What are the purposes and mechanisms of action of drugs used in anesthetic induction?

Purpose and Mechanism of Action of Drugs Used in Anesthetic Induction

Anesthetic induction drugs are designed to rapidly and safely transition patients from consciousness to unconsciousness while maintaining physiologic stability and creating optimal conditions for airway management.

Intravenous Induction Agents

Propofol

• Primary mechanism: Positive modulation of inhibitory GABA neurotransmission through GABAA receptors 1
• Pharmacodynamics: Produces rapid induction (within 40 seconds) due to quick blood-brain equilibration (1-3 minutes) 1
• Hemodynamic effects: Causes arterial hypotension (sometimes >30% decrease) with little change in heart rate if spontaneous ventilation is maintained 1
• Respiratory effects: Frequently associated with apnea in both adults and pediatric patients 1
• Clinical use: Most commonly used IV induction agent due to rapid onset and recovery profiles 2

Etomidate

• Mechanism: GABA receptor modulator similar to propofol but with different hemodynamic profile 2
• Dose: 0.2-0.3 mg/kg for induction 2
• Advantages: Maintains hemodynamic stability, making it particularly useful in hemodynamically unstable patients 2
• Disadvantages: Associated with pain on injection (35% of patients) and higher rates of postoperative vomiting (55%) 3

Ketamine

• Mechanism: NMDA receptor antagonist with sympathomimetic effects 4
• Dose: 1-2 mg/kg for induction 2
• Hemodynamic effects: Produces dose-dependent increases in heart rate, blood pressure, and cardiac output through sympathetic stimulation 4
• Special considerations:
  • Maintains systemic vascular resistance, making it useful for trauma care 4
  • Previously contraindicated in head injury due to concerns about increased intracranial pressure, but now frequently used in pre-hospital emergency anesthesia for head injury patients 4
  • May cause rigidity during induction (reported in 55% of patients) 3

Midazolam

• Mechanism: Benzodiazepine that enhances GABA effects 2
• Dose: 0.05-0.1 mg/kg for premedication or as part of induction 2
• Clinical use: Often used in co-induction techniques with propofol to reduce propofol requirements and risk of awareness 5
• Considerations: At 2 mg dose, does not compromise recovery in day-case surgery, but higher doses (5 mg) may delay discharge by approximately 20 minutes 5

Alfentanil and Other Opioids

• Purpose: Provide analgesia and reduce sympathetic response to laryngoscopy and intubation 3
• Advantages: Superior cardiovascular stability during induction and intubation compared to thiopental, midazolam, and etomidate 3
• Disadvantages: May cause rigidity and slightly slower onset of action 3
• Clinical consideration: Increases incidence of post-operative nausea and vomiting 5

Co-Induction Techniques

• Definition: Use of two or more drugs to induce anesthesia, exploiting synergistic effects 5
• Common combinations:
  • Midazolam (2 mg) + propofol: Reduces propofol requirements and risk of awareness 5
  • Ketamine + midazolam: Particularly useful in critically ill patients 5
  • Propofol + opioid (fentanyl or alfentanil): Provides stable induction but may cause bradycardia 5

Inhalational Induction Agents

Sevoflurane

• Advantages: Rapid onset/offset, less airway irritation, making it preferred for both induction and maintenance 2
• Environmental consideration: Lower environmental impact compared to desflurane 2
• Special populations: Preferred for mask induction in pediatric patients due to non-pungent odor 2

Desflurane

• Characteristics: Allows rapid emergence but has higher environmental impact 2
• Limitations: Not recommended as first choice due to environmental concerns 2

Nitrous Oxide

• Role: Used as an adjunct rather than primary agent 2
• Limitations: Increases risk of postoperative nausea and vomiting and delays bowel function recovery 2
• Environmental impact: Use should be minimized due to environmental concerns 2

Neuromuscular Blocking Agents

Non-depolarizing Agents (Rocuronium, Vecuronium, Cisatracurium)

• Purpose: Facilitate intubation and provide muscle relaxation 2
• Preference: Intermediate-acting agents are preferred 2

Succinylcholine

• Use: Rapid sequence induction 2
• Contraindication: Should be avoided in patients with myopathies 2

Adjunctive Medications

Alpha-2 Agonists (Dexmedetomidine, Clonidine)

• Effects: Provide sedation and analgesia with opioid-sparing effects 2
• Future role: May have increasing importance in co-induction techniques 5

Common Pitfalls and Safety Considerations

• Overdosing: Should be avoided by careful titration, especially in elderly or debilitated patients 2
• Monitoring: Appropriate monitoring including pulse oximetry, capnography, and neuromuscular monitoring is essential 2
• Awareness risk: Consider depth of anesthesia monitoring, especially with total intravenous anesthesia techniques 2
• Neuromuscular blockade reversal: Ensure complete reversal (TOF ratio ≥0.9) before extubation 2
• Pre-oxygenation: All patients should be pre-oxygenated before induction to prevent desaturation 6
• Cricoid pressure: Should be applied during induction to reduce aspiration risk but may be released if it impairs laryngoscopy view 6

Selection Principles for Induction Agents

• Patient factors: Consider age, hemodynamic status, and comorbidities 6
• Surgical factors: Duration, type of procedure, and positioning requirements 2
• Recovery goals: Consider whether rapid recovery is needed (e.g., day-case surgery) 5
• Environmental impact: Consider using agents with lower environmental footprint when possible 2