Forty-two questions were evaluated concerning management of emergencies and critical illnesses in paediatric and adult patients with sickle cell disease. The assessment covered the following areas: patient referral, vaso-occlusive crisis, acute chest syndrome, transfusion therapy, and priapism. The patient referral category included guidelines for admission to intensive care unit and management at specialized reference centers. The vaso-occlusive crisis topic encompassed pain management, hydration, incentive spirometry, and target oxygen saturation levels. For acute chest syndrome, the focus areas included imaging techniques such as lung ultrasound, computed tomography scans, and echocardiography; treatment with systemic corticosteroids; non-invasive ventilation; prophylactic and therapeutic anticoagulation; and procalcitonin and antibiotic therapy. The section on transfusion therapy addressed indications and methods of transfusion, as well as the diagnosis and prediction of delayed hemolytic transfusion reactions. A total of 45 recommendations were proposed, including 14 specific to adults, 13 specific to pediatrics, and 18 applicable to both adults and children, along with three therapeutic algorithms. The Grade of Recommendation Assessment, Development, and Evaluation (GRADE) methodology was adhered to throughout the process. Sixteen recommendations were based on a low level of evidence (GRADE 2+ or 2-), while 26 were based on evidence that could not be classified under the GRADE system and were therefore considered expert opinions. Finally, for three aspects of sickle cell disease management, the experts concluded that no reliable recommendations could be made based on the current state of knowledge. The recommendations and therapeutic algorithms received strong agreement from the experts.

Congenital intestinal atresia (CIA) is a common intestinal malformation in the neonatal period, and surgery is currently the main treatment method. The choice of postoperative feeding is crucial for the recovery of gastrointestinal function in children.

To compare and analyze the effects of different postoperative feeding methods on gastrointestinal function reconstruction in newborns with CIA.

Twenty-six children diagnosed with neonatal CIA, treated with minimally invasive surgery at Shijiazhuang Maternal and Child Health Hospital between January 2021 and May 2024, were selected for this single-center prospective randomized controlled study. They were divided into two groups using envelope randomization: Enteral nutrition (EN) group (n = 13) and parenteral nutrition (PN) group (n = 13). Baseline and clinical characteristics were collected, and recovery time of bowel sounds and time to first defecation were used as evaluation indices for gastrointestinal functional reconstruction. Differences between the groups were analyzed using t-test, χ 2 test, and Fisher's exact test. Spearman's correlation tests and linear regression models were employed to analyze factors influencing time to first defecation.

The time to bowel sound recovery (51.54 vs 65.85, P = 0.013) and first defecation (58.15 vs 76.62, P < 0.001) was shorter in the EN group compared to the PN group. Clinical improvements in the EN group, including discharge weight (P = 0.044), hospital stay (P = 0.027), white blood cell count (P = 0.023), albumin content (P = 0.013), and direct bilirubin content (P = 0.018), were also better than those in the PN group. No substantial differences in postoperative complications were found between the groups. Correlation analysis indicated that abdominal infection and operation time may relate to time to first defecation. Linear regression analysis demonstrated a considerable association between EN feeding and shorter time to first defecation. Abdominal infection and an operation time > 2 hours may be risk factors for prolonged time to first defecation.

EN substantially promotes the recovery of gastrointestinal function after CIA in neonates and can improve clinical outcomes in children. Future research should explore optimal EN practices to enhance clinical application and child health.

Fluid overload is associated with increased morbidity in patients in paediatric intensive care units (PICUs). This study aimed to evaluate pharmaceutical infusion management as a quality assurance measure to reduce fluid overload in routine paediatric intensive care.

This was a retrospective observational study in a PICU with two periods: a control period and a period after the implementation of pharmaceutical infusion management (PharmInfuManagement period). Pharmaceutical infusion management consisted of two components carried out simultaneously: the creation of flushing schedules to reduce incompatibilities and flushing volume and the reduction of dilution volume for six non-continuous intravenous (IV) drugs to reduce fluid intake because of IV drugs. The primary outcome was the number of patients with ≥5% fluid overload. In addition, daily furosemide dose (mg/kg/day), non-continuous IV drug volume (mL/kg/day), flushing volume (mL/kg/day) and number of incompatibilities were evaluated.

