Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study.

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.

A multicentric, randomized, controlled clinical trial to study the impact of bedside model-informed precision dosing of vancomycin in critically ill children-BENEFICIAL trial.

BACKGROUND: Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. METHODS: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400-600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400-600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. DISCUSSION: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. TRIAL REGISTRATION: Eudract number: 2019-004538-40. Registered on 2020-09-08 ClinicalTrials.gov NCT046666948. Registered on 2020-11-28.

Early Diagnostic and Prognostic Value of the Urinary TIMP-2 and IGFBP-7 in Acute Kidney Injury in Critically Ill Children.

Background: Acute kidney injury (AKI) is a hidden complication among children within pediatric intensive care units (PICU). Aim: To evaluate the early predictive and diagnostic value of Urinary [TIMP-2][IGFBP7] to detect AKI in PICU patients. Methods: A case-control study was conducted on 112 children (72 admitted to PICU and 40 healthy controls) Urinary [TIMP-2][IGFBP7] was measured within 24 hours of PICU admission. Results: Acute kidney injury developed in 52 (72.2%) out of 72 critically ill patients. The AKI group had significantly higher serum creatinine, CRP, and pediatric sequential organ failure assessment score (pSOFA) score (p = 0.001, 0.01, and 0.001, respectively) and significantly lower estimated creatinine clearance (eCCl) (p = 0.001). Urinary [TIMP-2][IGFBP7] was significantly higher in the AKI group as compared with the non-AKI group (p = 0.007). The duration of the PICU stay was 1.8-fold higher in the AKI group (p = 0.004). At the time of study enrollment, 7 (13.5%) patients had normal initial eCCl. 26 patients (50.0%) fulfilled the "Risk," 18 patients (34.6%) the "Injury," 1 patient (1.9%) the "Failure" and 0 patient (0%) the "Loss" criteria. Nine (17%) patients progressed to the next higher pediatrics risk, injury, failure, loss, end-stage renal disease (pRIFLE) stage. Urinary [TIMP-2][IGFBP7] was significantly higher in the "Failure" stage followed by "Injury," stage then the "Risk," stage (p = 0.001). Hypovolemia/dehydration had the highest [TIMP-2][IGFBP7] values followed by sepsis. Urinary [TIMP-2][IGFBP7] was significantly increased in mechanically ventilated and patients who received inotropic medications. Conclusions: [TIMP-2]·[IGFBP7] was higher in AKI patients compared with non-AKI ones especially cases with hypovolemia and sepsis. It may predict severe morbidity and mortality because its higher levels in mechanically ventilated children and those on positive inotropic support. How to cite this article: Ismail M, Abdelhamid N, Hasanin HM, Hamed HM, Motawie A, Kamel S, et al. Early Diagnostic and Prognostic Value of the Urinary TIMP-2 and IGFBP-7 in Acute Kidney Injury in Critically Ill Children. Indian J Crit Care Med 2024;28(10):970-976.

Intravenous lacosamide for acute repetitive seizures and convulsive status epilepticus in critically ill children.

