Pediatric Intensive Care Unit Patients Research Articles

Barriers and facilitators to early mobilisation programmes in the paediatric intensive care unit: A scoping literature review

AbstractBackgroundEarly mobilisation (EM) in paediatric intensive care units (PICU) is safe and feasible. Nurses, patients and family caregivers are integral to EM. Understanding their perspectives is necessary to implement and sustain EM for children in the PICU.AimTo identify and critique research literature on the perspectives of nurses, patients and families regarding EM in the PICU.Study designFor this scoping review, PubMed and EMBASE databases were searched. Included studies reported experiences of PICU nurses, caregivers and patients. Outcomes included feasibility, acceptability, satisfaction, benefits, facilitators, barriers, concerns, comfort with participation, and experiences and knowledge of EM. Exclusion criteria were: studies with preterm infants, other paediatric settings, review articles and editorials, studies of non‐mobility interventions or chest physiotherapy alone. Quality assessment tools for qualitative and quantitative designs were used.ResultsNine studies met the inclusion criteria: six quantitative and three qualitative studies. Six themes were identified: nurses' responses, concerns about patient risk factors and adverse events, equipment and staffing resources, family/caregivers' responses, patients' perspectives and overall impact.ConclusionsFindings demonstrate the importance of an interdisciplinary approach to address cultural, psychological and practical issues with EM. Unvalidated surveys conducted at single time points were used to measure nurses' perspectives. EM presents opportunities and challenges for family caregivers. Patients' experiences of EM are underrepresented in published research.Relevance to clinical practiceNurses and family caregivers are instrumental in EM in the PICU. Positive attitudes and competence are essential to PICU EM programme's success. Barriers may be minimized when programme benefits are understood.

Efficacy of an IgM preparation in the treatment of patients with sepsis: a double-blind randomized clinical trial in a pediatric intensive care unit

Aim: Additional treatments for sepsis to be administered alongside the standard therapy recommended by the Surviving Sepsis Campaign have recently undergone evaluation. Due to its anti-bacterial, anti-inflammatory and immunomodulatory properties, intravenous polyvalent immunoglobulin M (IgM)–enriched immunoglobulins (IgM preparation) has been investigated as one of these potentially valid adjunctive therapies. The aim of this trial was to assess the efficacy of an IgM preparation as adjuvant therapy in the treatment of pediatric patients with sepsis. Methods: In our study, 78 septic patients admitted to a pediatric intensive care unit (PICU) at the University Hospital Center “Mother Teresa” in Tirana, Albania, were randomized into two groups (intervention and control). All patients were treated according to standard PICU sepsis guidelines. Additionally, patients in the intervention group received the IgM preparation Pentaglobin® while patients in the control group received standard sepsis therapy, but no immunoglobulin administration. Results: The survival rate was higher in the intervention group (87%, N=34) than in the control group (64%, N=25), and this difference was statistically significant (P=0.03). Length of stay (LOS) was also significantly shorter in the intervention group. Conclusion: In this study conducted in Albania, use of an IgM preparation, in addition to standard sepsis therapy, led to a significant increase in the survival rate as well as a significant reduction in LOS compared with placebo, when administered in PICU patients with sepsis.

Community consultation in the pediatric intensive care unit for an exception from informed consent Trial: A survey of patient caregivers

AimTo explore perspectives of families in the pediatric intensive care unit (PICU) about an emergency interventional trial on peri-arrest bolus epinephrine for acute hypotension using Exception From Informed Consent (EFIC). MethodsWe performed face-to-face interviews with families whose children were hospitalized in the PICU. A research team member provided an educational presentation about the planned trial and administered a survey with open- and closed-ended items. Analyses included descriptive statistics for quantitative data and thematic analysis for qualitative data. ResultsSixty-seven participants contributed to 60 survey responses (53 individuals and 7 families for whom 2 family members participated). Most participants answered favorably toward the planned trial: 55/58 (95%) reported that the trial seemed “somewhat” or “very important”; 52/57 (91%) felt the use of EFIC was “somewhat” or “completely acceptable”; and 43/58 (74%) said they would be “somewhat” or “very likely” to allow their child to participate. Five themes emerged supporting participation in the planned trial: 1) trust in the clinical team; 2) familiarity with the study intervention (epinephrine); 3) study protocol being similar to standard care; 4) informed consent during an emergency was not feasible; and 5) importance of research. Barriers to potential participation included requests for additional time to decide about participating and misconceptions about study elements, especially eligibility. ConclusionsFamilies of PICU patients generally supported plans for an emergency interventional trial using EFIC. Future inpatient EFIC studies may benefit from highlighting the themes identified here in their educational materials.

