v. de sloovere co-assistenten 2014-2015 · muscles (orbicularis oculi, corrugator supercilii). *...
TRANSCRIPT
Neuromuscular blockade
V. De Sloovere
Co-assistenten
2014-2015
Outline
• Why
• Neuromusculaire junction: physiology andpharmacology
• Depolarising NMB
• Nondepolarising NMB
• Monitoring
• Reversal NMB
• Book: Basic’s of Anesthesia 6th edition R. Miller
Why?
• 1942 neuromuscular blockade: milestone in anesthesia
• 1954 increased mortality: suboptimale use ventilators,
no reversal drugs
• Goal: improve intubation and ventilation, immobility
during surgery
• Side effects: increased awareness?? Not too muchneuromuscular blocking but too little anesthesia
• NMB must be worn off before pt regains consciousness
• Residual paralysis is still a problem
• Treshold complete NMB reversal is TOF ratio > 0,9%
Physiology and pharmacology
Physiology and pharmacology
• Neuromuscular junction: prejunctional motor nerveending, synaptic cleft and postjunctional membrane
• Nicotine acetylcholine receptors on pre- andpostjunctional sites
• Neuromuscular transmission: impulse at motor nerveterminal with associated Ca+ influx: release ligand ACh
• ACh binds to ACHRs postjunctional: ∆ membranepermeability to ions (Na+ and K+)
• ↓ transmembrane potential: AP spreads over musclefibers: muscle contraction
• Ach hydrolyzed by Acetylcholinesterase.
Acetylcholine receptors
• Nicotine acetylcholine receptors:
Nm-junction: pre- and postjunctional
Sympatic ganglia
Central nervous system
• Muscarinic acetylcholine receptors
Parasympatic system
Prejunctional receptors
Postjunctional receptors
Extrajunctional receptors
• Present throughout skeletal muscles
• Normally suppressed by neuronal activity
• Prolonged inactivity, sepsis, denervation or
trauma to skeletal muscles: proliferation
extrajunctional receptors
• Nicotine receptors and muscarine receptors
Neuromuscular blocking agents
Depolarizing neuromuscular blocking
drugs
Succinylcholine• Ultra Short acting: 5-10 minutes
• 0,5-1,5 mg/kg IV
• Non-competitive binding
• Sustained depolarization postjunctional membrane: binding 2 alpha subunits.
• Phase I block, high dose or continuous infusion: phase II block
• Fasciculations → flaccid paralysis
• Breakdown: hydrolisis by plasmacholinestrase (produced in liver) to inactive metabolites (succinic acid and choline)
• Use?
Succinylcholine
Side effects:
• Cardiac dysrythmias: Sinus bradycardia, junctional rythm, sinus arrest
• Hyperkalemia (?patients at risk? And why?)
• Myalgia, myoglobinuria
• Increased intra-ocular pressure and intra-gastric pressure
• Neuromuscular diseases
• Extended burns, muscle trauma
• Liver failure
• Anti-cholinesterasedeficienty, gen mutations
• Trismus
• Malignant hyperthermia
Nondepolarising neuromuscular
blocking Drugs
• Longterm, intermediate and short acting
• Competitive to acetylcholine for nicotine cholinergicreceptors
• Which NDMB? : onset, metabolism, clearcance, duration of action
→ Tabel 12,6
Basics of anesthesia, sixth edition, Miller R.D., Pardo M.C.
• Fade
• Antagonisation: anticholinesterase agents
• Onset variable
Nondepolarising neuromuscular
blocking Drugs
Pharmacokinetics
• No central nervous systemic effects
• Influenced hypovolemia, hypothermia and hepatic or renal disease.
• Competitive binding to α- subunit
• Elimination: liver, plasma cholinesterase, Hofmann, or combination
• Highly ionic, H2O soluble, limited lipid solubility
Pharmacodynamics
• Effect NMB can be enhanced or diminished by certain conditions, drugs
• Dose, duration, breakdown → Tabel 12,6 Miller p151 Basics of anesthesia,
sixth edition, Miller R.D., Pardo M.C.
