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Objectives: Pertussis can cause life-threatening illness in infants. Data regarding neurodevelopment after pertussis remain scant. The aim of this study was to assess cognitive development of infants with critical pertussis 1 year after PICU discharge., Design: Prospective cohort study., Setting: Eight hospitals comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 18 additional sites across the United States., Patients: Eligible patients had laboratory confirmation of pertussis infection, were less than 1 year old, and were admitted to the PICU for at least 24 hours., Interventions: The Mullen Scales of Early Learning was administered at a 1-year follow-up visit. Functional status was determined by examination and parental interview., Measurements and Main Results: Of 196 eligible patients, 111 (57%) completed the Mullen Scales of Early Learning. The mean scores for visual reception, receptive language, and expressive language domains were significantly lower than the norms (p < 0.001), but not fine and gross motor domains. Forty-one patients (37%) had abnormal scores in at least one domain and 10 (9%) had an Early Learning Composite score 2 or more SDs below the population norms. Older age (p < 0.003) and Hispanic ethnicity (p < 0.008) were associated with lower mean Early Learning Composite score, but presenting symptoms and PICU course were not., Conclusions: Infants who survive critical pertussis often have neurodevelopmental deficits. These infants may benefit from routine neurodevelopmental screening.

Objectives: To examine issues regarding the granularity (size/scale) and potential acceptability of recommendations in a ventilator management protocol for children with pediatric acute respiratory distress syndrome., Design: Survey/questionnaire., Setting: The eight PICUs in the Collaborative Pediatric Critical Care Research Network., Participants: One hundred twenty-two physicians (attendings and fellows)., Interventions: None., Measurements and Main Results: We used an online questionnaire to examine attitudes and assessed recommendations with 50 clinical scenarios. Overall 80% of scenario recommendations were accepted. Acceptance did not vary by provider characteristics but did vary by ventilator mode (high-frequency oscillatory ventilation 83%, pressure-regulated volume control 82%, pressure control 75%; p = 0.002) and variable adjusted (ranging from 88% for peak inspiratory pressure and 86% for FIO2 changes to 69% for positive end-expiratory pressure changes). Acceptance did not vary based on child size/age. There was a preference for smaller positive end-expiratory pressure changes but no clear granularity preference for other variables., Conclusions: Although overall acceptance rate for scenarios was good, there was little consensus regarding the size/scale of ventilator setting changes for children with pediatric acute respiratory distress syndrome. An acceptable protocol could support robust evaluation of ventilator management strategies. Further studies are needed to determine if adherence to an explicit protocol leads to better outcomes.

Objectives: Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal CO2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol., Design: Prospective observational study., Setting: Eight tertiary care U.S. PICUs, October 2011 to April 2012., Patients: One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome., Measurements and Main Results: Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal CO2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed FIO2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5-12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6-12.0) (p < 0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol's recommendation 12% of the time and no changes 56% of the time., Conclusions: Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a pediatric mechanical ventilation protocol offering adequately explicit instructions for given clinical situations. An accepted protocol could also reduce confounding by mechanical ventilation management in a clinical trial.

Objective: Determine if the shortest sampling interval for laboratory variables used to estimate baseline severity of illness in pediatric critical care is equivalently sensitive across multiple sites without site-specific bias, while accounting for the vast majority of dysfunction compared with the standard 0- to 12-hour Pediatric Risk of Mortality III score., Design: Prospective random patient selection., Setting: General/medical and cardiac/cardiovascular PICUs in eight hospitals., Patients: Patients younger than 18 years admitted to the PICU., Interventions: None., Measurements and Main Results: A total of 376 patients were included. Measurements for Pediatric Risk of Mortality III laboratory variables (pH, PCO2, total CO2, PaO2, glucose, potassium, blood urea nitrogen, creatinine, total WBC count, platelet count, and prothrombin time/partial thromboplastin time) were recorded from 2 hours prior to PICU admission through 12 hours of PICU care except for data in the operating room. Decreasing the observation period from 0 to 12 hours post-PICU admission resulted in progressive decreases in the Pediatric Risk of Mortality III laboratory variables measured. However, allowing the observation period to start 2 hours prior to PICU admission to 4 hours reduced this loss to only 3.4%. Similar trends existed for each of the individual laboratory Pediatric Risk of Mortality III variables. There was a nearly identical distribution of laboratory Pediatric Risk of Mortality III points within the -2- to 4-hour period compared with the standard period. We did not detect any institutional bias using the -2- to 4-hour time period compared with the baseline., Conclusions: Prognostically important laboratory physiologic data collected within the interval from 2 hours prior to PICU to admission through 4 hours after admission account for the vast majority of dysfunction that these variables would contribute to Pediatric Risk of Mortality III scores. There was no institutional bias associated with this sampling period.

