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Neuromuscular Relaxants Reversal Agents

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Neuromuscular Relaxants + Reversal Agents Charles E. Smith, MD Professor, Case Western Reserve University Director, Cardiothoracic Anesthesia MetroHealth Medical Center – PowerPoint PPT presentation

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Title: Neuromuscular Relaxants Reversal Agents


1
Neuromuscular Relaxants Reversal Agents
  • Charles E. Smith, MD
  • Professor, Case Western Reserve University
  • Director, Cardiothoracic Anesthesia
  • MetroHealth Medical Center
  • Cleveland, Ohio

2
Objectives
  • Mechanism of action
  • Monitoring
  • Pharmacology
  • non-depolarizers
  • depolarizers
  • Reversal

3
Historical
  • 1942 dTC, long-acting, histamine
  • 1952 sux
  • 1954 6 fold ? in mortality with dTC
  • 1967 panc, long acting, CV stimulation
  • 1986 interm acting relaxants
  • vec no CV effects
  • atrac Hoffman elimination, histamine
  • 1990 to present newer agents to fill specific
    niche
  • roc, cis, miv, pip, dox rap withdrawn from
    market

4
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5
Classical Mechanism of Action
  • Non-depolarizers
  • bind to AchR, post junctional nicotinic receptor
  • competitively prevent binding of Ach to receptor
  • ion channel closed, no current can flow
  • Depolarizers- succinylcholine
  • mimic action of Ach
  • excitation of muscle contraction followed by
    blockade of neuromuscular transmission

6
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7
Postjunctional Nicotinic AchR
8
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9
Margin of Safety
  • Wide margin of safety of neuromuscular
    transmission
  • 70 receptor occupancy before twitch depression

10
Clinical Use
  • Anesthesia
  • facilitate tracheal intubation
  • paralysis for surgery mechanical ventilation
  • ICU
  • ? VO2
  • tetanus
  • status epilepticus
  • ? ICP
  • ? shivering

11
TOF Monitoring
  • TOF
  • 4 supramaximal stimuli at 2 Hz, every 0.5 sec
  • observe ratio of 4rth twitch to first
  • Loss of all 4 twitches
  • profound block
  • Return of 1-2 twitches
  • sufficient for most surgeries
  • Return of all 4 twitches
  • easily reversible

12
Onset Recovery of NM Block
13
Concept of Effective Dose
  • ED90 dose that produces 90 block ( SD) in
    average patient, derived from dose-response
    studies
  • Clinical practice
  • 3 x ED90 at start of case
  • smaller repeat doses during case
  • lighten up NM block at end of case
  • titrate opioids to respiratory rate
  • reverse after dressing applied

14
Effective Dose
  • Method to describe potency of NMBA
  • Derived from DRC in many patients
  • ED 90- dose that produces 90 block
  • ED 90 suc- 0.3 mg/kg
  • ED 90 roc- 0.3 mg/kg
  • ED 90 vec- 0.04 mg/kg

15
Altered Dose-Response
  • Some muscle groups more resistant- DRC
    shifted to right
  • diaphragm, larynx, eye, abdominal
  • Some muscle groups more sensitive- DRC
    shifted to left
  • muscles that maintain patency of upper airway
  • muscles of the thumb

16
Rocuronium Larynx v. Thumb
  • Muscles of the larynx, diaph, eye are more
    resistant to effects of non-depolarizers v. thumb

17
Vecuronium
  • ED90 0.04 mg/kg
  • intubating dose 0.1-0.2 mg/kg
  • onset 2-4 min, clinical duration 30-60 min
  • Maintenance dose 0.01-0.02 mg/kg, duration
    15-30 min
  • Metabolized by liver, 75-80
  • Excreted by kidney, 20-25
  • ½ life ? 60 minutes
  • Prolonged duration in elderly liver disease
  • No CV effects, no histamine release, no vagolysis
  • May precipitate after thiopental

18
Rocuronium
  • ED90 0.3 mg/kg
  • intubating dose 0.6-1.0 mg/kg
  • onset 1-1.5 minutes, clinical duration 30-60
    min
  • Maintenance dose 0.1-0.15 mg/kg, duration 15-30
    min
  • Metabolized by liver, 75-80
  • Excreted by kidney, 20-25
  • ½ life ? 60 minutes
  • Mild CV effects- vagolysis, no histamine release,
  • Prolonged duration in elderly liver disease
  • Only non-depolarizer approved for RSI

19
Cisatracurium
  • ED90 0.05 mg/kg
  • intubating dose 0.2 mg/kg
  • onset 2-4 minutes, clinical duration 60 min
  • Hofmann elimination not dependent on liver or
    kidney for elimination
  • Predictable spontaneous recovery regardless of
    dose
  • ½ life ? 60 minutes
  • No histamine release
  • CV stability
  • Agent of choice for infusion in ICU

