1. HYPERTHERMIC SYNDROMES
Dr. Prajwala Reddy

2. HYPERTHERMIA
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

3. PATHOPHYSIOLOGY
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.

4. 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 .

5. HEAT STROKE
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.

6. 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.

7. 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.

8. 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.

9. Causes
Increased heat production
Decreased heat loss
Reduced ability to acclimatize
Reduced behavioral responsiveness

10. 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.

11. 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

12. 3.Reduced ability to acclimatize 4.Reduced behavioral responsiveness

13. DIAGNOSIS
Clinical history&above signs and symptoms.
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.

14. MALIGNANT HYPERTHERMIA:
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.

15. 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

16. 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)

17. MANAGEMENT Dandrolin:
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 hours is recommended.
administration of dantrolene 1 mg/kg every 4-6 hours, or an equivalent amount given as a continuous infusion.

18. NEUROLEPTIC MALIGNANT SYNDROME
Neuroleptic malignant syndrome is a life- threatening, 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.

19. Five classes of available neuroleptic drugs:
Phenothiazines,
Thioxanthenes,
Butyrophenones,
Indoles,
Dibenzoxazepines.

20. clinical features:
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:
Sialorrhea
Tachycardia
Tachypnea, respiratory distress (31% ofcases)
Increased or labile blood pressure
Hypoxemia (low pulse oximeter reading)

21. 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 .

22. 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

23. 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.

24. SERITONIN SYNDROME
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.

25. 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.

26. 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

27. Severe serotonin syndrome can be life- threatening
Severe serotonin syndrome can be life- threatening. Signs and symptoms include:
High fever
Seizures
Irregular heartbeat
Unconsciousness

28. 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.

29. 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

30. TREATEMENT
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

31. THYROTOXICOSIS
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.

32. 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.

33. 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 anti- inflammatory 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

34. 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 thyroid- stimulating immunoglobulins in neonates
McCune-Albright syndrome with autonomous thyroid function
Hyperfunctioning thyroid nodule
Hyperfunctioning multinodular goiter
Thyroid-stimulating hormone (TSH)-secreting tumor

35. DIAGNOSIS
Primarily clinical, and no specific laboratory tests are available.
TESTS
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)

36. TREATEMENT
Supportive measures
Antiadrenergic drugs:
Propranolol-orally or via NG mg every 4-6th hrly.
IV 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  mcg/kg, followed by an infusion of mcg/kg per minute).
Thionamides:
PTU 200 mg q4h or methimazole 20 mg oralil q4-q6h; orally or NG tube.

37. Iodine 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.

38. Glucocorticoids:
Hydrocortisone IV 100 mg q8h or dexamethasone 1-2 mg q6h. 
Bile acid sequestrants:
 4 g of cholestyramine q6h via a nasogastric tube
Treatment of the underlying condition
Rarely plasmapheresis

39. 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
Personal protective equipment
can produce hyperthermia as an adverse effect

40. 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.

41. THANK U………….