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NBCRNA CRNA Certified Registered Nurse Anesthetist

15.3 Malignant Hyperthermia Protocol & Operating Room Crisis Management

Q: During active resuscitation and cooling of a patient experiencing a severe Malignant Hyperthermia crisis with a core temperature of 41.2°C, at what core body temperature must active hypothermic measures (cold saline infusions, ice packs, cavity lavage) be discontinued?

38.5°C (to prevent downward temperature drift and severe rebound hypothermia). According to MHAUS clinical management guidelines, active cooling measures (cold IV normal saline, ice packs to the axillae, groin, and neck, and cold bladder/gastric lavage) must be stopped once the patient's core body temperature drops to ≤ 38.5°C (101.3°F). Terminating active cooling at 38.5°C prevents downward thermal drift, which can otherwise cause severe rebound hypothermia, shivering, metabolic acidosis, coagulopathy, and secondary arrhythmias.

Q: During an elective microlaryngeal laser vocal cord resection using an electrosurgical laser under general endotracheal anesthesia with 40% O₂ and 60% N₂O, an explosive flash fire erupts within the patient's oral cavity and endotracheal tube. What is the correct immediate, simultaneous sequence of actions by the anesthesia provider?

Immediately pull the burning endotracheal tube, stop all airway gas flows, extinguish residual fire with sterile saline in the airway, and ventilate with room air. The established American Society of Anesthesiologists (ASA) Operating Room Airway Fire Protocol dictates an immediate 4-step emergency sequence: (1) PULL the endotracheal tube immediately and remove any burning debris/sponges from the airway to prevent inhalation of toxic combustion products and thermal airway burns, (2) STOP all gas flows (turn off oxygen and nitrous oxide and disconnect the circuit), (3) POUR sterile saline or water into the pharynx and airway to extinguish residual embers, and (4) Ventilate the patient via mask with room air (FiO₂ 0.21) or the lowest required oxygen concentration, followed by rigid or flexible bronchoscopy to evaluate the extent of tracheal and bronchial thermal injury.

Key Takeaways

Malignant Hyperthermia (MH) is an autosomal dominant pharmacogenetic myopathy caused primarily by mutations in the ryanodine receptor gene (RYR1), triggered by ALL halogenated volatile anesthetics and the depolarizing muscle relaxant succinylcholine.
The earliest and most sensitive clinical signs of MH are unexplained sudden tachycardia and an refractory surge in End-Tidal CO₂ (ETCO₂ > 60-80 mmHg) despite hyperventilation, plus masseter muscle rigidity (MMR); hyperthermia (>41°C) is a late sign accompanied by mixed metabolic/respiratory acidosis, hyperkalemia, and rhabdomyolysis.
Immediate MHAUS protocol: Call for help/MH cart, discontinue triggers, hyperventilate with 100% O₂ at ≥10 L/min, and administer Dantrolene sodium 2.5 mg/kg IV push repeated every 5-10 minutes up to 10 mg/kg (or Ryanodex 250 mg/vial in 5 mL sterile water).
Calcium Channel Blockers (e.g., Verapamil, Diltiazem) are strictly CONTRAINDICATED during an MH crisis treated with dantrolene due to the risk of fatal hyperkalemia and profound cardiovascular collapse.
Airway fire protocol mandates immediate 4-step sequence: (1) Pull endotracheal tube, (2) Stop all airway gas flows, (3) Pour sterile saline/water into airway, and (4) Mask ventilate with room air/low FiO₂ and evaluate airway with bronchoscopy.

Last updated: August 2026

15.3 Malignant Hyperthermia Protocol & Operating Room Crisis Management

Malignant Hyperthermia (MH) is a life-threatening, hypermetabolic pharmacogenetic crisis of skeletal muscle triggered by exposure to volatile inhalational anesthetics and succinylcholine. Without immediate diagnosis and targeted intervention with Dantrolene sodium, mortality exceeds $70 - 80\%$ ; with modern protocols, mortality is reduced to $<5\%$ .