Clinic:
• flaccid paralysis
• Histamine release
Nondepolarising neuromuscular
blocking Drugs
Long-acting NDNMD 1-2h
• Pancuronium: biquaternair aminosteroïd,
cave renal failure, vagolytic effect,
symphatomimetic effect, no histamine release
Long duration
Intermediate-acting NDNMB
• Rocuronium: aminosteroid compound,
different dosage different onset time (0,3-1
mg/kg), RSI, anaphylaxisis reported, renal
clearance, antidote
• Atracurium: bisquaternary ammonium
benzylisoquinoline, elimination by Hofmann
reaction and nonspecific, renal excretion
• Cisatracurium: benzylisoquinolinium, onset 3-
5 min, dose 0,15-0,2 mg/kg, Hofmann
elimination, organ independent clearance
• Vecuronuim: Monoquaternary aminosteroïd
Hepatic and renal excretion, No vagolytic
effect, no histamine release, antidote
Shortacting NDNMB
• Mivacurium: Benzyllisoquinoline, 0,2 mg/kg,
short acting, histamine release, elimination:
plasmacholinesterases
Drug interactions
• Diminished: calcium, corticisteroids,
anticonvulsants (Phenytoine), burns,
prolonged illness, NM diseases
• Enhanced: aminoglycosides, locale
anesthetica, inhalational anesthetics, anti-
arrythmica, dantrolene, magnesium, lithiums
tamoxifen
Monitoring Neuromuscular block
• Peripheral nerve stimulation: measuring force, electromyography, acceleration proportional to force.
→ visual, tactile, quantitative measurement
• Ulnar nerve, facial nerve (innervates?)
• Monitoring is a tool not a cure
• Standard of care monitoring
• Electric stimulation: current applied, duration current andposition electrodes:
• Different monitoring modalities:
Single twitch
Tetanus
Train of four
Double burst stimulation
Single Twitch:
• Supra maximal stimulus
interval 10 s (f <0,1Hz)
• Dose-respons curves
• Amplitude respons compared
to pre-blockade
• Little clinical use
(controle value required),
onset NMB
• >70 % twitch: recovery
Tetanus
• Continuous stimulation for 5 sec at 50 Hz
• Elicit minor degree NMB
• Painful!
• NDPNMB: fade
• DPNMB: no fade
Post tetanic count
• Deep neuromuscular block: No respons to
Single twitch, double burst, TOF
• Tetanic stimulation, 3 sec pause, single twitch
• Response in early stages of recovery (before
TOF)
• 6 min interval
• Post tetanic facilitation
Train of four
• 2Hz stimuli 4 times, TOF ratio: height of 4th to 1st twitch
• TOF ratio > 0,7: no fade, Extubation TOF ratio >0,9
• Twitch count
Double burst stimulation
• 2 burst of 3 electrical stimulations
interval 750 msec
• Detection small degrees NMB
(TOF ratio < 0,3)
• Easier to detect fade
• Close correlation to TOF
McGrath C D , and Hunter J M Contin Educ Anaesth CritCare Pain 2006;6:7-12
Clinic
Reversal
Avoid residual neuromuscular block:
• Residual block PAZA incidence 0,8-6,9%
• Nondepolarising NMB and Phase II block
• Wheiging adverse effects antagonisation
What?
• Anticholinesterase agents
• Anticholinergic agents
• Selective relaxant binding agents
Clinical signs of complete muscle
relaxant reversal
• Require awake, cooperative patient
• Ideal: test before extubation, beforeemergence
• Most clinical tests not specific for respiratoryfunction
• 5-second head lift, sustained handgrip, leg lift, eye opening
• Masseter strenght more sensitive notunfallible
When and what
When?
• TOF ratio: <0,9
• Clinical signs
• TOF 2/4
• What: anticholinesterases: inhibition activity
acetylcholinesterase : accumulation acetylcholine
at nicotine and muscarine receptors
• Neostigmine, pyridostigmine
• Side effect muscarine effects
• ALWAYS add Atropine/Glycopyrrolate
Deep neuromuscular block
• Indications: no absolute indications: option in robot assisted procedures,
eye surgery, laparascopic procedures: bariatric surgery, …
• Monitoring: 1-2 twitches post tetanic count
• Risks: residual NMB: hypoxia, pulmonary complications.
• Acetycholinesterase inhibitors: relatively slow in onset of reversal.
Side effects acetylcholine-induced muscarine receptor
stimulation bradycardia, hypersalivation, nausea and vomiting
• Co-administration of a muscarine agonist, such as atropine or
glycopyrrolate, to counteract some of these side effects.