Objective: Pertussis persists in the United States despite high immunization rates. This report characterizes the presentation and acute course of critical pertussis by quantifying demographic data, laboratory findings, clinical complications, and critical care therapies among children requiring admission to the PICU., Design: Prospective cohort study., Setting: Eight PICUs comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 17 additional PICUs across the United States., Patients: Eligible patients had laboratory confirmation of pertussis infection, were younger than 18 years old, and died in the PICU or were admitted to the PICU for at least 24 hours between June 2008 and August 2011., Interventions: None., Measurements and Main Results: A total of 127 patients were identified. Median age was 49 days, and 105 (83%) patients were less than 3 months old. Fifty-five (43%) patients required mechanical ventilation and 12 patients (9.4%) died during initial hospitalization. Pulmonary hypertension was found in 16 patients (12.5%) and was present in 75% of patients who died, compared with 6% of survivors (p < 0.001). Median WBC was significantly higher in those requiring mechanical ventilation (p < 0.001), those with pulmonary hypertension (p < 0.001), and nonsurvivors (p < 0.001). Age, sex, and immunization status did not differ between survivors and nonsurvivors. Fourteen patients received leukoreduction therapy (exchange transfusion [12], leukopheresis [1], or both [1]). Survival benefit was not apparent., Conclusions: Pulmonary hypertension may be associated with mortality in pertussis critical illness. Elevated WBC is associated with the need for mechanical ventilation, pulmonary hypertension, and mortality risk. Research is indicated to elucidate how pulmonary hypertension, immune responsiveness, and elevated WBC contribute to morbidity and mortality and whether leukoreduction might be efficacious.

Objective: To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit., Design: Prospective, observational study with 100% accrual of eligible patients., Setting: Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network., Patients: Four hundred nineteen children treated with morphine or fentanyl infusions., Interventions: None., Measurements and Main Results: Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03)., Conclusions: Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.

Objectives: To describe pediatric severe asthma care, complications, and outcomes to plan for future prospective studies by the Collaborative Pediatric Critical Care Research Network., Design: Retrospective cohort study., Setting: : Pediatric intensive care units in the United States that submit administrative data to the Pediatric Health Information System., Patients: Children 1-18 yrs old treated in a Pediatric Health Information System pediatric intensive care unit for asthma during 2004-2008., Interventions: None., Measurements and Main Results: Thirteen-thousand five-hundred fifty-two children were studied; 2,812 (21%) were treated in a Collaborative Pediatric Critical Care Research Network and 10,740 (79%) were treated in a non-Collaborative Pediatric Critical Care Research Network pediatric intensive care unit. Medication use in individual Collaborative Pediatric Critical Care Research Network centers differed widely: ipratropium bromide (41%-84%), terbutaline (11%-74%), magnesium sulfate (23%-64%), and methylxanthines (0%-46%). Complications including pneumothorax (0%-0.6%), cardiac arrest (0.2%-2%), and aspiration (0.2%-2%) were rare. Overall use of medical therapies and complications at Collaborative Pediatric Critical Care Research Network centers were representative of pediatric asthma care at non-Collaborative Pediatric Critical Care Research Network pediatric intensive care units. Median length of pediatric intensive care unit stay at Collaborative Pediatric Critical Care Research Network centers was 1 to 2 days and death was rare (0.1%-3%). Ten percent of children treated at Collaborative Pediatric Critical Care Research Network centers received invasive mechanical ventilation compared to 12% at non-Collaborative Pediatric Critical Care Research Network centers. Overall 44% of patients who received invasive mechanical ventilation were intubated in the pediatric intensive care unit. Children intubated outside the pediatric intensive care unit had significantly shorter median ventilation days (1 vs. 3), pediatric intensive care unit days (2 vs. 4), and hospital days (4 vs. 7) compared to those intubated in the pediatric intensive care unit. Among children who received mechanical respiratory support, significantly more (41% vs. 25%) were treated with noninvasive ventilation and significantly fewer (41% vs. 58%) were intubated before pediatric intensive care unit care when treated in a Pediatric Health Information System hospital emergency department., Conclusions: Marked variations in medication therapies and mechanical support exist. Death and other complications were rare. More than half of patients treated with mechanical ventilation were intubated before pediatric intensive care unit care. Site of respiratory mechanical support initiation was associated with length of stay.

Objective: To provide an updated overview of critical pertussis to the pediatric critical care community and describe a study of critical pertussis recently undertaken., Setting: The six sites, seven hospitals of the Collaborative Pediatric Critical Care Research Network, and 17 outside sites at academic medical centers with pediatric intensive care units., Results: Despite high coverage for childhood vaccination, pertussis causes substantial morbidity and mortality in US children, especially among infants. In pediatric intensive care units, Bordetella pertussis is a community-acquired pathogen associated with critical illness and death. The incidence of medical and developmental sequelae in critical pertussis survivors remains unknown, and the appropriate strategies for treatment and support remain unclear. The Collaborative Pediatric Critical Care Research Network Critical Pertussis Study has begun to evaluate critical pertussis in a prospective cohort., Conclusion: Research is urgently needed to provide an evidence base that might optimize management for critical pertussis, a serious, disabling, and too often fatal illness for U.S. children and those in the developing world.

Objective: A systematic review of weaning and extubation for pediatric patients on mechanical ventilation., Data Selection: Pediatric and adult literature, English language., Study Selection: Invited review., Data Sources: Literature review using National Library of Medicine PubMed from January 1972 until April 2008, earlier cross-referenced article citations, the Cochrane Database of Systematic Reviews, and the Internet., Conclusions: Despite the importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are even less clear, although a trial of spontaneous breathing would seem a prerequisite. Several indices have been developed in an attempt to predict weaning and extubation success but the available literature would suggest they offer no improvement over clinical judgment. Extubation failure rates range from 2% to 20% and bear little relationship to the duration of mechanical ventilation. Upper airway obstruction is the single most common cause of extubation failure. A reliable method of assessing readiness for weaning and predicting extubation success is not evident from the pediatric literature.

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.