What are the medications used in General Anesthesia (GA) and Spinal Anesthesia, including their Mechanism of Action (MOA)?

Medications Used in General and Spinal Anesthesia with Mechanisms of Action

General Anesthesia Medications

Induction Agents

Propofol is the primary intravenous induction agent, acting through GABA-A receptor potentiation to produce rapid unconsciousness, with typical induction doses of 1.0-2.0 mg/kg IV in adults, reduced to 0.5-1.5 mg/kg in elderly or cardiac patients. 1

• Mechanism of Action: Propofol enhances GABA-A receptor-mediated chloride channel opening, causing neuronal hyperpolarization and CNS depression 1
• Dosing: Standard induction is 1.0-2.0 mg/kg IV; elderly patients require 0.5-1.5 mg/kg due to reduced clearance and increased sensitivity 1
• Maintenance: Can be continued as infusion at 100-200 mcg/kg/min for general surgery, or 50-100 mcg/kg/min when combined with opioids 1
• Cardiovascular Effects: Causes dose-dependent decreases in preload and afterload, resulting in hypotension; slower administration (20 mg every 10 seconds) minimizes hemodynamic instability 1

Ketamine provides dissociative anesthesia through NMDA receptor antagonism, maintaining cardiovascular stability better than propofol, but carries higher risk of postoperative confusion in elderly patients. 2

• Mechanism of Action: Non-competitive NMDA receptor antagonist producing dissociative state with preserved airway reflexes 2
• Advantages: Theoretically counteracts hypotension through sympathetic stimulation 2
• Disadvantages: Associated with postoperative confusion, particularly in elderly patients; may cause disruptive movements 2
• Combination Use: When combined with propofol, produces deeper sedation but increases respiratory depression and hypoxemia risk 2

Etomidate is mentioned as an alternative induction agent but specific dosing and MOA details are limited in the provided guidelines. 2

Maintenance Agents

Volatile inhalational agents (isoflurane, desflurane, halothane) maintain anesthesia through multiple mechanisms including GABA-A receptor potentiation and two-pore potassium channel activation. 1, 3

• Mechanism of Action: Enhance inhibitory neurotransmission via GABA-A receptors while suppressing excitatory pathways 1
• Isoflurane: Maintains anesthesia at end-tidal concentrations of 0.7-1.2% 3
• Desflurane: Requires end-tidal concentrations of 1-4%; associated with faster emergence times 3
• Cardioprotective Effects: Volatile agents demonstrate cardioprotective properties during cardiac surgery and are recommended for major non-cardiac surgery in patients with heart disease 4

Adjunctive Medications

Opioids (fentanyl, morphine, alfentanil) provide analgesia through mu-opioid receptor agonism, reducing anesthetic requirements but increasing respiratory depression risk. 2, 1, 5

• Mechanism of Action: Mu-opioid receptor agonists inhibiting nociceptive transmission in spinal cord and brain 1
• Fentanyl: Preferred opioid at 1-2 mcg/kg for induction; reduces propofol maintenance requirements 1, 5
• Critical Warning: In neonates and pediatric patients, concomitant fentanyl and midazolam administration can cause severe bradycardia and hypotension 5
• Caution in Elderly: The Working Party does not support opioids as sole adjunct due to respiratory depression and postoperative confusion risk 2

Benzodiazepines (midazolam) provide anxiolysis and amnesia through GABA-A receptor modulation but should be avoided in elderly patients due to delirium risk. 2, 6, 5

• Mechanism of Action: Positive allosteric modulators of GABA-A receptors, enhancing chloride conductance 5
• Sedation Use: Commonly used during spinal anesthesia but should be used cautiously in very elderly patients 2
• Drug Interactions: Erythromycin doubles midazolam half-life; cimetidine increases steady-state concentrations 5
• Geriatric Caution: Long-acting benzodiazepines are strongly associated with postoperative delirium in patients over 60 years 6

Muscle Relaxants facilitate intubation and surgical conditions through neuromuscular junction blockade. 5

• Succinylcholine: Depolarizing agent causing initial fasciculations followed by paralysis; midazolam does not alter its dosing or duration 5
• Non-depolarizing agents (pancuronium, d-tubocurarine): Competitive acetylcholine receptor antagonists; used together with midazolam without clinically significant interactions 5

