ETOMIDATE( A

to Z )

How many of you are using etomidate in your anesthesia practice ?

Yes / NoWill use of etomidate benefit in your anesthesia practice ? Yes / NoIf you want to learn new drugs in anesthesia then, will you use etomidate ? Yes / No

Lecture 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• Etomidate & Adrenal Suppression• References• Case Discussions• Take Home message

History • Etomidate discovered by Janssen ( J & J ) Pharmaceuticals in 1964 at Belgium (others drugs discovered are haloperidol, droperidol, fentanyl, sufentanyl, alfentanyl & carfentanyl )

• 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• Brand name outside India-Hospira, Amidate & hypnomidate

Mechanism of Action

• Carboxylated Imidazole agent• Imidazole agent in IV anesthetic drugs• R-1-(1-ethylphenyl)imidazole-5-ethyl ester• Acts directly on the Gamma Amino Butyric Acid (GABA) receptor complex blocking neuroexcitation producing sedation/hypnosis/anesthesia without analgesia• Acidic pH - 6.9, pKa – 4.2, poorly water soluble and soluble in 35 % propylene glycol

Effects on different body system* CNS – Decrease ICP, Cerebral Blood flow and Cerebral MetabolismBut cerebral perfusion pressure maintained* CVS -- No or Minimal changes in Heart Rate, Blood Pressure and Cardiac OutputNo hemodynamic changes in response to painNo effect on Sympathetic tone* RS – Minimal changes in Respiratory Rate and Tidal Volume Slight elevation in arterial carbon dioxide tension (PaCO2)Transient apnea up to 90 seconds

Other Effects

* No histamine release * Very rare allergic reactions* Hepatic and Renal blood flow decreased but clinically accepted

PharmacokineticsOnset of Action : within 30 to 60 secondsPeak Effect : In 1 minuteDuration : 3 to 5 minute and terminated

by redistributionProtein Binding : 76 %Metabolism : Hepatic & Plasma EsteraseHalf-Life Distribution : 3 Minutes ( Anesthesia )Half-Life Redistribution : 30 Minutes ( Sedation )Half-Life Elimination : 3 hours ( Drowsiness )

Formulation of Drugs• 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.

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)

( To determine speech lateralization in patient prior to performing lobectomies to remove epileptogenic centers in brain )

Contra-Indications

• 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

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

Doses in different situations

• 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

Administration of Drug

• Never dilute Etomidate with DW in same Syringe• Preferably Large Vein for IV administration • Preadministration of lidocaine if possible (2 ml)• First dose to be completed within one arm-brain circulation (30 seconds )• All muscle relaxants, benzodiazepines, narcotics and ketamine are compatible with etomidate in same syringe except vecuronium and vit-c.

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.• Less than 10 years children manufacturer has not

recommended

Etomidate & Adrenal Suppression * 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 shold be avoided

Best Anesthetic Agent for PSAPSA ( Procedural Sedation and Analgesia)

• The American College of Emergency Physicians (ACEP) defines procedural sedation as "a technique of administering sedatives or dissociative agents with or without analgesics to induce a state that allows the patient to tolerate unpleasant procedures while maintaining cardiorespiratory function. Procedural sedation and analgesia (PSA) is intended to result in a depressed level of consciousness that allows the patient to maintain oxygenation and airway control independently

Etomidate is most preferred drug in

Hemodynamically unstable patients

then any other anesthetic agentsfor induction of anesthesia

What journals say about Etomidate

Etomidate + Ketamine Mixture• Most suitable mixture for short procedure• Best combination for RSI in trauma and sepsis

patients• Good alternative in pedo patients compare to

ketofol• Both counter act each other adverse effects like

myoclonus, nystagmus, injection site pain • Dose is 0.1mg/kg etomidate + 1 mg/kg ketamine• I have use almost in 50 short cases e.g.

colonoscopy, upper GI scopy and circumcision

Case Discussion

1) Colonoscopy in triple vessel disease

2) Ludwig’s Angina in old age patient

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 in PSA and RSI