What are the differences between intravenous (IV), intranasal, and buccal routes of administration for ketamine?

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Last updated: April 10, 2025View editorial policy

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From the Guidelines

Ketamine administration via intravenous (IV) route is recommended for its rapid onset and high bioavailability, making it ideal for emergency situations requiring immediate sedation or analgesia. When considering alternative routes, intranasal and buccal administration are options, but they have distinct advantages and considerations. Intranasal ketamine offers a moderate onset and good bioavailability, making it useful in pediatric settings or when IV access is challenging 1.

Comparison of Routes

  • IV ketamine: rapid onset (1 minute) and short duration of effect (10-15 minutes), with high bioavailability, but requires monitoring for respiratory depression and emergence reactions 1.
  • Intranasal ketamine: moderate onset (10-15 minutes) and good bioavailability, useful in pediatric settings or when IV access is challenging, but may cause local irritation.
  • Buccal ketamine: slower onset (15-30 minutes) and lower bioavailability, convenient for outpatient use, but may cause local irritation and has fewer systemic side effects.

Clinical Considerations

Ketamine produces a dose-dependent increase in heart rate, blood pressure, and cardiac output, mediated through stimulation of the sympathetic nervous system, making its use potentially dangerous in patients with ischemic heart disease, cerebrovascular disease, or hypertension 1. Emergence reaction, manifested by floating sensations, vivid dreams, hallucinations, and delirium, has been reported in 10%–30% of adults, but the use of midazolam in combination with ketamine is reported to minimize this reaction 1.

Route Selection

Route selection should consider clinical urgency, patient factors, and setting, with IV administration being the most suitable for emergency situations, and non-invasive routes being more convenient for outpatient use. Ketamine works by antagonizing NMDA receptors, producing dissociative anesthesia and analgesia, with additional effects on opioid receptors contributing to its pain-relieving properties.

From the Research

Administration Routes of Ketamine

  • Intravenous (IV) ketamine is more bioavailable than intranasal ketamine, and both are effective for acute depressive episodes 2
  • Intravenous ketamine is advantageous for post-operative analgesia and is associated with a reduction in total opioid requirements 2
  • Intranasal ketamine has been approved for use in treatment-resistant depression (TRD) in conjunction with an oral antidepressant in the United States and Europe 3
  • Nonparenteral forms of ketamine, such as intranasal formulations, have been used for acute pain management, but larger studies are needed to evaluate their effectiveness 4

Efficacy and Safety of Ketamine Administration

  • A single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD 5
  • Subanesthetic intravenous ketamine infusion is a safe and effective acute pain management modality for moderate to severely painful surgical procedures 6
  • Intravenous ketamine infusions on the medical-surgical ward are safe and cost-effective when an established acute pain service protocol is followed 6

Comparison of Administration Routes

  • There is limited research directly comparing the efficacy and safety of IV, intranasal, and buccal ketamine administration
  • However, studies suggest that IV ketamine may be more effective for acute pain management, while intranasal ketamine may be more convenient and easier to administer 2, 4
  • Buccal ketamine has not been extensively studied, and more research is needed to determine its efficacy and safety compared to other administration routes

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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