Malignant Hyperthermia

Malignant Hyperthermia Definition : a metabolic disease of the muscle, a hypermetabolic state caused by exposure of susceptible individuals to known trigger agents.

Malignant Hyperthermia Sustained, significant hypermetabolism Inherited component Abnormal handling of intracellular calcium levels “Triggered” by pharmacologic agents , possibly by heat/exercise

Trigger Agents for MH MH Trigger Agents Potent Volatile Anesthetics (eg. halothane, sevoflurane, desflurane) Succinylcholine Not MH Triggers Intravenous agents Opioids Non-depolarizing agents Ketamine Propofol Anxiolytics

Spectrum of Presentations of Malignant Hyperthermia The classic case Masseter muscle rigidity Associated with muscle disorders MH without anesthesia

Signs of Malignant Hyperthermia Specific Muscle Rigidity Increased CO2 Production Rhabdomyolysis Marked Temperature Elevation Non Specific Tachycardia Tachypnea Acidosis (Resp/Metabolic) Hyperkalemia

Summary of Clinical Signs

Muscle Rigidity and MH Jaw muscle rigidity may occur after succinylcholine More common in children Presages MH in 20-30% Generalized rigidity not always present When present, regularly associated with MH susceptibility With muscle breakdown and creatine kinase above 20,00IU, the likelihood of MH is very high.

Masseter Muscle Rigidity Stop Inhalation Agent No further succinylcholine Continue with nontrigger agents Awaken follow ET C02 patient Observe in ICU for 24 hours CK/electrolytes,Myoglobin Dantrolene as needed Recommend for biopsy

Disorders Associated with MH Susceptibility Central Core Disease Evans Myopathy Hypokalemic Periodic Paralysis ?sodium channel myotonias

Mimics of Malignant Hyperthermia Fever (without rigidity) Thyrotoxicosis Sepsis Pheochromocytoma Iatrogenic overheating Anticholinergic syndrome Faulty equipment Tourniquet (children) Fever and muscle symptoms NMS Hypoxic encephalopathy Ionic contrast agents in CSF Cocaine, amphetamine, ecstasy

What Tests Are Used To Diagnose MH? Current Concepts: Halothane, caffeine contracture test is the only gold standard Current Investigations: Molecular genetics Nuclear magnetic resonance for assessing ATP and creatine phosphate with/without exercise in vivo Calcium flux measurement in cultured muscle cells Local increase in pC02 following IM caffeine EMG changes in MH patients

What is the Incidence of MH? Original Concepts: Rare. One in 50,000 anesthetics Current Concepts: Clinically based information: One in 20,000 to 50,000 anesthetics depending on drugs, population Molecular Genetics based information: MH trait in 1 in 2,000-3,000 patients. Low penetrance

Immediate Therapy of Malignant Hyperthermia Have a plan! Discontinue inhalation agents, Succ Hyperventilate with 100% 02 Bicarbonate 1-2 mg/kg as needed Get additional help Dantrolene 2.5mg/kg Push. Repeat PRN Cool patient: gastric lavage, surface, wound Treat arrhythmias-do not use calcium channel blockers Arterial or venous blood gases Electrolytes, coagulation studies

Treatment of Malignant Hyperthermia - Acute Dantrolene-1 The only specific treatment for MH Administer as soon as diagnosis made 20mg/bottle-dissolve with 60ml sterile water Shake vigorously or warm bottles to dissolve Give 2.5mg/kg STAT Repeat as needed to control signs of MH

Treatment of Malignant Hyperthermia Dantrolene-2 After crisis controlled, give dantrolene 1mg/kg every 4-6 hours for 24 hours Continue dantrolene for 36 hours Recrudescence rate is 25%

Management of Malignant Hyperthermia Biochemical Markers Blood gasses – esp pCO2, pH, CK Myoglobinuria PT, PTT, INR, fibrin split products Liver enzymes, BUN

Morbidity and Mortality RHABDOMYOLYSIS RENAL FAILURE DIC if temp >41.50 C Hyperkalemia Acidosis

Prevention of Malignant Hyperthermia Preop personal/family history of anesthetic problems, neuromuscular disorders Temperature/endtidal CO2 monitoring during general anesthesia Recognition of masseter rigidity Investigation of unexplained tachycardia, hypercarbia, hyperthermia Availability of Dantrolene Avoiding MH triggers in MH susceptibles Using Succinylcholine in indication

Principles of Management of MH Susceptible Dantrolene not necessary preoperatively (dantrolene available) Avoid succinylcholine Avoid potent inhalation agents Discharge after about 2 hours in the recovery room if all signs are stable

Preparation for MH Susceptible Shut/disable vaporizers Flow 02 @ 10L/min for 20 minutes (through machine and ventilator) Change carbon dioxide absorbent Use non-trigger agents or local anesthesia Monitor temperature Have dantrolene available

Suggested Regimen for MH Patient Anxiolytic (ketamine permissible) Propofol/opioid induction Non-depolarizing relaxant Nitrous/narcotic/propofol Reversal of muscle relaxant Observe 4 hours

Drug Safety in MH MH Trigger Agents Potent Volatile Anesthetics (eg. halothane, sevoflurane, desflurane) Succinylcholine Not MH Triggers Intravenous agents Opioids Non-depolarizing agents Ketamine Propofol Anxiolytics

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