Dantrolene inhibits calcium release via RyR1 antagonism and impairs calcium-dependent muscle contraction.

This rapidly halts the increases in metabolism and secondarily results in a return to normal levels of catecholamines and potassium.

Dose is 2 mg/kg; repeat every 5 minutes until vital signs normalise, to a total dosage of 10 mg/kg if needed.

Dantrolene takes ~ 6 minutes to have any effect

The solution is prepared by mixing 20 mg of dantrolene with 3 g of mannitol in 60 ml of sterile water. Reconstitute each 20 mg vial with 60 ml sterile water. The powder for reconstitution contains mannitol and Sodium hydroxide. Use within 6 hours.

Since dantrolene is relatively insoluble, preparation is tedious and time consuming, and its preparation should not be the responsibility of the primary anesthesiologist involved in the patient’s management. (May occupy several nurses)

All patients who develop MH, require at least 24 hours of posttreatment management in a critical-care setting as there is chance of reappearance of symptoms ( known as recrudescence )

In the ICU, continue @1mg/kg q6h for 24 hours
May be given enterally if GIT function is normal (price ~ 1000 x less)

The actions of dantrolene include:

inhibition of release of Ca ++ from the SR, without affecting re-uptake
? antagonises the effects of Ca ++ at the actin/myosin – troponin/tropomyosin level
muscular weakness, which may potentiate NMJ blockade ~ 5-15 mg/kg produces significant muscular relaxation
there is no effect on NMJ transmission
up to 15 mg/kg there is no significant effect on the CVS
up to 30 mg/kg there is no significant effect on respiration

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