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Ketamine for Sedation in Severe Traumatic Brain Injury

Phase 4
Suspended
Conditions
Severe Traumatic Brain Injury
Intracranial Hypertension
Intracranial Hemorrhage, Hypertensive
Interventions
Other: Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam
Registration Number
NCT06429657
Lead Sponsor
Henry M. Jackson Foundation for the Advancement of Military Medicine
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.

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
50
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ketamine with propofolKetamine with propofolPropofol 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
SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepamStandard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepamStandard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam.
Primary Outcome Measures
NameTimeMethod
Mean ICPDuring the maximum 5-day course of study intervention.

Mean ICP

Number of ICP elevations greater than 22 mmHg for greater than 5 minutesDuring 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.

Secondary Outcome Measures
NameTimeMethod
Mean heart rateDuring the maximum 5-day course of study intervention.

Mean heart rate (HR).

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.

Total time spent with intracranial pressure (ICP) >22 mmHgDuring the maximum 5-day course of study intervention.

Total time spent with ICP \>22 mmHg (in minutes).

Total time spent with CPP <60 mmHgDuring the maximum 5-day course of study intervention.

Total time spent with CPP \<60 mmHg (in minutes).

Incidence of seizuresDuring the maximum 5-day course of study intervention.

Incidence of seizures (as documented by EEG).

Incidence of cardiac arrhythmiasDuring the maximum 5-day course of study intervention.

Incidence of cardiac arrhythmias (other than sinus tachycardia).

Incidence of post-traumatic stress disorder (PTSD) in outpatient settingOutpatient follow-up six months after intervention.

Incidence of PTSD at 6-month outpatient follow-up.

Mean Cerebral Perfusion Pressure (CPP)During the maximum 5-day course of study intervention.

Mean CPP (in minutes).

Total number of events where CPP <60 mmHg for greater than 5 minutesDuring the maximum 5-day course of study intervention.

Total number of events where CPP \<60 mmHg (in minutes) for greater than 5 minutes.

Glasgow Coma Outcome Scale extended (GOSE-TBI) scoresOutpatient 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.

Trial Locations

Locations (1)

Brooke Army Medical Center

🇺🇸

Fort Sam Houston, Texas, United States

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