OBJECTIVE: Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in critically ill children. The aim of the study was to evaluate the effectiveness and safety of intravenous lacosamide in critically ill children with acute repetitive seizures and convulsive status epilepticus. METHODS: This retrospective study included children who received intravenous lacosamide for acute repetitive seizures or convulsive status epilepticus from October 2017 to September 2022 and were admitted to the pediatric intensive care unit at a tertiary medical center. Children who were newly started on intravenous lacosamide were included and divided into two groups: (a) previously healthy, and (b) history of epilepsy and receiving antiseizure medications. Efficacy was defined as the cessation of seizures within 72 h of administering lacosamide. Adverse effects were defined using predefined criteria, and most were evaluated during the first 7 days. RESULTS: Sixty-seven children were enrolled, including 25 (37.3%) girls and 42 (62.7%) boys with a mean age of 7.20 ± 5.66 years. Among them, 30 (44.8%) had acute repetitive seizures, and 37 (55.2%) had convulsive status epilepticus. The seizure types were focal onset (n = 34, 50.7%), generalized onset (n = 27, 40.3%), and mixed type (n = 6, 9.0%). In the previously healthy group, 9 patients had acute repetitive seizures and 23 had convulsive status epilepticus, and the rates of seizure cessation when lacosamide was used as the first to fourth choice of antiseizure medication were 100.0%, 85.7%, 40.0%, and 50.0%, respectively, compared to 73.7%, 54.5%, 100.0%, and 0.0% in the patients with epilepsy (21 had acute repetitive seizures and 14 had convulsive status epilepticus). Sixteen (23.9%) patients developed bradycardia and 1 (1.5%) patient developed a rash. SIGNIFICANCE: The early use of intravenous lacosamide was effective with acceptable side effects in treating acute repetitive seizures and convulsive status epilepticus in critically ill children, including young infants and children less than 4 years old and those with different etiologies. PLAIN LANGUAGE SUMMARY: Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in pediatric intensive care units (PICUs), traditional intravenous antiseizure medications (ASMs) include phenytoin, valproic acid, levetiracetam, and phenobarbital. In this study, we categorized patients based on their epilepsy history and different etiologies. We observed that early use of lacosamide, even in young infants, demonstrated good efficacy and safety.

Assessing Clinical Variables Associated With Femoral Muscle Decay as Measured by Point-of-Care Ultrasound in Critically Ill Children.

OBJECTIVES: Skeletal muscle wasting is a common occurrence in critical illness, often resulting in intensive care unit (ICU)-acquired weakness. This study aims to identify clinical factors associated with muscle decay in mechanically ventilated critically ill children. Utilizing point-of-care ultrasound, a noninvasive and cost-effective tool, we assess muscle decay through ultrasound of the quadriceps femoris. METHODS: A prospective observational study was conducted in a single-center quaternary-care pediatric intensive care unit at a children's hospital. A convenience sample of 103 sedated and mechanically ventilated patients were enrolled in this study. Ultrasound measurements of quadriceps femoris muscle thickness were taken, and daily muscle decay rates were calculated. Demographic, clinical, and outcome data were analyzed for correlations with muscle decay. RESULTS: Among the enrolled patients, 67 had repeat measurements. Muscle thickness change aligned with prior studies, with a mean daily change of -1.9% [IQR -0.8, -5.0]. Adequate cumulative caloric intake (>60% of goal) correlated with less muscle decay compared with inadequate intake (-1.8 vs -2.4%, P < .001). Average daily muscle change correlated with both ICU and hospital length of stay (LOS) (r = .328, P = .007 and r = .393, P = .001). No significant correlations emerged between muscle change and mortality, disease severity, fluid balance, early mobilization, steroid exposure, or sedative and paralytic use. CONCLUSION: This study demonstrates early and frequent muscle decay in critically ill children, as detected by point-of-care ultrasound. Average daily muscle decay was associated with longer ICU and hospital LOS. Adequate cumulative caloric intake is linked to reduced muscle decay. These findings contribute to understanding muscle wasting in critically ill pediatric patients.

Nursing insights on the effectiveness of automated pupillometry in two distinct pediatric intensive care units.

PURPOSE: Automated pupillometry (AP) facilitates objective pupillary assessment. In this study, we aimed at assessing nursing perspective about the utility of AP in neurocritically ill children to understand acceptance and usage barriers to guide development of a standardized use protocol. METHODS: We conducted a web-based, cross-sectional, anonymous, Google™ survey of nurses at two independent pediatric ICUs which have been using AP over last four years. The survey included questions related to user-friendliness, barriers, acceptance, frequency of use, and method of documenting AP findings. RESULTS: A total of 31 nurses responded to the survey. A total of 25 nurses (80.6%) used the automated pupillometer and 19 (61.3%) nurses preferred to use the automated pupillometer on critically ill intubated patients. Respondents rated the pupillometer a median [IQR] frequency of use of 7/10 [4-9] and a mean user-friendliness of 8/10 [7-10]. Barriers to pupillometer use included pupillometer unavailability, technical issues, lack of perceived clinical significance, and infection control. CONCLUSION: Nurses have widely adopted the use of automated pupillometer in the PICU especially for critically ill intubated patients and rate it favorably for user-friendliness. Barriers against its use include limited resources, infection concerns, technical issues, and a lack of perceived clinical significance and training. Implementation of standardized PICU protocol for AP usage in critically ill children, may enhance the acceptance, increase usage and aid in objective assessments. PRACTICE IMPLICATIONS: These findings can be used to create a standardized protocol on implementing automated pupillometry in the PICU for critically ill children.