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

In 2019, EMA licensed intravenous (IV) zanamivir for severe influenza virus infection in children over 6 months as well as adults. Prior to that, it was possible via a compassionate use program. We present successful compassionate use of IV zanamivir in a 14-year-old female with severe influenza A(H3N2) and multi-organ failure, who had failed oral oseltamivir. Her illness was complicated by acute respiratory distress syndrome and rhabdomyolysis requiring extracorporeal membrane oxygenation and hemofiltration. Considering the broad safety margins with neuraminidase inhibitors, an adult dose of 600 mg IV BID was administered in this 60 kg patient. Influenza virus was cleared rapidly and undetectable on day 13. Creatine kinase (CK) values were dropping from 38,000 to 500 within nine days. Given the recent licensure of IV zanamivir, multi-center prospective observational studies in pediatric Intensive Care Unit patients would be beneficial to guide the most appropriate use of IV zanamivir in this vulnerable age group.

Characteristics and Outcomes of Patients Admitted to a Pediatric Intensive Care Unit in Southwest of Iran

Data on pediatric critical care in Iran are insufficient. This study was performed to determine the outcomes and characteristics of critically ill children admitted to a pediatric intensive care unit (PICU) in Ahvaz, Iran. A retrospective study was conducted among all patients in the PICU of Abuzar Hospital for one year. Their medical documents were reviewed. A total of 400 patients were identified. The average age of patients was 29.94±39.55 months, and 53.8% of them were males. Nearly half of the cases were under age one. The most prevalent causes of PICU admission were respiratory (36.5%), neurological (18.5%), and infection-related diseases (15%). Besides, 55.7% of patients (n=223) had no history of underlying health problems. Admissions were more frequent in winter (n=125; 31.3%) and spring (n=101; 25.3%). The mortality rate and the mean hospital length of stay (LOS) were 15.5% and 10.79±6.39 days, respectively. In addition, 231 patients had an abnormal respiratory rate and a quarter of them (n=97) required ventilation support. Moreover, 377 and 82 patients were malnourished and severely underweight, respectively. A significant association was found between the mortality of patients and malnutrition, as well as having consanguineous parents (P<0.001). The death rate was significantly higher in patients with infectious disease than non-infectious, as well as in long-stay PICU patients than in short-stay patients (P<0.05). Additional studies are required to find factors contributing to the disease burden among PICU patients in Iran to develop appropriate therapeutic strategies and improve the outcomes of pediatric patients.

Antibiotic treatment duration for culture-negative sepsis in the pediatric intensive care unit.

Sepsis remains a leading cause of morbidity and mortality in children. There is very limited guidance for sepsis treatment when cultures remain negative. This study sought to determine the effectiveness of short versus long course of antibiotics when treating culture-negative sepsis and assess for subsequent multidrug-resistant organism (MDRO) acquisition. Retrospective cohort study. Quaternary academic children's hospital. Pediatric intensive care unit (ICU) patients with culture-negative sepsis receiving a minimum of 72 hours of antibiotics. Patients found to have culture-negative sepsis from January 2017 to May 2020 were divided into two groups: short and long course of antibiotics. Various demographic and laboratory results were collected for each subject as available. Primary outcomes included mortality and lengths of stay. The secondary outcome was subsequent acquisition of a new MDRO. Eighty-six patients were treated for culture-negative sepsis with 43 patients in both the short- (< or = 7 days) and long-course (>7 days) treatment cohorts. Patients who received a short course of antibiotics had a lower overall mortality than those who received a long course (9.3% vs 25.6% p = 0.047), but there was no difference in 30-day mortality (p > 0.99). Patients in the short-course group had a shorter hospital length of stay (22 vs 30 days p = 0.018). New MDROs were found in 10% of all patients. Treatment of culture-negative sepsis with short-course antibiotics was not associated with worse outcomes in ICU patients. These findings warrant further investigation with a larger, prospective, multi-center study.

