Ppt on malignant hyperthermia

1. MALIGNANT
HYPERTHERMIA
PRESENTED BY : DR. SHASHI DUBEY
MODERATED BY: DR. PRATIKSHA AGRAWAL

2.  Malignant hyperthermia is a pharmacogenetic disorder inherited primarily
in an autosomal dominant pattern
 It is a rare [1:15000 (paediatric) & 1:40,000 (adult)] genetic hypermetabolic
state
 The earlier an episode of MH identified and treated –better the outcome.
 Men> Women

3. GENETIC FACTOR
 Gene for the Ryanodine (Ryr1) receptor located on chromosome 19
 Ryr1 is a calcium channel responsible for Ca2+ release from
sarcoplasmic reticulum & it play an important role in muscle
depolarization and closely associated dihydropyridine (DHP).
 Mutation in MH
 Uncontrolled release or increase in intracellular calcium in skeletal
muscle from sarcoplasmic reticulum .
 Loss of inhibition of troponin..
 Sustained muscle contraction.
 Markedly increased ATP.
 Uncontrolled hypermetabolic state.
 Increased oxygen consumption .
 Severe lactic acidosis
 Hyperthermia

5. PATHOPHYSIOLOGY
 Triggering agent
1) inhaled general anesthesia
Methoxyflurane
Halothane
Sevoflurane
Isoflurane
Desflurane
Enflurane
Ether
2) Depolarizing muscle relaxant
succinylcholine

6. CLINICAL FEATURES
 Timing of presentation :-
 Highly variable
The initial sign of MH may occur soon after induction with general
anaesthetic agent (volatile agent or succinylcholine )
OR
 Any time during the maintenance phase of anaesthesia.

7.  Sequence of clinical sign :-
 Unexplained and unexpected increased in ETCO2 .
 Unexplained and unexpected increased in heart rate .
 Tachypnea if spontaneous ventilation present .
 Unexplained decreased in O2 saturation .
 Unexplained and unexpected increase in body temperature ( above 38.8
) .
℃
 Unexpected metabolic and respiratory acidosis .
 More then one signs of the above should be present to make the diagnosis
of MH.

8. CLINICAL MANIFESTATION
INCREASED METABOLISM
 Increased co2 production (An unanticipated doubling and tripling of ETCO2
early and sensitive indicator)
 Increased O2 consumption
 Decreased mixed venous oxygen tension
 Metabolic acidosis
 Cyanosis
 Mottling
INCREASED SYMPATHETIC ACTIVITY
 Tachycardia
 Hypertension f/b hypotension
 Arrhythmia

9. HYPERTHERMIA
 Fever increase by 1degree Celsius every 5 minute
 Sweating
Muscle damage
 Masseter spasm
 Generalized rigidity
 Increased s. creatinine kinase
 Hyperkalaemia
 Hypernatremia
 Hyperphosphatemia
 Myoglobinaemia
 Myoglobinuria

10. Stage 1:- Sustained muscle contraction [ masseter spasm ,sinus tachycardia ]
 High metabolic level [ increased O2 and glucose consumption , increased CO2 ,lactic
acid and heat production ]
Stage 2 :-Progression stage
 Hypercarbia ( respiratory acidosis ) tachycardia and some cases visible muscle rigidity
occurs
 Switching to anaerobic metabolism can worsen acidosis due to the production of
lactic acid ,resulting in mixed respiratory and metabolic acidosis
 Once energy ( ATP ) store are depleted ,rhabdomyolysis occur and result in
hyperkalaemia and myoglobinuria [ increased CK , Renal failure ]
Stage 3:-last stage
 In this stage ,core body temperature rise by as much as 1 degree Celsius every few
minutes .
 Accelerated hyperthermia ( above 41degree Celsius ) is associated with a marked
increase in C02 production and increased oxygen consumption and can cause
widespread vital organ dysfunction and disseminated intravascular coagulation .

11. CONDITIONS AND DISORDERS THAT MAY
MIMIC MALIGNANT HYPERTHERMIA
 Anaphylactic reaction
 Alcohol therapy for limb arteriovenous malformation
 Contrast dye injection
 Hyperkalaemia
 Diabetic coma
 Drug toxicity or abuse
 Elevated end-tidal CO2 due to laparoscopic operation
 Environmental heat gain more than loss
 Equipment malfunction with increased carbon dioxide

12.  Freeman-Sheldon syndrome
 Generalized muscle rigidity
 Heat stroke
 Hypokalemic periodic paralysis
 Hypoventilation or low fresh gas flow
 Insufficient anesthesia and/or analgesia
 Malignant neuroleptic syndrome
 Muscular dystrophies (Duchenne and Becker)
 Myoglobinuria

13. LABORATORY TESTING
Send blood for :-
ABG –repeated ( Approx every 30 minute )
CBC
SERUM ELECTROLYTE
SERUM CK
COAGULATION SCREEN
CROSS MATCH
Send urine for :- MYOGLOBIN

15. DIAGNOSIS
 MH should be strongly suspected when the ETCO2 increased despite a
compensatory increase in minute ventilation .
 There is no confirmatory test for MH during an acute event .
 Determining if a clinical event represents a true MH episode can be
estimated using the MH Clinical Grading Scale ( Raw Score ) .

