Near Infrared Spectroscopy (NIRS) as Transfusion Indicator in Neurocritical Patients

Phase II Study of Usefulness of Near Infrared Spectroscopy to Optimize Red Blood Cells Transfusion in Neuro Critical Ill Patients With Severe Traumatic Brain Injury, Subarachnoid Hemorrhage or Intracerebral Hemorrhage.

Neurocritical ill patients are frequently transfused. Red blood cell transfusion (RBCT) in these patients has been associated with deleterious effects, including higher rates of nosocomial infections, multi-organ failure, and mortality. Therefore, it seems crucial to avoid any unnecessary RBCT.

Most critically ill patients tolerate hemoglobin levels near 7 g/dL without an increase in morbidity or mortality rates. In this regard, a recent sub-analysis of TRICC trial has showed that TBI patients may tolerate hemoglobin levels as low as 7 g/dL, but other studies including neurocritical patients suggested that severe anemia may worsen clinical outcome. Therefore, optimal hemoglobin levels in neurocritical care patients remain largely unknown. Some textbooks and guidelines recommend to transfuse these patients to reach hemoglobin levels near to 10 g/dL, despite the lack of a solid scientific background supporting this target.

Even though it has not been demonstrated, hemoglobin-based RBCT prescription could result in over- or under-transfusion in neurocritical patients. Alternatively, it has been suggested that more physiological transfusion triggers, using direct signals coming from the brain, will progressively replace arbitrary hemoglobin-based transfusion triggers in the neurocritical patients [65]. At the neurocritical units, patients are often monitored by using non-invasive methods, such as near infrared spectroscopy which indirectly measures regional cerebral oxygen saturation (rSO2). Changes in rSO2 values have been shown to directly correlate with changes in erythrocyte mass, thus increasing with RBCT and decreasing with blood losses. Moreover, rSO2 values also show a good correlation with clinical outcome and other variables which are often monitored in TBI patients.

The purpose of this study is to ascertain as to whether rSO2 levels are more efficacious than conventional hemoglobin levels in guiding RBCT in patients admitted to a neurocritical care unit.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Subarachnoid Hemorrhage; Intracerebral Hemorrhage
• Intervention / Treatment: Procedure: Red blood cells transfusion

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Seville, Spain, 41013
    • Hospital Universitario "Virgen del Rocío"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe traumatic brain injury (Glasgow coma scale < 9), subarachnoid hemorrhage (Hunt and Hess scale ≥ 3) or intracranial hemorrhage
• Moderate anemia. Hemoglobin levels > 7 g/dL and < 10 g/dL
• Hemodynamical stability (mean arterial pressure > 75 mm Hg)
• Respiratory stability (PaO2 / FiO2 ratio > 220)
• Expected length of ICU stay > 3 days

Exclusion Criteria:

• Patient's relatives' refusal to patient's inclusion in the study
• Active bleeding
• Ongoing need for blood products
• Patients necessitating ongoing resuscitation
• End-stage in which death is imminent
• Antecedents of angina or myocardial infarction (poor cardiopulmonary reserve)
• Deficient signal of rSO2 impeding its proper valuation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RBCT based on rSO2 value; Intervention: In the rSO2 - strategy group, patients will be transfused to attain a post-transfusion rSO2 values higher than 60%.	Procedure: Red blood cells transfusion; Patients will be transfused (one to one red blood cells unit transfusion)
Active Comparator: RBCT based on hemoglobin level value; Intervention: In the hemoglobin - strategy group, patients will be transfused to reach post-transfusion hemoglobin levels between 8.5 g/dL and 10 g/dL.	Procedure: Red blood cells transfusion; Patients will be transfused (one to one red blood cells unit transfusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Units of Packed Red Blood Cell Transfused	Number of units of packed packed red blood cell transfused, over the period that the patient was included into the protocol	duration of the protocol, an average of 15 days
Percentage of Transfused Patients in Each Group		duration of the protocol, an average of 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Mortality		length of the hospital stay, an average of 20 days
Length of Intensive Care Unit (ICU) Stay		The length of ICU stay, an avarege of 17 days
Long-term Mortality		1-year after hospital discharge
Unfavorable Glasgow Outcome Scale (GOS)	GOS measures the degree of disability associated with the brain injury Unfavorable GOS included the categories of: death.; vegetative status.; severe disability.	At hospital discharge, an average of 21 days

Collaborators and Investigators

• Sponsor: Hospitales Universitarios Virgen del Rocío
• Investigators: Principal Investigator: Santiago R Leal-Noval, MD, PhD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Chair: Victoria Arellano, MD, PhD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Chair: Rosario Amaya, MD, PhD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Chair: Antonio M Puppo, MD, PhD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Chair: Carmen M Ferrándiz, MD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Chair: Antonio J Marín, MD, PhD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Director: Francisco Murillo, MD, PhD, Hospital Universitario "Virgen del Rocío", Seville, Spain; Study Chair: Manuel Muñoz, Prof, MD, PhD, Prof Transfusion Medicine University of Malaga, Spain; Study Chair: Vicente Padilla, MD, Hospitales Universitarios Virgen del Rocío; Study Chair: Yael Corcia, MD, Hospitales Universitarios Virgen del Rocío; Study Chair: Aurelio Cayuela, MD, PhD, Hospital Universitario "Virgen del Rocío"

Publications and helpful links

General Publications

• Leal-Noval SR, Arellano-Orden V, Munoz-Gomez M, Cayuela A, Marin-Caballos A, Rincon-Ferrari MD, Garcia-Alfaro C, Amaya-Villar R, Casado-Mendez M, Dusseck R, Murillo-Cabezas F. Red Blood Cell Transfusion Guided by Near Infrared Spectroscopy in Neurocritically Ill Patients with Moderate or Severe Anemia: A Randomized, Controlled Trial. J Neurotrauma. 2017 Sep;34(17):2553-2559. doi: 10.1089/neu.2016.4794. Epub 2017 Jul 19.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 29, 2007
• First Submitted That Met QC Criteria: November 30, 2007
• First Posted (Estimate): December 3, 2007

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: March 21, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: transfusion; cerebral oxygenation; NIRS; red blood cell; near infrared spectroscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Brain Injuries; Hemorrhage; Brain Injuries, Traumatic; Subarachnoid Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: PI-0157/2006; PI 157/06