Cerebral Circulation in Critically Ill Children (CIRCU-REAPED)

Changes in Cerebral Circulation and Oxygenation During Hemodynamic Resuscitation in Critically Ill Children Without Head Trauma

The principal purpose of this study is to describe the changes in cerebral circulation (assessed by transcranial ultrasound) and oxygenation (assessed by Near InfraRed spectroscopy, NIRS) during resuscitation for hemodynamic failure (arterial hypotension or shock) in critically ill children treated with vasoactive or inotropic drugs.

The secondary objectives are :

i) to evaluate the association between an alteration of cerebral circulation and/or oxygenation and an alteration in macro-circulatory parameters (Mean Arterial Blood Pressure and cardiac output) or a bad outcome, ii) to study if cerebral autoregulation is impaired

Study Overview

• Status: Completed
• Conditions: Shock; Cerebral Lesion; Arterial Hypotension
• Intervention / Treatment: Device: Near InfraRed Spectroscopy assessment; Device: Transcranial Doppler Ultrasound assessment; Device: Cardiac output assessment

Detailed Description

Pediatric shock is a frequent and serious cause of hospitalization in pediatric intensive care unit that can lead to multi-organ failure and death.

Its early recognition improves patients' outcome, as well as the establishment of targeted guidelines pursuing normalization of macro-circulatory parameters (ie blood pressure and lactate).

However, regional hypoperfusion leading to organ failure can be present before the alteration of these parameters, and persist after their restoration.

Brain lesions are common in critically ill children with cerebral hypoperfusion, since they may have impaired autoregulation and permeable blood-brain barrier. Vasoactive and inotropic drugs used for hemodynamic resuscitation should restore systemic and regional circulation, but may be inadequate on brain perfusion because of i) their variable and unpredictable cardiovascular effects , and ii) a strong interindividual variability between patients. As such, the impact of this medication on cerebral circulation and oxygenation is unknown.

Monitoring cerebral circulation and oxygenation during a hemodynamic resuscitation using catecholamines is a first step to identify risk factors of an altered brain perfusion, and to improve treatment of shock.

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Hopital Robert Debre
  • Paris, France, 75015
    • Hopital Necker
  • Paris, France, 75012
    • Hôpital Trousseau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients hospitalized in 4 french Pediatric Intensive Care Units

Description

Inclusion Criteria:

Neonates and children from 0 to 18 years old hospitalized in pediatric intensive care unit (PICU) with hemodynamic failure requiring vasoactive or inotropic treatment. This includes :

• shock (tachycardia, troubles of peripheral perfusion with capillary refill time >3 sec, oliguria, with or without alteration of consciousness or arterial hypotension)
• isolated arterial hypotension if it needs medical treatment to readjust balance between oxygen demand and oxygen consumption

Exclusion Criteria:

• primitive cerebral lesion: traumatic or neurosurgical (including brain death states)
• preterm neonates of less than 37 weeks gestational age
• patients already receiving more than one catecholamine
• patients too instable, defined by a respiratory instability (pulse oxymetry of less than 80% during more than 5 minutes) and/or hemodynamic instability (variability of blood pressure and heart rate of more than 50%) and/or cardiorespiratory arrest.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Near InfraRed Spectroscopy (NIRS)	rScO2 and FTOE variations (left and right). A cerebral desaturation will be defined by a rScO2 delta >20% from the baseline value (before premedication).	3 hours
Variations of velocities of middle cerebral artery (left and right), in cm/s	Transcranial Doppler ultrasound	3 hours
Variations of pulsatility index of middle cerebral artery (left and right)	Transcranial Doppler ultrasound	3 hours
Variations of resistance index of middle cerebral artery (left and right)	Transcranial Doppler ultrasound	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure	Correlation between microcirculatory parameters (transcranial Doppler ultrasound and NIRS) and mean arterial pressure	3 hours
Cardiac output calculated with Left ventricular outflow tract velocity time integral (LVOT VTI) measured by cardiac ultrasound	Correlation between microcirculatory parameters (transcranial Doppler ultrasound and NIRS) and cardiac output (Qc), which will be calculated taking account these parameters and heart rate with this formula : Qc = [π x d2 x VTI x HR] / 4	3 hours
PEdiatric logistic organ dysfunction score (PELOD-2)	Correlation between cerebral perfusion (transcranial Doppler ultrasound and NIRS) and Organ Dysfunction assessed by PELOD-2 score. PELOD-2 score includes 10 variables corresponding to 5 organ dysfunctions. Values extend from 0 (best outcome) to 33 (worst outcome).	3 hours
Death in pediatric intensive care unit	Correlation between cerebral perfusion (transcranial doppler ultrasound and NIRS) and outcome (PELOD-2, death in PICU = pediatric intensive care unit)	3 hours
Cerebral autoregulation evaluation	Cerebral autoregulation will be estimated thanks to a Pearson coefficient correlation between mean arterial pressure (MAP) and rScO2. A ratio MAP/rScO2 > 0,5 defines an impaired cerebral autoregulation	3 hours

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Meryl Vedrenne-Cloquet, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Vedrenne-Cloquet M, Chareyre J, Leger PL, Genuini M, Renolleau S, Oualha M. Low Dosing Norepinephrine Effects on Cerebral Oxygenation and Perfusion During Pediatric Shock. Front Pediatr. 2022 Jul 6;10:898444. doi: 10.3389/fped.2022.898444. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2018
• Primary Completion (Actual): July 2, 2021
• Study Completion (Actual): July 2, 2021

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: November 2, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Brain perfusion; Catecholamines; Near InfraRed Spectroscopy; Pediatric shock
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension
• Other Study ID Numbers: 2018-A01392-53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No