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 .).

Hyponatremia in children with bronchiolitis admitted to the pediatric intensive care unit is associated with worse outcomes.

OBJECTIVE: To characterize the relationship between hyponatremia (serum sodium <135 mEq/L) and clinical outcomes in children ages 1 month to 2 years admitted to the pediatric intensive care unit (PICU) with bronchiolitis. STUDY DESIGN: Single-center retrospective cohort study comprising children who were admitted to the PICU between January 2009 and April 2011. Serum sodium concentrations, collected within the first 2 hours after admission to the PICU, were recorded and associations with clinical outcomes were calculated. Quantitative data are presented as mean ± SD or percentage. Student t-test, Fisher exact test, and χ(2) analyses were performed as appropriate. Subjects were excluded if they were previously diagnosed with chronic disease that would affect initial serum sodium concentration. RESULTS: Children with bronchiolitis were enrolled (n = 102; age = 10.7 ± 6.7 months). Twenty-three patients (22%) were diagnosed with hyponatremia within 2 hours of admission. Mortality (13% vs 0%; P = .011), ventilator time (8.41 ± 2 days vs 4.11 ± 2 days; P = .001), duration of stay in the PICU (10.63 ± 2.5 days vs 5.82 ± 2.09 days; P = .007), and noninvasive ventilator support (65% vs 24%; P = .007) were significantly different between subjects with hyponatremia vs those without. There were no differences in the number of patients with seizures, bronchodilator use, steroid use, intubation requirement, oxygen use at discharge, or hospital readmission. CONCLUSIONS: Pediatric patients diagnosed with bronchiolitis who present with a serum sodium concentration less than 135 mEq/L within 2 hours of admission to the PICU fare worse than their cohorts with normonatremia. A prospective study to evaluate the effects of hyponatremia appears justified.

Dexmedetomidine in a child with methylphenidate intoxication.

Methylphenidate intoxication, due to accidental ingestion, is a common occurrence in pediatrics. Symptoms of extreme agitation are typically controlled with benzodiazepines or barbiturates. There is, however, a legitimate risk of mechanical ventilation due to respiratory depression with increasing doses of benzodiazepines. The authors describe a case of 7-y-old girl with methylphenidate toxicity where dexmedetomidine was successfully used to manage agitation and cardiovascular stimulation without respiratory compromise.

Continuous hydromorphone for pain and sedation in mechanically ventilated infants and children.

OBJECTIVE: To describe dosing regimens and efficacy of continuous infusion hydromorphone in mechanically ventilated children. DESIGN: Retrospective review. SETTING: Tertiary care, pediatric hospital. PATIENTS: Ninety-two critically ill children (<18 years old). MAIN OUTCOME MEASURE(S): Hydromorphone dosing requirements, concomitant pain and sedation therapy, patient-specific pain scores (using Face Legs Activity Cry Consolability [FLACC] pain scale), and possible adverse drug events related to therapy. RESULTS: Starting dose was 0.024 +/- 0.04 mg/kg/h. Maximum dose was 0.05 + 0.1 mg/kg/h. Duration of therapy was 182 +/- 169 hours. Most patients received additional pain and sedation therapy. Most mean daily FLACC scores (66 percent) were below 1. Less than 10 percent of scores were above 3; only 1 score was above 6. Mean FLACC score, when averaged per patient course, was 1.004 +/- 0.71. Extracorporeal membrane oxygenation (ECMO) patients had a significantly higher initial and maximum dosing requirement than non-ECMO patients (p = 0.001). CONCLUSIONS: Continuous infusion hydromorphone appears to be an effective adjunctive analgesic in mechanically ventilated children.

A multicenter collaborative approach to reducing pediatric codes outside the ICU.

