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Created February 7, 2021, last updated about 3 years ago.
Collection: 133, Score: 991, Trend score: 0, Read count: 1169, Articles count: 3, Created: 2021-02-07 11:34:58 UTC. Updated: 2021-02-07 23:23:37 UTC.Notes
A. Physiochemistry
- A highly lipid-soluble alkylphenol.
- 2,6 di-isopropyl phenol
- 20 mL ampoules contain:
- 200 mg 1% propofol
- 10% soybean oil (solubiliser)
- 1.2% egg lecithin (emulsifier)
- 2.25% glycerol (make isotonic)
- Sodium hydroxide (buffer)
- pKa 11, pH 7
- 90% non-ionised @ pH 7.4
- weak acid
- stable at room temp, not light sensitive
- 1 mL = 0.1 g fat = 1.1 kcal
B. Pharmacokinetics
- Dose
- 2 mg/kg induction -> 2-6 mcg/mL
- 3-4 mg/kg in children
- 1 mg/kg load then: 10, 8, 6 mg/kg/h infusion (10m, 10m, cont) after 1 mg/kg loading - aims for blood conc of 3 ug/mL.
- Children: 15 mg/kg/h for 15 min, 13 mg/kg/h for 15 min, 11 mg/kg/h for 30 min then 9 mg/kg/h for 1-2 h, then 9 mg/kg/h for 2-4 h -> 3 ug/mL.
- Sedation 25-100 mcg/kg/min
- Plasma levels:
- major surg 4 mcg/mL (4-8 ug/mL)
- minor surg 3 mcg/mL
- 50% wake @ 1.07 mcg/mL (decrement lvl: 1.2 mcg/mL on TCI)
- 50% orientated @ 0.95 mcg/mL
- Psychomotor perfomance pre-op levels @ 0.3 mcg/mL
- Absorption - IV
- Distribution - Vdcc 0.5 L/kg, Vdss 2-10 L/kg
- Protein binding - 98% albumin
- Onset < 60s, peak 60-90s (slightly slower than thio: peak 30-60s); Offset 5-10 min (faster than thio).
- Metabolism - alpha1∆ 2 min, tß∆ 1h, CSHT-8h: 30 min. Conjugated to glucuronide & sulphate - water sol and renally excreted. 0.3% excreted unchanged.
- Clearance - 30 mL/kg/min.
- Children - larger central vol; longer CSHT (10m@1h & 20m@4h cf. 7m@1h & 10m@4h for adults); slower recovery; but require higher infusion rates and have higher clearance (req. same blood (=effect) conc as adults).
- NB: children have primarily pharmacokinetic differences not pharmacodynamic.
- Women - higher clearance.
C. Pharmacodynamics
- Mech - potentiates GABA inhibition.
- CNS - anaesthetic, anticonvulsant (?), antiemetic, antipruritic, amnesic.
- Not ant-analgesic like thio.
- Inc interthreshold range for temp
- CVS - 25-45% dec MAP, dec CO, dec SVR (dec SNS outflow; direct effect on veins, dec intracellular Ca mobilisation), HR unchanged (resets barorec response).
- Resp - resp depression (apnoea in 30% alone, 100% + narcotic), dec TV, inc RR, bronchodilation (slight), dep laryngeal reflexes.
- Renal - dec RBF, green urine.
- GIT - antiemetic, no hepatic effects.
- Haem - intralipid dec platelet aggregation.
- SEs - anaphylaxis rare; sig hypotension in volume depleted; hallucinations; abuse.
Daniel Jolley
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Collected Articles
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Paediatric anaesthesia · Jan 1999
Review Comparative StudyThe use of propofol infusions in paediatric anaesthesia: a practical guide.
Children require higher infusion rates of propofol than adults to maintain clinical anaesthesia. We aimed to produce a manual infusion regimen capable of maintaining a steady-state blood concentration of 3 microg ml(-1) in children aged 3-11 years. Pharmacokinetic parameter estimates were taken from published studies of infusion data in children and used in a pharmacokinetic simulation programme to predict likely propofol blood concentrations during infusions. ⋯ The context sensitive half-time in children was longer than in adults, rising from 10.4 min at 1 h to 19.6 min at 4 h compared to adult estimates of 6.7 min and 9.5 min, respectively. Children require higher infusion rates than adults to maintain steady state concentrations of 3 microg x ml(-1) and have longer context sensitive half-times than adults. These differences can be attributed to altered pharmacokinetics in this age group.
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Paediatric anaesthesia · Jul 2015
Review Meta AnalysisDoes a prophylactic dose of propofol reduce emergence agitation in children receiving anesthesia? A systematic review and meta-analysis.
Prophylactic propofol reduces emergence agitation in children after general anesthesia.
pearl -
Review
Propofol infusion syndrome: a structured literature review and analysis of published case reports.
Propofol infusion syndrome is a rare, potentially fatal condition first described in children in the 1990s and later reported in adults. We provide a narrative review of what is currently known about propofol infusion syndrome, including a structured analysis of all published case reports; child and adult cases were analysed separately as propofol is no longer used for long-term sedation in children. The review contains an update on current knowledge of the pathophysiology of this condition along with recommendations for its diagnosis, prevention, and management. ⋯ The cumulative dose of propofol was associated with an increased number of clinical features and the number of organ systems involved in adult cases only. Clinicians should consider propofol infusion syndrome in cases of unexplained metabolic acidosis, ECG changes, and rhabdomyolysis. We recommend early consideration of continuous haemofiltration in the management of propofol infusion syndrome.