Ketamine: Use in Anesthesia

Marland, Susan; Ellerton, John; Andolfatto, Gary; Strapazzon, Giacomo; Thomassen, Øyvind; Brandner, Brigitta; Weatherall, Andrew; Paal, Peter

doi:10.1111/cns.12072

Cited by 114 publications

(72 citation statements)

References 154 publications

(171 reference statements)

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“…This contrasts with the typical dose of ketamine used in anesthesia of up to 2 mg/kg 17 . A robust antidepressant effect of ketamine was achieved within four hours post-infusion compared with depressed subjects who received placebo 4 .…”

Section: Introductionmentioning

confidence: 85%

Mechanisms of ketamine action as an antidepressant

2018

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Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions in treatment-resistant patients. Although this finding has been met with enthusiasm, ketamine’s widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the unique antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine’s antidepressant actions but lack its undesirable effects. Here, we review hypotheses for the mechanism of action of ketamine as an antidepressant, including direct synaptic or extra-synaptic (GluN2B-selective) NMDAR inhibition, selective inhibition of NMDARs localized on GABAergic interneurons, and the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) activation. We also discuss links between ketamine’s antidepressant actions and downstream mechanisms regulating synaptic plasticity, including brain-derived neurotrophic factor (BDNF), eukaryotic elongation factor 2 (eEF2), mechanistic target of rapamycin (mTOR), and glycogen synthase kinase-3 (GSK-3). Mechanisms that do not involve direct inhibition of the NMDAR, including a role for ketamine’s (R)-ketamine enantiomer and hydroxynorketamine (HNK) metabolites, specifically (2R,6R)-HNK, are also discussed. Proposed mechanisms of ketamine’s action are not mutually exclusive and may act in a complementary fashion to exert the acute changes in synaptic plasticity, leading to sustained strengthening of excitatory synapses, which are necessary for antidepressant behavioral actions. Understanding the molecular mechanisms underpinning ketamine’s antidepressant actions will be invaluable for the identification of targets, which will drive the development of novel, effective, next-generation pharmacotherapies for the treatment of depression.

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Section: Introductionmentioning

confidence: 85%

Mechanisms of ketamine action as an antidepressant

2018

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“…only in 4 cases for analgesia) can be explained by local laws and environmental and logistical considerations. 18,19 Fluid therapy was used especially if ground rescue could be supported by air rescue (i.e. more rapid evacuation), but fluids should be warm due to the high risk of accidental hypothermia.…”

Section: Tablementioning

confidence: 99%

Epidemiological and medical aspects of canyoning rescue operations

Soteras

Subirats

Strapazzon

2015

Injury

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“…If analgesia is inadequate, racemic ketamine is added (20-40 mg boluses every 2 min) expecting that 80 mg (approximately 1 mg/kg) will be given. Half the dose is required if S-ketamine is used (Marland et al, 2013). The aim is to maintain verbal contact throughout.…”

Section: Scenariomentioning

confidence: 99%

“…The effects are complex but caution is urged particularly when additional doses are given. The sympathomimetic effects of ketamine on an irritable hypothermic heart have the potential for serious side effects (Marland et al, 2013).…”

Section: Do Patient Factors Influence Which Analgesia Can Be Used?mentioning

confidence: 99%

Managing Moderate and Severe Pain in Mountain Rescue

Ellerton¹,

Milani

Blancher

et al. 2014

High Altitude Medicine & Biology

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Many health care providers fail to recognize, assess, and treat pain adequately. Assessment scales and treatment protocols should be implemented in mountain rescue services to encourage better management of pain. Specific training in assessing and managing pain is essential for all mountain rescuers. Persons administrating analgesics should receive appropriate detailed training. There is no ideal analgesic that will accomplish all that is expected in every situation. A range of drugs and delivery methods will be needed. Thus, an 'analgesic module' reflecting its users and the environment should be developed. The number of drugs carried should be reduced to a minimum by careful selection and, where possible, utilizing drugs with multiple delivery options. A strong opioid is recommended as the core drug for managing moderate or severe pain; a multimodal approach may provide additional benefits.

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Ketamine: Use in Anesthesia

Cited by 114 publications

References 154 publications

Mechanisms of ketamine action as an antidepressant

Mechanisms of ketamine action as an antidepressant

Epidemiological and medical aspects of canyoning rescue operations

Managing Moderate and Severe Pain in Mountain Rescue

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