18. Interpretation of MH Grading Scale

19. DIAGNOSIS IN SUSPECTED INDIVIDUAL
 Gold Standard: In-Vitro Caffeine Test(IVCT) and Caffeine Halothane
Contracture Test(CHCT)
 IVCT: done by performing a muscle biopsy and exposing the muscle to
Caffeine and Halothane.
 CHCT: muscle biopsy is done and exposed to increasing concentrations of
Halothane and response noted.
 Preferred muscle: Vastus group and rectus abdominis

20. TREATMENT PROTOCOL FOR MH
 Discontinue volatile anesthetic & succinylcholine (triggering agents) &
attach charcoal filter to anesthesia breathing circuit.
 Notify surgeon, call for help
hyperventilate with 100% O2
 Mix Dantrolene sodium with sterile distilled water and administer 2.5mg/kg IV
as soon as possible. Titrate dantrolene to HR, Temperature and PaCO2 (serial
monitoring of ABG)
 Administer sodium bicarbonate for metabolic acidosis.
 Institute cooling measures –Lavage, cooling blanket, surface ice pack, cold
IV solution. Cooling should be stopped at 38 degree Celsius.
 Treat sever hyperkalaemia with dextrose 25-50gm iv and regular insulin 10-20
unit IV
 Administer anti arrhythmic agents if needed despite correction of
hyperkalaemia and acidosis.
 Monitor EtCO2, electrolyte, blood gases, CK, myoglobin, core temperature,
urine output and colour of urine, coagulation status.
 If necessary ,consult on call physician at the 24 hr MHAUS hotline, 1-800-644-

21. DANTROLENE
 Hydantoin derivative
 Directly interfere with muscle contraction by binding to Ryr receptor and
inhibit calcium release from sarcoplasmic reticulum.
 2.5mg/kg IV every 5 min until episode is terminated.
 Effective half life 6 hour
 To prevent relapse 1mg/kg IV every 6 hrs. for 24-48 hr.
 Some cases of acute malignant hyperthermia may require 10-20 mg of
Dantrolene.
 New formulation of Dantrolene (Ryenodex) require significantly less time for
reconstitution than older preparation.

22. Dantrolene can be stopped, or the interval between doses increased to every
8 or 12 hours if all of the following criteria are met:
 Metabolic stability for 24 hours
 Core temp is less than 38°C
 Creatine kinase (CK) is decreasing
 No evidence of myoglobinuria
 Muscle is no longer rigid

23. COMPLICATIONS/SIDE EFFECTS OF
DANTROLENE
 Generalized muscle weakness.
 Respiratory insufficiency or aspiration pneumonia.
 Phlebitis if given via peripheral veins.

24. COMPLICATIONS OF MH
 AKI
 DIC
 Cerebral edema
 Seizure
 Hepatic failure

25. EVALUATION OF SUSCEPTIBILITY
 Evaluation of susceptibility includes a history and physical examination to
detect any subclinical abnormality.
 Blood CK values, when determined in a resting, fasting state without recent
trauma, reflect muscle membrane stability.
 When the CK level is elevated in a close relative of a person with known
MHS, the relative may be considered to have MHS without contracture
testing.
 Dantrolene must be avoided before biopsy because it masks the response
to contracture-producing drugs.

26.  After a patient is diagnosed as being MHS, DNA testing for mutations should
follow.
 MHS patients and all patients who are not biopsy tested, but who present
with a clinical picture that suggests a high probability for MHS, should be
given advice.
 Awake episodes are uncommon, and if not experienced before diagnosis,
they are an unlikely problem.

27. ANAESTHESIA FOR SUSCEPTIBLE
INDIVIDUAL
 Nitrous oxide, barbiturates, etomidate, propofol, opioids and NDMR are
safe for such individuals.
 Potent volatile anesthetics and succinylcholine must be avoided, even in
the presence of dantrolene.
 Regional anesthesia should be preferred.
 A dedicated machine/workstation should be present for MH susceptible
patients.
 Preoperative dantrolene is never needed.

28.  If there is no dedicated machine for MHS patients, flushing the anesthesia
workstation to less than 5 parts per million (ppm) of the volatile anesthetic
agent concentration is generally accepted .
 Any facility using MH triggers on an inpatient or outpatient basis should
have dantrolene available immediately .

29. NONANAESTHETIC MALIGNANT
HYPERTHERMIA
 MH can be triggered by stress such as exercise and overheating, known as
“awake” MH.
 RyR1 mutations found to be present in the patients with exercise-induced
rhabdomyolysis.
 These responses are related to muscle movement or to increased
temperature.
 Stresses associated with these episodes include exercise and environmental
exposure to volatile non -anesthetic vapours.

30. THANK YOU