Assessment of the Delirium Prevalence Among Pediatric Patients Admitted to the Pediatric Intensive Care Unit in West of Iran

Background: Delirium is often not diagnosed or treated in pediatric intensive care unit (PICU). Delirium leads to a longer hospital stay period, which in turn can result in an increase in hospital treatment costs and an increase in the risk of nosocomial infections. Objectives: The present study aimed to determine the prevalence of delirium and its risk factors in PICU pediatric. Methods: This cross-sectional study was conducted in 2021 - 2022 in hospitals affiliated to Kermanshah University of Medical Sciences. The data collection instruments included the Richmond Agitation-Sedation Scale (RASS) and the Cornell Assessment of Pediatric Delirium (CAPD) questionnaire. Delirium was assessed by the researcher twice a day, in the morning and the evening. The assessment was carried out by a trained person, and the examination results were confirmed by an anesthesiologist who was a member of the research team. Data analysis was carried out using SPSS ver. 16. Results: According to our study results, the majority of the 89 examined patients were male (n = 52 cases, 59.8%), aged 13 - 16 years (n = 37 cases, 42.5%), and were admitted due to pneumonia (n = 24 cases, 27.6%). The prevalence of delirium was higher in patients with pain and those requiring oxygen therapy (P &lt; 0.05). Furthermore, the overall prevalence of delirium in PICU patients was 25.3% (n = 22 cases). Conclusions: Investigating the prevalence of delirium in all age groups – pediatric and adolescents, in particular – was found to be extremely important. It was also found that the prevalence of delirium in PICU patients was significant; therefore, it was recommended that necessary preventive and medical interventions should be made to deal with these patients.

Analysis of healthcare-associated infection in patients with pulmonary arterial hypertension associated with congenital heart disease in PICU: Evidence from a tertiary hospital in western China.

The present study intends to analyze the targeted surveillance and risk factors for healthcare-associated infection (HAI) in patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) in a Pediatric intensive care unit (PICU), and provide basis for formulating relevant prevention and control measures of HAI. Children (≤14 years old) who were admitted to the PICU for ≥2 calendar days from January 2018 to December 2021 were included. Targeted surveillance of HAI was described. A total of 7,828 patients in PICU were monitored, and the total hospitalization days of the patients were 36,174. 108 cases of HAI occurred, with a per-case infection rate of 1.38% and a per-thousand day infection rate of 2.99. 1,129 patients with CHD-PAH were included, among which the total hospitalization days were 1,483. In this subpopulation, 38 cases of HAI were diagnosed, with a per-case infection rate of 3.37% and a per-thousand day infection rate of 25.62. The main site of HAI was lower respiratory tract (43.51%), followed by blood infection (34.26%) and surgical site infection (9.26%). 36 strains of pathogenic bacteria were detected from patients with HAI. The top three pathogens with the highest detection rate were Klebsiella pneumoniae (6 episodes, 16.67%), Enterococcus faecium (6 episodes, 16.67%) and Acinetobacter baumannii (4 episodes, 11.11%). The incidence of VAP, CAUTI and CLABSI was 2.78, 0.08 and 1.66 per 1,000 catheter days respectively. Analysis revealed that patients with CHD-PAH were younger and prone to receive surgical corrections. CHD-PAH could significantly increase the length of ICU stay, ventilator days, times of central venous catheterization and central venous catheterization days. The choice of different central venous catheter types differed significantly between the two groups. Patients with CHD-PAH are characterized with excessive central venous catheterization operations, prolonged indwelling time, and more types of catheterization, which are considered to be risk factors for HAI, thus increasing the length of hospital stay. The clinical etiology is mainly G-bacteria, which requires reasonable selection of antibiotics and strict aseptic operation. Limiting unnecessary invasive procedures is helpful for reducing the incidence of postoperative HAI in PICU.

