Etomidate use in procedural sedation and analgesia

etomidate use in procedural sedation

1. Seminar Topic :- ETOMIDATE Presenter :- Dr Saurabh Wasule Moderator :- Dr D.B. Bhusare sir

2. Outline :- History Mechanism of Action Effects on different body systems Pharmacokinetics Formulation of Drug Indications Contra-indications Adverse effects Doses in different situations Administration of drug Safety Information Adrenal Suppression Take Home message

3. History Etomidate discovered by Janssen (J&J) Pharmaceuticals in 1964 at Belgium. First introduced as Anti-Fungal agent Introduced as IV Anesthetic agent (due to potent sedative properties) In Europe 1972 In USA 1983 In India 2013 Brand name in India -Troymidate, Lipuro & Etomid

4. Etomidate Etomidate is an imidazole derivative whose structure is unlike that of any other anesthetic It is ionized and water soluble at acidic pH and lipid soluble at physiologic pH. It is supplied as a 0.2% solution in 35% propylene glycol.

5. Mechanism of Action Carboxylated Imidazole agent Acts directly on the Gamma Amino Butyric Acid (GABA) receptor complex blocking neuroexcitation producing sedation/hypnosis/anesthesia without analgesia . Acidic pH - 6.9, рка 4.2, poorly water soluble and soluble in 35% propylene glycol

6. Pharmacokinetics Onset of Action : within 30-60 seconds Peak Effect: In 1 minute Duration :- 3 to 15 minute and terminated by redistribution Protein Binding: 76% Metabolism: Hepatic & Plasma Esterase Half-Life Distribution : 3 Minutes (Anesthesia) Half-Life Redistribution : 30 Minutes (Sedation) Half-Life Elimination : 3 hours (Drowsiness)

7. Formulation of Drug :- Available as Milky White Solution in 35% Propylene Glycol Strength is 2mg/ml and 10 ml bulb is available in Indian market Outside India 20 ml (40 mg) Preloaded Syringes also available in 2mg/ml strength Now Etomidate is available with Medium and Long chain triglycerides (MCT/LCT) for painless entry in vein.

8. Preparation emulsion preparation with medium chain triglycerides and soyabean oil. Etomidate- contain 20 mg of etomidate in 10 mL (2 mg mL-1). The pH of the propylene glycol solution is 8.1.

9. Adrenal Suppression At clinically relevant concentrations, etomidate inhibits the mitochondrial CYP isozyme (CYP11B) responsible for catalyzing the 11ẞ-hydroxylation reaction in cortisol synthesis. Even a single dose does.

10. Single dose etomidate causes measurable decrease in level of circulating cortisol But it never falls below physiological range Effect of low level remains up to 24 hours 100 to 200 mg hydrocortisone is preferable before etomidate administration In Sepsis and Septic Shocks there is already low level of cortisol so etomidate is not advisable for induction After three repeated doses etomidate should be avoided

11. Doses in different preparations For Sedation: 0.1 mg/kg up to three doses For G/A 0.3 to 0.4 mg/kg IV over 30-60 seconds In ICU: As continuous infusion 0.04 to 0.05 mg/kg/hr with continuous monitoring In Cushing Syndrome or law cortisol level pat. 0.2 mg/kg In Geriatric patients: 0.2 mg/kg In Pregnancy: 0.2 mg/kg In Pediatric Patients: 0.1 to 0.3 mg/kg

12. Effects on different systems:- * CNS - Decrease ICP, Cerebral Blood flow and Cerebral Metabolism But cerebral perfusion pressure maintained * CVS -- No or Minimal changes in Heart Rate, Blood Pressure and Cardiac Output No hemodynamic changes in response to pain No effect on Sympathetic tone

13. * RS - Minimal changes in Respiratory Rate and Tidal Volume Slight elevation in arterial carbon dioxide tension (PaCO2) Transient apnea up to 90 seconds

14. Other effects :- No histamine release Very rare allergic reactions Hepatic and Renal blood flow decreased but clinically accepted

15. Indications :- As Sedation (PSA) As Conscious Sedation As Hypnotic Agent Etomidate Interview in Lie Detector Test As Anesthetic Agent (preferred in cardiac patients) In Rapid Sequence Intubation (RSI) In Cardio version as Premedication In ICU as infusion ventilated/nonventilated patient As eSAM (Etomidate Speech And Memory Test)

16. Contraindications :- Proven sepsis with unstable hemodynamic patients. Abnormally Low Blood Pressure even with Rx Decreased Function of the Adrenal Gland Hypersensitivity of Etomidate Pediatric Patients less than 10 years age (but people have started using etomidate up to 2 years age with risk-benefit profile) In Pregnancy try to avoid as induction agent if other anesthetic agents are available. In Geriatric Patients with caution.

17. Adverse effects :- Transient Injection site pain up to 80% patients Skeletal Muscle movements mainly myoclonic (peripheral limb movements) up to 30% patients Myoclonus Adrenal Suppression up to 10% patients Hiccups Apnea up to 90 seconds Less frequently laryngospasm, nausea/vomiting, snoring, arrhythmia & increase in PaCO2

18. Safety information:- Etomidate causes drowsiness from 3 to 9 hours so Patients are instructed -Do note drive -Do not operative machinery - Do not drink alcohol for 24 hours Use with cautions in Geriatric and Pregnant pts.

19. Take home Message The drug of choice in all types of cardiomyopathies When etomidate is used as sole anesthetic agent for induction or in any short procedure fentanyl group drugs or ketamin are must as premedication because of very short duration effect of etomidate In Pregnancy with Heart Disease etomidate is drug of choice In traumatic brain injury and severe trauma patients with unstable hemodynamic patient etomidate is preferred Universally accepted anesthetic agent.

20. THANK YOU