Is ketamine (Ketamine) safe for use in patients with Traumatic Brain Injury (TBI)?

Ketamine is Safe and Effective for Use in Traumatic Brain Injury Patients

Ketamine (1-2 mg/kg for induction) is explicitly recommended for hemodynamically unstable TBI patients and is safe when used with controlled ventilation and adequate sedation. 1

Guideline-Based Recommendations for Ketamine in TBI

Induction and Intubation

• Ketamine 1-2 mg/kg is specifically recommended as the induction agent of choice for hemodynamically unstable TBI patients (e.g., polytrauma with hemorrhagic shock). 1
• High-dose fentanyl (3-5 µg/kg) should be co-administered with ketamine during rapid sequence intubation, though doses must be reduced in unstable patients. 1
• The primary concern during induction is maintaining adequate mean arterial pressure—any theoretical concerns about cerebral stimulation from ketamine are outweighed by the critical need to prevent hypotension. 1

Blood Pressure Targets During Ketamine Use

• Maintain systolic blood pressure >110 mmHg and mean arterial pressure >90 mmHg throughout the peri-induction period. 1
• Have vasoconstrictors (ephedrine or metaraminol) immediately available to treat any hypotension that occurs. 1
• Invasive arterial blood pressure monitoring is strongly preferred; if unavailable, use non-invasive blood pressure measurement at 1-minute intervals. 1

Ventilation Requirements

• Ketamine must be used in conjunction with controlled mechanical ventilation and end-tidal CO2 monitoring. 1
• Target PaCO2 of 4.5-5.0 kPa (approximately 34-38 mmHg) to avoid both hypocapnia-induced cerebral vasoconstriction and hypercapnia-induced ICP elevation. 1
• Maintain PaO2 ≥13 kPa (approximately 98 mmHg) to ensure adequate cerebral oxygenation. 1

Important Caveats and Management Considerations

Airway Secretions

• Both ketamine and pyridostigmine (if used) can increase upper airway secretions, potentially causing severe dyspnea. 1
• Pretreat with atropine or glycopyrrolate to attenuate excessive secretion production. 1
• The bronchodilatory effects of ketamine may be beneficial in patients with asthma or chronic obstructive pulmonary disease. 1

FDA Precautions to Consider

• The FDA label carries a precaution about increased cerebrospinal fluid pressure, recommending monitored settings with frequent neurologic assessments for patients with elevated intracranial pressure. 2
• However, this precaution is based on outdated evidence and is contradicted by current clinical guidelines and recent research. 1, 3, 4
• Monitor liver function tests if using ketamine as part of a recurrent dosing treatment plan, as hepatobiliary dysfunction can occur with repeated use. 2

Drug Interactions

• Avoid concomitant use with theophylline or aminophylline, as this combination may lower the seizure threshold. 2
• Use caution when combining with sympathomimetics or vasopressin, as ketamine may enhance their effects—closely monitor vital signs and adjust doses accordingly. 2
• When used with benzodiazepines, opioids, or other CNS depressants, monitor closely for profound sedation or respiratory depression. 2

Supporting Evidence from Recent Research

Intracranial Pressure Effects

• A 2022 retrospective study of 44 severe TBI patients found ketamine boluses were associated with a median ICP reduction of -3.5 mmHg and an increase in cerebral perfusion pressure of +2 mmHg. 3
• A 2023 multicenter analysis of 841 TBI patients found ketamine-exposed subjects had significantly fewer instances of elevated ICP compared to unexposed subjects (56.3% vs. 82.3%). 5
• A 2020 systematic review found no evidence of harm during ketamine use in acute brain injury patients, with only two studies showing small ICP increases while two others showed decreased ICP. 4

Safety Profile

• The 2023 multicenter study found no difference in mortality (12.2% vs. 15.5%) or disability measures between ketamine-exposed and unexposed TBI patients, despite ketamine being used in more severely injured subjects. 5
• Ketamine exposure was associated with lower concentrations of TBI protein biomarkers, suggesting potential neuroprotective effects. 5

Ongoing Research

• The BIKe trial (2025), a prospective randomized controlled trial, is currently investigating ketamine as an adjunct sedative in severe TBI patients to definitively establish safety and efficacy. 6

Clinical Algorithm for Ketamine Use in TBI

1. Assess hemodynamic stability: If systolic BP <110 mmHg or patient is polytrauma with hemorrhagic shock, ketamine is the preferred induction agent. 1, 7

2. Prepare adjunct medications: Have fentanyl (3-5 µg/kg, reduced if unstable), atropine/glycopyrrolate for secretions, and vasopressors immediately available. 1

3. Establish monitoring: Place arterial line if time permits; otherwise use NIBP at 1-minute intervals. Ensure end-tidal CO2 monitoring is functional. 1

4. Administer ketamine: Give 1-2 mg/kg IV for induction, titrating to lower end of range if hemodynamically unstable. 1

5. Maintain physiologic targets: Keep systolic BP >110 mmHg, MAP >90 mmHg, PaCO2 4.5-5.0 kPa, and PaO2 ≥13 kPa. 1

6. Ongoing sedation: Ketamine infusions (1 mg/kg/h) can be used for continuous sedation in mechanically ventilated TBI patients. 6