schedule at home without incident. Conclusions Opioid withdrawal symptoms in pediatric intensive care unit patients after prolonged fentanyl exposure can be avoided by using an enteral, 10-day, single daily dose methadone weaning protocol.

Pediatric and Neonatal Interfacility Transport: Results From a National Consensus Conference

The practice of pediatric/neonatal interfacility transport continues to expand. Transport teams have evolved into mobile ICUs capable of delivering state-of-the-art critical care during pediatric and neonatal transport. The most recent document regarding the practice of pediatric/neonatal transport is more than a decade old. The following article details changes in the practice of interfacility transport over the past decade and expresses the consensus views of leaders in the field of transport medicine, including the American Academy of Pediatrics’ Section on Transport Medicine.

Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias

BACKGROUND Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely. METHODS Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5°C±1°C for 72h, they were then slowly rewarmed by 0.5°C every 3h over 18h. In addition data of age-matched historic controls were collected for comparison. RESULTS Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension. CONCLUSION Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was feasible and could be conducted safely in pediatric and neonatal intensive care units experienced in the application of therapeutic hypothermia in critically ill neonates. However, including adjunct therapeutic hypothermia in the already involved treatment regimen of critically ill patients with hyperammonemia and encephalopathy adds to the complexity of care and should not be done unless it is proven efficacious in a randomized clinical trial.

Helicopter interfacility transport of pediatric trauma patients: Are we overusing a costly resource?

BACKGROUND Helicopter emergency medical services (HEMS) provide an important service to decrease interfacility transport times compared with ground ambulances. Although transport via HEMS is typically faster, the decreased transportation time comes at the expense of increased risks to the patient and flight crew and higher costs. Therefore, it is important to balance the immediate patient needs with the risk and expense of HEMS transport. Our objective was to determine how frequently pediatric patients who are interfacility transported to a Level 1 pediatric trauma center (PTC) receive a time-sensitive intervention. METHODS This was a 4-year (2008–2012) retrospective study of children aged 0 year to 18 years who were interfacility transported to a single Level 1 PTC by HEMS. Patients were identified using the trauma registry at the PTC. A previously published outcome was used to determine if patients received time-sensitive interventions. Driving distance to the PTC was determined using Google Maps. Data were analyzed using descriptive statistics. RESULTS A total of 207 cases were identified (median age, 7 years; interquartile range, 2–12 years; 29% female; median Injury Severity Score [ISS], 11; median Revised Trauma Score [RTS], 8). Forty-three percent (90 patients; 95% confidence interval, 37–50%) of patients received a time-sensitive intervention; these cases had a median age of 6 years (interquartile range, 2–11 years; 32% female; median ISS, 13; median RTS, 8). Of the 117 patients who did not receive time-sensitive interventions, 81% were within 120 driving miles of the PTC and 49% were within 60 miles. CONCLUSION This study suggests an overuse of HEMS for interfacility transfer of injured pediatric patients to a PTC. Although these patients likely required the resources of a PTC, they could perhaps have been transported by ground ambulance without detriment. Further research is needed to investigate how interfacility transport modes are selected and if these decisions can be improved without increasing evaluation times at transferring facilities. LEVEL OF EVIDENCE Epidemiologic study, level V.

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.

Haemodynamic response associated with both ictal and interictal epileptiform activity using simultaneous video electroencephalography/near infrared spectroscopy in a within-subject study

This paper reports the findings from a pilot study of four patients with medically refractory epilepsy undergoing pre-surgical evaluation with ages ranging from 5 to 17 years. Video electroencephalography recordings and data from a near infrared spectroscopy cerebral/somatic oximeter were gathered and related to electrographic seizure onset and offset as determined by a paediatric epileptologist. All four patients showed haemodynamic changes associated with epileptiform activities. The increased blood flow clearly coincided with epileptiform activity and continued to increase as the epileptiform activity built up. Regional cerebral oxygen saturation increased in the epileptogenic focus, perhaps due to loss of cerebrovascular autoregulation. These findings reinforce that near infrared spectroscopy can potentially be used in a wide spectrum of patients with epilepsy regardless of the underlying brain pathology.