Translation and Adaptation of the Japanese Version of the Revised Parental Stressor Scale: Pediatric Intensive Care Unit.

Introduction The physical, cognitive, and psychiatric disorders that occur in patients after leaving the intensive care unit (ICU) are collectively called post-intensive care syndrome (PICS). Moreover, PICS-family (PICS-F) refers to the long-term psychological and social disorders that occur in the family. The symptoms of PICS-F can be psychological, and stress is a known cause of these symptoms. The Parental Stressor Scale: Pediatric Intensive Care Unit (PSS: PICU) was developed to assess stress levels and related factors among the families of patients admitted to the PICU. It has been translated into several languages and was revised in 2021. However, a Japanese version of the revised PSS: PICU (J-R-PSS: PICU) has not yet been developed. This study aimed to develop a J-R-PSS: PICU and to test its acceptability for clinical use. Materials and methods A back-translation method, involving initial translation, review by bilingual experts, and subsequent re-translation to ensure accuracy, was used to develop the J-R-PSS: PICU. Families with patients in the PICU for >48 hours between November and December 2021 and those who were transferred out of the ICU were recruited. Moreover, the study documents with a QR code for a web questionnaire were provided and explained to family members. Stress scores and stressors of family members were collected from web questionnaires using the PSS: PICU as the primary endpoint. Other information about the patients and their families was collected from clinical records and questionnaires. Participants and an expert panel evaluated the clarity of each item, and the expert panel evaluated the relevance of each item. Results Twenty family members who met the inclusion criteria and provided informed consent were included. The J-R-PSS: PICU was developed using a back-translation method. For clarity, all items were clarified after a single modification by an interdisciplinary team. For relevance, all the items had a content validity index at an item level of ≥0.8 and a scale level of 0.94. Alpha coefficients were 0.93 for the overall scale and 0.69-0.97 for its subscales. Conclusion We developed the J-R-PSS: PICU with high content validity and internal consistency using a back-translation method.

Pupillary Light Reflex Detected by Ophthalmic Ultrasonography in Critically Ill Children With Difficult to Assess Pupils.

Direct visualization of the eye can be difficult or impossible when there is significant facial burns, trauma, or edema. We present 4 nonresponsive, critically ill children whose pupils could not be directly visualized. Ophthalmic ultrasound revealed pupillary reactivity at presentation and throughout their recovery. Determining pupillary reactivity in these nonresponsive patients impacted their initial triage, resuscitation, and medical management. We propose that ophthalmic point-of-care ultrasonography can assess the pupillary light reflex in critically ill children whose pupils cannot be directly visualized.

Trajectories of acute gastrointestinal injury grade in critically Ill children.

OBJECTIVE: To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU). METHODS: This retrospective cohort study was conducted at a large children's hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission. RESULTS: A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN. CONCLUSION: This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes.

Fluid accumulation in critically ill children: a systematic review and meta-analysis.