OBJECTIVES: The Child Health Corporation of America formed a multicenter collaborative to decrease the rate of pediatric codes outside the ICU by 50%, double the days between these events, and improve the patient safety culture scores by 5 percentage points. METHODS: A multidisciplinary pediatric advisory panel developed a comprehensive change package of process improvement strategies and measures for tracking progress. Learning sessions, conference calls, and data submission facilitated collaborative group learning and implementation. Twenty Child Health Corporation of America hospitals participated in this 12-month improvement project. Each hospital identified at least 1 noncritical care target unit in which to implement selected elements of the change package. Strategies to improve prevention, detection, and correction of the deteriorating patient ranged from relatively simple, foundational changes to more complex, advanced changes. Each hospital selected a broad range of change package elements for implementation using rapid-cycle methodologies. The primary outcome measure was reduction in codes per 1000 patient days. Secondary outcomes were days between codes and change in patient safety culture scores. RESULTS: Code rate for the collaborative did not decrease significantly (3% decrease). Twelve hospitals reported additional data after the collaborative and saw significant improvement in code rates (24% decrease). Patient safety culture scores improved by 4.5% to 8.5%. CONCLUSIONS: A complex process, such as patient deterioration, requires sufficient time and effort to achieve improved outcomes and create a deeply embedded culture of patient safety. The collaborative model can accelerate improvements achieved by individual institutions.

Continuous infusion pentobarbital for refractory status epilepticus in children.

The purpose of this retrospective medical chart review was to describe dosing regimens and outcomes in children who received continuous pentobarbital therapy for refractory status epilepticus. Thirty patients (age = 6.5 ± 5.1 years; 67% male) received a mean loading dose of 5.4 ± 2.8 mg/kg with an initial infusion of 1.1 ± 0.4 mg/kg/h. Maximum infusion dose was 4.8 ± 2 mg/kg/h. Thirty-three percent of patients achieved sustained burst suppression without relapse; 66.7% experienced relapse, but 60% of those (n = 12) eventually reachieved burst suppression. Children achieving burst suppression within 24 hours of pentobarbital initiation and those older than age 5 years were 1.5 times more likely to have a positive outcome. None of these variables, however, achieved significance (Fisher exact test). Ninety-three percent of patients required inotropes; 66% acquired an infection; 10% had metabolic acidosis; and 10% experienced pancreatitis. Poor outcomes (death, encephalopathy) were observed in 33% of patients.

Thrombosis risk factor assessment and implications for prevention in critically ill children.

OBJECTIVES: To describe nursing compliance with a computer-based pediatric thrombosis risk assessment tool; to generate an estimate of risk factors present in our population; and to explore relationships between risk factors and confirmed thrombotic events. DESIGN: Institutional review board-approved prospective, observational cohort study. SETTING: Pediatric intensive care unit within a tertiary care children's hospital. PATIENTS: All infants and children admitted to the pediatric intensive care unit during a 6-month study period (January 1, 2010-June 30, 2010). MEASUREMENTS AND MAIN RESULTS: Eight hundred admissions were enrolled, representing 742 patients. Thrombosis risk assessment scores were recorded for 707 admissions (88% of total). Mean age = 6.95 ± 6 yrs, mean weight = 28 ± 23 kg, 45% female. A total of 32 thrombi (14 prehospital and 18 in-hospital) were present in the study group. This translated to an overall occurrence rate of 4.3% (1.9% for prehospital and 2.4% for in-hospital). Logistic regression identified that for every 1-point increase in total thrombosis score, the risk of developing a symptomatic thrombus increased by 1.57-fold (95% confidence interval 0.192-5.5) to 2.12-fold (95% confidence interval 0.175-18.34), for prehospital and in-hospital thrombi, respectively (p < .05). The most important risk factors identified for development of any thrombus were thrombophilia (acquired or inherited) (p < .001), presence of a central catheter (p = .01), and age <1 or >14 yrs (p = .052). CONCLUSIONS: Incorporation of a scoring system into the bedside nursing assessment flow sheet was successful and identified children at risk for in-hospital thrombosis. The overall score appears to be most indicative of thrombus risk. These data may serve as a platform for future development of routine screening and possible interventional trials in critically ill children.

Persistent hiccups associated with epidural ropivacaine in a newborn.

