Dexmedetomidine Sedation in Mechanically Ventilated Critically Ill Children: A Pilot Randomized Controlled Trial.

OBJECTIVES: To assess the feasibility, safety, and efficacy of a sedation protocol using dexmedetomidine as the primary sedative in mechanically ventilated critically ill children. DESIGN: Open-label, pilot, prospective, multicenter, randomized, controlled trial. The primary outcome was the proportion of sedation scores in the target sedation range in the first 48 hours. Safety outcomes included device removal, adverse events, and vasopressor use. Feasibility outcomes included time to randomization and protocol fidelity. SETTING: Six tertiary PICUs in Australia and New Zealand. PATIENTS: Critically ill children, younger than 16 years old, requiring intubation and mechanical ventilation and expected to be mechanically ventilated for at least 24 hours. INTERVENTIONS: Children randomized to dexmedetomidine received a dexmedetomidine-based algorithm targeted to light sedation (State Behavioral Scale -1 to +1). Children randomized to usual care received sedation as determined by the treating clinician (but not dexmedetomidine), also targeted to light sedation. MEASUREMENTS AND MAIN RESULTS: Sedation with dexmedetomidine as the primary sedative resulted in a greater proportion of sedation measurements in the light sedation range (State Behavioral Scale -1 to +1) over the first 48 hours (229/325 [71%] vs 181/331 [58%]; p = 0.04) and the first 24 hours (66/103 [64%] vs 48/116 [41%]; p < 0.001) compared with usual care. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm compared with usual care (p = 0.002).There were more episodes of hypotension and bradycardia with dexmedetomidine (including one serious adverse event) but no difference in vasopressor requirements. Median time to randomization after intubation was 6.0 hours (interquartile range, 2.0-9.0 hr) in the dexmedetomidine arm compared with 3.0 hours (interquartile range, 1.0-7.0 hr) in the usual care arm (p = 0.24). CONCLUSIONS: A sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation, and reduced midazolam requirements. The findings of this pilot study justify further studies of sedative agents in critically ill children.

Understanding the global epidemiology of pediatric critical illness: the power, pitfalls, and practicalities of point prevalence studies.

OBJECTIVE: The point prevalence methodology is a valuable epidemiological study design that can optimize patient enrollment, prospectively gather individual-level data, and measure practice variability across a large number of geographic regions and healthcare settings. The objective of this article is to review the design, implementation, and analysis of recent point prevalence studies investigating the global epidemiology of pediatric critical illness. DATA SOURCES: Literature review and primary datasets. STUDY SELECTION: Multicenter, international point prevalence studies performed in PICUs since 2007. DATA EXTRACTION: Study topic, number of sites, number of study days, patients screened, prevalence of disease, use of specified therapies, and outcomes. DATA SYNTHESIS: Since 2007, five-point prevalence studies have been performed on acute lung injury, neurologic disease, thromboprophylaxis, fluid resuscitation, and sepsis in PICUs. These studies were performed in 59-120 sites in 7-28 countries. All studies accounted for seasonal variation in pediatric disease by collecting data over multiple study days. Studies screened up to 6,317 patients and reported data on prevalence and therapeutic variability. Three studies also reported short-term outcomes, a valuable but atypical data element in point prevalence studies. Using these five studies as examples, the advantages and disadvantages and approach to designing, implementing, and analyzing point prevalence studies are reviewed. CONCLUSIONS: Point prevalence studies in pediatric critical care can efficiently provide valuable insight on the global epidemiology of disease and practice patterns for critically ill children.

The burden of childhood influenza in a tertiary paediatric setting.