Background: Fluids are often administered for various purposes, such as resuscitation, replacement, maintenance, nutrition, or drug infusion. However, its use is not without risks. Critically ill patients are highly susceptible to fluid accumulation (FA), which is associated with poor outcomes, including organ dysfunction, prolonged mechanical ventilation, extended hospital stays, and increased mortality. This study aimed to assess the association between FA and poor outcomes in critically ill children. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases from inception to May 2024. Relevant publications were searched using the following terms: child, children, infant, infants, pediatric, pediatrics, critically ill children, critical illness, critical care, intensive care, pediatric intensive care, pediatric intensive care unit, fluid balance, fluid overload, fluid accumulation, fluid therapy, edema, respiratory failure, respiratory insufficiency, pulmonary edema, mechanical ventilation, hemodynamic instability, shock, sepsis, acute renal failure, acute kidney failure, acute kidney injury, renal replacement therapy, dialysis, mortality. Paediatric studies were considered eligible if they assessed the effect of FA on the outcomes of interest. The main outcome was all-cause mortality. Pooled analyses were performed by using random-effects models. This review was registered on PROSPERO (CRD42023432879). Findings: A total of 120 studies (44,682 children) were included. Thirty-five FA definitions were identified. In general, FA was significantly associated with increased mortality (odds ratio [OR] 4.36; 95% confidence interval [CI] 3.53-5.38), acute kidney injury (OR 1.98; 95% CI 1.60-2.44), prolonged mechanical ventilation (weighted mean difference [WMD] 38.1 h, 95% CI 19.35-56.84), and longer stay in the intensive care unit (WMD 2.29 days; 95% CI 1.19-3.38). The percentage of FA was lower in survivors when compared to non-survivors (WMD -4.95 [95% CI, -6.03 to -3.87]). When considering only studies that controlled for potential confounding variables, the pooled analysis revealed 6% increased odds of mortality associated with each 1% increase in the percentage of FA (adjusted OR = 1.06 [95% CI, 1.04-1.09). Interpretation: FA is significantly associated with poorer outcomes in critically ill children. Thus, clinicians should closely monitor fluid balance, especially when new-onset or worsening organ dysfunction occurs in oedematous patients, indicating potential FA syndrome. Future research should explore interventions like restrictive fluid therapy or de-resuscitation methods. Meanwhile, preventive measures should be prioritized to mitigate FA until further evidence is available. Funding: None.

Unlocking Vitality: A Comprehensive Review of Vitamin D's Impact on Clinical Outcomes in Critically Ill Children.

This comprehensive review explores the multifaceted role of vitamin D (VD) in critically ill children, examining its implications for clinical outcomes. Although this substance has long been known for its function in maintaining bone health, it is now becoming more widely known for its extensive physiological effects, which include immune system and inflammation regulation. Observational research consistently associates VD levels with outcomes like duration of hospitalization, mortality, and illness severity in critically ill pediatric patients. Mechanistically, it exerts anti-inflammatory and endothelial protective effects while modulating the renin-angiotensin system. Increasing VD levels through supplementation presents promise as a therapeutic strategy; however, further research is necessary to elucidate optimal dosage regimens and safety profiles. This review emphasizes the significance of comprehending the intricate relationship between VD and critical illnesses among pediatric populations.

Therapeutic plasma exchange in critically ill children: A single center experience.

INTRODUCTION: Therapeutic plasma exchange (TPE) is used in a wide spectrum of diseases in critically ill pediatric patients. We aim to review the indications, complications, safety, and outcomes of critically ill children who received TPE. METHODS: All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 19 years (January 2013-January 2023) were evaluated retrospectively. A total of 154 patients underwent 486 TPE sessions. RESULTS: Median age was 6 years (2-12.5) and 35 children had a body weight of <10 kg (22.7%). Number of organ failure was 4 (2-6). Liver diseases were the most common indication for TPE (31.2%) followed by sepsis with multiorgan dysfunction syndrome (27.3%). Overall survival rate was 72.7%. The highest mortality was observed in hemophagocytic lymphohistiocytosis group. Non-survivors had significantly higher number of organ failure (p < 0.001), higher PRISM score (p < 0.001), and higher PELOD score on admission (p < 0.001). Adverse events were observed in 68 (13.9%) sessions. Hypotension (7.8%) and hypocalcemia (5.1%) were the most frequent adverse events. CONCLUSION: TPE is safe for critically ill pediatric patients with experienced staff. Survival rate may vary depending on the underlying disease. Survival decreases with the increase in the number of failed organs.

