Neuroimaging and Neuromonitoring in Critically Ill Children With Sepsis

In critically ill children with severe sepsis, neurophysiologic derangements often proceed undetected and can lead to irreversible brain injury causing neurocognitive and behavioral deficits. The etiology of these impairments is unclear, however, it is likely that some of this neural injury is preventable. The overarching goal for this study is to show that acute acquired structural and microstructural brain injury occurs in critically ill children with severe sepsis, and that this injury is related to neuropsychological deficits and impaired cerebral autoregulation (CAR). Subjects will complete Magnetic resonance (MR) imaging within 2-10 days of recognition of their severe sepsis. Subjects will undergo serial interrogation of CAR for up to 10 days. CAR will be determined by the correlation of arterial blood pressure with middle cerebral artery flow velocity measured by transcranial doppler ultrasonography and cerebral oximetry derived from near-infrared spectroscopy. Subjects will also participate in a neuropsychological evaluation 6 months after enrollment to evaluate multiple domains of behavior and cognition.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Diagnostic test: MR imaging

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children admitted to the pediatric intensive care unit (PICU) at the Children's Hospital of Philadelphia (CHOP) with severe sepsis from an extracranial source and have no history of a preexisting underlying a neurologic disorder.

Description

Inclusion Criteria:

• Admission to the Children's Hospital of Philadelphia (CHOP) pediatric intensive care unit (PICU)
• Males or females ages ≥ 3.5 years and ≤ 18 years on day of sepsis recognition
• Meet published consensus criteria for severe sepsis or septic shock: a) ≥ 2 systemic inflammatory response syndrome criteria, b) suspected (based on attending physician) or confirmed systemic infection, and c) ≥ 2 or more organ system dysfunctions (severe sepsis) or cardiovascular dysfunction (septic shock).
• An indwelling arterial catheter.
• Parental/guardian permission (informed consent).
• The patient and parent/guardian are fluent in English.

Exclusion Criteria:

• History of neurologic disorder including (hypoxic ischemic injury, traumatic brain injury, epileptic encephalopathy, neurodevelopmental, neurometabolic or neurogenetic conditions, and structural brain anomalies).
• History of cancer or undergoing treatment for cancer.
• Meningitis or encephalitis as source of sepsis.
• Congenital heart disease.
• History of cardiac arrest.
• History of extracorporeal membrane oxygenation (ECMO) cannulation.
• Patients with contraindications to MR scanning.
• Pregnant or lactating females.
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• Previous enrollment in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sepsis; Children with severe sepsis or septic shock	Diagnostic test: MR imaging; Conventional structural imaging will be combined with advanced neuroimaging modalities to evaluate integrity of white matter tracts, regional brain perfusion, and the 3-dimensional volume of specific brain structures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI	Detection of signal abnormality on the patient's brain MRI scan.	2-10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR	Trends in functionality of CAR over the first 10 days of severe sepsis. Identification of the optimal blood pressure range where CAR is most functional.	Daily for 10 days

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Matthew Kirschen, MD, PhD, CHOP

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): September 27, 2019
• Study Completion (Actual): September 27, 2019

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 16, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Shock; Sepsis; Shock, Septic; Critical Illness
• Other Study ID Numbers: 16-012645

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