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Anaesthesiology
Neuromuscular Blocking Drugs
Built from Barash Clinical Anesthesia, 9th Edition
What’s inside
12 sections · 199 slides
Overview
- Scope of this topic
- Clinical uses of neuromuscular blocking drugs
- Residual paralysis as the central problem
Physiology of Neuromuscular Transmission
- Pathway from motor cortex to muscle fibre
- Nerve to muscle fibre innervation ratios
- Synthesis and storage of acetylcholine
- Calcium-triggered release of acetylcholine
- Neuromuscular junction anatomy and acetylcholine handling
- Causes of weakness acting on presynaptic release
- Presynaptic alpha-3 beta-2 receptors and fade
- The synaptic cleft and acetylcholinesterase
- Structure of the nicotinic muscle acetylcholine receptor
- Two types of nicotinic muscle receptor
- Receptor activation and end-plate potentials
- Upregulation of immature receptors
- Downregulation of mature receptors
How Blocking Drugs Are Characterised
- Quaternary ammonium chemistry
- Depolarizing versus nondepolarizing block
- Dose versus response relationship
- Definition of ED95 for blocking drugs
- ED95 values of the four common drugs
- Onset time
- Duration of action and recovery index
- Interpatient variation in drug response
- Spontaneous recovery on arrival in recovery room
Succinylcholine
- Structure and history of succinylcholine
- Mechanism of depolarizing block
- Features that distinguish depolarizing block
- Phase II block
- Pharmacokinetics of succinylcholine
- Cardiovascular and muscular side effects
- Prevention of postoperative myalgia
- Intragastric and intraocular pressure
- Intracranial pressure effects
- Hyperkalaemia after succinylcholine
- Treatment of acute hyperkalaemia
- Rhabdomyolysis and the paediatric black box warning
- Malignant hyperthermia, masseter spasm and anaphylaxis
- Atypical pseudocholinesterase
- The dibucaine number and management of prolonged block
- Duration of block by pseudocholinesterase genotype
- Succinylcholine for rapid sequence induction
- Dosing by body weight and by age
- Interaction with neostigmine
- Contraindications to succinylcholine
Nondepolarizing Blocking Drugs
- Characteristics of nondepolarizing block
- Role, history and mixing of nondepolarizing drugs
- Physical properties of nondepolarizing drugs
- Physiochemical properties of nondepolarizing neuromuscular blocking drugs
- Physiochemical properties: aminosteroid nondepolarizing drugs
- Physiochemical properties: aminosteroid nondepolarizing drugs (continued)
- Physiochemical properties: Atracurium
- Physiochemical properties: Atracurium (continued)
- Physiochemical properties: Cisatracurium
- Physiochemical properties: Cisatracurium (continued)
- Physiochemical properties: Mivacurium
- Physiochemical properties: Mivacurium (continued)
- Potency and speed of onset
- Intubating and maintenance dosing rules
- Pancuronium
- Vecuronium
- Rocuronium
- Rocuronium anaphylaxis and special populations
- Rocuronium in diabetes and in children
- Atracurium
- Cisatracurium
- Mivacurium
- Reversal of mivacurium
- Autonomic and respiratory adverse effects
Drug Interactions and Altered Responses
- Interactions between nondepolarizing drugs
- Sequential dosing kinetics and local anaesthetics
- Anaesthetic drug interactions
- Antibiotic and metabolic interactions
- Anticonvulsant and other drug interactions
- Cardiovascular drugs and steroids
- Organ dysfunction and drug choice
- Temperature and electrolyte effects
- Blocking drugs in the intensive care unit
- Neuromuscular disease and blocking drugs
Monitoring Neuromuscular Blockade
- Scale and significance of residual paralysis
- Guidelines recommending quantitative monitoring
- Insensitivity of clinical strength tests
- Evolution of neuromuscular assessment
- Peripheral nerve stimulator hardware
- Electrode placement and skin preparation
- Ulnar nerve stimulation site and target muscles
- Single twitch stimulation
- Train-of-four stimulation
- Train-of-four ratio
- The blind zone of subjective assessment
- Tetanic stimulation
- Sensitivity and limits of 100 Hz tetanus
- Double burst stimulation
- Post-tetanic count
Quantitative Monitoring
