Non depolarising Muscle relaxants

Action: Competitive antagonism of Acetylcholine at post synaptic nicotinic receptors. Attachment to one alpha sub-unit leading to a classic non-depolarising block

  1. T 4 /T 1 < 0.7 Train of four fade
  2. Tetanic fade
  3. Post tetanic facilitation
  4. Augmentation by other non-depolarising muscle relaxants and by depolarising muscle relaxants
  5. Reversal by Acetylcholine
  Pancuronium Vecuronium Atacurium Cisatacurium Mivacurium Rocuronium Rapacuronium Pipecuronium
Absorption Only given parenterally
Distribution Positive charged amonium ion limits molecules to the extracellular fluid, all have a small volume of distribution ~0.2 l/kg
Metabolism Deacetylation Deacetylation Hoffman degradation Hoffman degradation Plasma cholinesterase Minimal Hydoxylation Minimal
    3 deacetyl vecuronium Laudanosine
(eliptogenic)
10 isomers 		R cis-R 'cis isomer 3 isomers   ORG-9488 active metabolite  
Excretion Renal / Bile Renal / Bile Renal Renal Renal / Bile Renal / Bile Renal / Bile Renal / Bile
Chemistry Bi quaternary Amino steroid Mono quaternary Amino steroid Bi quaternary benzyl iso quinolone Bi quaternary benzyl iso quinolone Bi quaternary benzyl iso quinolone Bi quaternary Amino steroid Mono quaternary Amino steroid Bi quaternary Amino steroid
Dose E D 95 = dose to suppress the twitch by 95% of its original height.  Normal intubation dose is 2 x E D 95 and the dose used for a rapid sequence induction is normally 3-4 x  E D 95
E D 95 0.06 mg/kg 0.05 mg/kg 0.25 mg/kg 0.05 mg/kg 0.08 mg/kg 0.4 mg/kg 1.5 mg/kg 0.05 mg/kg
Intubation 0.1 mg/kg 0.1 mg/kg 0.5 mg/kg 0.1 mg/kg 0.15 mg/kg 0.4 mg/kg 1.5 mg/kg 0.07 mg/kg
Maximum block (min) 4-5 3-4 3-4 4.5-5.5 2-3 2-3 1.5 4-5
Clinical duration
(T 1 0-25%)		 90 45 40 30-40 15-20 30 10-15 95
Recovery index  min
(T 1 25-75%) 		  60 50 15-20 25 30 10-15 130
               

Succinyl choline


1 mg/kg

0.8-1.2


5-8


5


NO!
2-15 mg/kg/hr
Rapid sequence intubation n/a 0.2 mg/kg 0.75 mg/kg 0.2 mg/kg 0.25 mg/kg 0.6 mg/kg 2.5 mg/kg
Maximum block (min)   2-2.5 2-2.5 2.5-3 1.8-2.5 1.8-2.2 0.9-1.2
Clinical duration min
(T 1 0-25%)		   60 60 60 30-40 40-45 18-25
Recovery  index  min
(T 1 25-75%)		   80 80 15-20 30-35 40-45 15-25
Reversal by neostigmine   only >25% recovery only >25% recovery only >25% recovery only >25% recovery only >25% recovery even @ <25%
CD to 5 min
RI to 10 min
Infusion       1.2-1.5 mg/kg/min 4-10 mg/kg/min   accumulation of ORG-9488
Formulation Pavulon 2mg/ml Norcuron 4mg or 10mg powder Tracrium 10mg/ml Nimbex 2mg/ml Mivacron 2mg/ml Esmeron 10mg/ml powder Duramax 2mg/ml

Indications
  1. Endotracheal intubation.
    Elective sequence induction without residual gastric contents and controllable airways
    Rapacuronium at 2.5mg/kg appears to be a viable alternative to succinyldicholine for a rapid sequence induction and intubation
  2. Surgical relaxation.
    Considered to extend from maximul relaxation to return of 25% of twitch height
    Mivacurium for procedures < 15 minutes
    Vecuronium, Atracurium and Rocuronium for procedures < 30 minutes
    Pancuronium, Doxacurium and Pipecurium for procedures > 90 minutes
    Infusions of shorter acting drugs to avoid nadirs of muscle relaxation
    Mivacurium 4-10 ug/Kg/min
  3. Intensive care:
    Used when cooling the patient to prevent shivering and non shivering thermogenesis, both increase oxygen demand drastically.
    Mechanical ventilation.  Optimise patient ventilator synchrony, patient comfort and analgesia before even considering their usage
  4. Neonates
    Pancuronium the mg/kg = the adultdose. 
    Their increased sensitivity to non depolarising muscle relaxants is counteracted by the decreased concentrations attained as they have an increased volume of distribution
    The increase in heart rate is beneficial in maintaining cardiac output.
  5. Infants or children: Any agent acceptaple.  Expect a more rapid onset of block.   They have a higher cardiac output in relation to body weight
  6. Elderly:
    Atracurium or cisatracurium
    Declining renal and hepatic function (including pseudocholinesterase function)
    Delayed onset of block - Lower delivery of the drug to the neuromuscular junction
  7. Renal disease:
    Atracurium or cisatracurium
    Decreased renal clearance of pancuronium and vecuronium
    Decreased pseudocholinesterase activity with Mivacurium
    Increased volume of distribution with decreased clearance of Rocuronium
  8. Hepatic disease:
    Atracurium of cisatracurium
    Increased volume of distribution with prolongation of terminal half lives
    Decreased pseudocholinesterase activity with Mivacurium
  9. Cardiovascular disease:
    vecuronium, doxacurium or pipecuronium are used for cardiac bypass where controlled ventilation is continued after surgery
  10. Thermal injury:
    All agents used in larger than normal doses due to proliferation of nonjunctional Acetylcholine nicotinic receptors
  11. Reduced cholinesterase activity:
    Avoidance of Mivacurium
  12. Diseases that prolong muscle relaxation:

Atracurium or Vecuronium in small titrated doses Reversal of Mivacurium complicated with anticholinesterases

  Pancuronium Vecuronium Atacurium Cisatacurium Mivacurium Rocuronium Rapacuronium Pipecuronium
Effects                
Histamine release no no +++ no ++ no + no
Ganglionic blockade + no no no no no no no
Vagolytic ++ no no no no + no no
sympatho - mimetic ++ no no no no no no no
Cardio vascular                
Heart rate Increase +++ Stable Reflex increase ++ minor increase Reflex increase + Increase + Reflex increase + Stable
SVR Stable Stable Decrease ++ Minor
Decrease 		Decrease + Stable Stable Stable
CO Increase Stable Stable Stable Stable Stable Stable Stable
MAP Increase Stable Decrease Stable Decrease Stable Stable Stable
Respiratory Apnoea, don't give these drugs unless you have everything available to ensure intubation of the airway
broncho spasm No No Possibility Possibility Possibility No Possibility No
secretions Increased Increased Increased Increased Increased Increased Increased Increased
Central nervous system
Intra ocular pressure   Increased            
Intra cranial pressure   Increased            
Prophyria Not safe Not safe Safe Safe Safe Not safe Not safe Not safe
Date of First Publication: 2000-6-30 Date of Last Update: 2006/10/24Web page author: Click here