causes & epidemiology
- Malignant hyperthermia (MH) can be caused by any inhalational anesthetic, other than nitrous oxide.(29600483)
- Succinylcholine rarely can cause MH.
- Increased metabolic rate usually manifests with an increased end-tidal CO2 and/or minute ventilation:
- Increased end-tidal CO2 will occur if the minute ventilation is fixed (e.g., if the patient is deeply sedated).
- If the patient is able to trigger the ventilator, the patient may increase their respiratory rate in efforts to clear CO2. This may initially manifest as tachypnea with an elevated minute ventilation, which can obscure the increase in CO2 production.
- Increased volumetric CO2 production is the best index, if this is available (volumetric capnography integrates the amount of CO2 over time, to determine the total CO2 production by the patient). The volumetric CO2 should increase substantially in MH, regardless of whether the patient becomes tachypneic or how the ventilator settings are changed.
- Muscle rigidity may be an early finding:
- May be local or diffuse.
- Especially tends to involve the masseter muscles of the jaw.
- Rigidity may occur despite neuromuscular blockade.
- The key initial finding is the rate of temperature rise, which can be as rapid as 1-2 C every five minutes.
- Sweating is seen in ~20% of patients.(32305961)
- Ventricular tachycardia or ventricular fibrillation due to hyperkalemia.
- Cola-colored urine may occur, due to rhabdomyolysis.
- Issues with anesthesia circuit or surgical procedure:
- Ventilator error leading to hypoventilation and elevated pCO2.
- Saturation of anesthesia machine CO2 scavenger.
- Laparoscopic surgery with CO2 insufflation.
- Anaphylaxis or transfusion reaction.
- Thyroid storm.
- Serotonin syndrome.
- Neuroleptic malignant syndrome.
- Sympathomimetic intoxication.
Treatment must be initiated empirically, when the MH diagnosis is considered probable. The treatments are fairly benign, so it's generally better to err on the side of treatment.
call for help
- Call for an MH cart (if this is available in the operating room). If no MH cart is available, immediately seek help from your pharmacy. You may need:
- Dantrolene vials (enough to prepare 10 mg/kg at the bedside if needed). Sterile water will be needed to reconstitute the dantrolene.
- IV calcium (e.g., two 1-gram ampules of calcium chloride).
- IV insulin (e.g., 10 units for intravenous administration).
- D50W (e.g., two 50-ml ampules).
- Isotonic bicarbonate (e.g., two liters; this is generally formulated by adding three 50-mEq ampules of sodium bicarbonate to each liter of D5W).
- Refrigerated crystalloid, if available.
- Call the MH hotline for additional guidance if needed:
- In the United States or Canada: 1-800-644-9737
- Outside the United States: 001-209-417-3722
eliminate any residual anesthetic
- Hyperventilate with 100% oxygen at 2-3 times the normal minute ventilation, to clear any residual volatile anesthetic.
- If available, insert activated charcoal filters into the inspiratory and expiratory limbs of the anesthesia circuit. These may require replacement hourly, if they become saturated.
increase the minute ventilation
- Titrate the respiratory rate and tidal volume in order to achieve an end-tidal pCO2 of ~25 mm (~3.3 kPa), if possible. Subsequently, an ABG/VBG may be used to make further adjustments.
- If the patient isn't intubated, they will likely require intubation (using a non-depolarizing paralytic, such as rocuronium).
- 2.5 mg/kg IV immediately, then administer an additional 1-2.5 mg/kg IV q5min until symptoms subside
- Target a reduction in etCO2, rigidity, tachycardia, and hyperthermia.
- Large doses (>10 mg/kg) may be needed. However, if 10 mg/kg are given with absolutely no improvement, consider an alternative diagnosis and stop giving additional dantrolene.(29600483)
- How to reconstitute the dantrolene vials:
- DANTRIUM®/REVONTO® – Each 20 mg vial is reconstituted with 60 ml of sterile water and shaken until the solution is clear. About a dozen vials may need to be reconstituted initially! Seek an assistant to help with this.
- RYANODEX®– Each 250 mg vial is reconstituted with 5 ml of sterile water and shaken to ensure an orange-colored uniform, opaque suspension.
- Once stabilized, continue a maintenance dose of 1 mg/kg dantrolene IV q4-6hr (although fulminant cases may require a continuous infusion at 0.25 mg/kg/hour). Continue maintenance therapy until the patient has been stable and improving for 24 hours.
- ⚠️ Avoid calcium channel blockers, which may interact with dantrolene. However, dantrolene shouldn't be withheld from patients who have already received calcium channel blockers.
