Propofol
28/10/10
Class – IV hypnotic agent
Mechanism of Action - potentiates the inhibitory transmitters glycine & GABA which enhance spinal inhibition.
Pharmaceutics
- white
- oil-in-water emulsion
- 1% or 2%
- soyabean oil
- purified egg phosphatide
- soduim hydroxide
- lecthinin
Dose
- onset: 30-60 seconds
- induction Bolus - 1.5 - 2.0mg/kg -> maintenance 4 - 12mg/kg/hr
- children: induction dose : increase dose by 50% -> maintenance: increase by 25 to 50%
- plasma concentrations: sedation: 0.5 - 1.5 mcg/mL, hypnosis: 2 - 6 mcg/mL
Indications
1. Induction + maintenance of General Anaesthesia
2. Sedation
3. Status Epilepticus
4. N+V treatment in chemotherapy
Adverse Effects
- hypotension
- negative inotropy
- bradycadia
- propofol infusion syndrome -> see below
- apnoea
- pain on injection
- hypertriglyeridaemia
PK
Absorption - IV
Distribution – 97% protein bound, Vd large
Metabolism - hepatic
Elimination – urine, t1/2 = 10-70 min
Propofol Infusion Syndrome
25/10/10
Kam, P. C. et al (2007) “Propofol Infusion Syndrome – Review Article” Anaesthesia, 62, pages 690-701
= acute refractory bradycardia -> asystole + one or more of:
(1) metabolic acidosis
(2) rhabdomyolysis
(3) hyperlipidaemia
(4) enlarged or fatty liver
- ? direct mitochondrial respiratory chain inhibition
- ? impaired mitochondrial fatty acid metabolism
CLINICAL FEATURES
- our maximum dose should be 28mL/hr (70kg adult, 1% propofol at maximum of 4mg/kg/hr)
- on propofol!
- increasing inotrope support
- green urine
- cardiovascular collapse (reflected in PICCO, PAC, ECHO)
Risk Factors
- >4mg/kg/hr for 48 hours (large dose, long time)
- younger age
- acute neurological injury
- low carbohydrate intake
- catecholamine infusion
- corticosteroids infusion
INVESTIGATIONS
- unexplained lactic acidosis
- lipaemic serum
- propofol levels or chromatography (if available)
- ECG: Brugada like (coved type = convex-curved ST elevation in V1-V3),
RBBB, arrhythmia, heart block
- renal failure
- rhabdomyolysis (high CK, hyperkalaemia)
MANAGEMENT
- high index of suspicion
- monitor for early warning signs (lactate, CK, urinary myoglobin, ECG)
- discontinue immediately
- supportive care
- consider pacing
- adequate carbohydrate intake (6-8mg/kg/min)
- carnitine supplementation (theoretical benefit)
- haemodialysis and haemoperfusion (used with success)
- EMCO (2 case reports, readily reversible pathology)
Jeremy Fernando (2011)