Ketamine

Overview: 

 

Background

Ketamine, a phencyclidine analog, is a dissociative anesthetic agent that has been used as a general anesthetic since the 1960s.  Due to its very potent analgesic and anti-hyperalgesic properties, ketamine is used increasingly in subanesthetic doses in the treatment of chronic and acute pain.

Mechanism of Action

  • Ketamine's analgesic properties are predominantly due to the reversible antagonism of the N-methyl-D-aspartate (NMDA) receptor.
  • Effects on other receptors including μ-opioid receptors, muscarinic receptors, monoaminergic receptors, γ-aminobutyric acid receptors have been described and contribute to ketamine’s analgesic effects.
  • Ketamine has shown to prevent and to reverse central sensitization and to enhance descending inhibitory pain pathways. These effects address directly pathologic mechanisms underlying hyperalgesia and chronic pain. As a consequence, ketamine is known to be effective in the treatment of chronic pain and to be a preventive analgesic: ketamine has shown to reduce the risk of developing chronic pain after surgery when used perioperatively.
Clinical Use: 

 

Indications

  • Treatment of otherwise challenging to control acute pain
  • Analgesia for painful procedures such as dressing changes
  • Preventive analgesia during surgery, aiming at reducing pain and opioid requirements after surgery
  • Acute pain management in patients with very high opioid requirements, known opioid tolerance or opioid use disorder
  • Chronic pain management
  • Depression

 

Clinical Recommendations

Inpatients at UCSF can be treated with IV ketamine under the management of a qualified pain service (Acute Pain Service, Inpatient Chronic Pain Service, Inpatient Palliative Care Service.) Bolus administration of ketamine is associated with an increased incidence of unpleasant psychotropic side effects. It is preferable to administer ketamine as a continuous low-dose infusion.

 

Dosing

For inpatients in pain management, ketamine is administered as a continuous infusion with a dose range of 1-5 mcg/kg/min. Ketamine infusions can be administered for days to weeks.

For outpatients, ketamine is offered at UCSF for the treatment of mixed neuropathic pain conditions. Ketamine is administered in these patients as infusions with the aim to adminster approximately 80mg of ketamine infused in a 2-hour period. This regimen has demonstrated to result in longer lasting pain control.

Special Considerations: 

 

Side Effects

  • Tachycardia 
  • Hypertension
  • Nausea and vomiting
  • Dizziness, drowsiness
  • Diplopia
  • Open and closed eye visuals
  • Psychotropic side effects such as 
    • Unpleasant dreams
    • Dysphoria
    • Confusion
    • Delirium 
    • Hallucinations 

 

Contraindications

  • Severe hepatic dysfunction (eg, cirrhosis)
  • High-risk coronary artery disease
  • Poorly controlled psychiatric conditions involving psychosis, such as schizophrenia
  • Pregnancy
References: 

Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466.

Cohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):521-546

Orhurhu, Vwaire MD, MPH*; Orhurhu, Mariam Salisu MD, MPH†; Bhatia, Anuj MD, FRCPC‡; Cohen, Steven P. MD§,‖ Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials, Anesthesia & Analgesia: July 2019 - Volume 129 - Issue 1 - p 241-254

Author: 
Matthias Behrends