An exploratory assessment of the management of pediatric traumatic brain injury in three centers in Africa.

Purpose: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). Hospital care practices of pediatric TBI patients in LMICs are unknown. Our objective was to report on hospital management and outcomes of children with TBI in three centers in LMICs. Methods: We completed a secondary analysis of a prospective observational study in children (<18 years) over a 4-week period. Outcome was determined by Pediatric Cerebral Performance Category (PCPC) score; an unfavorable score was defined as PCPC > 2 or an increase of two points from baseline. Data were compared using Chi-square and Wilcoxon rank sum tests. Results: Fifty-six children presented with TBI (age 0-17 y), most commonly due to falls (43%, n = 24). Emergency department Glasgow Coma Scale scores were ≤ 8 in 21% (n = 12). Head computed tomography was performed in 79% (n = 44) of patients. Forty (71%) children were admitted to the hospital, 25 (63%) of whom were treated for suspected intracranial hypertension. Intracranial pressure monitoring was unavailable. Five (9%, n = 5) children died and 10 (28%, n = 36) inpatient survivors had a newly diagnosed unfavorable outcome on discharge. Conclusion: Inpatient management and monitoring capability of pediatric TBI patients in 3 LMIC-based tertiary hospitals was varied. Results support the need for prospective studies to inform development of evidence-based TBI management guidelines tailored to the unique needs and resources in LMICs.

The brain in pediatric critical care: unique aspects of assessment, monitoring, investigations, and follow-up.

As survival after pediatric intensive care unit (PICU) admission has improved over recent years, a key focus now is the reduction of morbidities and optimization of quality of life for survivors. Neurologic disorders and direct brain injuries are the reason for 11-16% of admissions to PICU. In addition, many critically ill children are at heightened risk of brain injury and neurodevelopmental difficulties affecting later life, e.g., complex heart disease and premature birth. Hence, assessment, monitoring and protection of the brain, using fundamental principles of neurocritical care, are crucial to the practice of pediatric intensive care medicine. The assessment of brain function, necessary to direct appropriate care, is uniquely challenging amongst children admitted to the PICU. Challenges in assessment arise in children who are unstable, or pharmacologically sedated and muscle relaxed, or who have premorbid abnormality in development. Moreover, the heterogeneity of diseases and ages in PICU patients, means that high caliber evidence is harder to accrue than in adult practice, nonetheless, great progress has been made over recent years. In this 'state of the art' paper about critically ill children, we discuss (1) patient types at risk of brain injury, (2) new standardized clinical assessment tools for age-appropriate, clinical evaluation of brain function, (3) latest evidence related to cranial imaging, non-invasive and invasive monitoring of the brain, (4) the concept of childhood 'post intensive are syndrome' and approaches for neurodevelopmental follow-up. Better understanding of these concepts is vital for taking PICU survivorship to the next level.

Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools.

OBJECTIVES: To identify available assessment tools for sedative/hypnotic iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence supporting their use, and describe areas of overlap between the components of these tools and the symptoms of anticholinergic burden in children. DATA SOURCES: Studies were identified using PubMed and EMBASE from the earliest available date until July 3, 2016, using a combination of MeSH terms "delirium," "substance withdrawal syndrome," and key words "opioids," "benzodiazepines," "critical illness," "ICU," and "intensive care." Review article references were also searched. STUDY SELECTION: Human studies reporting assessment of delirium or iatrogenic withdrawal syndrome in children 0-18 years undergoing critical care. Non-English language, exclusively adult, and neonatal intensive care studies were excluded. DATA EXTRACTION: References cataloged by study type, population, and screening process. DATA SYNTHESIS: Iatrogenic withdrawal syndrome and delirium are both prevalent in the PICU population. Commonly used scales for delirium and iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior, and state domains, and exhibit considerable overlap. In addition, signs and symptoms of an anticholinergic toxidrome (a risk associated with some common PICU medications) overlap with components of these scales, specifically in motor, cardiovascular, and psychiatric domains. CONCLUSIONS: Although important studies have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and delirium in the PICU population, the overlap in these scoring systems presents potential difficulty in distinguishing syndromes, both clinically and for research purposes.