Nutritional Intake in Children with Septic Shock: A Retrospective Single-Center Study.

Nutritional practice in children with severe sepsis or septic shock remains poorly described. We aimed to describe nutrition received by children with severe sepsis or septic shock and explore the association of nutritional intake with clinical outcomes. This study was a retrospective study of children who required pediatric intensive care unit (PICU) admission from 2009 to 2016. Outcomes were mortality, ventilator-free days (VFDs), and PICU-free days (IFDs). A total of 74 patients with septic shock or severe sepsis were identified. Forty-one (55.4%) patients received enteral nutrition (EN) only, 6 (8.1%) patients received parental nutrition (PN) only, 15 (20.3%) patients received both EN and PN, and 12 (16.2%) patients received intravenous fluids alone. Eight of 74 (10.8%) and 4 of 74 (5.4%) had adequate energy and protein intake, respectively. Patients who received early EN had lower odds of 28-day mortality (adjusted hazard ratio [HR] = 0.09, 95% confidence interval [CI]: 0.02, 0.45, p = 0.03) more 28-day VFDs (adjusted ß-coefficient = 18.21 [95% CI: 11.11, 25.32], p < 0.001), and IFDs (adjusted ß-coefficient = 16.71 [95% CI: 9.86, 23.56], p < 0.001) than patients who did not receive EN. Late EN was also associated with lower odds of mortality, more VFDs, and IFDs compared with no EN (HR = 0.06, 95% CI: 0.02, 0.23; p < 0.001; adjusted ß coefficient = 15.66, 95% CI: 9.31, 22.02; p < 0.001; and 12.34 [95% CI: 6.22, 18.46], p < 0.001; respectively). Inadequate calories and protein were not associated with mortality. EN in children with septic shock or severe sepsis was associated with improved clinical outcomes. Future prospective studies are required to explore the impact of EN timing and optimal nutritional intake in these children.

How to use meropenem in pediatric patients undergoing CKRT? Integrated meropenem pharmacokinetic model for critically ill children.

Standard dosing could fail to achieve adequate systemic concentrations in ICU children or may lead to toxicity in children with acute kidney injury. The population pharmacokinetic analysis was used to simultaneously analyze all available data (plasma, prefilter, postfilter, effluent, and urine concentrations) and provide the pharmacokinetic characteristics of meropenem. The probability of target fT > MIC attainment, avoiding toxic levels, during the entire dosing interval was estimated by simulation of different intermittent and continuous infusions in the studied population. A total of 16 critically ill children treated with meropenem were included, with 7 of them undergoing continuous kidney replacement therapy (CKRT). Only 33% of children without CKRT achieved 90% of the time when the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) for an MIC of 2 mg/L. In dose simulations, only continuous infusions (60-120 mg/kg in a 24-h infusion) reached the objective in patients <30 kg. In patients undergoing CKRT, the currently used schedule (40 mg/kg/12 h from day 2 in a short infusion of 30 min) was clearly insufficient in patients <30 kg. Keeping the dose to 40 mg/kg q8h without applying renal adjustment and extended infusions (40 mg/kg in 3- or 4-h infusion every 12 h) was sufficient to reach 90% fT > MIC (>2 mg/L) in patients >10 kg. In patients <10 kg, only continuous infusions reached the objective. In patients >30 kg, 60 mg/kg in a 24-h infusion is sufficient and avoids toxicity. This population model could help with an individualized dosing approach that needs to be adopted in critically ill pediatric patients. Critically ill patients subjected to or not to CKRT may benefit from the administration of meropenem in an extended or continuous infusion.

Usefulness of Non-Invasive Parameters (Inferior Vena Cava Diameter, Inferior Vena Cava Collapsibility, Inferior Vena Cava-Aortic Ratio) for Hemodynamic Monitoring in Critically Ill Children: A Systematic Review.

