Intracerebral Hemorrhage, Subarachnoid Hemorrhage, Traumatic Brain Injury
Conditions
Keywords
transfusion, NIRS, cerebral oxygenation, red blood cell, near infrared spectroscopy
Brief summary
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.
Interventions
PROCEDURERed blood cells transfusion
Patients will be transfused (one to one red blood cells unit transfusion)
Sponsors
Hospitales Universitarios Virgen del Rocío
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Units of Packed Red Blood Cell Transfused | duration of the protocol, an average of 15 days | Number of units of packed packed red blood cell transfused, over the period that the patient was included into the protocol |
| Percentage of Transfused Patients in Each Group | duration of the protocol, an average of 15 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | At hospital discharge, an average of 21 days | GOS measures the degree of disability associated with the brain injury Unfavorable GOS included the categories of: 1. death. 2. vegetative status. 3. severe disability. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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%.
Red blood cells transfusion: Patients will be transfused (one to one red blood cells unit transfusion) | 51 |
| 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.
Red blood cells transfusion: Patients will be transfused (one to one red blood cells unit transfusion) | 51 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 5 | 0 |
Baseline characteristics
| Characteristic | RBCT Based on rSO2 Value | RBCT Based on Hemoglobin Level Value | Total |
|---|---|---|---|
| Age, Continuous | 45.2 years STANDARD_DEVIATION 18.3 | 46.1 years STANDARD_DEVIATION 16.3 | 45.6 years STANDARD_DEVIATION 17.3 |
| APACHE II score | 14.6 units on a scale STANDARD_DEVIATION 4.8 | 13.8 units on a scale STANDARD_DEVIATION 4.2 | 14.1 units on a scale STANDARD_DEVIATION 4.5 |
| Arterial Hypertension (n) No | 37 participants | 36 participants | 73 participants |
| Arterial Hypertension (n) Yes | 14 participants | 15 participants | 29 participants |
| CPP (mm Hg) (N=17, 22) | 73.9 mm Hg STANDARD_DEVIATION 18.5 | 72.9 mm Hg STANDARD_DEVIATION 15.6 | 73.4 mm Hg STANDARD_DEVIATION 16.7 |
| Diabetes mellitus (n) No | 49 participants | 46 participants | 95 participants |
| Diabetes mellitus (n) Yes | 2 participants | 5 participants | 7 participants |
| Diagnosis Intra cerebral hemorrhage | 11 participants | 11 participants | 22 participants |
| Diagnosis Subarachnoid hemorrhage | 10 participants | 13 participants | 23 participants |
| Diagnosis Traumatic Brain Injury | 30 participants | 27 participants | 57 participants |
| Fisher scale (N=10, 13) | 3.9 units on a scale STANDARD_DEVIATION 0.3 | 3.8 units on a scale STANDARD_DEVIATION 0.4 | 3.8 units on a scale STANDARD_DEVIATION 0.4 |
| GCS | 9 units on a scale | 9 units on a scale | 9 units on a scale |
| Hemoglobin (g/L) | 110.9 g/L STANDARD_DEVIATION 21.2 | 114 g/L STANDARD_DEVIATION 21.6 | 112.4 g/L STANDARD_DEVIATION 21.3 |
| Hunt and Hess scale (N=10, 13) | 4.1 units on a scale STANDARD_DEVIATION 1.2 | 4.1 units on a scale STANDARD_DEVIATION 0.8 | 4.1 units on a scale STANDARD_DEVIATION 1 |
| ISS score (N=30, 27) | 28.0 units on a scale STANDARD_DEVIATION 9.8 | 29.0 units on a scale STANDARD_DEVIATION 9.6 | 28.5 units on a scale STANDARD_DEVIATION 9.6 |
| Modified Grab score (N=11, 11) | 6.7 units on a scale STANDARD_DEVIATION 3.9 | 5.9 units on a scale STANDARD_DEVIATION 3 | 6.3 units on a scale STANDARD_DEVIATION 3.4 |
| PbrO2 (mm Hg) (N=17, 22) | 21.9 mm Hg STANDARD_DEVIATION 5.7 | 22.8 mm Hg STANDARD_DEVIATION 5.6 | 22.4 mm Hg STANDARD_DEVIATION 5.6 |
| Sex: Female, Male Female | 16 Participants | 20 Participants | 36 Participants |
| Sex: Female, Male Male | 35 Participants | 31 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 51 | 0 / 51 |
| serious Total, serious adverse events | 0 / 51 | 0 / 51 |
Outcome results
Primary
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
Time frame: duration of the protocol, an average of 15 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RBCT Based on rSO2 Value | Number of Units of Packed Red Blood Cell Transfused | 0.9 units | Standard Deviation 1.1 |
| RBCT Based on Hemoglobin Level Value | Number of Units of Packed Red Blood Cell Transfused | 1.5 units | Standard Deviation 1.4 |
p-value: 0.03t-test, 2 sided
Primary
Percentage of Transfused Patients in Each Group
Time frame: duration of the protocol, an average of 15 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBCT Based on rSO2 Value | Percentage of Transfused Patients in Each Group | 54.3 percentage of transfused participant |
| RBCT Based on Hemoglobin Level Value | Percentage of Transfused Patients in Each Group | 70.5 percentage of transfused participant |
p-value: 0.07Chi-squared, Corrected
Secondary
Hospital Mortality
Time frame: length of the hospital stay, an average of 20 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBCT Based on rSO2 Value | Hospital Mortality | 3 participants |
| RBCT Based on Hemoglobin Level Value | Hospital Mortality | 5 participants |
p-value: 0.56Chi-squared, Corrected
Secondary
Length of Intensive Care Unit (ICU) Stay
Time frame: The length of ICU stay, an avarege of 17 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RBCT Based on rSO2 Value | Length of Intensive Care Unit (ICU) Stay | 21.00 days | Standard Deviation 10.23 |
| RBCT Based on Hemoglobin Level Value | Length of Intensive Care Unit (ICU) Stay | 20.41 days | Standard Deviation 11.06 |
p-value: 0.79t-test, 2 sided
Secondary
Long-term Mortality
Time frame: 1-year after hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBCT Based on rSO2 Value | Long-term Mortality | 12 participants |
| RBCT Based on Hemoglobin Level Value | Long-term Mortality | 12 participants |
p-value: 0.77Chi-squared, Corrected
Secondary
Unfavorable Glasgow Outcome Scale (GOS)
GOS measures the degree of disability associated with the brain injury Unfavorable GOS included the categories of: 1. death. 2. vegetative status. 3. severe disability.
Time frame: At hospital discharge, an average of 21 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBCT Based on rSO2 Value | Unfavorable Glasgow Outcome Scale (GOS) | 27 participants |
| RBCT Based on Hemoglobin Level Value | Unfavorable Glasgow Outcome Scale (GOS) | 36 participants |
p-value: 0.22Chi-squared, Corrected