Intravenous Anaesthetic Agents Overview

Intravenous Anaesthetic Agents

• Agents include Thiopentone, Methohexitone, Ketamine, Propofol, Etomidate, and Benzodiazepines.
• Intravenous Anaesthetic Agents (IVA) are drugs or combinations of drugs designed to safely induce and reversibly maintain anesthesia via injection or infusion.
• An effective IVA should cause loss of consciousness within one arm-brain circulation time (usually 30-60 seconds) at the appropriate dose.

Definition of IVA

• IVA is a drug or drug combination which induces anesthesia safely and reversibly via injection or infusion to maintain anesthesia
• This agent should cause a loss of consciousness within the one arm-brain circulation time.
• One arm-brain circulation time is the time it takes for IV injection to reach the brain through the heart (typically 30-60 seconds).

Intravenous Anaesthetic Agents (continued)

• General anesthetic agents produce reversible effects such as hypnosis, amnesia, analgesia, immobility, and inhibition of nociceptive reflexes.
• They also commonly reduce several autonomic reflexes, such as gag reflex, vasoconstriction, and tachycardia.

The Ideal IVA Agent

• Ideally, an IVA should have a long shelf life and resist microbial contamination, be water-soluble and easily dissolvable in a stable solution without preservatives.
• It should also be painless on injection and safe even if inadvertently injected into arteries.
• Furthermore, it needs to be non-irritating to surrounding tissues and non-toxic to the body.

Ideal IVA (continued)

• The ideal IVA should also require a small volume to be effective, act quickly, provide rapid recovery without cumulative effects (no active metabolites), have minimal excitatory side effects (e.g., cough, hiccups, involuntary movements), and not cause respiratory depression.
• The ideal agent should also avoid cardiovascular depression, have no interaction with non-depolarizing neuromuscular blocking agents (NMBA), exhibit no hypersensitivity or histamine release reactions, and not result in post-operative nausea and vomiting or emergence phenomena (e.g., delirium, nightmares).

Ideal IVA Agent (continued)

• An optimal IVA agent also should not affect cerebral blood flow, not disrupt endocrinological functions, not stimulate porphyria, require no dependency on liver and kidney function for metabolism or excretion, and be relatively inexpensive.

IVA - Advantages and Disadvantages

• Advantages:
  • Rapid and smooth induction.
  • Minimal equipment needed.
  • Easy administration of the drug.
• Disadvantages:
  • Difficult drug retrieval after administration.
  • Less control over the duration and depth of anesthesia.

IVA - Pharmacological Principles

• IV anesthetic agents are typically administered as aqueous solutions, not oil or emulsions.
• Only unbound (unionized) drug molecules cross the blood-brain barrier (BBB).
• Only the unionized fraction of the drug, present at a pH of 7.4, crosses the BBB to generate the anesthetic effect.
• Most IVAs are alkaline salt solutions or water-miscible emulsions, bypassing the absorption processes and delivering the drug directly into the bloodstream.

IVA Types

• Two main categories:
  • Rapidly acting: Barbiturates (Thiopentone, Methohexitone), Imidazoles (Etomidate), and Phenols (Propofol).
  • Slowly acting: Phencyclidines (Ketamine), Benzodiazepines (Diazepam, Midazolam), and Opioids (Fentanyl, Alfentanil, Sufentanil).

Thiopentone

• The most common IV anesthetic agent in Ghana.
• A sulfur analogue of Pentobarbitone with a pale yellow water-soluble powder form and a garlic odor.
• Solutions are often stabilized with 6% Na2CO3 to prevent precipitation.
• Prepared in various vial sizes (500mg, 1000mg).
• Solution is bacteriostatic and alkaline (pH of 2.5% solution = 10.5).
• Protein binding is high, reducing glomerular filtration.
• Dosing (IV) for induction range from 4-6mg/kg.

Thiopentone (continued)

• Most drugs in the body are metabolized by the liver and excreted by the kidneys.
• Chronic alcoholism increases the rate of metabolism of IVAs by increasing liver enzymes.
• Renal disease can slow drug excretion.

Thiopentone (continued)

• Pharmacokinetics:
  • Redistribution within the body.
  • Metabolism (primarily by liver oxidation and desulphuration).
  • Metabolites are active and are excreted in urine and bile.
• Use reduced doses in patients with renal or hepatic dysfunction.

Thiopentone (Pharmacodynamics)

• CNS: Sedative, hypnotic, potent anticonvulsant.
• CVS: Depressed myocardial contractility, blood pressure.
• RESP: Respiratory depression proportional to dose and speed of injection, increased irritability of respiratory mucosa (caution in asthma patients), bronchospasm, laryngeal spasm
• RENAL + UTERINE: Reduced renal blood flow (RBF), glomerular filtration rate (GFR), urine output
• Hepatic: Induction of liver enzymes, reduced liver blood flow
• Local Effects: Thrombophlebitis, pain, thrombosis, extravasation, intra-arterial injection.

Thiopentone Uses

• Induction of anesthesia.
• Sedation (bolus, not for infusions).
• Status epilepticus.
• Severe head injury.