International Survey of Critically Ill Children With Acute Neurologic Insults: The Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment Study.

OBJECTIVE: The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults. DESIGN: Prospective study. SETTING: Multicenter (n = 107 PICUs) and multinational (23 countries, 79% in North America and Europe). PATIENTS: Children 7 days to 17 years old admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, CNS infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the prevalence and outcomes of children with predetermined acute neurologic insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category score greater than or equal to 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurologic insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and traumatic brain injury subjects had the most unfavorable outcomes (49%). The most common neurologic insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. CONCLUSIONS: Neurologic insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurologic diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

Accuracy of a simplified equation for energy expenditure based on bedside volumetric carbon dioxide elimination measurement--a two-center study.

BACKGROUND & AIMS: Accurate assessment of resting energy expenditure (REE) and metabolic state is essential to optimize nutrient intake in critically ill patients. We aimed to examine the accuracy of a simplified equation for predicting REE using carbon dioxide elimination (VCO2) values. METHODS: We conducted a two-center study of metabolic data from mechanically ventilated children less than 18 years of age. Mean respiratory quotient (RQ) from the derivation set (n = 72 subjects) was used to modify the Weir equation to obtain a simplified equation based on VCO2 measurements alone. This equation was then applied to subjects at the second institution (validation dataset, n = 94) to predict resting energy expenditure. Bland-Altman analysis was used to assess the agreement between measured REE values, and REE estimated by the new equation as well as the Schofield equation. We also examined the accuracy of the new equation in classifying patients according to their metabolic state. RESULTS: Mean respiratory quotient (± SD) of 0.89 ± 0.09 in the derivation set was used to obtain a simplified equation, REE (kcal/day) = 5.534*VCO2 (L/min)*1440. In relation to the measured REE in the validation set, the mean bias (limits of agreement) for the REE predicted by this equation was -0.65% (-14.4-13.1%); and the overall diagnostic accuracy for classifying subjects as hypometabolic or hypermetabolic was 84%. Mean bias (limits) of agreement between measured and Schofield equation estimated REE was -0.1% (-40.5-40.7%). CONCLUSIONS: A simplified metabolic equation using VCO2 values was superior to the standard equation in estimating REE, and provided a reasonably accurate metabolic classification in mechanically ventilated children. In the absence of indirect calorimetry, bedside VCO2 monitoring could provide valuable continuous metabolic information to guide optimal nutrient intake.

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information.

A randomized trial of hyperglycemic control in pediatric intensive care.

BACKGROUND: Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear. METHODS: We randomly assigned children (≤16 years of age) who were admitted to the pediatric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4.0 to 7.0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12.0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services. RESULTS: A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0.36 days (95% confidence interval [CI], -0.42 to 1.14); the effects did not differ according to subgroup. Severe hypoglycemia (blood glucose, <36 mg per deciliter [2.0 mmol per liter]) occurred in a higher proportion of children in the tight-glycemic-control group than in the conventional-glycemic-control group (7.3% vs. 1.5%, P<0.001). Overall, the mean 12-month costs were lower in the tight-glycemic-control group than in the conventional-glycemic-control group. The mean 12-month costs were similar in the two groups in the cardiac-surgery subgroup, but in the subgroup that had not undergone cardiac surgery, the mean cost was significantly lower in the tight-glycemic-control group than in the conventional-glycemic-control group: -$13,120 (95% CI, -$24,682 to -$1,559). CONCLUSIONS: This multicenter, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although the incidence of hypoglycemia was higher with tight glucose control than with conventional glucose control. (Funded by the National Institute for Health Research, Health Technology Assessment Program, U.K. National Health Service; CHiP Current Controlled Trials number, ISRCTN61735247.).