Purpose: Volume measurement in critically ill children can be conducted using invasive procedure such as Central Venous Pressure (CVP), or non-invasive procedure such as measurement of Inferior Vena Cava (IVC) indices using ultrasonography. However, their accuracy and efficacy are still under scrutiny. We aim to compare CVP and IVC indices as non-invasive parameters in assessing volume status in critically ill children. Methods: We conducted a systematic review based on literature searching from four electronic databases which were PubMed, Cochrane, ScienceDirect, SpringerLink with keywords: "CENTRAL VENOUS PRESSURE", "INFERIOR VENA CAVA DIAMETER", "INFERIOR VENA CAVA COLLAPSIBILITY", "INFERIOR VENA CAVA AORTIC-RATIO", "VOLUME STATUS", "FLUID STATUS", "CRITICAL ILL", "CHILDREN", and "PEDIATRICS". We included relevant studies in English published from 2000 to 2023 on critically ill children aged 0-18 years. Comparison between CVP and IVC indices was resumed. Results: Eight articles were included in this study. Majority of the studies showed a consistent correlation between CVP and IVC indices. IVC-CI was the most common parameter evaluated in the included studies. There was moderate to strong correlations using IVC-CI and IVC-DI, and moderate correlation using IVC-Ao ratio. Conclusion: We found that non-invasive tools might have a potential role to measure volume in critically ill children equals to CVP. Further high-quality and longitudinal studies are needed to validate these findings and to establish a clear guideline for the non-invasive tool to be used in daily clinical practice.

Pattern of Fluid Overload and its Impact on Mortality Among Mechanically Ventilated Children: Secondary Analysis of the ReLiSCh Trial.

OBJECTIVES: To assess the pattern of fluid overload (FO) and its impact on mortality among mechanically ventilated children. METHODS: In this secondary analysis of an open-label randomized controlled trial (ReLiSCh trial, October 2020-September 2021), hemodynamically stable mechanically ventilated children (n = 100) admitted to a tertiary level pediatric intensive care unit (PICU) in North India were enrolled. The primary outcome was pattern of FO (FO% >10% and cumulative FO% from day 1-7); and secondary outcomes were pattern of FO among survivors and non-survivors, and prescription practices of maintenance fluid. RESULTS: The median (IQR) age was 3.5 (0.85-7.5) y and 57% were males. Common diagnoses were pneumonia (27%), scrub typhus (14%), Landry-Guillain-Barré syndrome (9%), dengue (8%), central nervous system infections (7%) and staphylococcal sepsis (6%). Common organ dysfunction included acute respiratory distress syndrome (ARDS) (41%), shock (38%), and acute kidney injury (AKI) (9%). The duration PICU stay was 11 (7-17) d and mortality was 12%. The FO% >10% was noted in 19% children; and there was significant increase in cumulative FO% from day 1-7 [1.2 (0.2-2.6)% to 8.5 (1.7-14.3)%, (p = 0.000)]. Among non-survivors, higher proportion had FO% >10% (66.7% vs. 12.5%, p 0.0001); and trend towards higher cumulative FO% on first seven days. From day 1-7, the percentage of maintenance fluid received increased from 60 (50-71)% to 70 (60-77)% (p = 0.691). CONCLUSIONS: One-fifth of mechanically ventilated children had FO% >10% and there was significant increase in cumulative FO% from day 1-7. Non-survivors had significantly higher degree of FO.

The parent perspective on paediatric delirium and an associated care bundle: A qualitative study.

