Carin W. M. Verlaat

Perceptions of parents on satisfaction with care in the pediatric intensive care unit: the EMPATHIC study

PurposeTo identify parental perceptions on pediatric intensive care-related satisfaction items within the framework of developing a Dutch pediatric intensive care unit (PICU) satisfaction instrument.MethodsProspective cohort study in tertiary PICUs at seven university medical centers in The Netherlands.ParticipantsParents of 1,042 children discharged from a PICU.ResultsA 78-item questionnaire was sent to 1,042 parents and completed by 559 (54%). Seventeen satisfaction items were rated with mean scores <8.0 (1, completely unimportant, to 10, very important) with standard deviations ≥1.65, and thus considered of limited value. The empirical structure of the items was in agreement with the theoretically formulated domains: Information, Care and Cure, Organization, Parental Participation, and Professional Attitude. The Cronbach’s α of the domains ranged between 0.87 and 0.94.ConclusionsParental perceptions on satisfaction with care measures were identified and prioritized. Reliabilities of the items and domains were of high level.

Inflammation and Organ Failure Severely Affect Midazolam Clearance in Critically Ill Children

RATIONALE Various in vitro, animal, and limited human adult studies suggest a profound inhibitory effect of inflammation and disease on cytochrome P-450 3A (CYP3A)-mediated drug metabolism. Studies showing this relationship in critically ill patients are lacking, whereas clearance of many CYP3A drug substrates may be decreased, potentially leading to toxicity. OBJECTIVES To prospectively study the relationship between inflammation, organ failure, and midazolam clearance as a validated marker of CYP3A-mediated drug metabolism in critically ill children. METHODS From 83 critically ill children (median age, 5.1 mo [range, 0.02-202 mo]), midazolam plasma (n = 532), cytokine (e.g., IL-6, tumor necrosis factor-α), and C-reactive protein (CRP) levels; organ dysfunction scores (Pediatric Risk of Mortality II, Pediatric Index of Mortality 2, Pediatric Logistic Organ Dysfunction); and number of failing organs were prospectively collected. A population pharmacokinetic model to study the impact of inflammation and organ failure on midazolam pharmacokinetics was developed using NONMEM 7.3. MEASUREMENTS AND MAIN RESULTS In a two-compartmental pharmacokinetic model, body weight was the most significant covariate for clearance and volume of distribution. CRP and organ failure were significantly associated with clearance (P < 0.01), explaining both interindividual and interoccasional variability. In simulations, a CRP of 300 mg/L was associated with a 65% lower clearance compared with 10 mg/L, and three failing organs were associated with a 35% lower clearance compared with one failing organ. CONCLUSIONS Inflammation and organ failure strongly reduce midazolam clearance, a surrogate marker of CYP3A-mediated drug metabolism, in critically ill children. Hence, critically ill patients receiving CYP3A substrate drugs may be at risk of increased drug levels and associated toxicity.

Congenital pulmonary lymphangiectasis presenting as a unilateral hyperlucent lung

Congenital pulmonary lymphangiectasis can be a cause of respiratory distress of the newborn infant. We present a case of congenital pulmonary lymphangiectasis presenting as a unilateral hyperlucent lung. Such a presentation has only once been previously described.

Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands

Objective: To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality. Design: Retrospective cohort study. Setting: Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012. Patients: Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included. Interventions: None. Measurements and Main Results: In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5–32] d vs median, 3 [interquartile range, 2–5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97–5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40–9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08–2.58). Conclusions: Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions.

Short-Term Health-Related Quality of Life of Critically Ill Children Following Daily Sedation Interruption

Objective: Our earlier pediatric daily sedation interruption trial showed that daily sedation interruption in addition to protocolized sedation in critically ill children does not reduce duration of mechanical ventilation, length of stay, or amounts of sedative drugs administered when compared with protocolized sedation only, but undersedation was more frequent in the daily sedation interruption + protocolized sedation group. We now report the preplanned analysis comparing short-term health-related quality of life and posttraumatic stress symptoms between the two groups. Design: Preplanned prospective part of a randomized controlled trial. Setting: Two tertiary medical-surgical PICUs in the Netherlands. Patients: Critically ill children requiring mechanical ventilation. Interventions: None. Measurements and Main Results: Eight weeks after a child’s discharge from the PICU, health-related quality of life was assessed with the validated Child Health Questionnaire and, only for children above 4 years old, posttraumatic stress was assessed with the Dutch Children’s Responses to Trauma Inventory. Additionally, health-related quality of life of all study patients was compared with Dutch normative data. Of the 113 patients from two participating centers in the original study, 96 patients were eligible for follow-up and 64 patients were included (response rate, 67%). No difference was found with respect to health-related quality of life between the two study groups. None of the eight children more than 4 years old showed posttraumatic stress symptoms. Conclusions: Daily sedation interruption in addition to protocolized sedation for critically ill children did not seem to have an effect on short-term health-related quality of life. Also in view of the earlier found absence of effect on clinical outcome, we cannot recommend the use of daily sedation interruption + protocolized sedation.

ORGAN FAILURE AND C-REACTIVE PROTEIN BOTH AFFECT MIDAZOLAM CLEARANCE IN CRITICALLY ILL CHILDREN: A POPULATION PK MODEL

Objectives To study the effect of organ failure and inflammation on midazolam clearance in critically ill children, using population pharmacokinetic modeling. Methods A total of 83 critically ill children (median age 5 months (range 1 day-17 years), n=523 samples) receiving intravenous midazolam for continuous sedation during mechanical ventilation were included. Disease severity was described using the validated and clinically used scores PELOD, PIM2 and PRISM II. Cytokines (IL-1, IL-2, IL-6, TNF-a) and C-reactive protein (CRP) were used as markers for inflammation. A population pharmacokinetic model for midazolam was developed using NONMEM 7.3. Body weight, age, severity of organ failure and inflammatory markers were considered as potential covariates. Results In a two-compartmental PK model, body weight was found as most significant covariate for clearance and volume of distribution. Moreover, both severity of organ failure (PELOD) and inflammation (IL6 and CRP) were significant determinants of clearance (p<0.01), and either of these factors improved the model significantly. With increasing number of organ failures, midazolam clearance significantly reduced. CRP was linearly correlated with clearance (slope −0.095), with higher CRP levels resulting in lower clearances. Either one of the covariates could explain part of the variability in clearance. Conclusion For midazolam clearance, apart from body weight, we found organ failure reflected by the PELOD score, and inflammation reflected by IL6 and CRP, as significant covariates. Most likely this effect is due to reduced activity of CYP3A in critically ill mechanically ventilated children. Both CRP concentration and organ failure should be considered when dosing midazolam and potentially other CYP3A substrates in critically ill children.