Etomidate - 5
Pharmacodynamics
Central Nervous System
- hypnosis
0.2 - 0.3 mg/kg IV --> onset in one "arm-to-brain" time;
duration 5 - 15 minutes - no analgesia
Effect vs Concentration, ng/ml: anesthesia 300-500 sedation 150-300 awake 150-250
- hypnosis may be in part related to GABA-adrenergic system
- decreases intracranial pressure (ICP)
- decreases cerebral blood flow (CBF)
- decreases cerebral metabolic rate for O2 (CMRO2)
- mean arterial pressure essentially unchanged
- so cerebral perfusion pressure increased
- and cerebral oxygen supply:demand ratio increased
- animal model: less brain injury after cerebral ischemic insult
- intraocular pressure (IOP) decreased for 5 minutes
- EEG effects
- similar to those associated with the barbiturates
- associated with grand mal seizures and seizure activity during surgery to remove seizure foci
- myoclonic movements (not seizure activity on EEG)
Respiratory
- CO2 response less depressed compared to barbiturates
- Induction bolus may lead to
- Brief hyperventilation
- With or without brief apnea
- Slight increase in PaCO2
- Occasionally hiccup or cough
- No histamine release
Cardiovascular System
- Etomidate has minimal effect on CV function
- Etomidate induction with 0.3 mg/kg results in
- Less than 10% change in
- MAP
- PAOP
- PAP
- CVP
- SV
- CI
- SVR
- Generally about 10% HR increase except
- Perhaps up to 20% increase in HR in patients with aortic or mitral valve disease (but myocardial O2 supply:demand ratio appears to be maintained favorably)
- Coadministration of fentanyl leads to greater drop in MAP and CI
- Endotracheal intubation is likely to result in signs of sympathetic response unless an opioid and/or inhalational agent has also been given
- Less than 10% change in
Endocrine System
-
Etomidate inhibits adrenal steroid synthesis
- Effect of etomidate infusion on steroid synthesis:
In 1983 increased morbidity and mortality was observed in ICU patients sedated with etomidate. Eventually, it was disovered that etomidate causes a reversible, concentration-dependent block of 11-beta-hydroxylase (plus some minor 17-alpha-hydroxylase block) leading to decreased production of cortisol, corticosterone and aldosterone.
The mechanism involved may via free imidazole binding of cytochrome-P450 leading to inhibition of ascorbic acid synthesis. Ascorbic acid is required for steroid production in humans. Vitamin C has been reported to restore cortisol levels to normal after use of etomidate. (Should we serve orange juice in the recovery room!?)
It appears that an induction dose of etomidate followed by a short maintenance period of up to a small number of hours does NOT result in a clinical problem involving steroid production. However, many hours to days of sedation should be avoided as it may be expected to lead to increased morbidity and mortality due to inhibition of steroid synthesis.
Other
- Etomidate enhances to some degree the action of nondepolarizing muscle relaxants
- Despite in vitro inhibition of aminolevulinic acid synthetase, etomidate has been used safely in porphyria without resulting in an acute attack
