Evaluating Low-Dose Ketamine for Chronic Pain Management

Cleveland Clinic has launched a standardized low-dose ketamine protocol as an opioid-sparing option for patients with chronic refractory pain.

Institutional experience suggests it can reduce long-term opioid exposure while preserving symptom control, though the data come from program-level reports rather than randomized trials.

The protocol is clinically relevant because many patients remain opioid-dependent despite limited benefit and rising harms; alternative, nonopioid strategies are needed to shift care toward safer long-term management.

It targets patients who have not responded to conventional regimens and who face ongoing opioid-related harms, contrasting with typical acute, opioid-centric pathways that prioritize short-term analgesia over tapering. The operational change is toward structured, nonopioid strategies delivered under monitored infusion conditions to pursue meaningful opioid reduction while maintaining clinical stability.

Dose guidance centers on a planned five-day infusion regimen delivered as continuous or semi-continuous infusions over five consecutive days, with typical starting rates commonly reported at 0.1–0.3 mg/kg/hr and pragmatic titration to effect or tolerability. Titration favors small, incremental increases—usually in predefined steps every several hours—with pauses or reductions for hemodynamic or neuropsychiatric signals. Pre-infusion prerequisites include comprehensive medication reconciliation, baseline vitals, review of cardiac history and psychotropic co-medications, and explicit documentation of treatment goals.

Safety monitoring requires continuous or frequent vital-sign checks during infusion, cardiac and respiratory observation when indicated, and serial mental-status and psychiatric assessments to detect psychomimetic effects early. Provide antiemetic prophylaxis and hemodynamic management plans, with procedures for brief rate reductions or vasoactive support if needed; maintain post-infusion observation to confirm return to baseline before discharge. Define clear exclusion criteria, escalation pathways for severe adverse events, and arrange follow-up contact to assess delayed effects.

Program-level outcomes from Cleveland Clinic suggest clinically meaningful opioid reductions and acceptable tolerability: some patients decreased opioid doses and many reported symptom improvement. Common adverse events were generally mild and transient (dizziness, nausea, brief perceptual changes). These observations represent institutional program data rather than randomized-trial evidence.

Key Takeaways:

• Cleveland Clinic’s standardized ketamine protocol operationalizes a five-day low-dose infusion approach to prioritize opioid reduction in chronic refractory pain.
• Patients with chronic refractory pain on prolonged opioids who have not achieved symptom control with standard measures are the intended group.
• Implementation will require structured monitoring, comprehensive medication reconciliation, referral to infusion-capable pain services, and explicit post-infusion follow-up.