Ketamine analgesia - mechanisms and current practice
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This document summarizes the current state of ketamine analgesia. It discusses ketamine's use in clinical reports for various pain conditions as well as its basic science mechanisms of action. While ketamine shows promise as an analgesic, particularly as an adjuvant to opioids, questions remain around its long-term effects, optimal dosing, administration methods, and side effects like potential urinary tract dysfunction and neurotoxicity. After 50 years of use and study, ketamine continues to be a promising analgesic but more research is still needed to answer outstanding questions.
Ketamine analgesia - mechanisms and current practice
- 1. Ketamine analgesia mechanisms and current practice • Current practice • Scientific base • Outstanding issues
- 2. • Neuropathic pain after spinal cord injury – Kvarnström et al 2004 • Opioid sparing in ICU mechanical ventilation – Buchheit 2017 • Multiple modes of administration – Persson 2010 • “Burst administration” – Mercadante 2009 • Intermittent infusions for diverse indications – Bell 2009 • Morphine sparing in renal colic (RCT) – Abbasi 2017 • Prevention of fentanyl-induced hyperalgesia and Mo tolerance – Laulin 2002 • Attenuation of acute postoperative hyperalgesia – Stubhaug 1997 • Oral ketamine for chronic pain 5 year FU– Marchetti 2016 • Analgesic effects of topical ketamine – Kopsky 2016 • Emergency department use promising – Pourmand 2017 • Status astmaticus – Goyal 2017 • Status epilepticus – Fang 2016 Ketamine analgesia CLINICAL REPORTS
- 3. Ketamine analgesia BASIC SCIENCE • NMDAR subunits – Paoletti • Enantiomers - Peltoniemi 2016 • Metabolism – Gao 2016 • Brain connectivity – Niesters 2012 • Antiinflammatory effects – Gao 2016 • Ketamine esters – Jose 2013 • Pharmacological implications • PK/PD diff, clin significance unclear • CYP2B6, CYP3A4, CYP2C9 • Low-dose effect on pain modulation • Immunomodulatory > suppressiv • Better effect/side effect ratio?
- 4. Ketamine analgesia CLINICAL SCIENCE Established role in short-term treatment Low quality evidence, inconclusive Urolog tox, hepatotox and cognitive deficits Promising, but damage to developing brain? Morphine sparing Ket No effect at 3 & 6 months PCA has no advantage, other modes may Solid role Adjunctive therapy to opioids Potentially serious, details unclear Effective in 12 week FU Comprehensive PK/PD presentation Potent antihyperalgesic effect • Chronic non-cancer pain - Bell 2009 Rev • Opioid adjuvant, ca pain – Bell 2017 Rev • Ketamine toxicity – Bell 2012 Rev • Neuroprotection neurologic injury – Bell 2017 • Ket + Mo vs Mo, acute pain - Ding 2014 Rev • Prevention of PPSP - McNicol 2014 Rev • Ket + opioids - Subramaniam 2004 Rev • Prehospital analgesia - Bredmose 2008 Rev • Hospice analgesia - Legge 2008 Rev • Urinary tract dysfunction - Myers 2016 • CRPS – Sigtermans 2009 • PK/PD – Peltoniemi 2016 • Antihyperalgesaia vs analgesia – Richebé 2005
- 5. Ketamine analgesia OUTSTANDING ISSUES Acute/postop pain, dosing Long-term benefit chronic pain? Analgesia/antihyperalgesia? Dose response anti-hyperalgesic effect Urinary tract dysfunction Neuroapoptosis Enantiomeric merit? Administration technology
- 6. ketamine for analgesia after 50 years…. STILL PROMISING BUT MORE QUESTIONS THAN ANSWERS!