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ketamine (Ketalar, special K)

Tradename: Ketalar. DEA-controlled substance: class 3. Indications: - general anesthesia, local anesthesia [8] - surgical & diagnostic procedures that do not require skeletal muscle relaxation - adjunctive agent for lower potency agents such as nitric oxide (NO) - anesthetic in combination with neuromuscular blocking agent for use in rapid sequence endotracheal intubation [6] - safe to use in children with increased intracranial pressure [7] - may be useful as a rescue agent for severely agitated patients presenting a danger that are difficult to sedate [10] - treatment of major depression - may be useful for treatment-resistant depression [11] - treatment of acute pain alone or in combination with opioid [12] - intranasal or nebulized ketamine may be useful for treating acute pain in the elderly [14] Contraindications: Caution: 1) for use by or under the directed of physician experienced in administering general anesthetics 2) resuscitation equipment should be available prior to administration Dosage: 1) 1-4.5 mg/kg, usually 1-2 mg/kg IV given at 0.5 mg/kg/min 2) 6.5-13 mg/kg IM 3) for maintenance, use induction dose as needed 4) pain adjunct: - 5-10 mg IM titrated to effect - subdissociative-dose IV ketamine (0.3 mg/kg) [9] - intranasal or nebulized for treating acute pain in the elderly [14] * Injection: 10 mg/mL (50 mL); 50 mg/mL (10 mL); 100 mg/mL (5 mL). * Nebulizer 0.75-1.5 mg/kg [15] Pharmacokinetics: 1) following a single dose a) unconsciousness lasts 10-15 minutes b) analgesia lasts 30-40 minutes c) amnesia may persist for 1-2 hours 2) hepatically metabolized 3) anesthetic action is terminated by redistribution from the CNS & hepatic conversion to a lower potency metabolite 4) terminal 1/2life is 10-15 minutes Adverse effects: 1) common (> 10%) - emergent psychological reactions (less with IM administration) - vivid dreams - visual hallucinations - hypertension - increased cardiac output - tachycardia - tonic-clonic movements - tremors - vocalization - dissociative symptoms [13] 2) less common (1-10%) - bradycardia, nausea/vomiting, hypotension, respiratory depression, anorexia, diplopia, pain at site of injection, rash, nystagmus 3) uncommon (< 1%) - laryngospasm, arrhythmias, myocardial depression, increase in cerebral blood, increased metabolic rate, increased intracranial pressure, increased intraocular pressure, increased skeletal muscle tone, fasciculations, hypersalivation, cough reflex may be depressed Drug interactions: 1) non-depolarizing muscle relaxants in combination prolong respiratory depression 2) hypnotic effect of thiopental may be antagonized 3) halothane in combination may result arrhythmia 4) theophylline in combination my result in seizures Laboratory: 1) specimen: plasma (heparin, EDTA) 2) methods: GLC Mechanism of action: 1) dissociative anesthetic with abuse potential - street name special K 2) rapidly acting general anesthetic with analgesic properties 3) NMDA receptor antagonist [5] 4) lowers intracranial pressure & increases cerebral perfusion in intubated children with increased intracranial pressure [7] Notes: - chirally pure enantiomer esketamine is an investigational intranasal ketamine for treatment of refractory depression

Related

NMDA receptor

Specific

esketamine (Spravato)

General

dissociative anesthetic NMDA receptor antagonist

Properties

INHIBITS: NMDA receptor MISC-INFO: elimination route LIVER 1/2life 2-4 HOURS therapeutic-range 0.5-6.5 UG/ML protein-binding 20-50% pregnancy-category ? safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. Clinical Guide to Laboratory Tests, 3rd edition, NW Tietz ed, WB Saunders, Philadelphia, 1995
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  5. Prescriber's Letter 10(11) 2003; detail doceument 191102
  6. Jabre P et al Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: A multicentre randomised controlled trial. Lancet 2009 Jul 1; PMID: 19573904 http://dx.doi.org/10.1016/S0140-6736(09)60949-1 - Wenzel V and Lindner KH. Best pharmacological practice in prehospital intubation. Lancet 2009 Jul 1; PMID: 19573905 http://dx.doi.org/10.1016/S0140-6736(09)61071-0
  7. Bar-Joseph G et al. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. J Neurosurg Pediatr 2009 Jul; 4:40. PMID: 19569909
  8. Deprecated Reference
  9. Motov S et al. Intravenous subdissociative-dose ketamine versus morphine for analgesia in the emergency department: A randomized controlled trial. Ann Emerg Med 2015 Mar 26 PMID: 25817884
  10. Isbister GK. Ketamine as rescue treatment for difficult-to-sedate severe acute behavioral disturbance in the emergency department. Ann Emerg Med 2016 Feb 18 PMID: 26899459 http://www.annemergmed.com/article/S0196-0644%2815%2901562-0/abstract
  11. Sanacora G, Frye MA, McDonald W et al A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017 Apr 1;74(4):399-405. Review. PMID: 28249076 - Abbasi J Ketamine Minus the Trip: New Hope for Treatment-Resistant Depression. JAMA. Published online November 8, 2017 PMID: 29117311 https://jamanetwork.com/journals/jama/fullarticle/2662752
  12. Brooks M First-Ever Ketamine Guidelines for Pain Management Released. Medscape - Jun 15, 2018. https://www.medscape.com/viewarticle/898134
  13. Anand A et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression. N Engl J Med 2023 May 24; [e-pub]. PMID: 37224232 https://www.nejm.org/doi/10.1056/NEJMoa2302399 - Freedman R. Ketamine and ECT in depression - Risks and rewards. N Engl J Med 2023 May 24; [e-pub] PMID: 37224235 https://www.nejm.org/doi/10.1056/NEJMe2305130
  14. Almodibeg B, Forget P Challenges of acute pain management in older patients. Age Ageing. 2024 Apr 1;53(4):afae061. PMID: 38557666 https://academic.oup.com/ageing/article/53/4/afae061/7638303
  15. Dove D, Fassassi C, Davis A et al Comparison of Nebulized Ketamine at Three Different Dosing Regimens for Treating Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind Clinical Trial. Ann Emerg Med. 2021 Dec;78(6):779-787. PMID: 34226073 Clinical Trial.