Transcript malignant hyperthermia

Dr. Prajwala Reddy
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An elevated body temperature due to failed
thermoregulation that occurs when a body
produces or absorbs more heat than it dissipates
MCC: heat stroke (acute temperature elevation
caused by exposure to excessive heat, or
combination of heat and humidity, that
overwhelms the heat-regulating mechanisms)
Adverse reactions to drugs(affect the central
nervous system)
Rare: Malignant hyperthermia
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hyperthermia occurs when the body temperature
rises without a change in the heat control centers
in preoptic-anterior hypothalamus
A fever occurs when the core temperature is set
higher, through the action of the pre-optic
region of the anterior hypothalamus. For
example, in response to a bacterial or viral
infection, certain white blood cells within the
blood will release pyrogens which have a direct
effect on the anterior hypothalamus, causing
body temperature to rise, much like raising the
temperature setting on a thermostat.
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Temperature> 37.5–38.3 °C (99.5–100.9 °F).
body temperatures above 40 °C (104 °F) can
be life-threatening.
Early stage: Heat exhaustion,( symptoms
include heavy sweating, rapid breathing and a
fast, weak pulse).
If progresses to heat stroke, -> hot, dry,
skin .
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Heatstroke is defined typically as hyperthermia
exceeding 41°C and anhidrosis associated with
an altered sensorium.
occurs when thermoregulation is overwhelmed
by a combination of excessive metabolic
production of heat (exertion), excessive
environmental heat, and insufficient or impaired
heat loss, resulting in an abnormally high body
temperature.
Heat stroke:1. Non-exertional (classic)
2.Exertional.
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EHS is characterized by hyperthermia,
diaphoresis, and an altered sensorium, which
may manifest suddenly during extreme physical
exertion in a hot environment.
A number of symptoms (eg, abdominal and
muscular cramping, nausea, vomiting, diarrhea,
headache, dizziness, dyspnea, weakness)
commonly precede the heatstroke and may
remain unrecognized.
Syncope and loss of consciousness also are
observed commonly before the development of
EHS.
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NEHS is characterized by hyperthermia,
anhidrosis, and an altered sensorium, which
develop suddenly after a period of prolonged
elevations in ambient temperatures
Core body temperatures greater than 41°C are
diagnostic, although heatstroke may occur
with lower core body temperatures.
Numerous central nervous system (CNS)
symptoms, ranging from minor irritability to
delusions, irrational behavior, hallucinations,
and coma have been described.
Other possible CNS symptoms include
seizures, cranial nerve abnormalities,
cerebellar dysfunction, and opisthotonos.
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Other signs and symptoms: nausea, vomiting,
headaches, and low blood pressure leadingto
fainting or dizziness,
In severe heat stroke:confused, hostile, or
seemingly intoxicated behavior. tachycardia
and tachypnea, hyppotension leading to pale
n cyonotic extremitisseizures(MC in young
children)
Eventually, organ failure, unconsciousness
and death.
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Causes
 Increased
heat production
 Decreased heat loss
 Reduced ability to acclimatize
 Reduced behavioral responsiveness
1.Increased heat production
• Increased metabolism(Infections ,Sepsis ,
Encephalitis, Stimulant drugs, Thyroid storm
,Drug withdrawal
• Increased muscular ( Exercise, Convulsions
,Tetanus , Strychnine poisoning ,
Sympathomimetics ,Drug withdrawal ,Thyroid
storm.
2.Decreased heat loss
• Reduced sweating(Dermatologic diseases ,Drugs
,Burns
• Reduced central nervous system (CNS)
responses(Advanced age ,Young age,
Alcohol,Barbiturates ,Other sedatives ).
• Reduced cardiovascular reserve (Advanced
age,Beta-blockers ,Calcium channel
blockers,Diuretics,Cardiovascular drugs that
Interfere with the cardiovascular responses to
heat and, therefore, can interfere with heat loss
• Drugs (Anticholinergics ,Neuroleptics,
Antihistamines.
