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Created February 7, 2021, last updated about 3 years ago.
Collection: 130, Score: 994, Trend score: 0, Read count: 1194, Articles count: 4, Created: 2021-02-07 07:17:49 UTC. Updated: 2021-02-07 11:05:46 UTC.Notes
Ketamine is a dissociative anaesthetic & potent analgesic.
- "Dissociative anaesthesia" refers to dissociation of thalamocortical and limbic systems on the EEG.
A. Physiochemistry
- phenylcyclidine (PCP) derivative
- pKa 7.5, weak acid (like thiopentone 60% nonionised @ pH 7.4)
- highly lipid soluble (4x thio)
- ampoule: 200 mg in 2 mL
- acidic solution of i) ketamine hydrochloride with ii) benzethonium chloride (preservative - neurotoxic !)
- 2 optical isomers - S(+)d ketamine has i) more rapid emergence due to higher metab, ii) less emergence SEs, iii) less cardiac depression, iv) 3x analgesic potency.
B. Pharmacokinetics
- Dose - 1.5-2 mg/kg IV, 10 mg/kg IM
- oral premed: 6-7 mg/kg po (15-30 min onset)
- Rx: asthma 20 mcg/kg/min
- analgesia: 0.1-0.3 mg/kg/h (no dysphoria @ 0.1, sometimes pleasant dreams @ 0.2 mg/kg/h). -[HPH 400mg in 50mL]
- TIVA: 10-50 mcg/kg/min
- Absorption - IV, IM, oral or PR
- Distribution - 8 L/kg
- Protein binding - 25% (thiopentone 75%, propofol 98%)
- Onset IV: 45-60s, peak 60s; IM: 3-5 min; Offset 15-30 min
- Metabolism - alpha∆ 11 min, ß ∆ 2.5 h. Hepatic p450 to N-demethylation to norketamine, hydroxylated to hydroxynorketamine, conjugated to water sol glucuronide derivatives.
- Norketamine has 1/5 activity of ketamine (? post-op S/Es).
- Clearance - 18 mL/kg/min (prop 25, thio 4 mL/kg/min)
C. Pharmacodynamics
- Mech - non-competitive NMDA antagonism (PCP site on NR1 subunit); anti-muscarinic; anti-monaminergic; inhibits peripheral reuptake of catecholamines; S+ enantiomer has some mu receptor activity; inhibits NO synthesis; inh non-NMDA glutamate rec.
- CNS - analgesia, amnesia, dissociative anaesthetic (thalamocortical - limbic system); inc CBF, CMRO2, ICP & IOP.
- CVS - direct cardiac depressant, but inc SNS outflow - inc CO, HR, MAP. Variable Vc & Vd.
- Resp - unaltered response to CO2; bronchodilator; inc salivary secretions; airway reflexes intact.
- GIT- inc BSL
- SEs - PONV, emergence delerium, ++ secretions, uterine hypertonicity at > 1.5 mg/kg
- Interactions - halothane prolongs duration by delaying its redistribution and metabolism.
Ketamine produces a dissociative state (unconsciousness where in cataleptic state, disconnected from surroundings associated with functional and electrophysiological dissociation between thalamo-neocortical and limbic system)
- Characteristically : eye open, slow nystagmus, varying purposeful movement and hypertonus unrelated to stimuli
- Advantages: sympathetic stimulation with preservation of BP esp in hypovolaemic state, preservation of airway reflexes, bronchodilation and intense analgesia
- Disadvantages: can theoretically precipitate myocardial ischaemia (increasing both workload and O2 requirements) increases CBF, increases PVR, emergence delirium (also anaesthetic end-point unclear and uncontrolled movements).
Daniel Jolley
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Collected Articles
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Ketamine has been used for decades for a variety of indications. Beyond the historical benefits and effects of ketamine, newer developments have occurred worthy of an update. This review will discuss common uses and indications for ketamine in the perioperative setting, as well as highlight newer indications in recent years. ⋯ Ketamine is regaining popularity in the field of anesthesia and beyond. New studies provide insight on the many indications and use that anesthesia providers may encounter during their perioperative care of patients. Ongoing research is needed to further elucidate ketamine's effects on the management of psychiatric conditions and potential indications for ketamine metabolites.
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Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model. ⋯ A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available.
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Acta Anaesthesiol Scand · Oct 2020
Observational StudyKetamine for rapid sequence intubation in adult trauma patients: A retrospective observational study.
In the trauma population, ketamine is commonly used during rapid sequence induction. However, as ketamine has been associated with important side effects, this study sought to compare in-hospital mortality in trauma patients after induction with ketamine versus other induction agents. ⋯ We found no statistically significant difference in mortality among patients intubated in the initial phase post-trauma with the use of ketamine compared with other agents (propofol, etomidate, or midazolam).
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Anesthesia and analgesia · Jul 2019
Meta AnalysisKetamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Why?
Although often used to manage chronic pain acutely, the longer-term benefits of ketamine infusions remain uncertain. Despite this there has been significant growth in using ketamine infusions to treat chronic pain, rationalised by ketamine’s expected effect to reduce central sensitisation.
What?
This meta-analysis identified a small benefit for up to two weeks after a ketamine infusion, although little evidence of longer-term benefit. There appears to be a dose-response effect, suggesting greater efficacy with high-dose ketamine infusions.
The underlying problem...
Most research on ketamine infusions focuses on perioperative analgesia. Trials invetsigating ketamine infusions for chronic pain are universally small, lack standardisation and are often low quality.
This meta-analysis unfortunately does not add clarity to the question of whether ketamine infusions have long-term benefit in chronic pain syndromes. Clinicians will continue to need to judge indication on a case-by-case basis...
summary