20
Succinylcholine
  • ED90 0.3 mg/kg
  • intubating dose 1.0-1.5 mg/kg
  • onset 30-45 sec, clinical duration 5-10 min
  • can be given IM or sublingual
  • dose to relieve laryngospasm 0.3 mg/kg
  • Maintenance dose no longer used
  • Metabolized by pseudocholinesterase
  • prolonged duration if abnormal pc (dibucaine
    20)
  • Prolonged effect if given after neostigmine

21
Succinylcholine Key Concepts
  • Bradycardia nodal rhythms after 2nd dose in
    adults after initial dose in children
  • Hyperkalemia cardiac arrest likely 1 week after
    major burns, or in children with Duchennes
    muscular dystrophy
  • Not contraindicated in patients with head injury
  • May cause malignant hyperthermia or masseter
    spasm
  • Duration increased by prior administration of
    neostigmine

22
Succinylcholine Adverse Effects
  • Bradycardia, nodal rhythms, asystole
  • Especially after 2nd dose give atropine, 0.6 mg,
    IV prior

23
Succinylcholine Adverse Effects
  • Hyperkalemia cardiac arrest in at risk
    patients
  • denervation, burns, myopathy
  • Malignant hyperthermia, masseter spasm
  • ? IOP- blood flow mechanism
  • Myalgias, ? intragastric pressure
  • ? dose requirement for non-depolarizers after sux
  • ? ICP- blood flow mechanism clinically irrelevant

24
Head Injury Sux
25
Sux Hyperkalemia
  • Burns, Hemiplegia, Paraplegia, Quadraplegia
  • ? extrajunctional receptors after burn or
    denervation
  • Danger of hyperkalemia with sux 48 hrs post
    injury until ?
  • Muscular Dystrophy
  • Miscellaneous
  • severe infections, closed head injury, crush,
    rhabdo, wound botulism, necrotizing pancreatitis
  • Renal failure pre-existing hyperkalemia
  • Acidosis ? extracellular K

26
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27
Residual NM Block
  • 1979 42 incidence with long acting drugs
    Viby-Mogensen
  • 1988 ? incidence with vec atrac Bevan, Smith,
    Donati- Mtl
  • 1992 ? ventilatory response to hypoxia, TOF
    0.6-0.7
  • 1997 ? pharyngeal muscle coordination with TOF
    0.6-0.8
  • 1997 panc is risk factor for postop pulmonary
    complications v. vec atrac RCT
    n 693 patients
  • 2003 45 incidence with interm acting drugs w/o
    reversal, TOF 0.9 Debaene, Plaud, Donati-
    France

28
Cholinesterase Inhibitors
  • ? Ach at nicotinic muscarinic receptors to
    antagonize NMB
  • Full reversal depends on diffusion,
    redistribution, metabolism excretion

29
Key Concepts of NMBA Reversal
  • Cholinesterase inhibitors indirectly reverse NMB
  • Head lift x 5 sec- reliable sign of reversal
  • Teeth clenching x 5 sec- reliable sign of
    reversal
  • Usually not difficult to reverse block if 2
    twitches are visible in response to TOF
  • Neostigmine is a minor risk factor for PONV
  • Anticholinergic agents should never be omitted
    with reversal

30
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31
Double Burst
  • TOF fade difficult to detect clinically until lt
    0.2
  • Use double burst
  • 2 short bursts of tetanic stimulation separated
    by 750 ms
  • Easier to detect fade residual block, 0.2-0.7

32
Clinical Evaluation
  • Reliable signs of adequate NM transmission
  • Head lift x 5 s
  • Leg lift x 5 s
  • Hand grip as strong as preop x 5 s
  • Sustained bite
  • Helpful, but unreliable
  • Normal Vt , Vc, cough

33
Reversal of NM Block
  • Clinical practice
  • if no evidence block 4 half-lives omit
    reversal
  • if still evidence block give reversal
  • if unsure give reversal
  • Rule of thumb
  • if 2 twitches of TOF visible, block is usually
    reversible
  • if no twitches visible, best to wait (check
    battery)
  • Neostigmine 2.5 mg/Glycopyrolate 0.5 mg
  • do not omit anti-cholinergic!

34
Suggamadex (Org 25969) Safer way to reverse NMB
  • Gijsenbergh et al, Anesthesiology
    2005103695-703. Belgium. Phase 1 study
  • Modified cyclodextrin
  • Encapsulates roc
  • Promotes dissociation of roc from AchR
  • No recurarization

35

Roc
Org 25969

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37
Summary
  • Indications tracheal intubation, surgery, mech
    ventilation
  • Choice of drug pharmacology other factors
    (histamine)
  • Onset of action
  • sux is fastest
  • roc is suitable alternative
  • Duration
  • non-depolarizing block easily reversible if 2
    twitches
  • residual block ? incidence with intermediate rx
  • Monitoring Reversal TOF, double burst,
    clinical signs
  • Suggmadex will likely replace neostigmine for
    reversal
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