Ketamine Protocol for In-Hospital Use

Purpose: Treatment of opioid-resistant pain and of opioid-induced neurotoxicity.

What is Ketamine: It is a “dissociative anesthetic” (the mind is ‘dissociated’ from the body and pain), meaning a patient ‘appears to remain awake’ but is actually unconscious and feels no pain when given full anesthetic doses.  With sub-anesthetic doses, pain/agitation are reduced without ‘loss of awareness/consciousness’.   It is particularly beneficial for neuropathic pain and opioid-resistant or difficult pain syndromes; and, as an adjuvant agent, can reduce the amount of narcotic required.
Physiological Effects to be expected (uncommon w/ sub-anesthetic doses):  tachycardia, increased secretions, diplopia, myoclonus, increased BP [occasionally hypotension].

Adverse Effects: increased salivation; hallucinations and vivid dreams when emerging from full anesthetic doses (but usually preventable if use a benzodiazepine prior to or while giving ketamine), but rare in pain management doses.  Avoid in patients with psychosis history.

Dosing Guidelines: Can be given po, subQ, IM, IV, intranasal.  The IV form is readily absorbed when given po/subling.  If given subling, give no other med or food/drink for 2 minutes following the ketamine.  Generally, ketamine is administered only for a few days [similar to steroid bursts] until new pain threshold established and pain controlled; then patient maintained on opiates again. SubQ route is preferred for patients in uncontrolled pain in-hospital (if inflammation occurs, give Dexamethasone 2mg subQ for treatment).  Once effective dose determined, establish continuous infusion and titrate every 24hrs.  If dose exceeds 700mg/24hrs w/o controlling pain, stop the ketamine.
Note: physician will write specific dosing for the ketamine, etc; it is a balancing act between the amount of ketamine and the amount of opioid.  The following is intended as a guide for staff and other physicians.

Continuous Infusion SubQ Protocol:
1. Obtain VS [BP, HR, RR, temp]; 1 hr after initial dose, then q4h x 24hrs and if stable, then prn.
2. Consider reducing opioid by 25-50% at initiation of ketamine, and then q6-12h by another 25-50%prn.
3. Mix IV concentrate in NS: 100mg in 100ml NS to give 1mg/ml.
4. Initiate subQ infusion to give ~100mg/24hr [4mg/hr].
5. If not effective after 1day, go to ~300mg/24hr. [12mg/hr]
6. After another 24hr, if not effective, go to ~500mg/24hr. [20mg/hr].
7. Continue rate at which pain control satisfactory and stop 3days after last increment.
8. If no pain control after reaching maximum 500mg/24hr for a full day, stop infusion.
9. Patient continues to use scheduled and breakthrough pain meds, keeping log of doses.
10. Ativan 0.5mg should be taken qhs as well, plus q 8h prn [if too “dreamy” feeling].

Oral dosing: [physician to write specific order and dose w/ titration]
Mix in fruit cordial to mask taste.
Test dose 25mg.
If no adverse reaction and/or pain reduced, continue 25mg qid and prn.
Max dose 200mg qid.
Give smaller dose more often if drowsiness occurs and doesn’t improve with reduction of opioid.

Sublingual dosing:
Use 100mg/ml concentrate.
Start with 25mg test dose; then follow oral dosing guidelines.



1. Fine PG. Ketamine: from anesthesia to palliative care. AAHPM Bulletin 2003.
2. Fitzgibbon EJ, Viola R. Parenteral ketamine as an analgesic adjuvant for severe pain: development and retrospective audit of a protocol for a palliative care unit. J Palliative Med 2005. 8;1:49-57.
3. Prommer E.  Ketamine: routes and techniques of administration.  AAHPM Annual Meeting, Austin, TX 2009.
4. Twycross R, Wilcock A. Hospice and palliative care formulary USA, 2nd Edition 2008. P.460.
5. Visser E, Schug SA.  The role of ketamine in pain management. Bioscience & Pharmacotherapy 2006.