Last Updated: 5/1/2008
DRUGS, EQUIPMENT AND DANTROLENE?
• This brochure provides a checklist of drugs and equipment that should be available to any clinical site where MH triggering anesthetics may be administered.
• It also discusses how the principal therapeutic drug, dantrolene, works and how much needs to be stocked.
WHAT IS MALIGNANT HYPERTHERMIA?
MH is an uncontrolled increase in skeletal muscle metabolism triggered in susceptible individuals by commonly used general anesthetics (isoflurane, desflurane, enflurane, ether, sevoflurane, methoxyflurane, cyclopropane and halothane) and the muscle relaxant, succinylcholine. The signs may include a greatly increased body metabolism, high end-tidal and blood CO2 levels that cannot be attributed to inadequate ventilation, tachycardia or arrhythmias, rapid and deep breathing in the non-paralyzed patient, profuse sweating (diaphoresis), dark red or cola-colored urine, muscle rigidity and/or high fever. If a severe episode occurs, death or brain damage usually results from cardiac arrest or a severe coagulation problem, but survivors can experience muscle or other internal organ damage.
HOW IS MH TREATED?
The syndrome must be identified and treated early for optimal outcome. Preparedness is essential to prevent death from MH.
In addition to an anesthesia machine (if used), EGG monitor, pulse oximeter and capnometer, all locations where general anesthesia is administered should contain:
• A plan to treat MH, such as the poster and procedure manual 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(s) (over and under the patient) and a refrigerator containing cold isotonic saline for IV infusion and for gastric, peritoneal or rectal irrigation, as appropriate. Ice is much more effective at cooling, though
core cooling using iced saline intravenously may be effective (0.5°C./liter in a 70 kg adult), the volume of IV saline that should be rapidly infused limits maximum effect. Beware of unintentional hypothermia!
An MH cart or kit containing the following drugs, equipment, supplies and forms should be immediately accessible to operating rooms.
Therapy should be aimed at prompt treatment of hyperkalemia, administration of dantrolene, hyper-ventilation, and cooling to target core temperature
38°C.
1. Dantrolene - 36 vials should be available in each institution where MH can occur, each to be diluted at the time of use with 60 ml sterile water for injection USP (without a bacteriostatic agent).
2. Sterile water for injection USP (without a bacteriostatic agent): Each vial of dantrolene should be reconstituted by adding 60 ml of sterile water for injection USP (without a bacteriostatic agent) and the vial shaken until the solution is clear. This water should be at room temperature or may be pre-warmed to body temperature (38-39°C or 98-99° F). We advise that the sterile water be stored in 100 ml vials, not bags, to avoid accidental IV administration of this hypotonic solution.
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 prescribed by the AHA, would be followed when treating all cardiac derangements caused by MH.
*Lidocaine or procainamide should not be given if a wide-QRS complex arrhythmia is likely due to hyperkalemia; this may result in asystole.
GENERAL EQUIPMENT1. 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 information.
3. Angiocaths: 16G, 18G, 20G, 2-inch; 22G, 1-inch; 24G, 3/4-inch (4 each) (for IV access and arterial line)
4. NG tubes: (sizes appropriate for your patient population)
5. Toomy irrigation syringes (60 ml x 2) with adapter for NG irrigation
6. Micro drip IV set (x 1)
Monitoring Equipment
1. Esophageal or other core (e.g., nasopharyngeal, tympanic membrane, rectal, bladder, pulmonary artery catheter) 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 for IV cooling
2. Large sterile Steri-Drape (for rapid drape of wound)
3. Urine meter x 1
4. Irrigation tray with piston (60cc irrigation) syringe
5. Large clear plastic bags for ice x 4
6. Small plastic bags for ice x 4
7. Bucket for ice
8. Test strips for urine analysis
Laboratory Testing Supplies
1. Syringes (3 ml) for blood gas analysis or ABG kits x6
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) If no immediate laboratory analysis is available, samples should be kept on ice for later analysis. This may well prove useful on retrospective review and diagnosis. Blood cultures are very useful and should be included to rule out bacteremia.
3. Urine collection container for myoglobin level. Pigrnenturia (e.g , brown or red urine and heme positive dipstick) indicates that renal protection is mandated, when the centrifuged or settled
sample shows clear supernatant, i.e., the coloration is due to red cells in the sample.