Spinal Anesthesia Medications

Local Anesthetics

Bupivacaine is the preferred local anesthetic for spinal anesthesia, with doses less than 10 mg (typically 7.5-10 mg of 0.5% hyperbaric solution) reducing hypotension in elderly patients while providing 2-5 hours of surgical anesthesia. 2, 6, 7

• Mechanism of Action: Voltage-gated sodium channel blocker preventing action potential propagation in sensory, motor, and autonomic nerve fibers 7
• Dosing: 7.5-10 mg of 0.5% hyperbaric bupivacaine for lower extremity surgery; lower doses (<10 mg) reduce associated hypotension 2, 6
• Duration: Provides 2-5 hours of anesthesia; somewhat shorter duration than tetracaine but with decreased hypotension incidence 7
• Baricity: Hyperbaric formulations allow attempted lateralization with fractured hip inferior to ameliorate hypotension 2

Lidocaine provides shorter-duration spinal anesthesia (less than 1 hour) through the same sodium channel blockade mechanism. 7

• Mechanism of Action: Voltage-gated sodium channel blocker with faster onset and shorter duration than bupivacaine 7
• Duration: Primarily useful for procedures lasting less than one hour 7
• Clinical Use: 60 mg (1.5 ml of 4% lidocaine in 10% dextrose) used for brief transurethral surgery 3

Tetracaine offers the longest duration of spinal anesthesia (2-5 hours) with more profound motor block than bupivacaine. 7

• Mechanism of Action: Sodium channel blocker with longer duration of action 7
• Characteristics: Provides somewhat longer anesthesia duration and more profound motor block than bupivacaine 7
• Disadvantage: Higher incidence of hypotension compared to bupivacaine; may have higher incidence of tourniquet pain in orthopedic procedures 7

Mepivacaine is an intermediate-duration local anesthetic associated with faster postoperative discharge times than bupivacaine. 8

• Clinical Advantage: Patients receiving mepivacaine spinal anesthesia spent only 206 minutes in recovery versus 291 minutes with bupivacaine 8

Adjunctive Intrathecal Medications

Fentanyl (20-25 mcg intrathecally) is the preferred intrathecal opioid, prolonging postoperative analgesia without the respiratory and cognitive depression associated with morphine or diamorphine. 2, 6

• Mechanism of Action: Mu-opioid receptor agonist acting directly on spinal cord dorsal horn receptors 2
• Dosing: 20-25 mcg added to local anesthetic solution 6
• Advantage Over Morphine: Fentanyl causes less respiratory and cognitive depression than morphine or diamorphine 2
• Duration: Prolongs postoperative analgesia beyond local anesthetic duration 2

Vasoconstrictors (epinephrine) prolong spinal anesthesia duration through local vasoconstriction reducing systemic absorption. 7

• Mechanism of Action: Alpha-adrenergic receptor agonism causing vasoconstriction and reduced local anesthetic absorption 7
• Efficacy: Greatest duration extension seen with tetracaine; lidocaine and bupivacaine benefit less from vasoconstrictor addition 7

Peripheral Nerve Block Medications

Local anesthetics for peripheral nerve blocks (femoral, fascia iliaca, sciatic) use the same sodium channel blockade mechanism as spinal anesthetics but are administered in higher volumes and lower concentrations. 2, 6, 9

• Recommended Blocks: Femoral nerve or fascia iliaca blocks are more amenable to ultrasound guidance and reduce deep hematoma risk in anticoagulated patients 9
• Psoas Compartment Block: Most reliable for blocking femoral, obturator, and lateral cutaneous nerve of thigh, but risks neuraxial spread and deep hematoma 2
• Clinical Benefit: Reduces postoperative opioid requirements and extends analgesia period 2, 6, 9

Critical Drug Interactions and Contraindications

Never combine spinal and general anesthesia simultaneously, as this causes precipitous intraoperative hypotension. 2, 10, 9

Propofol doses must be reduced when co-administered with valproate due to increased propofol blood levels and enhanced sedation/cardiorespiratory depression. 1

Erythromycin reduces midazolam clearance by approximately 50%, doubling its half-life and requiring dose reduction. 5

In patients on chronic anticoagulation, INR must be <1.5 for safe neuraxial anesthesia administration. 9