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Updated: Sep 19, 2025

Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents

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Adverse Effects Associated With High-Dose Ketamine Infusions For Refractory Pain And Psychiatric Conditions.

Elika D Javaheri¹, Christopher Wie², Stephen Covington²

¹Mayo Clinic Alix School of Medicine, Phoenix, AZ, USA. javaheri.elika@mayo.edu.

Current Pain and Headache Reports

|June 19, 2025

Summary

High-dose ketamine (HDK) use is linked to psychiatric issues like agitation and anxiety, alongside physical effects such as nausea and transient liver damage. Careful monitoring in clinical settings is advised, as adverse events are often dose-dependent.

Keywords:

Adverse Effects Complex Regional Pain Syndrome Emergence Reactions Hepatotoxicity Ketamine Treatment Resistant Depression

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Last Updated: Sep 19, 2025

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Area of Science:

Anesthesiology
Pharmacology
Toxicology

Background:

Higher doses of ketamine are increasingly utilized for various medical conditions, including Complex Regional Pain Syndrome (CRPS).
Understanding the adverse effects (AEs) specifically associated with high-dose ketamine (HDK) is crucial for safe clinical practice.

Purpose of the Study:

To review and examine the common adverse effects explicitly associated with high doses of ketamine (HDK).

Main Methods:

Literature review of studies investigating adverse effects of high-dose ketamine.
Analysis of reported psychiatric and physical adverse events across different administration routes (oral, intravenous, intranasal).

Main Results:

HDK is frequently associated with psychiatric AEs, including agitation, anxiety, and sleep disturbances.
Emesis (nausea and vomiting) is a common AE, with increased prevalence at higher ketamine doses.
Hepatotoxicity and ketamine-induced uropathy are potential AEs, with hepatotoxicity being dose-dependent and typically transient.

Conclusions:

While HDK appears safe when administered and monitored appropriately in a hospital setting, clinicians must be aware of potential dose-dependent adverse effects.
Psychiatric symptoms, emesis, hepatotoxicity, and uropathy are key adverse events to consider with HDK therapy.