1. Pathophysiology & Genetic Basis of MH

                      [MALIGNANT HYPERTHERMIA PATHOPHYSIOLOGY]

         [Trigger: Halogenated Volatiles / Succinylcholine]
                                 |
                                 v
           [Mutated RYR1 / Cav1.1 (DHP) Receptor Activation]
                                 |
                                 v
    >>> UNCONTROLLED CALCIUM EFFLUX FROM SARCOPLASMIC RETICULUM <<<
                                 |
                                 v
    [Intracellular Free Ca²⁺ Concentration Rises 5- to 10-Fold in Myoplasm]
                                 |
             +-------------------+-------------------+
             |                                       |
             v                                       v
     [Sustained Muscle Contraction]          [Massive ATP Depletion &
     (Rigor, Masseter Spasm, Rigidity)        Hypermetabolic State]
             |                                       |
             +-------------------+-------------------+
                                 |
                                 v
      [Uncoupled Oxidative Phosphorylation & Glycolysis Surge]
                                 |
     • Extreme CO₂ Production (ETCO₂ > 80 mmHg) & O₂ Consumption
     • Severe Combined Metabolic (Lactic) & Respiratory Acidosis
     • Massive Heat Production (Hyperthermia > 41-43°C)
                                 |
                                 v
      [Sarcolemmal Breakdown & Rhabdomyolysis]
     • Hyperkalemia (K⁺ > 6-8 mEq/L) ---> Lethal Ventricular Arrhythmias
     • Myoglobinuria (Cola Urine)    ---> Acute Renal Tubular Failure
     • Creatine Kinase (CK) Surge    ---> > 20,000 - 100,000+ U/L

Genetics & Associated Musculoskeletal Disorders

Inheritance: Autosomal dominant with variable penetrance and expressivity.
Primary Gene Mutation: $RYR1$ gene on chromosome 19q13.1 (encodes the skeletal muscle Ryanodine Receptor Type 1 calcium-release channel; accounts for $>70 - 80\%$ of cases). Other implicated mutations include $CACNA1S$ (dihydropyridine receptor $\alpha_1$ -subunit) and $STAC3$ .
Conclusively Associated Diseases:
- Central Core Disease (strongly linked to $RYR1$ mutations).
- King-Denborough Syndrome (dysmorphic features, myopathy, high MH risk).
- Multiminicore Disease.
Critical NBCRNA Distinction on Muscular Dystrophies: Duchenne and Becker muscular dystrophies are NOT classic Malignant Hyperthermia susceptibilities. However, administration of succinylcholine or volatile agents to patients with Duchenne/Becker dystrophy can trigger Anesthesia-Induced Rhabdomyolysis (AIR), causing sudden catastrophic hyperkalemic cardiac arrest. Succinylcholine is strictly contraindicated in all muscular dystrophies.

Triggering vs. Safe Agents

+---------------------------------------------------------------------------------------------------------+
|                                 MH PHARMACOLOGIC AGENT CLASSIFICATION                                   |
+------------------------------------+--------------------------------------------------------------------+
| Class Category                     | Specific Pharmacologic Agents                                      |
+------------------------------------+--------------------------------------------------------------------+
| **KNOWN TRIGGERS**                 | • **ALL Halogenated Volatile Gases:** Sevoflurane, Desflurane,     |
| *(Strictly Contraindicated)*       |   Isoflurane, Halothane, Enflurane                                 |
|                                    | • **Depolarizing NMBA:** Succinylcholine                           |
+------------------------------------+--------------------------------------------------------------------+
| **SAFE ANESTHETIC AGENTS**         | • **IV Hypnotics:** Propofol, Etomidate, Ketamine, Barbiturates    |
| *(Non-Triggering)*                 | • **Inhaled Non-Volatile:** Nitrous Oxide (N₂O)                    |
|                                    | • **Nondepolarizing NMBAs:** Rocuronium, Vecuronium, Cisatracurium |
|                                    | • **Reversal Agents:** Sugammadex, Neostigmine, Glycopyrrolate     |
|                                    | • **Opioids & Sedatives:** Fentanyl, Morphine, Remifentanil, Midazolam|
|                                    | • **Local Anesthetics:** ALL amides (Lidocaine, Bupivacaine, Ropi) |
|                                    |   and ALL esters (Tetracaine, Chloroprocaine)                      |
+------------------------------------+--------------------------------------------------------------------+

