Clinical trial NCT06644508: The Efficient PICU Fluid Care Evaluation
Official title: The Efficient PICU Fluid Care Evaluation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Respiratory Insufficiency Requiring Mechanical Ventilation
Fluid Overload
Fluid Balance
Keywords: Respiratory Insufficiency
Mechanical ventilation
Fluids
Fluid Balance
Edema
Fluid Overload
Lenght of mechanical ventilation
Childeren
Maintenance fluids
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2024-10-16
Enrollment: 90
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multicentre prospective study (clinical implementation evaluation) with a before-after design with continuous recruitment and single measurements
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Cumulative fluid balance on day 3 in ml/kg
timeFrame: From start mechanical ventilation to 72 hours after start of mechanical ventilation
Secondary outcomes:
measure: Daily cumulative fluid balance on in ml/kg
timeFrame: For 10 days, CFB is noted every day at 00:00
measure: Protein intake in gr/kg/day
timeFrame: For ten days after start of mechanical ventilation
measure: Bodyweight in grams
timeFrame: Bodyweight in grams will be measured at start of mechanical ventilation and at 72 hours after start of mechanical ventilation
measure: Daily cumulative diuretics dose in mg/kg
timeFrame: From start of mechnical ventilation for ten days, cumulative diuretic dose will be noted at 00:00
measure: Blood urea nitrogen (BUN) in mmol/L
timeFrame: BUN will be measured at 24 hours, 72 hours and at 120 hours after start of mechanical ventilation
measure: Daily creatinine level in µmol/L
timeFrame: Creatinine levels will be noted at: 24, 72 hours and 120 after start of mechanical ventilation
measure: Daily KDIGO stages (1,2 or 3) will be noted every 24 hours
timeFrame: From start of mechanical ventilation to 120 hours after start of mechanical ventilation.
measure: Daily potassium levels in mmol/L every 24 hours
timeFrame: From start of mechanical ventilation for ten days, at 08:00 in the morning
measure: Daily sodium levels in mmol/L every 24 hours
timeFrame: From start of mechanical ventilation for ten days, at 08:00 in the morning
measure: Daily lactate measurement in mmol/L every 24 hours
timeFrame: From start of mechanical ventilation for ten days, at 08:00 in the morning
measure: Daily pH measurement every 24 hours
timeFrame: From start of mechanical ventilation for ten days, at 08:00 in the morning
measure: Daily ketone levels in blood every 24 hours in mmol/L
timeFrame: From start of mechanical ventilation for ten days, at 08:00 in the morning
measure: Daily vasoactive-inotropic score every 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Daily highest heart rate in beats per minute from every previous 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Daily lowest heart rate in beats per minute from every previous 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Daily mean mean arterial pressure (so mean MAP) over every previous 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Daily mean heart rate in beats per minute over every previous 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Duration of IMV in days
timeFrame: From start of mechanical ventilation for ten days
measure: Duration of high flow nasal canula therapy after end of mechanical ventilation in hours
timeFrame: From the end of mechanical ventilation up to ten days after start of mechanical ventilation
measure: Need for extracorporeal organ support (ECMO) is noted (yes/no)
timeFrame: From start of mechanical ventilation to day ten after start of emchanical ventilation
measure: Daily mean oxygenation saturation index is noted every 24 hours only when SpO2 was below 97%
timeFrame: From start of mechanical ventilation for ten days
measure: Mean daily P/F ration is noted from every previous 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Lenght of pediatric intensive care (PICU) stay in days
timeFrame: From start of mechanical ventilation to 10 days after start mechanical ventilation
measure: Newly acquired pulmonary infections (yes/no)
timeFrame: From start of mechanical ventilation for ten days
measure: Total daily fluid balance is noted in ml/kg every 24 hours
timeFrame: From start of mechnical ventilation for ten dys
measure: Daily fluid intake in ml/kg every 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Caloric intake in kcal/kg every 24 hours
timeFrame: From start of mechanical ventilation for ten days
measure: Daily urine production in ml//kg from every 24 hours
timeFrame: From start of mechnical ventilation for ten days
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Amsterdam MC
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: ErasmusMC
state: Zuid-Holland
Study officials:
affiliation: Radboud University Medical Center
name: Joris Lemson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.0b013e31825bc54d.
citation: 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.
citation: 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.
citation: 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.
citation: 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, Goyer I, Valla FV; Metabolism Endocrinology and Nutrition section of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis. Intensive Care Med. 2022 Dec;48(12):1691-1708. doi: 10.1007/s00134-022-06882-z. Epub 2022 Oct 26.