Sixty-six patients were included in each period. Fluid overload of ≥5% occurred in 52% of patients in the control period and in 29% of patients in the PharmInfuManagement period (p=0.01). Flushing volume decreased from 0.7 mL/kg/day (median Q25/Q75 0.4/1.4) to 0.3 mL/kg/day (median Q25/Q75 0.1/0.7) (p<0.001) after implementation. During the PharmInfuManagement period, potentially incompatible drug combinations were reduced from 17.1% (86/504) to 8.2% (43/523) (p<0.001). The volume required for reconstitution and dilution of non-continuously administered IV drugs was reduced from 8.8 mL/kg/day (median Q25/Q75 7.1/12.6) to 6.8 mL/kg/day (median Q25/Q75 5.5/8.0) (p=0.02).

Pharmaceutical infusion management reduces incompatibilities and fluid overload in PICU patients.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations.

Background: Dehydration, a common condition where the amount water lost from the body exceeds intake, disrupts metabolic processes and negatively impacts health and performance. Rehydration, the process of restoring body fluids and electrolytes to normal levels, is crucial for maintaining physiological health. In vivo dehydration models are experimental systems used to study the effects of dehydration on living organisms. However, a comprehensive summary of in vivo models and the application of human rehydration strategies is lacking. Methods: This review provides a comprehensive overview of various in vivo models and rehydration strategies. Results: In vivo models, stimulated by fluid restriction, exercise, thermal exposure, and chemicals, have been used to study dehydration. Importantly, the principles, characteristics, and limitations of the in vivo models are also discussed, along with rehydration administration methods, including oral, intestinal, intravenous, subcutaneous, and intraperitoneal routes. Additionally, rehydration strategies and the application for managing different dehydration conditions both in daily life and clinical settings have been summarized. Conclusions: Overall, this review aims to enhance the understanding of the conditions in which in vivo dehydration models and rehydration strategies are applicable, thereby advancing research into the physiological and pathological mechanisms of dehydration and supporting the development of effective rehydration therapies.

The objective of this study was to evaluate the efficacy and safety of isotonic and hypotonic intravenous fluids in maintenance fluid therapy for term infants.

This was a multi-centre, prospective, observational study conducted in 21 participating centres from December 30, 2020, to June 30, 2023. The study included term newborns requiring parenteral fluid therapy for maintenance (NCT04781361). The fluid treatment was divided into two groups based on the concentration of sodium in the parenteral fluid, designated as hypotonic (NaCl <130 mmol/L) and isotonic (NaCl = 130-154 mmol/L). The primary outcomes were the change in mean plasma sodium (pNa) levels per hour (∆pNa mmol/L/h), the incidence of hyponatremia (pNa <135 mmol/L) and hypernatremia (pNa >145 mmol/L), and the occurrence of clinically significant changes in sodium levels (∆pNa >0.5 mmol/L/h).

A total of 420 patients from 21 centers were included. The ∆pNa was negative in the hypotonic fluid group and positive in the isotonic fluid group, with a significant difference between the groups [respectively -0.07 ± 0.03 (95% CI: -0.13 to -0.02); 0.04 ± 0.03 (95%CI: -0.02 to 0.09), p = 0.04]. There was no difference between the groups in terms of the development of hypernatremia or a clinically meaningful pNa increase. The hypotonic fluid group had a higher incidence of hyponatremia and a clinically meaningful sodium decrease compared to the isotonic fluid group [7.9% vs. 1.2% (OR:6.5, p:0.03)] and [12.2% vs.4.2% (OR:2.9, p = 0.03)].

Contrary to current understanding, this large-scale study is the first to demonstrate that the use of hypotonic fluids in maintenance fluid therapy for newborns poses a risk of hyponatremia development, whereas isotonic fluid therapy appears safe.

Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April-May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known: • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution.

To review the evaluation and management of fluid overload in critically ill children.

Emerging evidence associates fluid overload, i.e. having a positive cumulative fluid balance, with adverse outcome in critically ill children. This is most likely the result of impaired organ function due to increased extravascular water content. The combination of a number of parameters, including physical, laboratory and radiographic markers, may aid the clinician in monitoring and quantifying fluid status, but all have important limitations, in particular to discriminate between intra- and extravascular water volume. Current guidelines advocate a restrictive fluid management, initiated early during the disease course, but are hampered by the lack of high quality evidence.

Recent advances in early evaluation of fluid status and (tailored) restrictive fluid management in critically ill children may decrease complications of fluid overload, potentially improving outcome. Further clinical trials are necessary to provide the clinician with solid recommendations.