• Exogenous factors(High ambient
temperatures,High ambient humidity
3.Reduced ability to acclimatize
4.Reduced behavioral responsiveness
DIAGNOSIS
Clinical history&above signs and symptoms.
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MANAGEMENT
Primarily to decrease the temperature.
Passive cooling techniques:resting,cool shady areas
etc.,
Active cooling methods :Tapid sponging over
head,neck& trunk , Drinking water, dehumidifying
air conditioning, immersion method.
Medical emergency : If temperature>40degrees
Core if unconcious or showing signs of confusion.
IV hydration,Gastric lavage with iced saline&even
hemodialysis to cool the blood.
Underlying cause must be removed&occasionally
use of counter drugs
Supportive.
Antipyretics have no role.
MALIGNANT HYPERTHERMIA:
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Malignant hyperthermia (MH) is a sub clinical
myopathy.
life-threatening clinical syndrome of
hypermetabolism involving the skeletal muscle.
It is triggered in susceptible individuals
primarily by the volatile inhalational anesthetic
agents(Halothane) and the muscle relaxant
succinylcholine, though other drugs have also
been implicated as potential triggers.
MH is an inherited an autosomal dominant trait
with reduced penetrance.
It is ass with mutations RYR1& CACNA1S
genes that is found both in humans and in
swine.
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In persons susceptible to MH, the ryanodine
receptor in skeletal muscle is abnormal, this
abnormality interferes with regulation of calcium in
the muscle.
This abnormal receptor that controls calcium
release causes a buildup of calcium in skeletal
muscle, resulting in a massive metabolic reaction.
This hypermetabolism causes increased carbon
dioxide production, metabolic and respiratory
acidosis, accelerated oxygen consumption, heat
production, activation of the sympathetic nervous
system, Rhabdomyolysis leads to increased levels
of potassium, myoglobin, and creatine kinase, as
well as edema formation. (DIC), and multiple organ
dysfunction and failure
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EARLY CLINICAL SINGS
Increase in end-tidal carbon dioxide (even
with increasing minute ventilation),
tachycardia, muscle rigidity, tachypnea, and
hyperkalemia.
Later signs: fever, myoglobinuria, and
multiple organ failure.
DIAGNOSIS:
The caffeine halothane contracture test (CHCT)
Molecular genetic testing (DNA testing)
MANAGEMENT
Dandrolin:
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The initial dose is 2.5 mg/kg, repeated every 5
minutes until reversal of the reaction occurs or a
total dose of 10 mg/kg (or 20 mg/kg, .
Cooling and early treatment of hyperkalemia are
desirable.
Calcium-channel blockers should be avoided if
dantrolene is used, because they may cause
hypekalemia
Once the initial reaction is controlled, continued
monitoring in (ICU) for 24-48 hours is
recommended.
administration of dantrolene 1 mg/kg every 4-6
hours, or an equivalent amount given as a
continuous infusion.
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Neuroleptic malignant syndrome is a lifethreatening, neurological disorder most often
caused by an adverse reaction to neuroleptic
or antipsychotic drugs.
NMS often occurs shortly after the initiation
of neuroleptic treatment, or after dose
increases.
Five classes of available neuroleptic drugs:
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Phenothiazines,
Thioxanthenes,
Butyrophenones,
Indoles,
Dibenzoxazepines.
clinical features:
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Muscular rigidity (typically, “lead pipe” rigidity)
Hyperthermia (temperature >38°C)
Diaphoresis
Pallor
Dysphagia
Dyspnea
Tremor
Incontinence
Shuffling gait
Psychomotor agitation
Delirium progressing to lethargy, stupor, coma
Other general examination findings indicative of autonomic
dysregulation include the following:
Diaphoresis
Sialorrhea
Tachycardia
Tachypnea, respiratory distress (31% ofcases)
Increased or labile blood pressure
Hypoxemia (low pulse oximeter reading)
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DIAGNOSIS
No laboratory test result is diagnostic for NMS.
