Carol Nicholson

Pediatric critical care medicine: Planning for our research future

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.

Tolerance and Withdrawal From Prolonged Opioid Use in Critically Ill Children

OBJECTIVE: After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS: Relevant manuscripts published in the English language were searched in Medline by using search terms “opioid,” “opiate,” “sedation,” “analgesia,” “child,” “infant-newborn,” “tolerance,” “dependency,” “withdrawal,” “analgesic,” “receptor,” and “individual opioid drugs.” Clinical and preclinical studies were reviewed for data synthesis. RESULTS: Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS: Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

Impact of pediatric critical illness and injury on families: a systematic literature review.

OBJECTIVE. We sought to inform decision-making for children and families by describing what is known and remains unknown about the impact of childhood critical illness and injury on families. This report also was designed as a tool for research planning and design so that meaningful studies are performed and duplication is avoided. DESIGN. After a national scholarship competition and the identification of 3 medical student summer scholars, a literature search was conducted by using the National Library of Medicine and a PubMed keyword search system at the National Institutes of Health. RESULTS. A total of 115 reports were reviewed and assigned to the 5 following categories characterizing the impact of pediatric critical illness/injury on families: stressors, needs, specific domains (psychological, physical, social), coping, and interventions. The reports reviewed indicate that pediatric critical illness and injury is stressful for the entire family. The effects on parents, siblings, and marital cohesion were variably described. Needs of family members (eg, rest, nutrition, communication) were identified as being unmet in many studies. Permanent impact on siblings and marital relationships has been considered detrimental, but these conclusions are not adequately quantified in presently available studies. Reviewed reports minimally investigated cultural diversity, effects on fathers versus mothers, siblings, socioeconomic status, and financial burden. Studies were often anecdotal and included small sample sizes. Methodologic limitations were numerous and varied and seriously narrowed the significance of the studies we reviewed. The reports that we evaluated were largely limited to those of English-speaking families, white people, and married mothers. CONCLUSIONS. Future research should use more rigorous methods in the measurement of impact of childhood critical illness and injury on families. Families of critically ill and injured children would benefit from the practitioners of pediatric critical care acquiring enhanced knowledge and sensitivity about famliy communication and dynamics.

Weaning and extubation readiness in pediatric patients.

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.

Parents' perspectives on physician-parent communication near the time of a child's death in the pediatric intensive care unit

Objective: Communicating bad news about a child’s illness is a difficult task commonly faced by intensive care physicians. Greater understanding of parents’ scope of experiences with bad news during their child’s hospitalization will help physicians communicate more effectively. Our objective is to describe parents’ perceptions of their conversations with physicians regarding their child’s terminal illness and death in the pediatric intensive care unit (PICU). Design: A secondary analysis of a qualitative interview study. Setting: Six children’s hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Participants: Fifty-six parents of 48 children who died in the PICU 3–12 months before the study. Interventions: Parents participated in audio recorded semistructured telephone interviews. Interviews were analyzed using established qualitative methods. Measurements and Main Results: Of the 56 parents interviewed, 40 (71%) wanted to provide feedback on the way information about their child’s terminal illness and death was communicated by PICU physicians. The most common communication issue identified by parents was the physicians’ availability and attentiveness to their informational needs. Other communication issues included honesty and comprehensiveness of information, affect with which information was provided, withholding of information, provision of false hope, complexity of vocabulary, pace of providing information, contradictory information, and physicians’ body language. Conclusions: The way bad news is discussed by physicians is extremely important to most parents. Parents want physicians to be accessible and to provide honest and complete information with a caring affect, using lay language, and at a pace in accordance with their ability to comprehend. Withholding prognostic information from parents often leads to false hopes and feelings of anger, betrayal, and distrust. Future research is needed to investigate whether the way bad news is discussed influences psychological adjustment and family functioning among bereaved parents.

Follow-up study of complicated grief among parents eighteen months after a child's death in the pediatric intensive care unit.

OBJECTIVE We previously demonstrated that parents whose children die in a pediatric intensive care unit (PICU) have a high level of complicated grief symptoms 6 months after the death. In this study, we investigate the change in the extent of complicated grief symptoms among these parents between 6 and 18 months postdeath and identify factors predicting improvement. METHODS One hundred thirty-eight parents of 106 children completed surveys at 6 and 18 months. Surveys included the Inventory of Complicated Grief (ICG), measures of grief avoidance, attachment, caregiving and social support, and demographics. Multivariable analysis was performed using generalized estimating equations to identify characteristics independently associated with improvement in ICG score. RESULTS ICG scores were 33.4 ± 13.6 at 6 months and 28.0 ± 13.5 at 18 months, representing an improvement in ICG score of 5.4 + 8.0 (95% confidence interval [CI] 4.1-6.8, p < 0.001). Variables independently associated with greater improvement in ICG score included traumatic death and greater grief avoidance. Variables independently associated with less improvement included being the biological parent and having more responsive caregiving. Parents with one or two surviving children had more improvement in ICG score than those with no surviving children whereas parents with three or more surviving children had less improvement. CONCLUSION Complicated grief symptoms decrease among parents between 6 and 18 months after their childs death in the PICU; however, high symptom levels persists for some. Better understanding of the trajectory of complicated grief will allow parents at risk for persistent distress to receive professional support.

Critical care for pediatric asthma: Wide care variability and challenges for study

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.

Critical Pertussis Illness in Children: A Multicenter Prospective Cohort Study*

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.

The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial

Objectives: Nosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population. Design: Randomized, double-blinded, comparative effectiveness trial. Setting: Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Patients: Two hundred ninety-three long-term intensive care patients (age 1–17 yrs) expected to require >72 hrs of invasive care. Interventions: Patients were stratified according to immunocompromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat. Measurements and Main Results: There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011). Conclusion: Compared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune-competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient.

Complicated Grief and Associated Risk Factors Among Parents Following a Child’s Death in the Pediatric Intensive Care Unit

OBJECTIVE To investigate the extent of complicated grief symptoms and associated risk factors among parents whose child died in a pediatric intensive care unit. DESIGN Cross-sectional survey conducted by mail and telephone. SETTING Seven childrens hospitals affiliated with the Collaborative Pediatric Critical Care Research Network from January 1, 2006, to June 30, 2008. PARTICIPANTS Two hundred sixty-one parents from 872 families whose child died in a pediatric intensive care unit 6 months earlier. MAIN EXPOSURE Assessment of potential risk factors, including demographic and clinical variables, and parent psychosocial characteristics, such as attachment style, caregiving style, grief avoidance, and social support. MAIN OUTCOME MEASURE Parent report of complicated grief symptoms using the Inventory of Complicated Grief. Total scale range is from 0 to 76; scores of 30 or higher suggest complicated grief. RESULTS Mean (SD) Inventory of Complicated Grief scores among parents were 33.7 (14.1). Fifty-nine percent of parents (95% confidence interval, 53%-65%) had scores of 30 or higher. Variables independently associated with higher symptom scores in multivariable analysis included being the biological mother or female guardian, trauma as the cause of death, greater attachment-related anxiety and attachment-related avoidance, and greater grief avoidance. CONCLUSIONS Parents who responded to our survey experienced a high level of complicated grief symptoms 6 months after their childs death in the pediatric intensive care unit. However, our estimate of the extent of complicated grief symptoms may be biased because of a high number of nonresponders. Better understanding of complicated grief and its risk factors among parents will allow those most vulnerable to receive professional bereavement support.