Adequate fluid management in the perioperative period in paediatric patients is essential for restoring and maintaining homeostasis and ensuring adequate tissue perfusion. A well-designed infusion regimen is crucial for preventing severe complications such as hyponatraemic encephalopathies. The composition of perioperative fluid solutions is now guided by an understanding of extracellular fluid physiology. Various crystalloid and colloidal products are available for use, but a comprehensive approach requires careful consideration of their drawbacks and limitations. Additionally, the unique characteristics of different patient groups must be taken into account. This review will provide the reader with physiological considerations for perioperative fluids and describe indications for perioperative intravenous fluid therapy in paediatric patients. The current evidence on perioperative fluid therapy is finally summarised in practical recommendations.

Intravenous maintenance fluid therapy (IV-MFT) is one of the most prescribed, yet one of the least studied, interventions in paediatric acute and critical care settings. IV-MFT is not typically treated in the same way as drugs with specific indications, contraindications, compositions, and associated adverse effects. In the last decade, societies in both paediatric and adult medicine have issued evidence-based practice guidelines for the use of intravenous fluids in clinical practice. The main objective of this Viewpoint is to summarise and compare the rationales on which these international expert guidelines were based and how these recommendations affect IV-MFT practices in paediatric acute and critical care. Although these guidelines recommend the use of isotonic fluids as a standard in IV-MFT, some discrepancies and uncertainties remain regarding the systematic use of balanced fluids, glucose and electrolyte requirements, and appropriate fluid volume. IV-MFT should be considered in the same way as any other prescription drug and none of the components of IV-MFT prescription should be overlooked (ie, choice of drug, dosing rate, duration of treatment, and de-escalation). Furthermore, most evidence that was used to inform the guidelines comes from high-income countries. Although some principles of IV-MFT are universal, the direct relevance to and feasibility of implementing the guidelines in low-income and middle-income countries is uncertain.

The purpose of perioperative fluid management in children is to maintain adequate volume status, electrolyte level, and endocrine system homeostasis during the perioperative period. Although hypotonic solutions containing glucose have traditionally been used as pediatric maintenance fluids, recent studies have shown that isotonic balanced crystalloid solutions lower the risk of hyponatremia and metabolic acidosis perioperatively. Isotonic balanced solutions have been found to exhibit safer and more physiologically appropriate characteristics for perioperative fluid maintenance and replacement. Additionally, adding 1-2.5% glucose to the maintenance fluid can help prevent children from developing hypoglycemia as well as lipid mobilization, ketosis, and hyperglycemia. The fasting time should be as short as possible without compromising safety; recent guidelines have recommended that the duration of clear fluid fasting be reduced to 1 h. The ongoing loss of fluid and blood as well as the free water retention induced by antidiuretic hormone secretion are unique characteristics of postoperative fluid management that must be considered. Reducing the infusion rate of the isotonic balanced solution may be necessary to avoid dilutional hyponatremia during the postoperative period. In summary, perioperative fluid management in pediatric patients requires careful attention because of the limited reserve capacity in this population. Isotonic balanced solutions appear to be the safest and most beneficial choice for most pediatric patients, considering their physiology and safety concerns.

Intravenous fluid therapy is the most common intervention in critically ill children. There is an increasing body of evidence questioning the safety of high-volume intravenous fluid administration in these patients. To date, the optimal fluid management strategy remains unclear. We aimed to test the feasibility of a pragmatic randomised controlled trial comparing a restrictive with a standard (liberal) fluid management strategy in critically ill children.

Multicentre, binational pilot, randomised, controlled, open-label, pragmatic trial. Patients <18 years admitted to paediatric intensive care unit and mechanically ventilated at the time of screening are eligible. Patients with tumour lysis syndrome, diabetic ketoacidosis or postorgan transplant are excluded.

1:1 random assignment of 154 individual patients into two groups-restrictive versus standard, liberal, fluid strategy-stratified by primary diagnosis (cardiac/non-cardiac). The intervention consists of a restrictive fluid bundle, including lower maintenance fluid allowance, limiting fluid boluses, reducing volumes of drug delivery and initiating diuretics or peritoneal dialysis earlier. The intervention is applied for 48 hours postrandomisation or until discharge (whichever is earlier).

The number of patients recruited per month and proportion of recruited to eligible patients are feasibility endpoints. New-onset acute kidney injury and the incidence of clinically relevant central venous thrombosis are safety endpoints. Fluid balance at 48 hours after randomisation is the efficacy endpoint. Survival free of paediatric intensive care censored at 28 days is the clinical endpoint.

Ethics approval was gained from the Children's Health Queensland Human Research Ethics Committee (HREC/21/QCHQ/77514, date: 1 September 2021), and University of Zurich (2021-02447, date: 17 March 2023). The trial is registered with the Australia New Zealand Clinical Trials Registry (ACTRN12621001311842). Open-access publication in high impact peer-reviewed journals will be sought. Modern information dissemination strategies will also be used including social media to disseminate the outcomes of the study.