33: LONG-TERM CARDIAC AND FUNCTIONAL OUTCOMES OF MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN

Introduction: Multi-system Inflammatory Syndrome (MIS-C) is a hyperinflammatory state involving two or more organs associated with a previous diagnosis of SARS-CoV-2. Cardiac dysfunction is described in 80-85% of cases. Currently, there is a knowledge gap regarding long-term cardiac and functional outcomes in children diagnosed with MIS-C. Methods: We conducted a retrospective chart review of children < 21 years admitted to our hospital for MIS-C between January 2020 and January 2022. We collected demographic, clinical, laboratory, imaging data [left ventricular ejection fraction (LVEF), coronary artery dilation (CAD)], and functional status score (FSS) during hospital stay and long-term (up to 6 months) follow up. Using a student t-test and chi-square test, we compared the outcomes of children admitted to the pediatric intensive care unit (PICU) vs outside the PICU. Results: Out of the 40 children admitted to the hospital with MIS-C during the study period, 16 (40%) were admitted to the PICU while 24 (60%) were admitted outside the PICU. Of the PICU patients, 13.33% showed CAD and 31.25% had a LVEF ≤55% on at least one echocardiogram during their hospital stay. Of the echocardiograms completed on the non-PICU patients (n=22), 18.18% showed CAD and 9.09% had a LVEF ≤55% on at least one echo during admission. Between PICU and non-PICU patients, there was a significant (p ≤ 0.05) difference in mean length of stay (13.56 vs. 6.16 days respectively), lowest LVEF (56.14% vs 62.58%), and change in Functional Status Score (ΔFSS) (0.5 vs 0.0). Of the 16 PICU patients, 11 had follow-up echocardiogram and none had persistent CAD and/or LVEF ≤55%. Of the 20/24 (83.33%) non-PICU patients with echocardiograms at follow-up, 10% displayed persistent coronary artery dilation while none had LVEF ≤55%. At follow-up, a significant proportion of non-PICU patients had persistent CAD as compared to PICU patients (p≤0.0001), but there was no difference in LVEF and ΔFSS amongst the two cohorts. Conclusions: A significant proportion of children admitted outside the PICU had persistent coronary abnormalities at up to 6 month follow up compared to patients admitted in the PICU. However, none of the patients had persistent low LVEF (≤55%) or functional disability at up to 6 month follow up (ΔFSS).

427: BLOOD CELL-FREE DNA (CFDNA) ANALYSIS FOR DIAGNOSIS OF INFECTIONS AND OUTCOMES IN THE PEDIATRIC ICU

Introduction: Severe infections requiring ICU care warrant prompt diagnosis and initiation of treatment. Most conventional tests (CT) for infectious diagnosis have variable sensitivity, specificity and turn-around times. There is a need for a test with high sensitivity, specificity and shorter time to result in order to facilitate management decisions in critically ill patients. Cell free DNA (cfDNA) analysis - Karius test (KT) is emerging as an effective tool for early diagnosis of infections. However, there is a lack of sufficient data on KT in critically ill children. Our study aimed at evaluating the utility of KT for diagnosis of infections and outcomes in Pediatric ICU (PICU). Methods: Our retrospective study included children between 0 to 21 years of age who were admitted to our PICU between January 2019 and April 2022 and who had KT and CT done during PICU stay. Demographic, clinical, treatment, and outcome data were collected. KT and CT results were analyzed to determine their agreement and impact on diagnosis and management. Comparisons were made between PICU patients with positive KT and CT and those with only positive KT using student t-test (significant p≤0.05). Results: Among 67 PICU patients identified, the median (IQR) age was 96 (24-156) months, with 55% males and 93% hispanic; 41 (61%) had a positive KT with median (IQR) turn-around time for KT result 2.3 (2.1-3.1) days. KT confirmed diagnosis independently in 13 (19%) while in 20 (30%) patients, KT matched CT results and both KT and CT confirmed absence of infection in 20 (30%). KT facilitated the diagnosis and management of infections (initiation/change/discontinuation of antimicrobials) in 53/67 (79%) PICU patients. The overall survival was 98% in our cohort. The median (IQR) hospital length of stay (LOS) in our cohort was 14.5 (9-25) days. There was a significant difference in LOS among those PICU patients who had positive KT and CT versus those with positive KT and negative CT (p=0.03). Conclusions: Our study highlights the utility of blood cfDNA (Karius) test for microbiologic diagnosis amongst critically ill children. In a significant proportion (79%) of PICU patients, KT facilitated the decision regarding antimicrobials in critically ill children with a relatively short turn-around time for diagnosis.

