The Efficient PICU Fluid Care Evaluation

Overview

The goal of this clinical trial is to evaluate and prevent fluid overload in critically ill, mechanically ventilated children. The main questions it aims to answer are: 1. What is the effect of a restrictive fluid strategy on cumulative fluid balance on day three of invasive mechanical ventilation? 2. What is the feasibility (e.g. adherence to target intake, fluid balance and nutritional goals) of maintaining a neutral fluid balance? Researchers will compare the effects of strict adherence to the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) guidelines regarding fluid balance (i.e. restricting fluid intake and preventing a positive fluid balance) to current local practice. From the start to the end of invasive mechanical ventilation participants will be treated according to local practice or with the strict aim to prevent a positive fluid balance. Aiming to prevent a positive fluid balance, if this is possible given the clinical context, is at descretion of the attending physician. Minimal caloric intake requirements must be met. Participants are studied for ten days during invasive mechanical ventilation or until discharge from the intensive care

Detailed description

Objectives

* Compare current practices with strict adherence to ESPNIC guidelines regarding fluid management in critically ill children. * Assess the effectiveness of maintaining a neutral cumulative fluid balance by day 3 (CFB3).

Study Design

* Type: Multicenter prospective study with a before-after design, continuous recruitment, and single measurements. * Groups:

1. Current practice group. 2. ESPNIC guideline adherence group (restrictive fluid management).

Treatment

* Current Practice Group: Standard PICU treatment per local protocols. * ESPNIC Guideline Adherence Group: Strict restrictive fluid strategy beginning within 24 hours of intubation, focusing on preventing cumulative positive fluid balance. ESPNIC guidelines recommend restricting total fluid intake to 65-80% of the Holliday and Segar formula. The Holliday and Segar formula is tailored for children under 10 kg: 150 ml/kg/day for neonates and 100 ml/kg/day for one-year-olds. This study will aim for a 65% restriction based on these calculations.

Feeding Enteral nutrition starts within 24-48 hours unless contraindicated, with caloric intake reaching 100% of resting energy expenditure by day 7 and protein intake exceeding 1.5 g/kg/day.

Diuretics The choice and route of diuretics will be at the treating physician's discretion.

Duration of Intervention Start: Onset of mechanical ventilation. End: End of mechanical ventilation.

Study Procedures Children will have routine blood samples taken daily during invasive mechanical ventilation (IMV), which align with standard clinical diagnostics. Body weight will be measured at admission, on day 3, and before extubation. Data on fluid intake, feeding, medication, and urine output will be gathered prospectively in the electronic patient dossier (EPD).

Adverse Events All adverse events will be recorded, with serious adverse events (SAEs) reported to the sponsor promptly.

Interventions

• Other Strict adherence to European guidelines
  The goal is to maintain a neutral fluid balance throughout the course of intubation if clinical practice allows. Therefore: * From the start of mechanical ventilation, the maximum maintenance fluids is 65% of the maintenance fluids proposed by the Holliday \& Segar formula. Fluid resuscitation in the first hours after intubation is at the discretion of the attending physician. * Any other interventions to maintain a neutral fluid balance (e.g., starting diuretics, reducing fluid boluses, decrea

Primary outcome measures

• Cumulative fluid balance on day 3 in ml/kg [Time frame: From start mechanical ventilation to 72 hours after start of mechanical ventilation]

Secondary outcome measures (12)

• Daily cumulative fluid balance on in ml/kg [Time frame: For 10 days, CFB is noted every day at 00:00]
• Protein intake in gr/kg/day [Time frame: For ten days after start of mechanical ventilation]
• Bodyweight in grams [Time frame: Bodyweight in grams will be measured at start of mechanical ventilation and at 72 hours after start of mechanical ventilation]
• Daily cumulative diuretics dose in mg/kg [Time frame: From start of mechnical ventilation for ten days, cumulative diuretic dose will be noted at 00:00]
• Blood urea nitrogen (BUN) in mmol/L [Time frame: BUN will be measured at 24 hours, 72 hours and at 120 hours after start of mechanical ventilation]
• Daily creatinine level in µmol/L [Time frame: Creatinine levels will be noted at: 24, 72 hours and 120 after start of mechanical ventilation]
• Daily KDIGO stages (1,2 or 3) will be noted every 24 hours [Time frame: From start of mechanical ventilation to 120 hours after start of mechanical ventilation.]
• Daily potassium levels in mmol/L every 24 hours [Time frame: From start of mechanical ventilation for ten days, at 08:00 in the morning]
• Daily sodium levels in mmol/L every 24 hours [Time frame: From start of mechanical ventilation for ten days, at 08:00 in the morning]
• Daily lactate measurement in mmol/L every 24 hours [Time frame: From start of mechanical ventilation for ten days, at 08:00 in the morning]
• Daily pH measurement every 24 hours [Time frame: From start of mechanical ventilation for ten days, at 08:00 in the morning]
• Daily ketone levels in blood every 24 hours in mmol/L [Time frame: From start of mechanical ventilation for ten days, at 08:00 in the morning]

