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DANTROLENE

CLASS

Muscle relaxant

PRESENTATION

Orange lyophilised powder. 

Formulations

  • 20mg dantrolene vial (with 3g mannitol)
  • 250mg dantrolene vial

INDICATIONS & DOSING

Malignant hyperthermia

  • Adult; 200mg (10x 20mg vials) or 250mg (1x 250mg vial) IV bolus
  • Paediatric; 2.5mg/kg IV bolus
  • Repeat dose every 10-15 minutes until clinical resolution
  • Maximum dose 10mg/kg unless manifestations of syndrome reappear

PRACTICALITIES

Administration

  • Reconstitute 20mg dantrolene vial with 60ml of water
  • Reconstitute 250mg dantrolene vial with 5ml of water 

Incompatibilities

  • Sodium chloride
  • 5% dextrose
  • Precipitates in some glass containers, mix in vials provided 

Practice tips

  • Ensure intravenous line is patent, avoid extravasation due to high pH

PHARMACOKINETICS

Onset

  • IV; minutes 

Duration of action

  • 3-5 hours 

Metabolism

Majority hepatic metabolism to inactive metabolites, specific metabolic pathways unknown 

Elimination

15-25% renal excretion, specific elimination pathways unknown

MECHANISM

Inhibition of ryanodine receptors in the sarcoplasmic reticulum of skeletal muscle reduces muscle contraction

DESIRED CLINICAL EFFECTS

Musculoskeletal

  • Skeletal muscle relaxation
  • Termination of malignant hyperthermic crisis 

Cardiovascular

  • Improves beta-adrenergic receptor responsiveness

OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES

Respiratory

  • Respiratory failure in those with respiratory depression or compromise, secondary to muscle weakness 

Renal

  • Volume depletion secondary to mannitol load 

Neurological

  • Sedation 

Gastrointestinal

  • Dysphagia
  • Fatal and non-fatal hepatic dysfunction 

Other

  • Extravasation, alkaline tissue necrosis

CONSIDERATIONS

Precautions

  • Hepatic disease
  • Where spasticity is required to maintain posture or respiratory function 

Obstetric 

ADEC category B2 

Drug interactions

  • Co-administration with calcium-channel blockers (specifically verapamil) may lead to fatal hyperkalaemia
  • Potentiates the effects of drugs with respiratory depressant action
  • Potentiates the effects of CNS depressants
  • Potentiates the effect of neuromuscular blockers

REFERENCES

Drug information has been compiled from multiple sources including

  • Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
  • Micromedex (IBM)
  • BJA Education (Oxford Academic)
  • Pharmacology for Anaesthesia and Intensive Care (Cambridge)
  • Australian Prescriber (NPS MedicineWise)

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