- Principles of quantitative monitoring
- Setting supramaximal current
- Single twitch mode on a quantitative monitor
- Mechanomyography and electromyography
- Acceleromyography
- Kinemyography and the TOFcuff
- Comparison of technologies against mechanomyography
- Normalization of acceleromyography values
- Two forms of measurement bias
- Train-of-four ratio bias between monitoring modalities
- Summary of train-of-four ratio differences (bias) at a given level of neuromuscular block
- Time bias between monitoring modalities
- Summary of the time difference (bias) between monitoring modalities to reach a given train-of-four ratio compared to mechanomyography
- Practical implications of acceleromyography bias
- Documented harms of residual paralysis
- Recovery and hospital consequences of residual paralysis
- Studies of patient harm with residual paralysis
- Quantitative monitoring modality and cutoff showing patient harms when residual paralysis was present, 26 studies
- Quantitative monitoring modality and cutoff showing patient harms when residual paralysis was present, 26 studies (continued)
- Quantitative monitoring modality and cutoff showing patient harms when residual paralysis was present, 26 studies (continued)
- Quantitative monitoring modality and cutoff showing patient harms when residual paralysis was present, 26 studies (continued)
- Central versus peripheral muscle responses
- Choice of monitoring site for extubation safety
- Relative sensitivity of monitoring muscles
- Dangers of monitoring at the eye muscles
- Muscle sensitivity compared with the adductor pollicis
- Data summary for relative muscle sensitivity to neuromuscular block compared to the adductor pollicis muscle
- Muscle sensitivity compared with the first dorsal interosseous
- Data summary for relative muscle sensitivity to neuromuscular block compared to the first dorsal interosseous muscle
- Receptor occupancy and margin of safety
- Receptor occupancy across depths of block
- Receptor occupancy estimates for the six levels of neuromuscular blockade
- Barriers to adopting quantitative monitoring
- Practical and equipment barriers
- Implementing a practice change
Reversal of Neuromuscular Blockade
- Depth of block definitions
- Six levels of neuromuscular block
- Mechanism of anticholinesterase reversal
- Properties of the anticholinesterase drugs
- The neostigmine ceiling effect
- Experimental evidence for the ceiling effect
- Depth of block and neostigmine effectiveness
- Timing of neostigmine administration
- The zone of blind paralysis
- Recommendations for pharmacologic reversal of nondepolarizing block
- Basis for neostigmine dosing decisions
- Neostigmine doses by depth of block
- Dose and speed of recovery from minimal block
- Patient factors affecting neostigmine reversal
- Muscarinic side effects and anticholinergic cover
- Salivation, bowel motility and nausea
- Neostigmine-induced weakness
- Who is at risk of neostigmine weakness
- Hand grip strength after neostigmine in awake volunteers
- Dose limits when block may be fully recovered
- Airway effects of neostigmine after full recovery
- Neostigmine weakness after sugammadex rescue
- Neostigmine cost over time
- Current relative cost of reversal drugs
- Edrophonium
Sugammadex and Future Binding Drugs
- Structure and binding specificity of sugammadex
- Binding strength and clinical consequence
- Mechanism of sugammadex reversal
- Sugammadex dosing by depth of block
- Delayed sugammadex reversal in the elderly and in comorbidity
- Pharmacokinetics of sugammadex
- Safety profile and drug interactions
- Coagulation and renal failure effects
- Hypothermia and low-dose sugammadex
- Sugammadex dosing weight in obesity and children
- Re-paralysing a patient after sugammadex
- Comparison of the two reversal strategies
- Calabadion 2 and its binding partners
Key Points
- Key points on physiology and receptors
- Key points on drug characteristics
- Key points on monitoring
- Key points on reversal
- Practical sequence for safe extubation
References
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- Barash, Cullen, and Stoelting's Clinical Anesthesia, 9th Edition