They are to assess severity and complications or
rule out other diagnostic possibilities
Increased LDH ,Increased creatine kinase
(50-100% of cases) Increased AST and ALT
,Increased alkaline phosphatase ,Hyperuricemia
,Hyperphosphatemia ,Hyperkalemia,
Myoglobinemia ,Leukocytosis (70-98% of cases),
Thrombocytosis ,Proteinuria ,Decreased serum
iron,Increased CSF protein ,Hypocalcemia,
Myoglobinuria ,Metabolic acidosis .
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MANAGEMENT
discontinue all neuroleptic agents. In most
cases, symptoms will resolve in 1-2 weeks.
Episodes precipitated by long-acting depot
injections of neuroleptics can last as long as a
month.
Rx- mainly supportive; directed toward
controlling the rigidity and hyperthermia and
preventing complications (eg, respiratory
failure, rhabdomyolysis, renal failure).
Limited evidence supports the use of
dantrolene and bromocriptine to hasten clinical
response; other interventions that have been
used include amantadine, lorazepam, and
electroconvulsive therapy
Dantrolene will also lower an elevated
temperature in disorders other than MH, such
as thyroid storm, neuroleptic malignant
syndrome (NMS), and sepsis. Each 20-mg vial
of lyophilized powder contains sodium
hydroxide for a pH of 9-10 and mannitol,
which makes the solution isotonic.
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It is a potentially life threatening drug
reaction that causes the body to have too
much serotonin, a chemical produced by
nerve cells.
Serotonin syndrome most often occurs when
two drugs that affect the body's level of
serotonin are taken together at the same
time.
The drugs cause too much serotonin to be
released or to remain in the brain area.
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Migraine medicines called triptans taken
together with antidepressants called selective
serotonin reuptake inhibitors (SSRIs) and
selective serotonin/norepinephrine reuptake
inhibitors (SSNRIs)
Older antidepressants called monoamine
oxidase inhibitors (MAOIs) can also cause
serotonin syndromewhen taken with
SSRIs/SSNRIs, as well as meperidine (Demerol, a
painkiller) or dextromethorphan (cough
medicine).
Drugs of abuse, such as ecstasy and LSD have
also been associated with serotonin syndrome.
Tricyclic antidepressants.
Symptoms occur within minutes to hours:
• Agitation or restlessness
• Diarrhoea
• Fast heartbeat and high blood pressure
• Hallucinations
• Increased body temperature
• Loss of coordination
• Nausea
• Overactive reflexes
• Rapid changes in blood pressure
• Vomiting
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Severe serotonin syndrome can be lifethreatening. Signs and symptoms include:
High fever
Seizures
Irregular heartbeat
Unconsciousness
DIAGNOSIS
Use of serotonergic drug along with three of the
following signs or symptoms:
• Agitation
• Diarrhoea
• Heavy sweating not due to activity
• Fever
• Mental status changes such as confusion or
hypomania
• Muscle spasms (myoclonus)
• Overactive reflexes (hyperreflexia)
• Shivering
• Tremor
• Uncoordinated movements (ataxia)
Other possible causes have been ruled out.
Tests:
• Blood cultures (to check for infection)
• Complete blood count (CBC)
• CT scan of the brain
• Drug (toxicology) and alcohol screen
• Electrolyte levels
• Electrocardiogram (ECG)
• Kidney and liver function tests
• Thyroid function tests
TREATEMENT
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Hospitalisation for at least 24 hours for close
observation.
Benzodiazepines such as diazepam (Valium) or
lorazepam (Ativan) to decrease agitation,
seizure-like movements, and muscle stiffness
Cyproheptadine (Periactin), a drug that blocks
serotonin production
Intravenous (through the vein) fluids
Withdrawal of medicines that caused the
syndrome
SUPPORTIVE
Its an clinical effect of excess thyroid hormone
usually from gland hyper function.
THYROID STROM
Thyroid storm, also referred to as thyrotoxic
crisis, is an acute, life-threatening,
hypermetabolic state induced by excessive
release of thyroid hormones (THs) in
individuals with thyrotoxicosis.
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CLINICAL PRESENTATION
Fever, tachycardia, hypertension,
Neurological (Anxiety ,Altered behavior, Seizures,
coma , Hyperreflexia and transient pyramidal signs)
GI abnormalities(Nausea and vomiting ,Diarrhea
,Abdominal pain ,jaundice )
Hypertension may be followed by congestive heart
failure that is associated with hypotension and shock.