196. Repeat Tracheal Aspirates in Pediatric Intensive Care Patients: Frequency, Resistance and Antimicrobial Use

Abstract Background Tracheal aspirates (TA) are frequently obtained in the pediatric intensive care unit (PICU); however, no data exists on the frequency or clinical management of multiple TA cultures on the same PICU patient. In this study, we describe the frequency of repeat TAs in PICU patients, the emergence of multidrug resistant organisms (MDRO), frequently cultured pathogens of TAs, and associated antibiotic prescribing patterns. Methods We identified 70 PICU patients between 2018-2019 who met our criteria for retrospective chart review with ≥ 2 TAs obtained during their hospitalization. The following information was collected: patient demographics, number of TAs per patient, microbiology with susceptibilities, antibiotic use, and clinical data summarizing patient condition. Descriptive statistics established the frequency and time between initial and repeat TAs, reason for collection, antibiotic exposure, and frequency of MDRO development. Results Preliminary data on 15 patients showed 90 total TA cultures, with a median of 4 [IQR 2.5, 8] cultures per patient during their PICU stay (Figure 1). The median days between cultures was 10 [IQR 4, 26]. Most patients were &amp;lt; 5 years of age (n=14; 94%), male (n=13; 87%), and were admitted to the medical ICU service (n=8, 53%). Fever (46%) was the most common reason for TA collection followed by vital sign changes and secretion burden (34% and 32% respectively). A total of 133 organisms were isolated, with Pseudomonas aeruginosa (n=32), Methicillin-susceptible Staphylococcus aureus (n=16), and Klebsiella oxytoca (n=11) comprising the top pathogens (Figure 2). Eleven of the 15 patients (73.3%) had the same organism detected on ≥ 2 separate cultures. A total of 616 antibiotic days were prescribed with 149 (24%) antibiotic days prescribed for the TA result specifically. Six (40%) patients developed a MDRO after a median of 14.5 antibiotic days [IQR 11.75, 37.5]. Figure 1Number of tracheal aspirate cultures per patient Figure 2 Frequency of identified pathogens Conclusion Repeat TAs are performed in the PICU, often identifying the same pathogen repeatedly, likely representing colonization. Development of resistance is common and only one-fourth of TAs are directly treated with antibiotics. These data provide an opportunity to further explore clinical criteria to maximize the impact of TA cultures in the PICU. Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.

Implementing Standardized Post-Intensive Care Syndrome Education by an Advanced Practice Registered Nurse in the Pediatric Intensive Care Unit

Implementing Standardized Post-Intensive Care Syndrome Education by an Advanced Practice Registered Nurse in the Pediatric Intensive Care Unit

1076: QUALITY IMPROVEMENT INITIATIVE TO PREVENT FLUID OVERLOAD IN PEDIATRIC INTENSIVE CARE UNIT PATIENTS

Introduction: Fluid administration for critically ill children frequently exceeds hydration requirements and is associated with increased morbidity and mortality. The global aim of this ongoing single-center quality improvement (QI) initiative is to standardize and implement process improvement tools to detect and prevent fluid overload (FO) in patients admitted to the Pediatric Intensive Care Unit (PICU). Our SMART aim is to reduce the incidence of percent fluid overload (%FO) >/= 10% at 72 hours of PICU admission by 20% in the first 6 months. Methods: In collaboration with key stakeholders, we used Plan-Do-Study Act (PDSA) QI methodology to develop electronic health record (EHR)-based tools and education sessions to help providers detect and prevent FO in PICU patients. We conducted a retrospective chart review with a convenience sample to obtain baseline metrics. We assessed current FO understanding and perceptions of proposed interventions with anonymous surveys distributed to PICU attendings, fellows, residents, advanced practice providers and nurses. In April 2022, we implemented a single screen “Fluid Management accordion” within our EHR that displays all clinical markers used to evaluate a patient’s fluid status, and an EHR-based %FO calculator. In July 2022, we added PICU admission order set modifications to include a total fluid goal. Outcome metrics are collected monthly. Quarterly follow up surveys began in July 2022 and will trend intervention impact and perceptions. Results: Chart review (n=562) revealed a 40% baseline incidence of %FO >/= 10% at 72 hours of PICU admission. Pre-implementation, most respondents (n=115) agreed that we could improve our awareness to patients’ fluid status (92%) and that using standardized EHR orders and tools would be helpful (76%). Few (27%) reported knowing how to calculate %FO. Three months after initial EHR tool launch, many survey respondents (n=49) reported using the fluid management accordion at least once (40%) and 43% reported knowing how to calculate %FO. Six-month implementation data will be available in October 2022. Conclusions: To date we have standardized EHR-based tools for FO detection. We suspect that with continued education and feedback we will likely see a reduction in %FO incidence in our PICU population.