AIMS: To explore how parents experienced their child with delirium and how parents viewed our delirium management bundle. DESIGN: We conducted a qualitative exploratory descriptive study using semi-structured individual or dyad interviews. METHODS: Twelve semi-structured interviews with 16 parents of 12 critically ill children diagnosed with delirium in a paediatric intensive care unit were conducted from October 2022 to January 2023 and analysed through a reflexive thematic analysis. FINDINGS: We generated five themes: (1) knowing that something is very wrong, (2) observing manifest changes in the child, (3) experiencing fear of long-term consequences, (4) adding insight to the bundle, and (5) family engagement. CONCLUSION: The parents in our study were able to observe subtle and manifest changes in their child with delirium. This caused fear of lasting impact. The parents regarded most of the interventions in the delirium management bundle as relevant but needed individualization in the application. The parents requested more information regarding delirium and a higher level of parent engagement in the care of their child during delirium. IMPACT: This paper contributes to understanding how parents might experience delirium in their critically ill child, how our delirium management bundle was received by the parents, and their suggestions for improvement. Our study deals with critically ill children with delirium, their parents, and staff working to prevent and manage paediatric delirium (PD) in the paediatric intensive care unit. REPORTING METHOD: The consolidated criteria for reporting qualitative research guidelines were used to ensure the transparency of our reporting. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution to the research design. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL COMMUNITY?: - It increases awareness of the parent's perspective on PD in critically ill children. - It shows how PD might affect parents, causing negative emotions such as distress, frustration, and fear of permanent damage. - It shows that the parents in our study, in addition to the care bundle, requested more information on delirium and more involvement in the care of their delirious child.

Identification and validation of an explainable prediction model of acute kidney injury with prognostic implications in critically ill children: a prospective multicenter cohort study.

Background: Acute kidney injury (AKI) is a common and serious organ dysfunction in critically ill children. Early identification and prediction of AKI are of great significance. However, current AKI criteria are insufficiently sensitive and specific, and AKI heterogeneity limits the clinical value of AKI biomarkers. This study aimed to establish and validate an explainable prediction model based on the machine learning (ML) approach for AKI, and assess its prognostic implications in children admitted to the pediatric intensive care unit (PICU). Methods: This multicenter prospective study in China was conducted on critically ill children for the derivation and validation of the prediction model. The derivation cohort, consisting of 957 children admitted to four independent PICUs from September 2020 to January 2021, was separated for training and internal validation, and an external data set of 866 children admitted from February 2021 to February 2022 was employed for external validation. AKI was defined based on serum creatinine and urine output using the Kidney Disease: Improving Global Outcome (KDIGO) criteria. With 33 medical characteristics easily obtained or evaluated during the first 24 h after PICU admission, 11 ML algorithms were used to construct prediction models. Several evaluation indexes, including the area under the receiver-operating-characteristic curve (AUC), were used to compare the predictive performance. The SHapley Additive exPlanation method was used to rank the feature importance and explain the final model. A probability threshold for the final model was identified for AKI prediction and subgrouping. Clinical outcomes were evaluated in various subgroups determined by a combination of the final model and KDIGO criteria. Findings: The random forest (RF) model performed best in discriminative ability among the 11 ML models. After reducing features according to feature importance rank, an explainable final RF model was established with 8 features. The final model could accurately predict AKI in both internal (AUC = 0.929) and external (AUC = 0.910) validations, and has been translated into a convenient tool to facilitate its utility in clinical settings. Critically ill children with a probability exceeding or equal to the threshold in the final model had a higher risk of death and multiple organ dysfunctions, regardless of whether they met the KDIGO criteria for AKI. Interpretation: Our explainable ML model was not only successfully developed to accurately predict AKI but was also highly relevant to adverse outcomes in individual children at an early stage of PICU admission, and it mitigated the concern of the "black-box" issue with an undirect interpretation of the ML technique. Funding: The National Natural Science Foundation of China, Jiangsu Province Science and Technology Support Program, Key talent of women's and children's health of Jiangsu Province, and Postgraduate Research & Practice Innovation Program of Jiangsu Province.

Validation of Indirect Calorimetry in Children Undergoing Single-Limb Non-Invasive Ventilation: A Proof of Concept, Cross-Over Study.

