Acute Brain Injury, Acute Respiratory Distress Syndrome, Acute Respiratory Failure, Traumatic Brain Injury
Conditions
Keywords
emergency care, acute respiratory failure, trauma, oxygen, disability, acute care, critical care, mortality, brain injury, mechanical ventilation
Brief summary
Despite almost universal usage of supplemental oxygen therapy in patients presenting in the emergency department with traumatic brain injury (TBI), optimal oxygen levels are unclear. The investigators propose a pilot multi-center randomized controlled trial to test the hypothesis that maintaining intermediate normal as opposed to high normal oxygen levels in patients presenting in the emergency department with TBI is feasible, and to obtain preliminary data on the efficacy of the two approaches to oxygen therapy. The aim is that the investigators produce pilot data, which could inform the design of potential subsequent larger clinical trials.
Detailed description
Despite the worldwide burden of traumatic brain injury (TBI), medical research on the field as opposed to other health problems is underrepresented. Consequently, there are few data to support commonly used interventions for the management of TBI, especially in the setting of the emergency department. For example, despite almost universal usage of supplemental oxygen therapy, the effects of different oxygenation levels under normobaric conditions on outcomes of patients presenting in the emergency department with TBI are unknown. On the one hand, liberal oxygenation may provide a margin of safety against hypoxemia and may be needed to meet the high oxygen demands of an acutely altered brain physiology. On the other hand, there are increasing concerns that excessive oxygen supplementation may have harmful effects, such as central nervous system toxicity, cerebral vasoconstriction, impaired immunity leading to predisposition to infections (including pneumonia) and acute lung injury/acute respiratory distress syndrome. Such effects could be avoided by intermediate normal oxygen levels. Taken together, the relative merits and risks of the abovementioned two approaches to oxygen therapy (namely, intermediate normal versus high normal oxygen levels) of patients with TBI in terms of important clinical outcomes (namely, development of nosocomial pneumonia, acute respiratory distress syndrome, disability and mortality) remain undefined. This suggests the need for randomized controlled trials. However, randomized controlled trials focusing on patient-centered outcomes should be preceded by pilot randomized controlled trials, which demonstrate a separation in treatment and protocol compliance (feasibility) associated with the studied interventions. Therefore, the investigators propose a pilot multi-center randomized controlled trial to test the hypothesis that maintaining intermediate normal as opposed to high normal oxygen levels in patients presenting in the emergency department with TBI is feasible, and to obtain preliminary data on the efficacy of the two approaches to oxygen therapy.
Interventions
OTHEROxygen
Oxygen to achieve assigned SpO2 (or FiO2) targets will be administered to study subjects. The treating clinician can alter oxygenation targets at any time if deemed necessary. The oxygenation goal will be based on SpO2 rather than arterial oxygen saturation (SaO2) or arterial pressure oxygen (PaO2) from arterial blood gases. However, PaO2 can be used instead in situations where the treating clinician considers that peripheral perfusion is poor or SpO2 readings are unreliable. Assigned SpO2 targets will apply to the study subjects for a total duration of 6 hours from intubation or until death or until transfer to the operating theater (whatever comes first).
Sponsors
Evangelismos Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
To avoid selection bias, the allocation sequence will be blinded from researchers involved in patient enrolment. Although study subjects will be unaware of the assigned group, blinding of treating clinicians is not considered feasible.
Intervention model description
Enrolled patients will be randomly allocated using opaque sealed envelopes to either intermediate normal oxygen or high normal oxygen group. The asymptomatic maximal procedure, with an allocation ratio of 1:1 and a maximum tolerated imbalance of 2 will be used to randomize subjects.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patient ≥18 years * Glasgow Coma Scale ≤ 8 * Non-penetrating traumatic brain injury * Intubated patient
Exclusion criteria
* Age \<18 years * Lack of intention to admit to the intensive care unit * Moribund patient expected to die within 24 hours * Expected need for mechanical ventilation \< 24 hours * Time interval from intubation to group allocation more than 60 minutes * Penetrating traumatic brain injury * Pregnancy * Lack of equipoise of the treating clinician * Lack of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean area-under-curve (AUC) for SpO2 | Measurements will be obtained each hour for a total duration of 6 hours from intubation. | SpO2 will be recorded each hour for a total duration of 6 hours from intubation. Subsequently, mean area-under-curve (AUC) will be calculated for each group. This will demonstrate the feasibility of the study. |
| Mean area-under-curve (AUC) for FiO2 | Measurements will be obtained each hour for a total duration of 6 hours from intubation. | FiO2 will be recorded each hour for a total duration of 6 hours from intubation. Subsequently, mean area-under-curve (AUC) will be calculated for each group. This will demonstrate the feasibility of the study. |
| PaO2 | Measurements will be obtained at least once during 6 hours from intubation. | PaO2 will be recorded at least once during 6 hours from intubation. Subsequently, PaO2 values (mmHg) will be calculated for each group. This will demonstrate the feasibility of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nosocomial pneumonia | Within 7 days of subject enrollment | Incidence of nosocomial pneumonia will be recorded for each arm |
| Extended Glasgow Outcome Score (GOS-E) | At 6 months following subject enrollment | A combined outcome of disability and mortality at 6 months using the Extended Glasgow Outcome Score will be assessed |
| Acute Respiratory Distress Syndrome (ARDS) | Within 7 days of subject enrollment | Incidence of ARDS will be recorded for each arm |
| All-cause mortality | Within 28 days of subject enrollment | All-cause mortality will be recorded during ICU stay |
Countries
Greece
Outcome results
None listed