Ketamine
Chemical
Phencyclidine derivative, dissociative anaesthetic
Use
- Induction GA
- Conscious sedation
- Analgesia
- 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
- NMDA Antagonism
- Voltage sensitive Ca2+ channel inhibition
- Muscarinic antagonist
- Facilitates descending inhibitory monoaminergic pathways → inhibits reuptake of CA → INDIRECT SYMPATHOMIMETIC
- 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