970: PHYSIOLOGY-BASED VENTILATOR COMPUTER DECISION SUPPORT OUTPERFORMS CLINICIANS IN AN IN SILICO TRIAL

Introduction: Intensivists are routinely required to titrate alveolar minute ventilation based on blood gas information. Survey data show that intensive care trainees feel insufficiently trained in ventilator management. Bedside decision support has the potential to facilitate more efficient ventilator titration and serve as a teaching tool for trainees. Methods: We developed an online ventilator calculator based upon arterial partial pressure of carbon dioxide (PaCO2) and Henderson-Hasselbalch equations, allowing clinicians to input ventilator parameters as well as current and desired blood gas information. We validated predictions among arterial blood gas (ABG) values from a single quaternary academic pediatric intensive care unit (PICU). We included all ABG values obtained between 1/1/2010 and 12/31/2020 among PICU patients receiving invasive pressure control, volume control, or volume targeted ventilation and concurrent pharmacologic muscle relaxation with a repeat blood gas analysis within 1-24 hours. We excluded ABGs from patients on extracorporeal support. We subsequently performed a retrospective in-silico trial on a subset of ABGs meeting criteria for ventilator weaning (pCO2 < 30 and pH > 7.35 or pCO2 < 50 and pH > 7.50) or escalation (pCO2 > 50 and pH < 7.30 or pCO2 > 45 and pH < 7.20), excluding patients with traumatic brain injury. Clinician behavior was compared against calculator recommendations, with a goal of achieving an ABG value that met neither weaning nor escalation criteria. Results: There were 16,835 included ABGs among 664 patients, with a median (IQR) time between ABGs of 3.8 (2.2-4.4) hours. The median (IQR) difference between predicted and actual PaCO2 values was 0.00 (-3.06-3.00) mmHg. 11,460/16,835 (68.1%) PaCO2 values were within 5 mmHg of predicted, and 14,902/16,835 (88.5%) were within 10 mmHg. There were 2,433 ABGs among 350 patients included in the in-silico trial. Calculator recommendations were preferable to clinician behavior in 1,149/1,534 (74.9%) weaning scenarios and 605/899 (67.3%) escalation scenarios. Conclusions: Computer decision support outperformed clinician actions in this retrospective in-silico trial and may provide a useful teaching tool for trainees. Prospective study is needed to determine feasibility and user satisfaction.

Assessment of aberrant DNA methylation two years after paediatric critical illness: a pre-planned secondary analysis of the international PEPaNIC trial

ABSTRACT Critically ill children requiring intensive care suffer from impaired physical/neurocognitive development 2 y later, partially preventable by omitting early use of parenteral nutrition (early-PN) in the paediatric intensive-care-unit (PICU). Altered methylation of DNA from peripheral blood during PICU-stay provided a molecular basis hereof. Whether DNA-methylation of former PICU patients, assessed 2 y after critical illness, is different from that of healthy children remained unknown. In a pre-planned secondary analysis of the PEPaNIC-RCT (clinicaltrials.gov-NCT01536275) 2-year follow-up, we assessed buccal-mucosal DNA-methylation (Infinium-HumanMethylation-EPIC-BeadChip) of former PICU-patients (N = 406 early-PN; N = 414 late-PN) and matched healthy children (N = 392). CpG-sites differentially methylated between groups were identified with multivariable linear regression and differentially methylated DNA-regions via clustering of differentially methylated CpG-sites using kernel-estimates. Analyses were adjusted for technical variation and baseline risk factors, and corrected for multiple testing (false-discovery-rate <0.05). Differentially methylated genes were functionally annotated (KEGG-pathway database), and allocated to three classes depending on involvement in physical/neurocognitive development, critical illness and intensive medical care, or pre-PICU-admission disorders. As compared with matched healthy children, former PICU-patients showed significantly different DNA-methylation at 4047 CpG-sites (2186 genes) and 494 DNA-regions (468 genes), with most CpG-sites being hypomethylated (90.3%) and with an average absolute 2% effect-size, irrespective of timing of PN initiation. Of the differentially methylated KEGG-pathways, 41.2% were related to physical/neurocognitive development, 32.8% to critical illness and intensive medical care and 26.0% to pre-PICU-admission disorders. Two years after critical illness in children, buccal-mucosal DNA showed abnormal methylation of CpG-sites and DNA-regions located in pathways known to be important for physical/neurocognitive development.

