Drugs, Equipment, and Dantrolene - Managing MH
An MHAUS Online Brochure
Last Updated: 10/1/2004

WHAT IS MALIGNANT HYPERTHERMIA?

MH is an uncontrolled increase in skeletal muscle metabolism triggered in susceptible individuals by commonly used general anesthetics (isoflurane, desflurane, sevoflurane, halothane) and the muscle relaxant succinylcholine.  The signs include a greatly increased body metabolism, muscle rigidity, high CO2 production, tachycardia, diaphoresis and high fever.  Death or brain damage usually results from cardiac arrest, but survivors can experience muscle or other internal organ damage.

All volatile inhalation (gas) anesthetics are triggering agents, as is the muscle relaxant succinylcholine, but nitrous oxide is not a trigger and can be used safely.

(see also MHAUS brochure “What is Malignant Hyperthermia” for a more complete description of MH)

HOW IS MH TREATED?

The syndrome must be identified and treated early for optimal outcome.  Preparedness is essential to prevent death from MH. 

  • This brochure provides a checklist of drugs and equipment that should be available to any clinical site where MH triggering anesthetics are administered. 
  • It also discusses how the principle therapeutic drug, dantrolene, works and how much needs to be stocked. 

In addition to an anesthesia machine (if used), ECG monitor, pulse oximeter and capnometer, all locations where general anesthesia is administered should contain:

  • A plan to treat MH, such as the poster available from MHAUS.  The MH Hotline can be contacted at: 1-800-MH-HYPER.
  • A means to continuously monitor end-tidal CO2, blood oxygen saturation and core body temperature by electronic probe.
  • A means to actively cool a patient; e.g., a hypothermia blanket and a refrigerator containing cold saline solution.
  • An MH cart or kit containing the following drugs, equipment, supplies and forms should be immediately accessible to operating rooms.

DRUGS

  1. Dantrolene sodium for injection – 36 vials (each able to be diluted at the time of use with 60 ml sterile water)
  2. Sterile water for injection USP (without a bacteriostatic agent) to reconstitute dantrolene – 1,000 ml x 2
  3. Sodium bicarbonate (8.4%) – 50 ml x 5
  4. Furosemide 40 mg/amp x 4 ampules
  5. Dextrose 50% – 50 ml vials x 2
  6. Calcium chloride (10%) 10 ml vial x 2
  7. Regular insulin 100 units/ml x 1 (refrigerated)
  8. Lidocaine for injection, 100 mg/5 ml or 100 mg/10 ml in preloaded syringes (3).  Amiodarone is also acceptable.  ACLS protocols, as proscribed by the AHA, would be followed when treating all cardiac derangements caused by MH.

GENERAL EQUIPMENT

  1. Syringes (60 ml x 5) to dilute dantrolene
  2. Mini-spike® IV additive pins x 2 and Multi-Ad fluid transfer sets x 2 (to reconstitute dantrolene).  Call MHAUS for ordering info.
  3. Angiocaths:  16G, 18G, 20G, 2-inch; 22G, 1-inch; 24G, ¾-inch (4 each) (for IV access and arterial line)
  4. NG tubes: (sizes appropriate for your patient population)
  5. Blood pump
  6. Irrigation tray with piston syringe (x 1) for NG irrigation
  7. Toomy irrigation syringes (60 ml x 2) for NG irrigation
  8. Micro drip IV set (x 1)

MONITORING EQUIPMENT

  1. Esophageal or other core temperature probes
  2. CVP kits (sizes appropriate to your patient population)
  3. Transducer kits for arterial and central venous cannulation.

    NURSING SUPPLIES

    1. A minimum of 3,000 ml of refrigerated cold saline solution
    2. Large sterile Steri-Drape (for rapid drape of wound)
    3. Three-way irrigating foley catheters:  (sizes appropriate for your patient population)
    4. Urine meter x 1
    5. Irrigation tray with piston syringe
    6. Large clear plastic bags for ice x 4
    7. Small plastic bags for ice x 4
    8. Bucket for ice

    LABORATORY TESTING SUPPLIES

    1. Syringes (3 ml) for blood gas analysis or ABG kits x 6
    2. Blood specimen tubes (each test should have 2 pediatric & 2 large tubes):  (A) for CK, myoglobin, SMA 19 (LDH, electrolytes, thyroid studies); (B) for PT/PTT, fibrinogen, fibrin split products; (C) CBC, platelets; (D) blood gas syringe (lactic acid level)
    3. Urine collection container for myoglobin level.  Pigmenturia indicates that renal protection is mandated, unless the centrifuged or settled sample shows clear supernatant, i.e., the coloration is due to red cells in the sample.
    4. Urine dipstick:  hemoglobin

    FORMS 

    1. Laboratory request forms:  ABG form x 6; hematology form x 2; chemistry form x 2; coagulation form x 2; urinalysis form x 2; physician order form x 2
    2. Adverse Metabolic Reaction to Anesthesia (AMRA) Report form (obtained from the MH Registry)
    3. Consult form, if needed, for requesting a consultation from another physician

    HOW IS THE ANESTHESIA MACHINE PREPARED FOR MHS PATIENTS?