2. Clinical Presentation: Early vs Late Signs

+---------------------------------------------------------------------------------------------------------+
|                                    MH CLINICAL PROGRESSION PHASES                                       |
+------------------+--------------------------------------------------+-----------------------------------+
| Clinical Phase   | Key Signs & Symptoms                             | Diagnostic & Clinical Significance|
+------------------+--------------------------------------------------+-----------------------------------+
| **Earliest &     | • **Unexplained Sudden Tachycardia**             | • Earliest clinical sign          |
|   Most Sensitive | • **Profound Surge in ETCO₂ (>60-80 mmHg)**      | • Refractory to doubling or       |
|   Signs**        |   unresponsive to hyperventilation               |   tripling minute ventilation     |
|                  | • **Masseter Muscle Rigidity (MMR)**             | • "Jaws of steel" post-succinyl- |
|                  | • Tachypnea & Tachypnea-induced Exhaustion       |   choline prevents laryngoscopy   |
+------------------+--------------------------------------------------+-----------------------------------+
| **Intermediate   | • Generalized skeletal muscle rigidity (rigor)   | • Occurs despite full chemical    |
|   Signs**        | • Combined respiratory & metabolic acidosis      |   neuromuscular blockade          |
|                  | • Skin mottling, sweating, and cyanosis          | • Mixed venous PO₂ drops near 0   |
|                  | • Cardiac arrhythmias (PVCs, ventricular tach)   | • Sympathetic overactivity        |
+------------------+--------------------------------------------------+-----------------------------------+
| **Late Signs**   | • **Severe Rapid Hyperthermia (>41°C / 106°F)**  | • Core temp rises >1°C q5min      |
| *(Indicates      | • Hyperkalemia (K⁺ > 6 - 8 mEq/L)                | • Peaked T waves, sine waves, VF  |
|   Severe Muscle  | • Myoglobinuria (tea- or cola-colored urine)     | • Acute tubular necrosis / AKI    |
|   Necrosis)*     | • Marked Creatine Kinase elevation (>20,000 U/L) | • Peaking at 12-24 hours post-MH  |
|                  | • Disseminated Intravascular Coagulation (DIC)   | • Diffuse microvascular bleeding  |
+------------------+--------------------------------------------------+-----------------------------------+

3. MHAUS Emergency Treatment Protocol (Step-by-Step)

Upon suspecting an MH crisis, activate the standardized Malignant Hyperthermia Association of the United States (MHAUS) protocol immediately:

+---------------------------------------------------------------------------------------------------------+
|                              MHAUS EMERGENCY CRISIS MANAGEMENT PROTOCOL                                 |
+------+-----------------------------+--------------------------------------------------------------------+
| Step | Action Item                 | Protocol Execution Details                                         |
+------+-----------------------------+--------------------------------------------------------------------+
| **1**| **Call for Help & MH Cart** | • Declare MH emergency; notify surgical team to halt procedure     |
|      |                             | • Call MHAUS 24/7 Crisis Hotline: **1-800-644-9737 (1-800-MH-HYPER)**|
+------+-----------------------------+--------------------------------------------------------------------+
| **2**| **Discontinue Triggers**    | • Shut off volatile vaporizers and halt succinylcholine            |
|      |                             | • Do NOT waste time changing anesthesia machine or circuit         |
|      |                             | • Insert activated charcoal filters (Vapor-Clean) on limbs         |
|      |                             | • Switch to TIVA (Propofol / Opioids)                              |
+------+-----------------------------+--------------------------------------------------------------------+
| **3**| **Hyperventilate 100% O₂**  | • Flush circuit with 100% O₂ at maximum fresh gas flows (≥10 L/min)|
|      |                             | • Hyperventilate at 2 to 3 times normal minute ventilation to      |
|      |                             |   blow off massive CO₂ production                                  |
+------+-----------------------------+--------------------------------------------------------------------+
| **4**| **Administer Dantrolene**   | • **Initial Dose: 2.5 mg/kg IV push immediately**                  |
|      |                             | • Repeat 1 - 2.5 mg/kg every 5-10 minutes until signs subside      |
|      |                             | • Cumulative dose may exceed **10 mg/kg** in severe crises         |
+------+-----------------------------+--------------------------------------------------------------------+
| **5**| **Treat Acidosis**          | • Administer Sodium Bicarbonate 1 - 2 mEq/kg IV guided by ABG      |
+------+-----------------------------+--------------------------------------------------------------------+
| **6**| **Treat Hyperkalemia**      | • **Calcium Chloride 10 mg/kg (or 1 g)** or Calcium Gluconate 3 g  |
|      |                             |   IV to stabilize cardiac membranes                                |
|      |                             | • **Regular Insulin 10 units IV + D50W 50 mL (25 g)**              |
|      |                             | • Sodium Bicarbonate + Hyperventilation + Albuterol                |
+------+-----------------------------+--------------------------------------------------------------------+
| **7**| **Treat Arrhythmias**       | • Use Amiodarone (150-300 mg), Lidocaine, or Beta-blockers         |
|      |                             | • **STRICTLY AVOID CALCIUM CHANNEL BLOCKERS (Verapamil/Diltiazem)**|
+------+-----------------------------+--------------------------------------------------------------------+
| **8**| **Initiate Active Cooling** | • Infuse cold 0.9% Normal Saline IV (1000 mL q10min x 30-40 min)   |
|      |                             | • Ice packs to groin, axillae, neck; gastric/bladder cold lavage   |
|      |                             | • **STOP COOLING AT 38.5°C** to prevent rebound hypothermia        |
+------+-----------------------------+--------------------------------------------------------------------+
| **9**| **Maintain Renal Output**   | • Target Urine Output **≥ 1 - 2 mL/kg/hr** to flush myoglobin      |
|      |                             | • Administer IV crystalloid fluids, Mannitol 0.25 g/kg, Lasix      |
+------+-----------------------------+--------------------------------------------------------------------+
|**10**| **ICU Monitoring & Recrud.**| • Transfer to ICU for continuous hemodynamic and lab monitoring    |
|      |                             | • **Recrudescence occurs in ~20% of cases within 24 - 36 hours**   |
|      |                             | • Maintenance Dantrolene: 1 mg/kg IV q4-6h or 0.25 mg/kg/hr for 24h|
+------+-----------------------------+--------------------------------------------------------------------+