Pediatric Intensive Care Unit Patients: Sedation, Monitoring, and Neurodevelopmental Outcomes.

The design and conduct of pediatric sedation studies in critically ill patients have historically been challenging due to the complexity of the pediatric intensive care unit (PICU) environment and the difficulty of establishing equipoise. Clinical trials, for instance, represent 1 important means of advancing our knowledge in this field, but there is a paucity of such studies in the literature. Accounting for ground-level factors in planning for each trial phase (eg, enrollment, intervention, assessment, and follow-up) and the presence of broader system limitations is of key importance. In addition, there is a need for early planning, coordination, and obtaining buy-in from individual study sites and staff to ensure success, particularly for multicenter studies. This review synthesizes the current state of pediatric sedation research and the myriad of challenges in designing and conducting successful trials in this particular area. The review poses consideration for future research directions, including novel study designs, and discusses electroencephalography monitoring and neurodevelopmental outcomes of PICU survivors.

Utility of Pediatric Early Warning Sign Score in Predicting Outcome of PICU Admissions at a Suburban Tertiary Care Hospital

Abstract Assessment of the severity of illness is very important in intensive care unit care for quality assessment, assessing prognosis, and proper counseling. The goal of the study was to see how well the Pediatric Early Warning Sign (PEWS) score predicted the outcome of pediatric intensive care unit patients. This prospective cross-sectional study included children younger than 18 years. PEWS was calculated at presentation. The outcomes analyzed were mortality (primary outcome), need for mechanical ventilation, inotropic support, and length of stay (LOS). A median score was calculated and compared across the outcome groups. The performance of the PEWS was assessed for calibration and discrimination, and the best cutoff was determined. This study included 237 patients with a median score of 6 (range 4–9). Twenty-two (9.3%) patients required ventilator support and 66 (26.6%) inotropic support. The overall mortality rate was 5.1%, and 16.4% had prolonged LOS (&gt;4 days). The median score of patients was significantly higher among those who died (8.5 vs. 6; p = 0.001), required ventilator support (8 vs. 6; p = 0.001), inotropic support (7 vs. 6; p = 0.030), and prolonged LOS (7 vs. 6; p = 0.001). On calibration, PEWS was found to have a good fit to predict mortality, the need for ventilator support, inotropic support, and prolonged LOS. Receiver operating characteristic curves for the PEWS model yield an area under the curve of 0.966 for mortality, 0.951 for ventilator support, 0.626 for inotropic support, and 0.760 for prolonged LOS. A cutoff value of &gt; 7 was found to be the best to predict the outcome. PEWS is a robust tool to easily prognosticate the patient on the basis of clinical parameters.

Evaluating IL-6 and IL-10 as rapid diagnostic tools for Gram-negative bacteria and as disease severity predictors in pediatric sepsis patients in the intensive care unit.