OBJECTIVE: To report a case of persistent hiccups associated with epidural ropivacaine in a newborn infant. CASE SUMMARY: A term female infant (3.05 kg) received epidural ropivacaine for pain control during and after an operative procedure to correct a tracheoesophageal fistula. Three intermittent doses of ropivacaine were administered during the operative period (total dose 2.29 mg/kg) followed by a continuous epidural (caudal) infusion (0.1% ropivacaine; initial dose 0.23 mg/kg/h plus fentanyl 0.46 µg/kg/h). The infant was extubated in the recovery area and transferred to the intensive care unit. Within hours of transfer, she developed persistent hiccups. The epidural infusion was titrated for pain control, up to 0.32 mg/kg/h (ropivacaine). The hiccup frequency increased to every 10-30 seconds, with the patient appearing hypotonic with lip trembling and intermittent tongue fasciculation. An electroencephalogram did not show any epileptiform activity or focal features consistent with seizure activity. The epidural infusion was reduced to 0.26 mg/kg/h (ropivacaine), with dramatic improvement in hiccups and tone. The infusion was discontinued and complete resolution of hiccups was observed. DISCUSSION: Ropivacaine is commonly used for infiltration anesthesia and peripheral and epidural block anesthesia. Use of the Naranjo probability scale determined that our patient's hiccups were probably caused by ropivacaine. To our knowledge, this is the first report of persistent hiccups associated with epidural ropivacaine. CONCLUSIONS: Clinicians should consider the potential of neurotoxicity, manifested as persistent hiccups, when epidural ropivacaine is administered to young infants.

Retrospective review of emergency response activations during a 13-year period at a tertiary care children's hospital.

OBJECTIVES: Pediatric in-hospital arrests are uncommon but are associated with poor outcomes. In preparation for implenting a Rapid Response Team (RRT) at The Children's Hospital, we reviewed our data collection of 13 years of emergency response team (ERT) activations. We describe demographic and clinical variables, including outcomes of ERT activations at a free-standing tertiary care children's hospital. METHODS: Analysis was performed on data collected from January 1993 through July 2007. Variables collected included age, sex, admission diagnosis, core event, admission diagnosis and secondary diagnosis, medical division or winter/nonwinter months, day/night shifts, survival of core event, survival to discharge, and primary attending service. RESULTS: There were 1537 ERT activations in the database, 203 were eliminated due to missing data or were adult visitors/employees. The remaining 1334 were included for analysis. Our results showed 39%(511) of all ERT activations occurred in patients under 1 year of age. The most common admission diagnosis category was cardiac disease. There was no statistical significance between summer and winter months although more activations occurred during daytime hours (P < .001). Survival rate of an ERT was 90%, with a 78% survival rate to discharge. CONCLUSION: Our data support the general belief that younger children with chronic disease are at highest risk for ERT activations. These risk factors should be taken into consideration when planning patient placement, medical staffing, and the threshold for ICU consultations or admissions. More extensive multisite studies using clinical data are necessary to further identify hospitalized children at risk for sudden decompensation.

Prolonged dexmedetomidine infusions in critically ill infants and children.

OBJECTIVE: To present our institutional experience with prolonged dexmedetomidine (DEX) infusions in critically ill infants and children. DESIGN: Retrospective medical chart review between January 1, 2007 and December 1, 2007. SETTING: Tertiary care pediatric teaching hospital. PARTICIPANTS: Infants and children (up to 18 years of age) who received DEX for a duration greater than 24 hours. MAIN OUTCOME MEASURES: DEX dosing schema and rationale for use. Indices describing DEX efficacy and tolerability including change in patient-specific sedation scores, change in blood pressure and heart rate, and change in conventional analgesia and sedation requirements. RESULTS: Twenty-nine patients (age 5.32 +/- 6.1 y) were evaluated. DEX therapy was initiated at 0.36 +/- 0.16 mcg/kg/hour. One-third of patients received a loading dose (0.5-1 mcg/kg) prior to the start of the infusion. Duration of DEX therapy was 110 +/- 83 hours (range 32-378 hours; median 76 hours). Rationale for adding DEX to sedation regimens included: intent to extubate (n=12), intent to reduce benzodiazepine and opioid use (n=10), exclusive continuous sedation (n=5) and management of drug withdrawal (n=2). Sedation scores remained stable during DEX therapy. Use of conventional analgesia and sedation was generally reduced while receiving DEX. Initiation of therapy was associated with a transient, yet statistically significant reduction in HR (from 120 +/- 28 bpm to 107 +/-N 27 bpm) (P = 0.002), but without a change in blood pressure. CONCLUSIONS: Prolonged DEX infusions were associated with a reduction in concomitant analgesia and sedation medications. DEX was well tolerated with the exception of heart rate, which decreased during the initiation of therapy but may not represent a clinically significant reduction.

Evaluation of a scoring system for assessing prognosis in pediatric acute liver failure.

