CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 18: M A L IG N A N T
H Y P E R T H E R M IA
27-year-old male with acute appendicitis undergoing a halothane
inhaled anesthetic with acute onset of hyperthermia, tachypnea, respiratory
acidosis, hyperkalemia, and family history of similar events. The tentative
diagnosis is MH.
Biochemical mechanism: Uncoupling of oxidative phosphorylation.
Treatment: Supportive care with attempts to bring temperature down,
correct blood gas and electrolyte abnormalities, and give dantrolene.
C L IN IC A L C O R R E L A T IO N
Malignant hyperthermia is an untoward response of susceptible individuals to
preoperative anesthesia utilizing halothane and succinylcholine, although
other inhalation anesthetics such as enflurane and isoflurane have been recog-
nized as milder prompts for this complication of anesthesia. The frequency of
occurrence is 1 in 15,000 children and 1 in 100,000 adults. The inheritance is
dominant in 50 percent of cases and recessive in 20 percent, suggesting a more
complex basis for this response. The clinical findings are muscle rigidity,
hyperthermia, seizure, cardiac arrhythmias, and sometimes death. Prevention
is the key, in that every patient should be queried about personal or family his-
tory of complications during surgery. Once a patient is found to have MH, the
clinician should alert other family members to the same possibility. The mus-
cle relaxant, dantrolene, is the treatment of choice. Even with prompt recogni-
tion and therapy, mortality is as high as 5 percent.
A PPR O A C H TO O X ID A TIV E PH O SPH O R Y L A T IO N
(U N C O U P L IN G )
Understand how malignant hyperthermia is caused by the uncoupling
of oxidative phosphorylation.
Understand the biochemical mechanism for the heat production.
Be familiar with the mechanism of how dantrolene reverses the effects.
Malignant hyperthermia: An unusual adverse response to some inhala-
tion anesthetics such as halothane in which there is an acute dramatic
elevation in body temperature as well as tachypnea, muscle rigidity, and