To explore the diagnostic performance of interleukin (IL)-6 and IL-10 in discriminating Gram bacteria types and predicting disease severity in intensive care unit (ICU)-hospitalized pediatric sepsis patients. We retrospectively collected Th1/Th2 cytokine profiles of 146 microbiologically documented sepsis patients. Patients were categorized into Gram-positive (G+) or Gram-negative (G-) sepsis groups, and cytokine levels were compared. Subgroup analysis was designed to eliminate the influence of other inflammatory responses on cytokine levels. After propensity score matching, 78 patients were matched and categorized according to Gram bacteria types. Compared with G+ sepsis, IL-6 and IL-10 were significantly elevated in G- sepsis (p < 0.05). Spearman test proved the linear correlation between IL-6 and IL-10 (r = 0.654, p < 0.001), and their combination indicators (ratio and differences) were effective in identifying G- sepsis. In the subgroup analysis, such cytokine elevation was significant regardless of primary infection site. However, for patients with progressively deteriorating organ function [new or progressive multiple organ dysfunction syndrome (NPMODS)], differences in IL-6 and IL-10 levels were less significant between G+ and G- sepsis. In the receiver operating characteristic (ROC) curves of the G- sepsis group, the area under the curve (AUC) value for IL-6 and IL-10 was 0.679 (95% CI 0.561-0.798) and 0.637 (95% CI 0.512-0.762), respectively. The optimal cutoff value for diagnosing G- sepsis was 76.77 pg/ml and 18.90 pg/ml, respectively. While for the NPMODS group, the AUC for IL-6 and IL-10 was 0.834 (95% CI 0.766-0.902) and 0.781 (95% CI 0.701-0.860), respectively. IL-6 and IL-10 are comparably effective in discriminating G+/G- sepsis in pediatric intensive care unit (PICU) patients. The deteriorated organ function observed in ICU patients reveals that complex inflammatory responses might have contributed to the cytokine pattern observed in severe sepsis patients, therefore confounding the discriminating efficacy of Th1/Th2 cytokines in predicting Gram bacteria types.

Incidence of iatrogenic withdrawal syndrome and associated factors in surgical pediatric intensive care

BackgroundIatrogenic withdrawal syndrome (IWS) is a complication of prolonged sedation/analgesia in pediatric intensive care unit (PICU) patients. The epidemiology of IWS is poorly understood, as validated diagnostic tools are rarely used. The main objective of our study was to use the WAT-1 score to assess the incidence of IWS in our unit. The secondary objectives were to evaluate the consequences of IWS, associated factors, and management modalities. Material and methodsFrom July 2018 to January 2019, 48 children receiving endotracheal ventilation and sedation/analgesia by continuous infusion (>48 h) of benzodiazepines and/or opioids were included. As soon as sedation/analgesia was decreased and until 72 h after its complete discontinuation, the WAT-1 score was determined every 12 h. Substitution therapy was used for 98% of patients upon opioid and/or benzodiazepine withdrawal. IWS was defined as a WAT-1 score ≥3. Factors associated with IWS were assessed by univariate analysis. ResultsIWS occurred in 25 (52%) patients. IWS was associated with a higher number of ventilator-associated pneumonia episodes (17 [68%] vs. one [4%]) and a longer PICU stay (13 [7; 25] vs. 9.0 [5.0; 10.5]) (p<0.001). Overall, 11 patients developed IWS after less than 5 days of sedation/analgesia. Severe head injury was associated with IWS (p = 0.03). Neither sedation discontinuation nor IWS prevention was standardized. ConclusionThe high incidence and adverse consequences of IWS require improved prevention. Risk groups should be defined and a standardized withdrawal protocol established. The occurrence of IWS should be monitored routinely using a validated score.

Risk Factors for Mortality and Antimicrobial Regimens in Pediatric Intensive Care Unit Patients with Carbapenem-Resistant Enterobacteriaceae Infections: A Six-Year Retrospective Study.

Limited data are available on the characteristics, risk factors, and antimicrobial treatment of critically ill pediatric patients with carbapenem-resistant Enterobacteriaceae (CRE) infections. This study was to identify the risk factors for 30-day mortality in pediatric intensive care unit (PICU) patients with CRE infections and compare the clinical outcomes of different antimicrobial regimens. A retrospective, observational cohort study was performed on patients admitted to the PICU with positive CRE cultures between January 2016 and December 2021. For the 56 patients, the overall 30-day mortality was 50% (n=28). Multivariable logistic regression analysis revealed that pediatric critical illness score (PCIS; HR = 0.879; 95% CI, 0.827-0.935; P < 0.001) and serum albumin levels (HR = 0.921; 95% CI, 0.860-0.987; P = 0.019) were independently associated with 30-day mortality. At the same time, there was no significant difference in 30-day mortality (42.9% versus 45.5%, P = 0.854) or clinical efficiency rate (53.4% versus 40.9%, P = 0.374) between with and without polymyxin B therapy. The study revealed PCIS and serum albumin levels were the independent mortality-related risk factors of CRE infections in critically ill pediatric patients. Treatment with polymyxin B could not reduce 30-day mortality. Future prospective cohort studies are needed to investigate the optimal antimicrobial regimens for CRE infection in PICU patients.