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)