Transfusion-related Acute Lung Injury: a Prospective Cohort Study in Critically Ill Children (TRALI)

Transfusions cause more adverse events in children than in adults. Patients in pediatric intensive care units (PICU) are particularly exposed to transfusions of plasma-rich blood products (red blood cell (RBC), plasma and platelets) and the risk of adverse events after a transfusion is particularly high in this vulnerable population. Transfusion-related acute lung injury (TRALI), an acute inflammation of the lungs that impairs gas exchange leading to acute respiratory failure, is one of the 2 most deadly transfusion complications in the general population. There is limited evidence on TRALI incidence and impact in critically ill children. This reduces the awareness of PICU team for this complication, and makes the decision process to transfuse particularly difficult. Moreover, acute lung injury is highly prevalent in critically ill children. It is therefore complex to ascertain if the high frequency of respiratory deteriorations observed after a transfusion in PICU is explained by the transfusion itself or by the evolution of the patient's critical illness.

The investigators will conduct a cohort study of consecutive transfused critically ill children, with a control group of matched non-transfused children. The primary objective is to determine if transfusion of RBC, plasma and/or platelets in PICU is an independent risk factor of TRALI, and to compare the respiratory evolution in the two matched (transfused and non-transfused) groups. The secondary objectives will include the determination of the incidence rate, risk factors and clinical impact of TRALI in transfused PICU patients. The investigators will study both "classic TRALI" and "delayed TRALI".

Study Overview

• Status: Completed
• Conditions: Acute Lung Injury
• Intervention / Treatment: Other: Blood transfusion

Detailed Description

Study Design This prospective cohort study will include all consecutive transfused patients admitted to the participating PICUs over a one-year period and a control group of matched non-transfused patients. The primary objectives will be assessed using the complete cohort of transfused and non-transfused patients. Secondary objectives will be studied in transfused patients.

Outcomes The primary outcome measure is TRALI (definite, probable, and delayed TRALI) as defined in section. In the non-transfused patients, the definition of Acute Lung Injury will be the same as the one used as a criterion for defining TRALI, and the observation period will be a similar 72-h period, starting at the same time zero.

Primary Objectives

• Objective #1a: to determine if the transfusion of RBC, plasma or platelets is an independent risk factor of TRALI in critically ill children.
• Objective #1b: to compare the progression of the respiratory function, in particular the SpO2/FiO2 ratio, in transfused and non-transfused PICU patients.

Secondary Objectives

• Objective #2.a : To determine the incidence rate of classic (definite or probable) TRALI and of delayed TRALI in transfused PICU patients.
• Objective #2.b : To characterize the risk factors of classic (definite or probable) TRALI and of delayed TRALI in transfused PICU patients.
• Objective #2.c : To compare the progression of respiratory parameters after a 1st transfusion in PICU patients with classic TRALI, delayed TRALI, and without TRALI.
• Objective #2.d : To compare the outcomes of transfused PICU patients with and without classic (definite or probable) TRALI and delayed TRALI.
• Objective #2.e : To describe the inflammatory profile of PICU patients with definite, probable, and delayed TRALI.

• Study Type: Observational
• Enrollment (Actual): 717

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A9
      • Alberta Children's Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • St. Justine's Hospital
    • Montreal, Quebec, Canada, H4A 3J1
      • Montreal Children's Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All children admitted to a participating PICU will be considered eligible for inclusion.

Description

Inclusion Criteria:

• admission to the PICU

Exclusion Criteria:

• gestational age < 40 weeks at entry into PICU
• post-term age less than 3 days or more than 18 years at PICU admission
• patients on extra-corporeal membrane oxygenation or ventricular assist device
• pregnancy present at entry into the PICU
• admission to PICU just after labor

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Transfused critically ill children; Any infusion of RBC, plasma or platelets will be considered a transfusion.	Other: Blood transfusion
Non-transfused critically ill children; For each transfused patient (index patient), one matched non-transfused control will be identified and included in the control group. The matching will be conducted using four criteria in hierarchical order: gender; age ± 10%; baseline Hemoglobin level (± 15 g/L); and Pediatric Risk of Mortality III score (PRISM III score ± 10%).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Transfusion-related acute lung injury	72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of PICU stay (days)	28 days
28-day all cause mortality	28 days
Multiple organ dysfunction syndrome (MODS)	28 days

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: Canadian Blood Services
• Investigators: Principal Investigator: Guillaume Emeriaud, MD, PhD, St. Justine's Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: November 20, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 24, 2015

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Transfusion-related acute lung injury, Red Blood Cell
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hematologic Diseases; Thoracic Injuries; Transfusion Reaction; Wounds and Injuries; Acute Lung Injury; Lung Injury; Transfusion-Related Acute Lung Injury
• Other Study ID Numbers: CHUSJ-MP-21-2016-1070