Rocuronium

[SH4:p238-p240]

Quick summary

 

 

Usage

 

 

Structure

Structure

• Monoquaternary aminosteroid nondepolarising NMBD

Pharmacodynamics

Effects by systems

CVS

• Like other aminosteroid NMBDs,
  --> Rocuronium has no CVS or histamine release effect
• But unlike other aminosteroid NMBDs,
  --> Rocuronium has a slight vagolytic effect at high doses

Muscle relaxation

• Laryngeal muscles are more resistant to the effect of rocuronium than adductor pollicis
  * Rapid onset of action at adductor pollicis, like suxamethonium
  * But at laryngeal adductors, action of rocuronium is delayed compared to suxamethonium
• Laryngeal adductor muscles and diaphragm are more resistant to rocuronium than adductor pollicis
  --> Complete suppression of single-twitch response at the adductor does not confirm laryngeal muscle and diaphragm are paralysed

Pharmacokinetics (PK)

Absorption

IV or IM

Distribution

• Vd = 203 mL/kg

Metabolism

• Deacetylation does NOT occur
• Unlike vecuronium, rocuronium does not have active metabolite

Elimination

• Rocuronium is mostly excreted unchanged in the bile
  * Up to 50% in 2 hours
• Renal excreation of rocuronium may be > 30%
• Clearance = 3.7 mL/kg/min

Action profile

• Onset of action = within 1 - 2 minutes
• Duration of action = 20 - 35 minutes
  * With 2 x ED95
  * Action is longer at higher doses
• Low potency
  --> Large number of rocuronium molecules are administered
  --> Greater number of molecules available to diffuse into the NMJ
  --> More rapid onset of action
• At doses of 3 or 4 times the ED95
  --> Onset of action resembles suxamethonium
• Elimination half-time = 73 minutes

Pharmaceutics

Presentation

• 25 mg in 2.5 mLs
• 50 mg in 5 mLs
• 100 mg in 10 mLs

Composition

• Active = Rocuronium bromide
• Inactive
  * Sodium acetate
  * NaCl
  * Acetic acid
  * Water
• pH 3.8 - 4.2

Storage

• Store at 2 - 8 degrees Celcius
• Discard after 12 weeks in room temperature

Clinical

Administration

• ED95 = 0.3 mg/kg
• Rocuronium 0.45 mg/kg
  --> Acceptable intubation condition after 90 seconds
• Rocuronium 0.6 mg/kg
  * Acceptable intubation condition after 60 seconds
  * Clinical duration (duration till recovery to 25% control twitch height) = 30 - 40 min
  * Total duration (duration till recovery to 90% control twitch height) = 50 minute
• Rocuronium 1.0 mg/kg
  * Clinical duration = almost one hour
• Maintenance dose = 0.15mg/kg
  * Given when twitch height has recovered to 25% of control height, or when there is 2-3 response to train of four stimulation
• As infusion,
  * 0.3 - 0.6 mg/kg/hour
  * 0.3 - 0.4 mg/kg/hour with inhalational anaesthetics

NB:

• Doses higher than 1.0 mg/kg do not improve speed of onset, but prolong the route of administration, and the dosage for each different route.

Interaction

Effects of rocuronium is increased in the following conditions

• Hypokalaemia
• Hypocalcaemia
• Hypermagnesaemia
• Hypoproteinaemia
• Dehydration
• Acidosis
• Hypercapnia
• Cachexia

Special consideration

Obesity

• If the dosage is calculated based on real body weight
  --> Duration of action may be prolonged

Renal dysfunction

• In renal failure, rocuronium may produce a modestly prolonged duration of action

Hepatic dysfunction

• Liver disease increase Vd
  --> Can prolong duration of action

Elderly

(>70 year old)

• Similar speed of onset
• Prolonged duration of action
  * Due to decreased hepatic clearance
• Pharmacodynamics is unchanged

Hypothermia

• NMJ effect of rocuronium is increased and duration prolonged

Sugammadex

[Anesthesiology 2006 April Vol 140(4): "Sugammadex: A revolutionary approach to neuromuscular antagonism"]

• A modified gamma-cyclodextrin
• Forms very tight 1:1 complexes with aminosteroid-based relaxants
  --> Irreversible chelating agent for rocuronium, pancuronium, and vecuronium
• Sugammadex does not have equal affinity with all aminosteroids
  * Reversal of pancuronium requires a larger dose
  * Trials cited seem to be based on rocuronium, but the editorial said it works well for vecuronium as well
• Does not reverse the effect of benzylisoquinolinium NMBDs
• Seems to have minimal side effects
• Does not require co-administration of anticholinergic drugs
• Depends entirely on renal elimination
  --> When rocumonium is bound to sugammadex, hepatic elimination is no longer available

Cyclodextrin

[Wikipedia]

• Cyclodextrin are cyclic oligosaccharides
• Alpha-cyclodextrin is a 6 sugar ring molecule
• Beta-cyclodextrin is a 7 sugar ring molecule
• Gamma-cyclodextrin is a 8 sugar ring molecule

Trivia

History

 

Others

Brand name = Esmeron