Rhabdomyolysis
Thyroid storm is almost invariably fatal if left
untreated, rapid diagnosis and aggressive treatment
are critical.
It is extremely rare in children.
ETIOLOGY
Thyroid storm is precipitated by the following
factors in individuals with thyrotoxicosis:
• Sepsis
• Surgery
• Anesthesia induction
• Radioactive iodine (RAI) therapy
• Drugs (anticholinergic and adrenergic drugs, eg,
pseudoephedrine; salicylates; nonsteroidal antiinflammatory drugs [NSAIDs]; chemotherapy[4]
• Excessive thyroid hormone (TH) ingestion
• Withdrawal of or noncompliance with antithyroid
medications
• Diabetic ketoacidosis
• Direct trauma to the thyroid gland
• Vigorous palpation of an enlarged thyroid
• Toxemia of pregnancy and labor in older
adolescents; molar pregnancy
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Thyroid storm can occur in children with
thyrotoxicosis from any cause but is most
commonly associated with Graves disease.
Other causes of thyrotoxicosis associated
with thyroid storm include the following:
Transplacental passage of maternal thyroidstimulating immunoglobulins in neonates
McCune-Albright syndrome with
autonomous thyroid function
Hyperfunctioning thyroid nodule
Hyperfunctioning multinodular goiter
Thyroid-stimulating hormone (TSH)-secreting
tumor
DIAGNOSIS
Primarily clinical, and no specific laboratory tests
are available.
TESTS
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TSH
T4&T3,free T4,T3 resin uptake,24hr iodine
uptake
Mild normocytic Anemia , Mild neutropenia(in
Graves)
ESR,Calcium,LFT
Thyroid Auto antibodies
Isotope scan(Nodular ds or subacute
thyroiditis
Visual fields , acuity &eye movements(if
Ophthalmopathy present)
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TREATEMENT
measures
Antiadrenergic drugs:
Propranolol-orally or via NG tube @60-80 mg
every 4-6th hrly.
IV 0.5-1 mg over 10 min followed by 1-2 mg
over 10 min every few hours, adjusted based
on vital signs .
IV short acting beta-1 blockers-Esmolol
(loading dose of 250-500 mcg/kg, followed
by an infusion of 50-100 mcg/kg per minute).
Thionamides:
 PTU
200 mg q4h or methimazole 20 mg oralil
q4-q6h; orally or NG tube.
 Iodine
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preparations:
Iodine compounds (Lugol iodine or potassium
iodide) orally or via a NG tube to block the
release of THs (at least 1 h after starting
antithyroid drug therapy). In adults, SSKI is a
given at a dose of 5 drops every 6 hours, or
Lugol's iodine at a dose of 10 drops every 8
hours. .
These agents are particularly effective at
preventing peripheral conversion of T4 to T3.
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Glucocorticoids:
Hydrocortisone IV 100 mg q8h or
dexamethasone 1-2 mg q6h.
 Bile acid sequestrants:
• 4 g of cholestyramine q6h via a nasogastric
tube
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 Treatment
of the underlying condition
 Rarely plasmapheresis
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Various stimulant drugs:
Amphetamines,
• Cocaine,
• PCP(phencyclidine)
• LSD(Lysergic acid diethylamide
• MDMA (3-4 methylenedioxymethamphetamine)
 The use of anticholinergics, more specifically
muscarinic antagonists cause mild hyperthermic
episodes due to its parasympatholytic effects.
 Drugs that decouple oxidative phosphorylation
also cause hyperthermia. From this group of
drugs the most well known is 2,4-Dinitrophenol
which was used as a weight loss drug
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 Personal
protective equipment
can produce hyperthermia as an adverse effect
 Adrenal
gland tumor, called
pheochromocytoma.
 Damage to the central nervous system, from
brain hemorrhage,
 Status epilepticus,
 Other kinds of injury to the hypothalamus
can also cause hyperthermia.