Knowledge
Collections of articles, notes and knowledge from the metajournal community.
Airway
Analgesia
Anesthesia
Complications
Covid
Critical care
Decision making
Drugs
Epidural
Intrathecal
Intravenous anesthetics
Neuromuscular agents
Obstetric anesthesia
Opioid
Pain
Pediatric anesthesia
Perioperative medicine
Postoperative complications
Regional anesthesia
Sugammadex
-
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.
-
Etomidate (Amidate™) is short-acting intravenous anesthetic agent first developed in 1964. It is available and used in the United Kingdom, Europe, New Zealand, United States, but not Australia.
Advocates highlight etomidate's hemodynamic stability when used for induction. Critics point to the well-established adrenocortical suppression, and wide-range of suitable alternatives (propofol, ketamine, thiopentone) in trained hands.
A. Physiochemistry
- Carboxylated imidazole
- 2 isomers - only R(+) hypnotic
- Haemodynamic stability, minimal respiratory depression, cerebral protection, wide margin of safety.
- Originally formulated in propylene glycol (painful), now in soybean lipid.
B. Pharmacokinetics
- Dose - 0.3 mg/kg (0.1-0.4 mg/kg)
- Absorption - IV
- Distribution - 4 L/kg
- Protein binding - 75% (like thiopentone)
- Onset 30-60s ; Offset
- Metabolism - alpha1 ½ 2.5m, alpha2 ½ 30m, tß½ 3.5h; hepatic ester hydrolysis of ester side chain.
- Clearance - 20 mL/kg/min
C. Pharmacodynamics
- Mech - probably by GABAa receptors.
- CNS - hypnosis; no analgesic action; ⇣ CBF and CMRO2
- CVS - stable; may have slight dec MAP 15% due to ⇣ SVR.
- Resp - minimal; sometimes brief hypoventilation or apnoea post-induction.
- Endo - adrenocortical suppression - inhibits 11ß-hydroxylase (11-deoxycortisol → cortisol). Temporary & reversed by vit C.
- ⇡ ICU mortality when used for sedation.
- SEs - excitatory phenom, involuntary muscle movement (50%), PONV (30%), thrombophlebitis (20%), pain on injection.
-
-
-