Eligibility criteria

Inclusion criteria

• Age < 10 years and weight < 35 kg
• Receiving invasive mechanical ventilation (IMV) due to respiratory failure
• Inclusion possible within 24 hours of start of IMV
• Expected duration of IMV > 48 hours

Exclusion criteria

• Preterm (<37weeks gestational age)
• Preexistent (clinical) diagnosis of kidney disease
• Congenital cardiac defect with hemodynamic consequences or reduced cardiac function
• (Ongoing) shock with need for fluid resuscitation and/or vasoactive drugs
• Cardiovascular (including diuretics) drug use on admission (home medication)
• Pre-existent (clinical) diagnosis of liver failure
• Right of left heart failure
• Pulmonary hypertension
• ECMO treatment
• Receiving total parenteral nutrition on admission which won't be stopped
• Failure to include within 12 hours after start of IMV
• Expected duration of IMV < 48 hours
• Parents or caretakers unable to understand/speak Dutch language
• Surgery < 48 hours

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 3 centers

• Radboudumc — Nijmegen
• Amsterdam MC — Amsterdam
• ErasmusMC — Rotterdam

Publications

• Arrahmani I, Ingelse SA, van Woensel JBM, Bem RA, Lemson J. Current Practice of Fluid Maintenance and Replacement Therapy in Mechanically Ventilated Critically Ill Children: A European Survey. Front Pediatr. 2022 Feb 23;10:828637. doi: 10.3389/fped.2022.828637. eCollection 2022. PMID 35281243
• Valentine SL, Sapru A, Higgerson RA, Spinella PC, Flori HR, Graham DA, Brett M, Convery M, Christie LM, Karamessinis L, Randolph AG; Pediatric Acute Lung Injury and Sepsis Investigator's (PALISI) Network; Acute Respiratory Distress Syndrome Clinical Research Network (ARDSNet). Fluid balance in critically ill children with acute lung injury. Crit Care Med. 2012 Oct;40(10):2883-9. doi: 10.1097/CCM.0 PMID 22824936
• Ingelse SA, Geukers VG, Dijsselhof ME, Lemson J, Bem RA, van Woensel JB. Less Is More?-A Feasibility Study of Fluid Strategy in Critically Ill Children With Acute Respiratory Tract Infection. Front Pediatr. 2019 Dec 10;7:496. doi: 10.3389/fped.2019.00496. eCollection 2019. PMID 31921715
• Diaz F, Nunez MJ, Pino P, Erranz B, Cruces P. Implementation of preemptive fluid strategy as a bundle to prevent fluid overload in children with acute respiratory distress syndrome and sepsis. BMC Pediatr. 2018 Jun 26;18(1):207. doi: 10.1186/s12887-018-1188-6. PMID 29945586
• Charaya S, Angurana SK, Nallasamy K, Jayashree M. Restricted versus Usual/Liberal Maintenance Fluid Strategy in Mechanically Ventilated Children: An Open-Label Randomized Trial (ReLiSCh Trial). Indian J Pediatr. 2025 Jan;92(1):7-14. doi: 10.1007/s12098-023-04867-4. Epub 2023 Oct 18. PMID 37851328
• Brossier DW, Tume LN, Briant AR, Jotterand Chaparro C, Moullet C, Rooze S, Verbruggen SCAT, Marino LV, Alsohime F, Beldjilali S, Chiusolo F, Costa L, Didier C, Ilia S, Joram NL, Kneyber MCJ, Kuhlwein E, Lopez J, Lopez-Herce J, Mayberry HF, Mehmeti F, Mierzewska-Schmidt M, Minambres Rodriguez M, Morice C, Pappachan JV, Porcheret F, Reis Boto L, Schlapbach LJ, Tekguc H, Tziouvas K, Parienti JJ, Goye PMID 36289081

Identifiers

NCT: NCT06644508 · 2023-16717

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