Influenza is usually considered a mild winter-time illness but can be associated with a range of serious complications. We undertook a retrospective medical record review to study the impact of admissions of children with laboratory-confirmed influenza to The Children's Hospital at Westmead, Sydney, during 2007. One hundred and twenty-two children were identified, representing 530 hospital admission days. There was no clearly documented evidence of influenza vaccination for any patient eligible for vaccination. Fever (97.5%) and cough (69.7%) were the most frequent manifestations. Admissions occurred almost entirely between June and September with a peak in July (n=61, 50%). Two-thirds of the children were aged less than 2 years (median 1.5 years). Most (61.5%) had an underlying chronic medical disorder. Lumbar puncture was performed in 28 (23%) children, mostly infants aged less than 3 months (n=18). Antibiotics were commonly prescribed (67.2%), but use of available influenza-specific antiviral agents was uncommon (13.1%). The nosocomial infection rate was 9.8% and the clinical staff vaccination rate was low (less than 30%). Pneumonia was the most common complication (12.3%). No influenza-related deaths occurred. Influenza in young children poses a significant burden to health care services, tertiary admissions representing the tip-of-the-iceberg. Vaccination rates are inappropriately low in both eligible patients and hospital clinical staff. Early 'point of care' testing, use of influenza-specific antiviral agents, and extension of current vaccination schedules to include all children aged six to 23 months could considerably reduce over-investigation, unnecessary use of antibiotics and the health care impact of influenza.

Enhanced surveillance for serious complications of influenza in children: role of the Australian Paediatric Surveillance Unit.

Influenza contributes significantly to disease burden among children aged less than five years. Existing influenza surveillance systems do not provide detailed data on clinical presentation, management, vaccination status, risk factors and complications in hospitalised children, or link such data with laboratory results. Following a number of child deaths due to influenza in 2007, the Australian Government Department of Health and Ageing approached the Australian Paediatric Surveillance Unit (APSU) to examine the feasibility of enhancing APSU surveillance to identify children hospitalised with severe complications of influenza. Active, national, weekly surveillance was conducted during September 2007 with reporting by 1,256 Australian paediatricians working in hospitals and outpatient settings. The weekly report card return rate was 93%; detailed clinical data were provided on 88% of all notified cases and 15 children met the case criteria for severe complications of influenza. Admission to hospital occurred within 48 hours of onset of symptoms in over half of the children, of whom 13 had influenza A and two had influenza B, confirmed mostly by polymerase chain reaction on nasopharyngeal aspirate. Serious complications included pneumonia, presumed viral (67%), secondary bacterial infection, shock, cardiomyopathy, myocarditis and hypoglycaemia. No child aged six months or older had been vaccinated against influenza, including three children with underlying chronic conditions. No eligible child received an antiviral agent for influenza. Length of hospital stay ranged from 2 to 34 days; four children were admitted to a Paediatric Intensive Care Unit and one was ventilated. This study demonstrates the feasibility of using the established APSU mechanism for enhanced emergency surveillance during disease outbreaks, emergence or importation.

Early application of generic mortality risk scores in presumed meningococcal disease.

OBJECTIVE: Mortality from meningococcal disease typically occurs within 24 hrs of intensive care unit (ICU) admission. An early, accurate mortality-risk tool may aid in trial design for novel therapies. We assessed the performance of two generic scores that assign mortality risk within 1 hr of ICU admission: the Preintensive Care Pediatric Risk of Mortality (Pre-ICU PRISM) and Pediatric Index of Mortality (PIM). DESIGN: Prospective, observational study over 21 months. SETTING: Two tertiary pediatric ICUs accepting referrals from southeast England. PATIENTS: Patients were 165 consecutive children with meningococcal disease. Ages ranged from 0.1 to 17 yrs (median 2.3 yrs). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PIM demonstrated greater sensibility, with complete data collected in 93% of cases, compared with 35% for the pre-ICU PRISM. Both scores discriminated well. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval, 0.81-1.00) for PIM and 0.94 (95% confidence interval, 0.88-0.98) for Pre-ICU PRISM; this did not change when applied to the subgroup of patients with complete data. Both scores calibrated poorly, overestimating mortality in the medium-risk strata (and also in the high-risk stratum in the case of Pre-ICU PRISM). When used as a stratification tool for a hypothetical trial (60% reduction in mortality, 80% power), the scores allowed for a reduction in study size by 50% (PIM) and 43% (pre-ICU PRISM). CONCLUSIONS: Pre-ICU PRISM and PIM both discriminate well but calibrate poorly when applied to a cohort of children with meningococcal sepsis. Both scores provide an effective means of stratification for clinical trial purposes. The main advantage for PIM appears to be ease of data collection.