· PC
· PK
· PD
· Logistics
|
|
Propofol (PPF) |
Ketamine (KET) |
|
Enantiomers |
Non-racemic |
S-ketamine (available): -↑potency 2x -↓Neg inotropy -↓Psychotomimesis R-ketamine: -Bronchodilation |
|
Additives |
Soybean oil 100mg/mL (dissolve) Glycerol 22.5mg/mL (tonicity) Egg lecithin 12mg/mL Disodium edetate (antibacterial) NaOH (pH adjust)
Egg + oil -> risk of bacterial contamination |
Benzethonium chloride 1 in 10,000 (antibacterial) |
|
Pain on IV injection |
Yes (TRPA1 activation?) |
No |
|
|
Propofol |
Ketamine |
|
Distribution |
|
|
|
-VD |
4L/kg |
3L/kg |
|
-%Plasma protein binding |
98% |
25% (aids fast onset) |
|
-Lipid solubility |
High |
Highest (faster onset) |
|
-% unionized at pH 7.4 |
>99% |
?>99% |
|
-t1/2ke0 |
2.6 mins |
0.5 mins (faster onset) |
|
-t1/2α |
10 mins |
2.7mins (faster offset after bolus or short infusion) |
|
Metabolism |
|
|
|
-Site |
Liver and other ? kidney ? skin |
Liver |
|
-System |
Phase 1: 3A4, 2B6, 2C9, -Oxidation Phase 2: -Glucuronidation -Sulfation |
Phase 1: 3A4, 2B6 -N-demethylation |
|
-Clearance |
30-60mL/kg/min |
17mL/kg/min (slower, risk of accumulation) |
|
-Metabolites |
Nil active |
Norketamine 30% as active (effect prolonged, less predictable) |
|
-Liver failure |
Safe |
↑LFTs |
|
Excretion |
|
|
|
-Route |
Metabolites 100% renal PPF 0.3% renal
|
Metabolites 90% urine |
|
-t1/2β |
5-12 hours |
2 hours |
|
-Renal failure |
No significant effect |
Norketamine accumulation |
|
Time course |
|
|
|
-Onset |
IV 30-60 seconds No other route |
IV 30 seconds IM 1-5mins PO 15-30mins |
|
-Duration |
Bolus: 5-10 mins (dependent upon size) CSHT 10mins at 1 hour, 45 minutes at 8 hours |
Bolus: 30-60 mins (dependent upon size) CSHT profile similar to that of propofol |
|
|
Propofol |
Ketamine |
|
Mechanism |
|
|
|
-Major target |
GABA-A positive allosteric modulator ↑gCl-, prevent depolarisation |
Non-competitive NMDA antagonist (PCP site) ↓ICF [Ca2+] |
|
-Minor targets |
Agonist: glycine receptor Antagonist: NMDA, AMPA, 5-HT (i.e. cleaner) |
Agonist: 2PK, 5-HT3, mu opioid Antagonist: VDNaC, L-Ca2+, nnAChR, other opioid Monoamine reuptake (i.e. dirtier) |
|
CNS |
|
|
|
-Amnesia |
Cp50 1-2mcg/mL |
Yes |
|
-Hypnosis |
Cp50 2-3mcg/mL |
Yes |
|
-Immobility |
Cp50 15mcg/mL Standard deviation 5mcg/mL i.e. unreliable alone |
Yes |
|
-Dissociation |
No |
Yes (thalamo-cortical) Eyes open, nystagmus |
|
-Psych effects |
Rare |
Delirium, hallucination, nightmares |
|
-Analgesia |
No |
Yes (major advantage) |
|
-Anti-hyperalgaesia |
No |
Acute: yes (↓excitability -> ↓ wind-up) Chronic: yes (↓long term potentiation, ↓hyperalgesia, ↓allodynia, ↓phantom pain, ↓chronic pain) |
|
-Anti-emesis |
Yes (5-HT3 antagonist) |
Pro-emetic (5-HT3 agonist) |
|
-Anti-epileptic |
Myoclonus at induction (10%?) ↓seizures |
↓seizures |
|
-EEG signature |
↓frequency, ↓amplitude ∝ depth |
Variable EEG monitoring inappropriate |
|
-CMRO2 |
↓ |
↑ |
|
-CBF |
↓ |
↑ |
|
-Neuroprotection |
↓CMRO2 -> protect against ischaemia |
Neurotoxic in developing brain Unclear effect in adult: -Bad: ↑CMRO2 -> ↑vulnerable to ischaemia -Good: inhibits VDCC -> ↓ICF [Ca2+] -> ↓excitotoxicity |
|
CVS |
|
|
|
-SNS outflow |
↓ |
↑ |
|
-HR |
↓ |
↑ |
|
-Contractility |
↓ (↓L-Ca2+ channel activity) |
Direct: ↓ Indirect SNS ↑ |
|
-SVR |
↓↓ |
Direct: nil? SNS ↑ |
|
-mAP |
↓ |
Direct: nil? SNS ↑ |
|
-Overall: |
High risk if shocked |
Safer if shocked But dangerous if already SNS +++ e.g. Adrenaline infusion |
|
Resp |
|
|
|
-Bronchodilation |
Yes |
Yes, R-ketamine (significant effect) |
|
-Airway reflexes |
↓ |
Maintained |
|
-Airway secretions |
- |
↑ |
|
-RR, TV |
↓ |
↔ |
|
-↓PaO2 response |
↓ |
↔ |
|
-↑PaCO2 response |
↓ |
↔ |
|
-Overall: |
Need airway + breathing support |
Often spont vent, patent airway |
|
|
Propofol |
Ketamine |
|
Use as sole agent |
No |
Anaesthetic + analgesic |
|
Use in 3rd world |
Not ideal |
Ideal -Cheap -Sole agent -Airway, breathing, circulation stable |
|
TCI available |
Yes |
No |
|
Cost |
Expensive |
Cheap |
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