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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
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
Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam administered according to the institutional SOC guidelines.
Brooke Army Medical Center
Fort Sam Houston, Texas, United States
Number of ICP elevations greater than 22 mmHg for greater than 5 minutes
ICP elevations \> 22 mmHg for greater than 5 minutes.
Time frame: During the maximum 5-day course of study intervention, while patient is sedated and has intracranial pressure monitor in place in the ICU setting
Mean ICP
Mean ICP
Time frame: During the maximum 5-day course of study intervention.
Total time spent with intracranial pressure (ICP) >22 mmHg
Total time spent with ICP \>22 mmHg (in minutes).
Time frame: During the maximum 5-day course of study intervention.
Mean Cerebral Perfusion Pressure (CPP)
Mean CPP (in minutes).
Time frame: During the maximum 5-day course of study intervention.
Total time spent with CPP <60 mmHg
Total time spent with CPP \<60 mmHg (in minutes).
Time frame: During the maximum 5-day course of study intervention.
Total number of events where CPP <60 mmHg for greater than 5 minutes
Total number of events where CPP \<60 mmHg (in minutes) for greater than 5 minutes.
Time frame: During the maximum 5-day course of study intervention.
Vasopressor dependency index (VDI)
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.
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Time frame: During the maximum 5-day course of study intervention.
Incidence of seizures
Incidence of seizures (as documented by EEG).
Time frame: During the maximum 5-day course of study intervention.
Incidence of cardiac arrhythmias
Incidence of cardiac arrhythmias (other than sinus tachycardia).
Time frame: During the maximum 5-day course of study intervention.
Mean heart rate
Mean heart rate (HR).
Time frame: During the maximum 5-day course of study intervention.
Incidence of post-traumatic stress disorder (PTSD) in outpatient setting
Incidence of PTSD at 6-month outpatient follow-up.
Time frame: Outpatient follow-up six months after intervention.
Glasgow Coma Outcome Scale extended (GOSE-TBI) scores
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.
Time frame: Outpatient follow-up six months after intervention.