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 MHAUS or the NAMH Registry of MHAUS)
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, or taping in the "OFF" position. Most vaporizers have a significant reservoir of anesthetic that cannot be drained, thus draining is not an acceptable choice. Some consultants recommend changing CO2 absorbent (soda lime or baralyme). Flow lOL/min O2 through circuit via the ventilator for at least 20 minutes. Newer anesthesia "work stations" may require up to 40 minutes for purging residual gases; consult manufacturer information. 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.
WHERE DO I GET AN AMRA FORM TO REPORT AN MH EPISODE?
North American MH Registry of MHAUS Children's Hospital of Pittsburgh, PA
1-888-274-7899 https://www.mhreg.org/Downloads.aspx
MHAUS Sherburne, NY 607-674-7901 http://www.mhaus.org
HOW DOES THE ANTIDOTE DANTROLENE WORK?
Dantrolene is the only currently accepted specific treatment for MH. Dantrolene suppresses the exaggerated rise in muscle cell calcium that seems to trigger MH by binding to the calcium channel site in muscle that is responsible both for calcium release and, likely, calcium entry into the cell. Current evidence indicates that during the initiation of MH, intracellular calcium levels rise due both to abnormal release from the sarcoplasmic reticulum and calcium entry from the extracellular space; dantrolene restores the balance between calcium release, entry and uptake.
Dantrolene does not significantly potentiate the effects of non-depolarizing relaxants or interfere with reversal of muscle relaxants unless there is an associated neuromuscular disease. 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 while not delaying administration, dantrolene should be infused through the largest possible vein.
When used with calcium channel blockers (verapamil or diltiazem), dantrolene 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 for 24 hours with intravenous dantrolene, he or she may be switched to oral dantrolene until the CK level is trending down and there is no further evidence of acidosis or hypermetabolism and temperature spikes.
IS PRETREATMENT WITH DANTROLENE NECESSARY?
No.Can warming the sterile water facilitate mixing?
MHAUS recommends using the manufacturer's instructions regarding the reconstitution of dantrolene. MHAUS acknowledges that warmed diluent (37-39°C) may expedite the reconstitution and delivery of dantrolene during an MH crisis, but we are unable to unequivocally recommend this practice as there is no evidence such practice would result in an improvement in clinical outcome. If used, warmed diluent (without bacteriostatic sterile water, only) should not exceed 39°C. Great care must be taken when using warmed fluids for intravenous administration, as various warming methods may produce wide variation in temperatures, and a potential for vascular burns exists if too hot a solution is used. While there is no published evidence, we do not believe that warmed solutions change the chemistry or structure of dantrolene.
WHO SHOULD STOCK DANTROLENE & HOW MUCH?
All facilities, including ambulatory surgery centers and offices, where MH triggering anesthetics (isoflurane, desflurane, enflurane, sevoflurane, methoxyflurane, cyclopropane halothane and succinylcholine) are administered, should stock a minimum of 36 vials of dantrolene, along with the other drugs and devices necessary to treat an MH reaction. If none of these agents is ever in use in the facility, then dantrolene need not be kept at hand.
WHERE SHOULD DANTROLENE SODIUM FOR INJECTION BE KEPT?
Dantrolene 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); the water for diluting dantrolene should not be stored in a refrigerator; it may be stored in a warming cabinet designed to maintain fluid temperatures between 35-40o° C. All anesthesia and surgical team members should be aware of this location.
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 be available wherever general anesthesia is administered.
Responsibility for treatment rests with the facility where the surgery is performed. 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 24 months from the date of manufacture. Although fulminant MH episodes are unusual, they do happen. 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?
At this printing, the cost of maintaining 36 vials in stock is approximately $1260* per year, $105/month* or $3.45/day*, a tiny fraction of most facility budgets and a very small price to pay for patient safety. The cardiac defibrillator, like other emergency drugs in an institution's "code charts" is a necessary emergency tool in all OR suites, is seldom used, and is paid for in time by each patient's charges. In fact, many hospitals have 30-50 such units deployed at all times. Dantrolene, an emergency drug that is kept in only one location within most institutions, is an appropriate parallel to that situation and, in this context, is relatively inexpensive when prorated.
*Prices are subject to change.
MH Hotline
Medical professional have access to expert physicians who are available 24/7, to successfully manage an MH crisis or to answer pre-, post or intraoperative anesthesia questions.
1-800-MH-HYPERor 1 (800) 644-9737 II Outside the
North American MH Registry of MHAUS
The North American MH Registry of MHAUS registers information about specific patients and their families. The Registry is located at Children's
(See www. mhreg.org)
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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
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