    Ensure that anesthetic vaporizers are disabled by removing, draining or taping in the “OFF” position.  Some consultants recommend changing CO2 absorbent (soda lime or baralyme).  Flow 10L/min O2 through circuit via the ventilator for at least 20 minutes.  If fresh gas hose is replaced, 10 minutes is adequate.  During this time a disposable, unused breathing bag should be attached to the Y-piece of the circle system and the ventilator set to inflate the bag periodically.  Use new or disposable breathing circuit.  Use the expired gas analyzer to confirm absence of volatile gases, as some newer machines are not so easily cleaned of volatile agents. 

    TO REPORT AN MH EPISODE TO THE NORTH AMERICAN MH REGISTRY, WHERE ARE THE FORMS OBTAINED?

    North American MH Registry of MHAUS (www.mhaus.org)
    Children’s Hospital of Pittsburgh
    Anesthesiology Dept, Room 7449
    3705 Fifth Ave at DeSoto St
    Pittsburgh PA 15213-2583
    1-888-274-7899

    (or through MHAUS)

    HOW DOES THE ANTIDOTE DANTROLENE WORK?

    Dantrolene is the only specific treatment for MH.  Dantrolene sodium decreases the release of calcium from the storage sites in muscle (the sarcoplasmic reticulum) by binding to the calcium channel site in muscle that causes calcium release into the cell.  Following the initiation of MH, intracellular calcium levels rise due to abnormal release from the sarcoplasmic reticulum; dantrolene restores the balance between release and uptake.

    Dantrolene does not significantly potentiate the effects of non-depolarizing relaxants or interfere with reversal of muscle relaxants.  When dantrolene is used with non-depolarizing muscle relaxants, care should be taken to ensure muscle strength has returned prior to extubation.  Dantrolene does not interfere with reversal of the muscle relaxant’s effect. 

    Dantrolene may cause significant muscle weakness in patients with pre-existing muscle disease and should be used with extreme caution in those patients.  Phlebitis often follows administration of dantrolene, and therefore should be infused through the largest possible vein.

    When used with calcium channel blockers, dantrolene sodium for injection may produce life-threatening hyperkalemia and myocardial depression.  Otherwise there does not appear to be significant negative interaction with other drugs.

    Once a patient has been successfully treated with intravenous dantrolene, he or she may be switched to oral dantrolene for several days.

    IS PRETREATMENT WITH DANTROLENE NECESSARY?

    No.

    WHO SHOULD STOCK DANTROLENE & HOW MUCH?

    All facilities, including ambulatory surgery centers and offices, where MH triggering anesthetics (halothane, enflurane, isoflurane, desflurane, sevoflurane, and succinylcholine) are administered, should stock a minimum of 36 vials of dantrolene sodium for injection, along with the other drugs and devices necessary to treat an MH reaction.  If potent volatile agents are not used, and succinylcholine is available for resuscitation, a minimum of 36 vials of dantrolene sodium for injection should be available.  If none of these is used or available, then dantrolene sodium for injection need not be present.

    WHERE SHOULD DANTROLENE SODIUM FOR INJECTION BE KEPT?

    Dantrolene sodium for injection should be kept in or very close to the operating room, so that it is available immediately if MH occurs.  Dantrolene may be stored at room temperature.  A supply of sterile water for injection USP (without a bacteriostatic agent) should be kept nearby to mix with dantrolene before injection (60 ml/vial).

    ARE THERE ANY ADVANTAGES IN SHARING A SUPPLY OF DANTROLENE?

    No.  Minutes count in an MH emergency.  The Professional Advisory Council of MHAUS strongly recommends that an adequate supply of dantrolene sodium for injection be available wherever general anesthesia is administered.

    Responsibility for treatment rests with the facility where the surgery is performed and, therefore, sharing is not a good alternative.

    DOESN’T DANTROLENE OUTDATE TOO QUICKLY AND COST TOO MUCH TO KEEP ON HAND FOR AN OCCURRENCE WHICH IS NOT VERY LIKELY TO HAPPEN?

    No.  At present, dantrolene has a shelf life of three years from the date of manufacture.  Although fulminant MH episodes are unusual, they do happen; and, sadly, patients still die from MH.  Remember that dantrolene is like a defibrillator; it is kept ready for use at all times, even though the need is rare.  The cost can be prorated among all patients.

    WHAT IS THE COST OF DANTROLENE?

    The cost of maintaining 36 vials in stock is approximately $909 per year, $76/month or $2.51/day – a tiny fraction of most facility budgets and a very small price to pay for safety.  The cardiac defibrillator is a necessary emergency tool in all OR suites, is used seldom, and is paid for in time by each patient’s charges.  Dantrolene sodium for injection is an appropriate parallel to that situation and is cheap when prorated.  Contact Procter & Gamble Pharmaceuticals Customer Service at 1-800-448-4878 for current pricing, routine ordering, reordering and emergency orders.

    _________________________________________

    There is still much that is not known about malignant hyperthermia.  Research is
    continuing. The information in this brochure is consistent with current medical opinion. 
    Application to specific patient needs should be discussed with a physician.
    Contact the MH Hotline for current information:     1 (800) MH-HYPER
    _________________________________________

    All brochures may be purchased online through our eSHOP.