Intracranial Hemorrhage, Hypertensive, Intracranial Hypertension, Severe Traumatic Brain Injury
Conditions
Keywords
TBI, Severe TBI, Traumatic Brain Injury, Sedation, Ketamine
Brief summary
This protocol is for an open-label randomized trial evaluating the safety of using ketamine in combination with propofol for sedation versus the standard of care analgosedation in patients admitted to the intensive care unit with severe traumatic brain injury.
Detailed description
Patients meeting eligibility criteria and consent having been obtained by LAR will undergo randomization to either the ketamine with propofol intervention arm or the standard of care control arm. Patients enrolled in the intervention arm will receive propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine, for sustained ICP elevations over 22mHg for greater than 5 minutes not attributed to other causes (coughing etc.). In the control arm, patients will receive their institutional analgosedation protocol. The sedation protocols will be continued until removal of intracranial pressure monitoring. This study will take place during the participant's hospital care. The clinical team will administer treatment using standard practices, including all safety precautions available. Side effects will be monitored closely and may decide to discontinue the subject's participation in the study should the subject's health or safety are at risk. The research team will performed one outpatient follow-up after study intervention ends.
Interventions
DRUGKetamine with propofol
Propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine
OTHERStandard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam
Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam administered according to the institutional SOC guidelines.
Sponsors
Uniformed Services University of the Health Sciences
Brooke Army Medical Center
Henry M. Jackson Foundation for the Advancement of Military Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults 18-65 years of age * Severe traumatic brain injury (TBI), with a Glasgow Coma Scale (GCS) ≤ 8, requiring intracranial monitoring * Placement of intracranial pressure monitor * Receiving treatment in an intensive care unit (ICU)
Exclusion criteria
* Significant cardiovascular disease with recent coronary intervention * Pregnancy * Prisoners * Known allergy to ketamine or propofol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of ICP elevations greater than 22 mmHg for greater than 5 minutes | During the maximum 5-day course of study intervention, while patient is sedated and has intracranial pressure monitor in place in the ICU setting | ICP elevations \> 22 mmHg for greater than 5 minutes. |
| Mean ICP | During the maximum 5-day course of study intervention. | Mean ICP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total time spent with CPP <60 mmHg | During the maximum 5-day course of study intervention. | Total time spent with CPP \<60 mmHg (in minutes). |
| Total number of events where CPP <60 mmHg for greater than 5 minutes | During the maximum 5-day course of study intervention. | Total number of events where CPP \<60 mmHg (in minutes) for greater than 5 minutes. |
| Vasopressor dependency index (VDI) | During the maximum 5-day course of study intervention. | Relationship between vasopressor infusion dose and mean arterial blood pressure. VDI= (dobutamine dose × 1) + (dopamine dose × 1) + (norepinephrine dose × 100) + (vasopressin × 100) + (epinephrine × 100))/MAP indicating the relationship of high VDI and poor outcome. |
| Incidence of seizures | During the maximum 5-day course of study intervention. | Incidence of seizures (as documented by EEG). |
| Total time spent with intracranial pressure (ICP) >22 mmHg | During the maximum 5-day course of study intervention. | Total time spent with ICP \>22 mmHg (in minutes). |
| Mean heart rate | During the maximum 5-day course of study intervention. | Mean heart rate (HR). |
| Incidence of post-traumatic stress disorder (PTSD) in outpatient setting | Outpatient follow-up six months after intervention. | Incidence of PTSD at 6-month outpatient follow-up. |
| Glasgow Coma Outcome Scale extended (GOSE-TBI) scores | Outpatient follow-up six months after intervention. | GOSE-TBI assessment resulting in subjective measure of 0-8 regarding recovery after injury with higher score indicating greatest recovery to pre-injury life, will be conducted at 6-month outpatient follow-up. |
| Incidence of cardiac arrhythmias | During the maximum 5-day course of study intervention. | Incidence of cardiac arrhythmias (other than sinus tachycardia). |
| Mean Cerebral Perfusion Pressure (CPP) | During the maximum 5-day course of study intervention. | Mean CPP (in minutes). |
Countries
United States
Outcome results
None listed