Management Algorithms and Acute Crises

Mechanism

Molecular Mechanism of Malignant Hyperthermia

When the pharmacological trigger (e.g. sevoflurane) interacts with the mutated RYR₁ receptor, a continuous and uncontrolled flow of calcium ions (Ca²⁺) occurs from the terminal cisternae of the sarcoplasmic reticulum towards the cellular muscle sarcoplasm. This massive increase in intracellular calcium persistently and uninterruptedly stimulates the actin-myosin muscle contraction cycle, inducing severe generalized muscle stiffness and massively increasing glucose and ATP consumption.

This acute hypermetabolic state saturates the cellular capacity for respiratory and mitochondrial clearance, causing extreme lactic acidosis, massive tissue rhabdomyolysis with critical elevations in serum potassium (life-threatening hyperkalemia), and uncontrolled production of carbon dioxide and extreme body heat (42^).

Immediate Malignant Hyperthermia Rescue Protocol

In the presence of early initial clinical signs of suspicion (rapid doubling of alveolar EtCO₂ refractory to hyperventilation, severe unexplained sinus tachycardia, massive muscle rigidity of the masseter muscle and rapidly progressive hyperthermia), the following rescue protocol should be initiated:

1. Immediately cease administration of all active halogenated gases and discontinue use of succinylcholine if appropriate. Remove the vaporizers from the anesthesia machine and purge the circuit with maximum flows of 100% fresh oxygen at a rate of 10 L/min.
2. Administer Dantrolene Sodium immediately: Initial bolus dose of 2.5 mg/kg rapid IV. Dantrolene acts as a specific direct antagonist of calcium release by binding to the mitochondrial receptor RYR₁, blocking the skeletal muscle calcium channel and stopping cellular hypermetabolism.
3. Continuously repeat intravenous boluses of dantrolene of 1.0 - 2.5 mg/kg repeatedly until control of hypermetabolism is achieved (stabilization of EtCO₂ levels and core body temperature). Cumulative doses can reach up to 10 mg/kg in severe cases.
4. Immediate supportive treatment: initiate aggressive active cooling of the patient with cold saline intravenous solutions at 4^, gastric, rectal and intraperitoneal lavage with ice water; Aggressive treatment of hyperkalemia with glucose solutions and rapid IV insulin, and 8.4% sodium bicarbonate to control metabolic acidosis.

Clinical

Clinical Case 1: Acute Crisis of Malignant Hyperthermia (MH)

Malignant Hyperthermia is a life-threatening autosomal dominant hereditary channelopathy selectively triggered by the administration of all inhalational halogenated anesthetic gases and by the depolarizing relaxant succinylcholine.

It is associated with point mutations in the skeletal muscle ryanodine receptor type 1 gene (RYR₁, located on chromosome 19q13.2) that controls the release of calcium from the muscular sarcoplasmic reticulum.

Clinical Case 2: Perioperative Anaphylactic Shock

The incidence of perioperative anaphylaxis varies according to regions and the types of local anesthetic or relaxant agents used. Non-depolarizing neuromuscular relaxants are the main drugs involved in anaphylactic reactions of the immunoglobulin E (IgE) type mediated by bonding bridges with quaternary ammonium groups.

Phase 1: Minute 0 to 1 Clinical Recognition of Anaphylaxis Crisis

Acute initial cardiovascular symptoms: unexplained and severe drop in blood pressure (extreme arterial hypotension, complete vascular collapse resistant to ephedrine/phenylephrine boluses), extreme progressive reflex tachycardia, immediate increase in airway pressure in controlled ventilation due to severe bronchospasm, and signs of generalized facial edema or erythematous dermal rash.

Phase 2: Minute 1 to 3 Priority Rescue Intervention with Adrenaline

Immediately stop the infusion of any suspected active drug in the peripheral line. Administer as a priority Adrenaline in rapid intravenous boluses adjusted to severity: in cases of moderate shock, boluses of 10 - 20 µg IV repeatedly; In the presence of imminent cardiovascular collapse or cardiac arrest, initiate classic CPR protocol by administering rapid direct intravenous boluses of 1.0 mg of slow adrenaline every 3-5 minutes.

Phase 3: Minute 3 to 10 Support with Intravenous Volume and Cellular Adjuvants

Massive administration of isotonic crystalloid volume through large caliber peripheral venous accesses at a rate of 20 - 40 mL/kg to counteract the massive leakage of capillary volume secondary to the release of histamine. Secondary adjuvants: Methylprednisolone (1 - 2 mg/kg IV) or hydrocortisone to prevent late biphasic anaphylactic reactions, and intravenous H₁ and H₂ blocking antihistamines.