Thiopentone Contraindications

• Absolute: Airway obstruction, previous hypersensitivity to barbiturates, acute intermittent porphyria, no IV access.
• Relative: Severe CVS, heavy sedation/alcohol intake, severe hepatic/renal failure, neuromuscular diseases, poorly controlled asthma, extremes of age.
• Complications: Extravascular injection (resulting in tissue necrosis), Intra-arterial injection (causing intense pain and vasospasm), Anphylaxis.

Ketamine

• Preparations: 10mg/ml, 50mg/ml, 100mg/ml in 10ml, 2ml, and 1ml vials with benzothonium chloride preservative.
• Properties: Phencyclidine derivative introduced 1965, soluble in water, pH 3.5—5.5, pKa 7.5
• Mechanism of Action: N-methyl-d-aspartate receptor antagonist (NMDA). More lipid soluble than thiopentone.
• Metabolism: In the liver to norketamine (20% potency), excreted in urine. Induces enzymes leading to tolerance and dependence.
• Pharmacodynamics: Slow onset. Smooth induction. Dissociative anesthesia (patients gaze distant, hypertonus, muscle movements, jaw rigidity, nystagmus). Intenses analgesia, but superficial sedation. ↑CBF,↑ICP,↑IOP,↑CMRO2 ↑ SVR, ↑ HR. ↑ Cardiac output & myocardial O2 requirements.
• Respiratory: Low doses maintain airway reflexes. High doses can depress reflexes, causing bronchodilation. ↑secretions.
• GIT: Salivation, nausea, vomiting
• Muscle: Hypertonus, clonic tonic activity
• Uses: Induction of anesthesia (especially in poor-risk patients, difficult airways), TIVA, adjunct analgesia, burns dressing, radiotherapy. Field situations (outside hospital).
• Contraindications: Hypertension, ischemic heart disease, epilepsy, ↑ ICP or ↑ IOP or CVA, penetrating eye injury, head injury, psychosis.

Propofol

• An IV anesthetic agent introduced in 1981.
• Presentation: 1% or 2% solution in milky white emulsion; 10ml, 20ml, 50ml, 100ml vials and ampoules. Contains soybean oil, egg phosphatide, glycerol.
• Contains preservatives. Must be used within 6 hours of opening.
• Mechanism of Action: Thought to be GABA-mediated. Very lipid soluble, almost insoluble in water (97-98% protein bound).
• Metabolism: Mostly metabolised in the liver to inactive glucuronides; some excreted unchanged in urine.
• Pharmacodynamics:
  • Induction by IV only.
  • Minimal hangover
  • Rapid and induction and recovery.
  • Unable to use eyelash reflex to measure unconsciousness.
  • Pain at injection site (use large vein)
  • Involuntary muscle movements.
• Respiratory System: Obtunds airway reflexes, allowing passage of laryngeal mask airway without coughing or laryngospasm
• CNS: Onset of action 20-40 seconds.
• CVS: Reduced cardiac output (20%), ↓SVR, severe bradycardia, asystole
• Uses: Induction of anesthesia, day-care anesthesia, sedation, during surgery (la technique, endoscopy), in ICU, and TIVA (Total intravenous anesthesia).
• Side Effects: Pain on injection, CVS depression, respiratory depression, myoclonus; allergic reactions; Propofol infusion syndrome
• Induction doses: <60 years: 2–2.5 mg/kg; >60 years with severe illness (American Society of Anesthesiologists [ASA] grade III/IV): 1–1.5 mg/kg; older children (>3 years): 3–3.5 mg/kg.

Benzodiazepines

• Types: Short-acting (Midazolam), intermediate-acting (Temazepam), long-acting (Diazepam).
• Lorazepam is a very long-acting benzodiazepine not typically used for children.
• Mechanism of Action: Sedative, hypnotic, anticonvulsant, muscle relaxant, hyperpolarization of nerve membranes, acting on GABA receptors.
• Pharmacokinetics: Good oral bioavailability, extensive distribution (high lipid solubility and protein binding). Primarily metabolized by liver oxidation and glucuronidation, yielding active metabolites; excretion mainly through the kidneys. Enterohepatic recirculation can contribute to prolonged effects.
• CNS: Sedative, hypnotic, anticonvulsant, muscle relaxant, ↓CBF, ↓ICP, ↓IOP, ↓CMRO2, anterograde amnesia.
• Uses: Premedication (anxiolysis, sedation, amnesia), insomnia, agitation, induction of anesthesia, co-induction with propofol, muscle relaxant in spastic conditions, anticonvulsant.
• Midazolam: Short-acting, water-soluble, 99% metabolized, 1% excreted unchanged. One active metabolite (alpha-hydroxymidazolam). Dosing: IV 0.07-0.15 mg/kg and oral 0.05-0.1 mg/kg. May cause slight fall in blood pressure and cardiac output, especially in elderly

This quiz covers key intravenous anaesthetic agents including Thiopentone, Ketamine, and Propofol. Learn about the definitions, effects, and mechanisms of action involved in safely inducing anesthesia. Gain a comprehensive understanding of how these agents work within the context of anesthesia practices.