ACTRN12621001311842.

V5/23 May 2023.

Sepsis is one of the main causes of morbidity and mortality worldwide. Fluid resuscitation is among the most common interventions and is associated with fluid overload (FO) in some patients. The objective of this systematic review and meta-analysis was to summarise the available evidence on the association between FO and morbimortality in children with sepsis.

A systematic search was carried out in PubMed/Medline, Embase, Cochrane and Google Scholar up to December 2022 (PROSPERO 408148), including studies in children with sepsis which reported more than 10% FO 24 hours after admission to intensive care. The risk of bias was assessed using the Newcastle-Ottawa scale. Heterogeneity was assessed using I2, considering it absent if <25% and high if >75%. A sensitivity analysis was run to explore the impact of the methodological quality on the size of the effect. Mantel-Haenszel's model of random effects was used for the analysis. The primary outcome was to determine the risk of mortality associated with FO and the secondary outcomes were the need for mechanical ventilation (MV), multiple organ dysfunction syndrome (MODS) and length of hospital stay associated with FO.

A total of 9 studies (2312 patients) were included, all of which were observational. Children with FO had a higher mortality than patients without overload (46% vs 26%; OR 5.06; 95% CI 1.77 to 14.48; p<0.01). We found no association between %FO and the risk of MODS (OR: 0.97; 95% CI 0.13 to 7.12; p=0.98). Children with FO required MV more often (83% vs 47%; OR: 4.78; 95% CI 2.51 to 9.11; p<0.01) and had a longer hospital stay (8 days (RIQ 6.5-13.2) vs 7 days (RIQ 6.1-11.5); p<0.01).

In children with sepsis, more than 10% FO 24 hours after intensive care admission is associated with higher mortality, the need for MV and length of hospital stay.

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology.

Fluid resuscitation with crystalloids has been used in humans for more than 100 years. In patients with trauma, sepsis or shock of any etiology, they can help modify the clinical course of the illness. However, these solutions are medications which are not side-effect free. Recently, they have been questioned in terms of quantity (fluid overload) and their composition. The most frequently used crystalloids, both in high and low-income countries, are 0.9% normal saline (NS) and Ringer's lactate. The first descriptions of the use of sodium and water solutions in humans date from the cholera epidemic which spread throughout Europe in 1831. The composition of the fluids used by medical pioneers at that time differs greatly from the 0.9% NS used routinely today. The term "physiological solution" referred to fluids which did not cause red blood cell hemolysis in amphibians in in vitro studies years later. 0.9% NS has an acid pH, a more than 40% higher chloride concentration than plasma and a strong ion difference of zero, leading many researchers to consider it an unbalanced solution. In many observational studies and clinical trials, this 0.9% NS composition has been associated with multiple microcirculation and immune response complications, acute kidney injury, and worse clinical outcomes. Ringer's lactate has less sodium than plasma, as well as other electrolytes which can cause problems in patients with traumatic brain injury. This review provides a brief summary of the most important historical aspects of the origin of the most frequently used intravenous crystalloids today.

(1) Objective: We performed a systematic review to explore the prevalence of intravenous (IV) rehydration therapy in hospital settings, and we assessed it by patient groups and populations. (2) Methods: A systematic review of major databases and grey literature was undertaken from inception to 28 March 2022. Studies reporting prevalence of IV rehydration therapy in a hospital setting were identified. The data were synthesised in a narrative approach. (3) Results: Overall, 29 papers met the inclusion criteria. The prevalence of IV rehydration therapy in paediatric patients ranged from 4.5% (hospitalised with diarrhoea and dehydration) to 100% (admitted to the emergency department with mild to moderate dehydration caused by viral gastroenteritis), and in adults this ranged from 1.5% (had single substance ingestion of modafinil) to 100% (hospitalised with hypercalcemia). The most common indication for IV rehydration therapy in paediatric patients was dehydration due to fluid loss from the gastrointestinal tract. Other causes included malnutrition, neuromuscular disease, bronchiolitis, and influenza. In adults, indications for IV rehydration therapy were much more diverse: fever, diarrhoea, drug intoxication, hypercalcemia, cancer, and postural tachycardia syndrome; (4) Conclusions: This systematic review showed that IV rehydration therapy in paediatric patients is often used to treat dehydration and diarrhoea, while in adults it has a broader spectrum of use. While IV rehydration therapy is important in correcting fluid problems and electrolyte status, the maintenance fluid prescribing practices vary considerably, and guidelines are scarce.