• Recent studies: high-dose neostigmine is associated with postoperative
complications: muscle weakness and reintubation
• Introduction Sugammadex: improve surgical conditions without adverse
events
• Rocuronium bolus and continuous infusion aiming PTC 1-2.
Selective NMB reversal agentsSugammadex
• Antagonisation steriodal NDNMB: encapsulating, modified
gamma cyclodextrine
• Fast (2-3min)
• No CV side effects
• Cannot intubate-cannot ventilate
• Expensive! Only use on indication
1. General Principles for Avoidance of Residual Paralysis
* NMBDs should only be administered to patients who require
this therapy. Dosing should be individualized based on surgical
necessity, patient factors, and presence of coexisting disease.
* Long-acting NMBDs (e.g., pancuronium) should be avoided.
Intermediate-acting NMBDs should be used whenever feasible.
* Clinical tests of muscle function (head lift, jaw clenching, grip
strength, tidal volume, etc.) are unreliable predictors of recovery
of neuromuscular function.
* To exclude with certainty the possibility of residual paralysis in
patients at risk, clinicians should use objective (quantitative)
neuromuscular monitoring tests.
* Ideally, neuromuscular function should be monitored
objectively (quantitatively) in all patients receiving NMBDs.
2. Principles of Monitoring in Clinical Practice
* Objective (quantitative) monitoring of neuromuscular function should be used.
* Peripheral nerve stimulator units should display the delivered current output, which should be at least 30 mA.
* Assessment of neuromuscular responses should take into consideration the musculature group that is monitored. The time course (onset, recovery) of muscle relaxants is different at peripheral muscles (adductor pollicis) than at central muscles (orbicularis oculi, corrugator supercilii).
* Adequate spontaneous recovery should be established before pharmacologic antagonism of NMBD block with anticholinesterases. This requirement does not apply to reversal with sugammadex.
* The timing of tracheal extubation should be guided by quantitative monitoring tests such as TOF >0.9 or DBS3,3 >0.9.
3. Principles for Pharmacologic Reversal with Anticholinesterases
* During anesthetic techniques that do not enhance the effects of muscle relaxants (such as total IV anesthesia), a minimal TOF count of 2 should be present before administration of anticholinesterases.90
* During anesthetic techniques that enhance the effects of muscle relaxants (such as inhaled volatile anesthesia), a TOF count of 4 should be present before administration of anticholinesterases.19,90
* If recovery to TOF >0.90 is documented by MMG (quantitatively), neostigmine administration should be withheld. Administration of neostigmine to fully recovered patients may decrease upper airway muscle activity and tidal volume.64
4. Reversal Considerations in Clinical Practice * No neuromuscular monitor or peripheral nerve stimulator used.
I. Clinical tests of adequacy of reversal are unreliable—pharmacologic reversal should be administered routinely and only when spontaneous muscle activity is present.
* Peripheral nerve stimulator—subjective (visual, tactile) assessment
I. TOF count 1 or no TOF response—delay reversal.
II. TOF count 2 or 3—administer pharmacologic reversal.
III. TOF with fade (TOF <0.40)—administer pharmacologic reversal.
IV. TOF with no perceived fade (TOF ≥0.40)—administer
pharmacologic reversal, consider low dose (20 μg/kg) of neostigmine.91
* Quantitative evoked response monitor (e.g., AMG, KMG, and EMG)
I. No TOF response or TOF count of 1—delay reversal.
II. TOF count 2 or 3—administer pharmacologic reversal.
III. TOF <0.40—administer pharmacologic reversal.
IV. TOF = 0.40 to 0.90—administer pharmacologic reversal, consider low
dose (20 μg/kg) of neostigmine.
V. TOF >0.90—no reversal recommended
References
• S.J. Brul, S. Murphy Residual neuromuscular block: lessons unlearned. Part II:
methods to reduce the risk of residual weakness Anesth Analg 2010 Jul;
111(1):129-40
• Basics of anesthesia, sixth edition, Miller R.D., Pardo M.C.
Basishandboek voor het studeren!
• Clinical anesthesia, sixth edition, Barash P.G.,Cullen B.F., Stoelting R.K.
Cahalan M., Stock M.C.