Ketamine analgesia CLINICAL REPORTS 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 SCIENCE 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 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

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