Dantrolene Sodium: Formulations & Pharmacology

Mechanism of Action: Dantrolene binds specifically to the ryanodine receptor 1 ( $RYR1$ ) channel, blocking intracellular calcium release from the sarcoplasmic reticulum into the myoplasm, halting uncoupled muscle contraction and metabolic runaway.
Formulations Comparison:
- Ryanodex (Nanocrystalline Suspension): Each vial contains $250 \text{ mg}$ dantrolene sodium + $125 \text{ mg}$ mannitol. Reconstitutes with only $5 \text{ mL}$ sterile water in $<10 \text{ seconds}$ . A single vial provides the entire loading dose for a $100 \text{ kg}$ patient.
- Revonto / Dantrium (Lyophilized Formulation): Each vial contains $20 \text{ mg}$ dantrolene sodium + $3000 \text{ mg}$ ( $3 \text{ g}$ ) mannitol + sodium hydroxide. Requires $60 \text{ mL}$ sterile water per vial and vigorous shaking. A $70 \text{ kg}$ patient requires $\approx 9$ vials for initial loading ( $180 \text{ mg}$ ); a $100 \text{ kg}$ patient at $10 \text{ mg/kg}$ requires $50 \text{ vials}$ and $3 \text{ Liters}$ of sterile water.

The Calcium Channel Blocker Lethal Trap

Administering calcium channel blockers (such as Verapamil or Diltiazem) in the presence of Dantrolene is strictly contraindicated. The combination produces profound hyperkalemia, myocardial contractility depression, and refractory lethal cardiovascular collapse.

Definitive Diagnosis: Caffeine-Halothane Contracture Test (CHCT)

Gold Standard: In vitro muscle contracture testing of a freshly biopsied vastus lateralis muscle exposed to caffeine and halothane solutions. Abnormal contracture confirms MH susceptibility. Performed only at specialized testing centers.
Genetic Screening: Sequence analysis of $RYR1$ and $CACNA1S$ mutations. A positive genetic test confirms susceptibility, but a negative genetic test does not rule out MH due to undiscovered mutations.

4. Operating Room Airway Fire Crisis Protocol

Airway fires represent one of the most catastrophic emergencies in head, neck, and ENT anesthesia. Combustion requires the Surgical Fire Triad:

Fuel: Endotracheal tube, tracheal drapes, alcohol prep, sponges.
Oxidizer: Oxygen ( $FiO_2 > 0.30$ ), Nitrous Oxide ( $N_2O$ supports combustion equally with oxygen).
Ignition Source: Electrosurgical unit (bovie), laser (CO₂, Nd:YAG), electrocautery.

