Is ketamine safe for use in patients with traumatic head injuries?

Ketamine Safety in Traumatic Head Injury

Ketamine is safe and recommended for use in traumatic brain injury patients, particularly those who are hemodynamically unstable, as it maintains cerebral perfusion pressure while providing adequate sedation without causing hypotension. 1, 2

Guideline-Based Recommendations

The Association of Anaesthetists explicitly recommends ketamine 1-2 mg/kg as the induction agent for hemodynamically unstable trauma patients with brain injury, stating that maintaining blood pressure outweighs any theoretical concerns about cerebral stimulation. 1 This represents a paradigm shift from historical contraindications that were based on inadequately controlled early studies. 3, 2

Key Clinical Context

• Historical concerns about ketamine increasing intracranial pressure (ICP) are of little practical significance and should not prevent its use in head injury patients. 3
• The American Society of Anesthesiologists specifically endorses ketamine for brain injury patients due to its unique hemodynamic benefits, including maintaining or increasing cerebral perfusion pressure through sympathomimetic effects. 3
• The FDA label does note that ketamine can increase cerebrospinal fluid pressure, requiring monitored settings with frequent neurologic assessments, but this does not constitute an absolute contraindication. 4

Critical Requirements for Safe Use

Ketamine must always be used with controlled mechanical ventilation and specific physiologic targets to ensure safety in TBI patients:

Mandatory Ventilation Parameters

• PaCO₂ must be maintained at 4.5-5.0 kPa (approximately 34-38 mmHg) with end-tidal CO₂ monitoring. 1, 2
• PaO₂ should be ≥13 kPa while avoiding hyperoxia. 1
• Brief periods of PaCO₂ 4.0-4.5 kPa are acceptable only if impending uncal herniation. 1

Blood Pressure Targets

• Maintain systolic BP >110 mmHg and mean arterial pressure (MAP) >90 mmHg throughout the peri-induction period. 1, 5
• Keep systolic BP <150 mmHg if within 6 hours of injury and immediate surgery is not planned. 1, 5
• Have vasoconstrictors (ephedrine or metaraminol) immediately available to treat any hypotension. 1

Co-Administration Requirements

• High-dose fentanyl (3-5 µg/kg) should be co-administered during rapid sequence intubation, with reduced doses in unstable patients. 1, 2
• Consider pretreatment with atropine or glycopyrrolate to attenuate excessive secretion production. 2

Evidence Supporting Safety

Recent high-quality research contradicts historical concerns:

• A 2023 multicenter retrospective analysis of 841 TBI patients found no difference in mortality (12.2% vs. 15.5%, P=0.391) or disability between ketamine-exposed and unexposed groups, despite ketamine being used in more severely injured patients. 6
• The same study found ketamine exposure was associated with significantly fewer instances of elevated ICP (56.3% vs. 82.3%, P=0.048). 6
• A 2022 study of 44 severe TBI patients with refractory ICP demonstrated ketamine boluses reduced ICP by a median of -3.5 mmHg (p<0.001) and increased CPP by 2 mmHg (p<0.001). 7
• A 2020 systematic review found no evidence of harm during ketamine use in acute brain injury patients, with only two small studies showing minimal ICP increases while two others showed decreased ICP. 8
• A 1997 study in mechanically ventilated TBI patients on propofol sedation found ketamine decreased ICP by 2-5 mmHg across all doses studied (1.5,3, and 5 mg/kg). 9

Important Caveats and Monitoring

Emergence Reactions

• Emergence reactions occur in 10-30% of adults, manifesting as floating sensations, vivid dreams, hallucinations, and delirium. 3
• Co-administration of midazolam can minimize these reactions. 3
• Minimize verbal, tactile, and visual stimulation during recovery while maintaining vital sign monitoring. 4

Seizure Risk

• Seizure activity was statistically more likely in ketamine-exposed TBI patients (3.1% vs. 1.0%, P=0.010) in one large multicenter study. 6
• Avoid ketamine in patients receiving theophylline or aminophylline, as it may lower the seizure threshold. 4

Cardiovascular Considerations

• In patients with sepsis or critical illness, ketamine's hemodynamic response may be blunted or reversed. 3
• The European Society of Cardiology recommends avoiding ketamine in patients with ischemic heart disease, cerebrovascular disease, or hypertension due to cardiovascular stimulant effects. 3
• Closely monitor vital signs when co-administering with sympathomimetics or vasopressin, as ketamine may enhance their effects. 4

Respiratory Monitoring

• Respiratory depression may occur with overdosage or rapid administration—maintain adequate oxygenation and ventilation. 4
• Closely monitor respiratory rate and pulse oximetry when co-administering with opioids, benzodiazepines, or other CNS depressants. 4

Practical Algorithm for Use

1. Confirm hemodynamic instability or need for rapid sequence intubation in TBI patient
2. Establish invasive arterial monitoring (or NIBP at 1-minute intervals if time does not allow)
3. Prepare vasoconstrictors (ephedrine/metaraminol) at bedside
4. Administer high-dose fentanyl (3-5 µg/kg, reduced in unstable patients)
5. Give ketamine 1-2 mg/kg IV over 30 seconds
6. Immediately secure airway with neuromuscular blockade (suxamethonium 1.5 mg/kg or rocuronium 1 mg/kg)
7. Initiate controlled ventilation targeting PaCO₂ 4.5-5.0 kPa and PaO₂ ≥13 kPa
8. Maintain BP targets (SBP >110 mmHg, MAP >90 mmHg) with vasoconstrictors as needed
9. Monitor ICP continuously if monitor in place, with frequent neurologic assessments

The evidence overwhelmingly supports ketamine as a safe and beneficial agent for TBI patients when used with appropriate ventilation control and hemodynamic monitoring.