- Continuous monitoring of the core temperature is essential (preferably via a bladder or esophageal temperature probe).
- Initiate cooling if the core temperature is >39C (102.2F), or if the temperature is rapidly rising.
- Techniques will vary depending on the context, but may include:
- Application of ice packs.
- Evaporative cooling (moisten the patient with lukewarm water and fan the patient).
- Place a cooling blanket below the patient.
- Reduce the temperature of gas being administered via the ventilator (e.g., remove the warmer).
- Administration of refrigerated crystalloid solutions.
- Cold lavage of the surgical field (if a large cavity is open).
- Adaptive external cooling device involving circulating cold water (e.g., Arctic Sun).
- Stop cooling when the temperature has fallen below <38 C (100.4F), to avoid an excess drop in temperature. However, close monitoring of the patient's temperature should continue.
- More on physical cooling techniques here.
- Initiate therapy if EKG changes occur, or if the potassium is >5.9 mM.
- Typical regimen:
- IV calcium (either 1 gram calcium chloride or 3 grams calcium gluconate, repeat PRN).
- 10 units insulin intravenously.
- 2 ampules of D50W (i.e., 100 ml total volume of D50W).
- Isotonic bicarbonate fluid resuscitation (i.e., 3 ampules of 50-mEq sodium bicarbonate within a liter of D5W).
- For refractory hyperkalemia, may also administer a beta-2 agonist (e.g., high-dose inhaled albuterol).
- More on hyperkalemia therapy here.
- Treatment involves adequate fluid resuscitation. The initial fluid of choice for resuscitation might be isotonic bicarbonate (D5W with three 50-mEq ampules of bicarbonate per liter), as this may be beneficial for hyperkalemia, acidosis, and rhabdomyolysis.
- Ideally target a urine output of >1 ml/kg/hour with the use of crystalloid. However, monitor fluid balance carefully and avoid volume overload.
- If the patient fails to respond favorably to crystalloid infusion, then reduce the fluid administered to avoid ongoing fluid overload.
- Examine for compartment syndrome. This may occur and require fascial release surgery.
- More on the treatment of rhabdomyolysis here.
management of DIC
- Severe MH can cause disseminated intravascular coagulation (DIC).
- Management of DIC is discussed further in the chapter on DIC here.
- Hemodialysis may be needed if medical therapies fail to control hyperkalemia.
- ECMO or cardiopulmonary bypass may be needed for refractory cardiac arrest.
parameters to monitor as the patient recovers:
- Core temperature (ideally via a continuous esophageal or bladder temperature probe).
- Check fingerstick glucose hourly, if insulin was administered.
- End-tidal CO2, volumetric capnography if available, ventilator parameters.
- Serial examination for rigidity (including the extremities and masseter muscles).
- Labs should be followed carefully until clinical improvement: (29600483)
- Creatinine kinase.
- Electrolytes, including Ca/Mg/Phos.
- INR, PTT, and fibrinogen (MH can cause DIC).
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questions & discussion
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Succinylcholine-induced malignant hyperthermia may be extremely difficult to diagnose in the context of a complex critically ill patient who is intubated outside of the operating room (since deterioration will be assumed to reflect the patient's underlying disease). This may be easily avoided by using rocuronium for the intubation of critically ill patients.
- Immediate management of MH will often be necessary before a definitive diagnosis is made. Dantrolene is very safe, so when in doubt empiric therapy should be provided without delay.
- MHAUS guide to managing a crisis is here (and also incorporated into the treatment section above).
- 29600483 Riazi S, Kraeva N, Hopkins PM. Updated guide for the management of malignant hyperthermia. Can J Anaesth. 2018 Jun;65(6):709-721. English. doi: 10.1007/s12630-018-1108-0 [PubMed]
- 31677658 Kim KSM, Kriss RS, Tautz TJ. Malignant Hyperthermia: A Clinical Review. Adv Anesth. 2019 Dec;37:35-51. doi: 10.1016/j.aan.2019.08.003 [PubMed]
- 32008650 Ellinas H, Albrecht MA. Malignant Hyperthermia Update. Anesthesiol Clin. 2020 Mar;38(1):165-181. doi: 10.1016/j.anclin.2019.10.010 [PubMed]
- 32305961 Yang L, Tautz T, Zhang S, Fomina A, Liu H. The current status of malignant hyperthermia. J Biomed Res. 2019 May 30;34(2):75-85. doi: 10.7555/JBR.33.20180089 [PubMed]