                      [EMERGENCY AIRWAY FIRE 4-STEP SEQUENCE]

               STEP 1: PULL THE ENDOTRACHEAL TUBE IMMEDIATELY
               (Remove burning foreign body from patient's airway)
                                     |
                                     v
               STEP 2: STOP ALL AIRWAY GAS FLOWS
               (Turn off O₂ and N₂O; disconnect breathing circuit)
                                     |
                                     v
               STEP 3: EXTINGUISH WITH STERILE SALINE / WATER
               (Pour sterile saline/water directly into airway and pharynx)
                                     |
                                     v
               STEP 4: VENTILATE WITH ROOM AIR & EVALUATE AIRWAY
               • Mask ventilate with 100% room air (or minimum FiO₂ needed)
               • Perform rigid / flexible bronchoscopy to assess mucosal damage
               • Re-intubate with smaller tube or perform emergency tracheostomy

Loading diagram...

Malignant Hyperthermia Emergency Protocol Flowchart

Test Your Knowledge

During maintenance of general anesthesia with sevoflurane for an exploratory laparotomy, a 19-year-old male develops sudden unexplained sinus tachycardia of 135 bpm. The capnograph reveals an ETCO₂ increase from 38 mmHg to 72 mmHg over 8 minutes, despite increasing minute ventilation from 6 L/min to 15 L/min. Arterial blood gas shows: pH 7.12, PaCO₂ 76 mmHg, HCO₃⁻ 18 mEq/L, Base Excess -9 mEq/L, and K⁺ 6.8 mEq/L. Core temperature is 37.4°C. What is the most appropriate immediate pharmacologic intervention?

Administer Diltiazem 0.25 mg/kg IV push to control supraventricular tachycardia

Administer Dantrolene sodium 0.5 mg/kg IV push and increase sevoflurane to deepen anesthesia

Discontinue sevoflurane, flush circuit with 100% O₂ at ≥10 L/min, and administer Dantrolene sodium 2.5 mg/kg IV push immediately

Administer Succinylcholine 1.0 mg/kg to treat suspected light anesthesia and chest wall rigidity

Test Your Knowledge

A CRNA preparing to treat an acute Malignant Hyperthermia crisis in an 80 kg adult has access to standard lyophilized Dantrium (20 mg vials) and Ryanodex (250 mg vials). Which statement accurately compares these two formulations regarding reconstitution and loading dose requirements?

Ryanodex requires 60 mL of sterile water per vial and provides 20 mg of dantrolene, requiring 10 vials for the initial loading dose

A loading dose of 2.5 mg/kg requires 200 mg of dantrolene; this can be administered as a single vial of Ryanodex (250 mg reconstituted in 5 mL sterile water in <10 seconds) versus 10 vials of Dantrium (each requiring 60 mL sterile water for a total of 600 mL)

Dantrium contains no mannitol, whereas Ryanodex contains 30 g of mannitol per vial, increasing the risk of hyperosmolar diuresis

Both Dantrium and Ryanodex must be reconstituted exclusively with 5% Dextrose in Water (D5W) to prevent precipitation of calcium salts

Test Your Knowledge

During active resuscitation and cooling of a patient experiencing a severe Malignant Hyperthermia crisis with a core temperature of 41.2°C, at what core body temperature must active hypothermic measures (cold saline infusions, ice packs, cavity lavage) be discontinued?

35.0°C (to ensure complete resolution of all hypermetabolic cellular processes)

36.5°C (to return the patient to normal physiologic baseline normothermia)

37.0°C (as soon as the patient reaches standard normal temperature)

38.5°C (to prevent downward temperature drift and severe rebound hypothermia)

Test Your Knowledge

During an elective microlaryngeal laser vocal cord resection using an electrosurgical laser under general endotracheal anesthesia with 40% O₂ and 60% N₂O, an explosive flash fire erupts within the patient's oral cavity and endotracheal tube. What is the correct immediate, simultaneous sequence of actions by the anesthesia provider?

Immediately pull the burning endotracheal tube, stop all airway gas flows, extinguish residual fire with sterile saline in the airway, and ventilate with room air

Increase fresh gas oxygen flow to 100% at 15 L/min to blow smoke out of the lungs, then perform emergency cricothyroidotomy

Clamp the endotracheal tube with a Kelly clamp, continue ventilating with 100% N₂O, and apply a carbon dioxide fire extinguisher to the face

Administer 100 mg of succinylcholine IV to prevent patient coughing, then slowly withdraw the endotracheal tube over a bougie

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