Malignant Hyperthermia

Question 1

Which anesthetics trigger MH?

Answer 1

Halothane, enflurane, isoflurane, desflurane, sevoflurane (esp with succinylcholine)

Question 2

Who is susceptible to MH?

Answer 2

It is a genetic disorder, autosomal DOMINANT.

Question 3

Where are the mutations for MH?

Answer 3

There are mutations in 6 genetic loci
Primary mutations in type 1 ryanodine receptor (RYR1) located on the calcium-storage organelle of sarcoplasmic reticulum in skeletal muscle cells

Question 4

What are the A site and the I site? How do these change in MH?

Answer 4

RYR1 opens when intracellular Ca2+ is low through its high affinity A site and closes at high Ca2+ levels through its low affinity I site

In mutated receptors, trigger agents increase the affinity of the A site and decrease the affinity of the I site to Ca2+ thus significantly increasing Ca2+ release from the sarcoplasmic reticulum

Question 5

What blood test can be done to diagnose MH?

Answer 5

Blood test for “leaked cell constituents” (creatine kinsase, K+, phosphate, myoglobin, acidosis, kidney function)

Question 6

What are the susceptibility tests available for MH?

Answer 6

Genetic tests (not easy, there are 70-80 mutations in RYR1 alone)

Halothane contracture tests (determine contraction of muscle biopsy bathed in halothane, only 70% specificity)

Question 7

What are the treatment options for MH? How do they work?

Answer 7

Dantrolene IV blocks Ca2+ release from RYR1

Supportive therapy for hyperthermia, acidosis, organ dysfunction

These reduce death rate of MH from 80% to 10%