BACKGROUND & AIMS: Pediatric acute liver failure (PALF) results in death or need for liver transplantation (LT) in up to 50% of patients. A scoring system for predicting death or LT (Liver Injury Units [LIU] score) in PALF was previously derived by our group, and used peak values during hospital admission of total bilirubin, prothrombin time/international normalized ratio, and ammonia as significant predictors of outcome. The aims of this study were to test the predictive value of the LIU score in a subsequent validation set of patients and to derive a hospital admission LIU (aLIU) score predictive of outcome. METHODS: Data were obtained from 53 children admitted with PALF from 2002 to 2006. Outcome was defined at 16 weeks as alive without LT, death, or LT. RESULTS: Survival without LT at 16 weeks for each LIU score quartile was 92%, 44%, 60%, and 12%, respectively (P < .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 86.3. An admission LIU score was derived using admission total bilirubin and prothrombin time/international normalized ratio. Survival without LT at 16 weeks for each quartile using the aLIU score was 85%, 77%, 69%, and 31% (P = .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 83.7. CONCLUSIONS: The original LIU score is a valid predictor of outcome in PALF. The aLIU score is promising and needs to be validated in subsequent patients.

Characterization of acute liver failure and development of a continuous risk of death staging system in children.

BACKGROUND/AIMS: Acute liver failure (ALF) in children has been associated with an overall mortality of approximately 70% in the pretransplant era and 50-80% survival in those undergoing orthotopic liver transplantation. There is currently no system for staging severity of ALF in children. The aim of this study was to characterize pediatric ALF in a tertiary hospital and to derive a scoring system to stratify severity of ALF based on predicted mortality. METHODS: Prospective data collection of 81 children from December 1993-2003 who presented with ALF. Data recorded included peak laboratory values, clinical characteristics, and survival. RESULTS: Transplant-free survival was 56% with overall survival including those undergoing OLT of 72%. Transplantation rate was 22% with transplant survival of 72%. Of the peak laboratory values analyzed, total bilirubin, prothrombin time/INR, and ammonia were the most predictive of death or a need for liver transplant. A simple risk staging system was developed based on the ability of these three laboratory measurements to predict mortality. CONCLUSIONS: The survival in pediatric ALF has improved in recent years. Risk staging for ALF could potentially be used in clinical research for risk-adjusted outcomes analysis and to help stratify patients for clinical studies according to mortality risk.

Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics.

OBJECTIVE: High-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) have been reported to improve oxygenation in children with acute hypoxemic respiratory failure (AHRF), but their roles in the treatment of AHRF remains unknown. The use of HFOV improves oxygenation by increasing lung recruitment. iNO can improve oxygenation in AHRF, but it may have limited efficacy in patients with poor lung inflation. Based on these findings, we hypothesized that the combined treatment of HFOV and inhalation of low-dose NO would improve oxygenation and survival in children with severe AHRF compared with children treated with conventional mechanical ventilation (CMV) or either treatment alone. SETTING: Tertiary pediatric intensive care units at seven academic centers. DESIGN: Post hoc analysis of data from children enrolled in a multicenter, randomized, masked study of the use of iNO in the treatment of AHRF. PATIENTS: A total of 108 pediatric patients with AHRF defined as an oxygenation index of >15 twice within 6 hrs. Mode of ventilation (HFOV or CMV) was determined by the patient's physician based on guidelines to maximize oxygenation. The patient was then randomized to treatment with or without iNO. Comparisons were made between patients who were treated with HFOV plus iNO (n = 14), HFOV alone (n = 12), CMV plus iNO (n = 35), and CMV alone (n = 38). INTERVENTIONS: Ventilation with CMV or HFOV with or without iNO. MEASUREMENTS AND MAIN RESULTS: We found that the change in Pao /Fio ratio was greatest in the HFOV plus iNO group compared with the other treatment groups at 4 hrs (p =.02) and 12 hrs (p =.01). After 24 hrs of treatment, both HFOV plus iNO and HFOV alone resulted in greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.005). After 72 hrs, treatment with HFOV alone resulted in a greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.03). There was no difference in predefined treatment failures between treatment groups. CONCLUSIONS: We conclude that the combination of HFOV with iNO causes a greater improvement in oxygenation than either treatment strategy alone in children with severe AHRF. We speculate that the enhanced lung recruitment by HFOV enhances the effects of low dose iNO on gas exchange.