Muscle Relaxants

Muscle Relaxants


What are they used for?

Facilitate intubation of the trachea  Facilitate mechanical ventilation  Optimized surgical working conditions


Muscle Relaxants


How skeletal muscle relaxation can be achieved?

  

High doses of volatile anesthetics Regional anesthesia Administration of neuromuscular blocking agents


Proper patient positioning on the operating table

Muscle Relaxants


Muscle relaxants must not be given without adequate dosage of analgesic and hypnotic drugs Inappropriately given : a patient is paralyzed but not anesthetized

Muscle Relaxants


How do they work?



Neuromuscular junction
  

Nerve terminal Motor endplate of a muscle Synaptic cleft

  

Nerve stimulation Release of Acetylcholine (Ach) Postsynaptic events

Neuromuscular Junction (NMJ)

Binding of Ach to receptors on muscle end-plate

Muscle Relaxants


Depolarizing muscle relaxant



Succinylcholine Short acting Intermediate acting Long acting

Nondepolarizing muscle relaxants

  

Depolarizing Muscle Relaxant

 

Succinylcholine What is the mechanism of action?

     

Physically resemble Ach Act as acetylcholine receptor agonist Not metabolized locally at NMJ Metabolized by pseudocholinesterase in plasma Depolarizing action persists > Ach Continuous end-plate depolarization causes muscle relaxation

Depolarizing Muscle Relaxant




Succinylcholine
What is the clinical use of succinylcholine?  Most often used to facilitate intubation What is intubating dose of succinylcholine?  1-1.5 mg/kg  Onset 30-60 seconds, duration 5-10 minutes

Depolarizing Muscle Relaxant



Succinylcholine  What is phase I neuromuscular blockade?



What is phase II neuromuscular blockade?

 

Resemble blockade produced by nondepolarizing muscle relaxant Succinylcholine infusion or dose > 3-5 mg/kg

Depolarizing Muscle Relaxant



Succinylcholine  Does it has side effects?

       

Cardiovascular Fasciculation Muscle pain Increase intraocular pressure Increase intragastric pressure Increase intracranial pressure Hyperkalemia Malignant hyperthermia

Nondepolarizing Muscle Relaxants



What is the mechanism of action?

   

Compete with Ach at the binding sites Do not depolarized the motor endplate Act as competitive antagonist Excessive concentration causing channel blockade Act at presynaptic sites, prevent movement of Ach to release sites

Nondepolarizing Muscle Relaxants



Long acting


Pancuronium Atracurium Vecuronium Rocuronium Cisatracurium Mivacurium

Intermediate acting
   

Short acting


Nondepolarizing Muscle Relaxants



Pancuronium
   

Aminosteroid compound Onset 3-5 minutes, duration 60-90 minutes Intubating dose 0.08-0.12 mg/kg Elimination mainly by kidney (85%), liver (15%) Side effects : hypertension, tachycrdia, dysrhythmia,

Nondepolarizing Muscle Relaxants



Vecuronium
 

  

Analogue of pancuronium much less vagolytic effect and shorter duration than pancuronium Onset 3-5 minutes duration 20-35 minutes Intubating dose 0.08-0.12 mg/kg Elimination 40% by kidney, 60% by liver

Nondepolarizing Muscle Relaxants



Atracurium


Metabolized by
 

Ester hydrolysis Hofmann elimination

  

Onset 3-5 minutes, duration 25-35 minutes Intubating dose 0.5 mg/kg Side effects :
 

histamine release causing hypotension, tachycardia, bronchospasm Laudanosine toxicity

Nondepolarizing Muscle Relaxants



Cisatracurium
     

Isomer of atracurium Metabolized by Hofmann elimination Onset 3-5 minutes, duration 20-35 minutes Intubating dose 0.1-0.2 mg/kg Minimal cardiovascular side effects Much less laudanosine produced

Nondepolarizing Muscle Relaxants



Rocuronium
 

 

Analogue of vecuronium Rapid onset 1-2 minutes, duration 20-35 minutes Onset of action similar to that of succinylcholine Intubating dose 0.6 mg/kg Elimination primarily by liver, slightly by kidney

Alteration of responses
     

Temperature Acid-base balance Electrolyte abnormality Age Concurrent diseases Drug interactions

Alteration of responses


Concurrent diseases
 

Neurologic diseases Muscular diseases

 

Myasthenia gravis Myasthenic syndrome (Eaton-Lambert synrome)

 

Liver diseases Kidney diseases

Alteration of responses


Drug interactions
      

Inhalation agents Intravenous anesthetics Local anesthetics Neuromuscular locking drugs Antibiotics Anticonvulsants Magnesium

Monitoring Neuromuscular Function

What are the purposes of monitoring?


Administer additional relaxant as indicated Demonstrate recovery

Monitoring Neuromuscular Function

How to monitor?
 

Clinical signs Use of nerve stimulator

Monitoring Neuromuscular Function



Clinical signs


Signs of adequate recovery

  

Sustained head lift for 5 seconds Lift the leg (child) Ability to generate negative inspiratory pressure at least 25 cmH2O, able to swallow and maintain a patent airway Other crude tests : tongue protrusion, arm lift, hand grip strength

Monitoring Neuromuscular Function



Use of nerve stimulator

  

 

Single twitch : single pulse 0.2 msec Tetanic stimulation Train-of-four : series of 4 twitch, 0.2 msec long, 2 Hz frequency, administer every 1015 seconds Double burst stimulation Post tetanic count

Evoked responses during depolarizing and nondepolarizing block

Hierarchy of Neuromuscular Blockade

Fraction of receptor occupied by nondepolarizing muscle relaxant

Response to nerve stimulator

Whole body signs

99-100 95 90 75 50 30

No response Posttetanic facilitation present One of four twitch of TOF present Four twitch of TOF present, TOF ratio 0.7 100-Hz tetanus sustained 200-Hz tetanus sustained

Flaccid, extreme relaxation Diaphragm moves, hiccough possible Abdominal relaxation adequate for most prcedure Tidal volume and vital capacity normal Passes inspiratory pressure test Head lift and hand-grip sustained

Antagonism of Neuromuscular Blockade

Effectiveness of anticholinesterases depends on the degree of recovery present when they are administered


Anticholinesterases


 

Neostigmine  Onset 3-5 minutes, elimination halflife 77 minutes  Dose 0.04-0.07 mg/kg Pyridostigmine Edrophonium

Antagonism of Neuromuscular Blockade



What is the mechanism of action?

 

Inhibiting activity of acetylcholineesterase More Ach available at NMJ, compete for sites on nicotinic cholinergic receptors Action at muscarinic cholinergic receptor
  

Bradycardia Hypersecretion Increased intestinal tone

Antagonism of Neuromuscular Blockade



Muscarinic side effects are minimized by anticholinergic agents



Atropine


Dose 0.01-0.02 mg/kg

 

Scopolamine glycopyrrolate

Reversal of Neuromuscular Blockade



Goal : re-establishment of spontaneous respiration and the ability to protect airway from aspiration