Ketamine

Chemical

Phencyclidine derivative, dissociative anaesthetic

Use

  1. Induction GA
  2. Conscious sedation
  3. Analgesia
  4. Severe asthma

Presentation

2mL vial → 200mg in 2mL, clear colourless solution

  • pKa 7.5 → 40% ionised at pH 7.4
  • H2O soluble → EXTREMELY LIPID SOLUBLE

ISOMERISM solution contains 50:50

  • Ketamine contains an asymmetrical carbon atom with 2 optical isomers (enantiomers)

S (+)

  • 3 x potent
  • Intense analgesia/anesthesia
  • Lower emergence reactions
  • More rapid metabolism/recovery
  • Less CVS stimulation

R (-) = more bronchodilation & psych SE

Dose

ANALGESIA: 0.1 – 0.2mg IV bolus → then 0.1 – 0.3mg/kg/hr thereafter

SEDATION: 0.3 – 0.5mg IV

GA: 1 – 2mg/kg IV

Route

IV/IM/PO/PR

↓

But poor OBA 16% due to high 1st pass metabolism

Onset

30 – 60sec IV → 3 – 8mins IM

DoA

Return of consciousness

10 – 20mins

MoA

  1. NMDA Antagonism
  2. Voltage sensitive Ca2+ channel inhibition
  3. Muscarinic antagonist
  4. Facilitates descending inhibitory monoaminergic pathways → inhibits reuptake of CA → INDIRECT SYMPATHOMIMETIC
  5. Weak opioid receptor agonism

PD

CNS

  • Dissociative anaesthesia with slow nystagmic gaze
    • Dissociates thalamus (relays sensory info from RAS to C. Cortex) from Limbic Cortex (awareness & sensation)
  • Amnesia → anterograde
  • Analgesia
  • Emergence delirium → visual, auditory, illusion & delirium
  • Cerebral protection → ↑CMRO2 & ↑CBF

(Directly dilates cerebral arteries)

RESP

  • ↑airway secretions → anticholinergic
  • Preserves laryngeal reflexes
  • Bronchodilation → ↑symp & Ca2+ channel inhibition
  • ↑PAP → ↑symp NS

CVS

  • ↑MAP, PAP, CVP, HR, CO, myocardial O2 requirements
    • Actually a Direct – ve Inotrope
    • But with ↑symp NS & adequate catecholamine stores, therefore CVS stimulating effects predominate

NB: can be unmasked in ICU patients with ↓catecholamine stores

GI

  • Salivation = antimuscarinic
  • ↑BSL = ↑symp

PK

A

Lipid soluble → absorbed, but poor poor OBA 16%

Due to high 1st pass metabolism

D

  • Large → 5L/kg
  • PPB small 12%
  • Rapidly crosses placenta
  • *HIGH LIPID SOLUBILITY *
  • Peak plasma 1 min post IV

↓

Rapidly distributed to VRG

Extreme lipid solubility & ↑CBF = rapid crosses BBB & ↑brain [   ]

↓

Subsequently redistributed from brain to less well perfused tissues

M

High hepatic ER

  • Clearance 18mL/kg/min
  • ∆HBF will alter clearance
  • DE-METHYLATION by CYP450 to NORKETAMINE (25% potency)

↓

HYDROXYLATION & CONJUGATION to inactive & glucuronide metabolites

E

H2O soluble metabolites excreted by kidney

<5% unchanged

Faecal excretion <5% dose

Adverse Effects

Tolerance (enzyme induction

IHD/HTN/CCF = Increases myocardial work

Increases ICP, CBF and CMRO2

Pregnancy = reduces uterine BF

Prolongs SUX activity

Unmasks myocardial depression when given w sympatholutic

Enhances NDMR block