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Muscle Relaxants — 10-Mark Long Answer (MD Anaesthesia)

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1. Introduction

• Barash/Stoelting's Clinical Anesthesia 9e, p. 1596

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2. Physiology of the Neuromuscular Junction

• Presynaptic α₃β₂ receptors regulate ACh mobilization; their blockade explains fade with train-of-four (TOF) stimulation.
• Miller's Anesthesia 10e, p. 3219; Barash 9e, p. 1604

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3. Classification of NMBDs

A. By Mechanism

B. By Chemical Structure

C. By Duration of Action (at 2× ED95 intubating dose)

• Miller's Anesthesia 10e, p. 3247; Barash 9e, p. 1615

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4. Depolarizing NMBD — Succinylcholine

• ED95: 0.3 mg/kg (intubating dose: 1–1.5 mg/kg)
• Onset: <1 minute (fastest of all NMBDs)
• Duration: 10–15 min (at 1–1.5 mg/kg)

• No fade to TOF or tetanic stimulation
• No post-tetanic potentiation
• Potentiated (not reversed) by anticholinesterases
• Preceded by fasciculations
• Antagonized by prior nondepolarizing NMBDs

1. Hyperkalemia — extrajunctional receptor proliferation → K⁺ efflux (0.5–1 mEq/L rise normally; life-threatening in burns, denervation, prolonged immobilization, neuromuscular disease → AVOID)
2. Malignant hyperthermia (triggering agent)
3. Bradycardia — direct muscarinic effect; worse with second dose
4. Raised IOP, ICP, intragastric pressure
5. Postoperative myalgia — due to fasciculations
6. Masseter spasm / trismus
7. Prolonged block with pseudocholinesterase deficiency (dibucaine number used for diagnosis)

• Barash 9e, pp. 1607–1612; Miller's 10e, p. 3220

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5. Nondepolarizing NMBDs

Mechanism

• Fade to TOF and tetanic stimulation
• Post-tetanic potentiation/facilitation
• Reversed by anticholinesterases (neostigmine, edrophonium) or sugammadex (aminosteroids)
• NO fasciculations

Potency and Onset

• Rocuronium's molar potency is ~13% of vecuronium and ~9% of cisatracurium, explaining its rapid onset.
• Miller's 10e, p. 3271; Barash 9e, p. 1617

Individual Drugs

Elimination

• Aminosteroids (pancuronium, vecuronium, rocuronium): Primarily renal (pancuronium), hepatic (vecuronium 40–50%), or both (rocuronium). Avoid pancuronium in renal failure.
• Benzylisoquinoliniums — Atracurium/cisatracurium undergo Hofmann elimination (spontaneous non-enzymatic degradation at physiologic pH and temperature) + ester hydrolysis → organ-independent — ideal for hepatic/renal failure.
• Mivacurium — hydrolyzed by butyrylcholinesterase (fastest plasma clearance of all NMBDs); prolonged block with pseudocholinesterase deficiency.
• Miller's 10e, pp. 3289–3293; Barash 9e, p. 1625

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6. Monitoring Neuromuscular Blockade

Peripheral Nerve Stimulation Patterns

• Profound/deep block: PTC = 0 (no response to PTC)
• Deep block: PTC 1–10, no TOF response
• Moderate block: TOF 1–3 twitches present
• Shallow block: TOF 4 twitches + fade
• Minimal/full recovery: TOF ratio ≥0.90 (required for safe extubation)

• Barash 9e, p. 1626; Miller's 10e, p. 3220

Differential Muscle Sensitivity

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7. Reversal of Neuromuscular Blockade

A. Anticholinesterase Agents (Neostigmine, Edrophonium)

• Neostigmine (0.03–0.07 mg/kg, max 5 mg) — most commonly used; also inhibits muscarinic receptors (bradycardia, secretions, gut motility) → always co-administered with glycopyrrolate or atropine
• Most effective when TOF ≥ 2 twitches are present (moderate block); ineffective at profound block
• Ceiling effect — increasing dose beyond 5 mg of neostigmine does not improve reversal; can paradoxically worsen neuromuscular block ("neostigmine weakness") by depolarizing block at high ACh concentrations
• Hypokalemia, acidosis, hypothermia reduce neostigmine efficacy
• Barash 9e, p. 1635

B. Sugammadex (Selective Relaxant Binding Agent)

• Can reverse any depth of block
• No muscarinic side effects → no need for anticholinergic
• Lower incidence of residual paralysis (~5% vs. 30–40%)
• Can reverse RSI-dose rocuronium in "can't intubate, can't oxygenate" scenarios
• Barash 9e, p. 1641; Miller's 10e, p. 3220

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8. Drug Interactions

• Barash 9e, pp. 1623–1624; Miller's 10e, pp. 3305–3307

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9. Special Situations

Renal Failure

• Avoid pancuronium (>70% renal excretion)
• Prefer atracurium/cisatracurium (Hofmann elimination)
• Rocuronium and vecuronium: prolonged action, use with caution

Hepatic Failure

• ↑ volume of distribution → higher initial dose needed
• Avoid vecuronium and rocuronium in severe failure (hepatic clearance dependent)
• Prefer cisatracurium/atracurium

Burns / Denervation / Upper Motor Neuron Lesions

• Extrajunctional receptor proliferation → life-threatening hyperkalemia with succinylcholine → absolutely contraindicated >48 h after injury
• ↑ resistance to nondepolarizing NMBDs (upregulation)

Myasthenia Gravis

• Extreme sensitivity to nondepolarizing NMBDs (receptor loss)
• Relative resistance to succinylcholine
• Use 10–20% of standard nondepolarizing dose; titrate with monitoring

ICU Use

• Prolonged NMBD infusion → ICU-acquired weakness, myopathy
• Short-term use (≤48 h) in ARDS + prone ventilation reduces barotrauma and may reduce mortality
• Avoid in diabetics on corticosteroids (↑ myopathy risk)
• Barash 9e, pp. 1445, 1447

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10. Succinylcholine vs. Rocuronium for RSI — Summary

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Key Examination Points to Remember

1. NMBDs do not cause sedation, analgesia, or amnesia — always combine with anesthesia.
2. Succinylcholine is the only depolarizing NMBD in clinical use; fastest onset and shortest duration.
3. Phase II block resembles nondepolarizing block: TOF fade + post-tetanic potentiation.
4. Hofmann elimination of atracurium/cisatracurium is organ-independent — best for multi-organ failure.
5. TOF ratio ≥0.90 by quantitative acceleromyography is the only reliable endpoint for safe extubation.
6. Sugammadex is the only agent capable of reversing profound rocuronium/vecuronium block.
7. Speed of onset is inversely proportional to molar potency — rocuronium's low potency explains its fast onset.
8. Residual paralysis occurs in 30–40% of patients reversed with neostigmine — a major patient safety concern.

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