BACKGROUND: The accurate assessment of resting energy expenditure (REE) is essential for personalized nutrition, particularly in critically ill children. Indirect calorimetry (IC) is the gold standard for measuring REE. This methodology is based on the measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2). These parameters are integrated into the Weir equation to calculate REE. Additionally, IC facilitates the determination of the respiratory quotient (RQ), offering valuable insights into a patient's carbohydrate and lipid consumption. IC validation is limited to spontaneously breathing and mechanically ventilated patients, but it is not validated in patients undergoing non-invasive ventilation (NIV). This study investigates the application of IC during NIV-CPAP (continuous positive airway pressure) and NIV-PS (pressure support). METHODS: This study was conducted in the Pediatric Intensive Care Unit of IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, between 2019 and 2021. Children < 6 years weaning from NIV were enrolled. IC was performed during spontaneous breathing (SB), NIV-CPAP, and NIV-PS in each patient. A Bland-Altman analysis was employed to compare REE, VO2, VCO2, and RQ measured by IC. RESULTS: Fourteen patients (median age 7 (4; 18) months, median weight 7.7 (5.5; 9.7) kg) were enrolled. The REE, VO2, VCO2, and RQ did not differ significantly between the groups. The Limits of Agreement (LoA) and bias of REE indicated good agreement between SB and NIV-CPAP (LoA +28.2, -19.4 kcal/kg/day; bias +4.4 kcal/kg/day), and between SB and NIV-PS (LoA -22.2, +23.1 kcal/kg/day; bias 0.4 kcal/kg/day). CONCLUSIONS: These preliminary findings support the accuracy of IC in children undergoing NIV. Further validation in a larger cohort is warranted.

Plasma and red blood cell concentrations of zinc, copper, selenium and magnesium in the first week of paediatric critical illness.

BACKGROUND & AIMS: Critically ill children are at risk of micronutrient deficiencies, which might lead to poor clinical outcomes. However, the interpretation of micronutrient concentrations in plasma is complicated due to age-dependent and critical illness-dependent changes. Certain red blood cell (RBC) concentrations might reflect the overall body status more reliably than plasma levels in the presence of systemic inflammatory response. This study longitudinally examined micronutrient concentrations in both plasma and RBC in critically ill children. METHODS: This secondary analysis of the PEPaNIC RCT investigated the impact of early versus late initiation of parenteral macronutrient supplementation in critically ill children. All children received micronutrients when EN was insufficient (<80 % energy requirements). Blood samples were obtained on days 1, 3, 5 and 7 of Paediatric Intensive Care Unit (PICU) admission. Inductively coupled plasma mass spectrometry was used to measure zinc, selenium, and copper in plasma and selenium, copper, and magnesium in RBCs. Plasma magnesium was measured with colorimetric detection. Micronutrient concentrations were compared with age-specific reference values in healthy children and expressed using Z-scores. Changes in micronutrient concentrations over time were examined using the Friedman and post hoc Wilcoxon signed-rank tests. RESULTS: For 67 critically ill children, median (Q1; Q3) age 9.5 (5.5; 13.2) years, PIM3 score -2.3 (-3.1; -0.8), samples were available at various time points during their PICU stay. For 22 patients, longitudinal samples were available. On day 1, the median plasma Z-score for zinc was -5.2 (-5.2; -2.9), copper -1.6 (-2.9; -0.2), selenium -2.6 (-3.8; -1.0), magnesium -0.2 (-1.6; 1.3), and median RBC Z-score for copper was 0.5 (-0.1; 1.3), selenium -0.3 (-1.1; 0.7), magnesium 0.2 (-0.4; 1.3). In the longitudinal analysis, plasma zinc was significantly higher on day 5 (Z-score -3.2 (-4.6; -1.4)) than on day 1 (Z-score -5.2 (-5.2; -3.0), p = 0.032), and plasma magnesium was significantly higher on day 3 (Z-score 1.1 (-0.7; 4.0)) than on day 1 (Z-score -0.3 (-1.6; 0.5), p = 0.018). Plasma copper and selenium remained stable, and the RBC concentrations of all micronutrients remained stable during the first five days. CONCLUSIONS: Most patients had low plasma zinc, copper and selenium concentrations in the first week of their PICU stay, whereas they had normal to high RBC concentrations. More research is needed to examine the relationships between micronutrients and clinical outcome.