Definition

Elevation of core body temperature above the normal diurnal range of 36C to 37.5C due to failure of thermoregulation Hyperthermia is not synonymous with the more common sign of fever, which is induced by cytokine activation during inflammation, and regulated at the level of the hypothalamus

Hyperthermia
The most important causes of severe hyperthermia (greater than 40C or 104F) caused by failure of thermoregulation are:
Heat stroke Neuroleptic malignant syndrome Malignant hyperthermia Drug Induced

Physiology
Body temperature is maintained within a narrow range by balancing heat load with heat dissipation. Body's heat load results from both metabolic processes and absorption of heat from the environment As core temperature rises, the preoptic nucleus of the anterior hypothalamus stimulates efferent fibers of the ANS to produce sweating and cutaneous vasodilation.

Thermoregulation
Thermal Receptors
cold and warm
Skin and viceral

Preoptic nuclei Anterior Hypothalamus

Efferent Responses Cold

Behavioural Cutaneous vasoconstriction Shivering, non-shivering

Warm
Behavioural Cutaneous vasodilation Sweating,Panting

Hipertermia - Murdin Amit

Physiology
Evaporation is the principal mechanism of heat loss in a hot environment, but this becomes ineffective above a relative humidity of 75% Other methods of heat dissipation
Radiation- emission of infrared electromagnetic energy Conduction- direct transfer of heat to an adjacent, cooler object Convection-direct transfer of heat to convective air currents

These methods cannot efficiently transfer heat when environmental temperature exceeds skin temperature.

Physiology
Temperature elevation O2 consumption and metabolic rate hyperpnea and tachycardia Above 42C (108F), oxidative phosphorylation becomes uncoupled, and a variety of enzymes cease to function. Hepatocytes, vascular endothelium, and neural tissue are most sensitive to these effects, but all organs may be involved. As a result, these patients are at risk of multiorgan system failure.

How does the newborn lose body heat?

Four ways a newborn may lose heat to the environment. Most cooling of the newborn occurs during the first minutes after birth.

Heat Regulation
Four mechanisms of heat loss/dissipation:
Radiation Convection Conduction Evaporation

Radiation
Physical transfer of heat between the body and the environment by electromagnetic waves 65% of heat transfer under normal circumstances Modified by insulation (clothing, fat layer), cutaneous blood flow

Convection
Energy transfer between the body and a gas or liquid Affected by temperature gradient, motion at the interface, and liquid Not usually a major source for heat loss or dissipation, but this increases with wind and body motion

Conduction
Direct transfer of heat energy between two surfaces Responsible for only a small proportion of heat loss under normal circumstances

Levels of Hyperthermia
There are three levels of hyperthermia - Heat cramps: painful muscle spasms/cramps usually in legs, arms or abdomens. - Heat exhaustion: when no action is taken when a cramp becomes evident. - Heat stroke: can cause impaired mental function, leading to unconsciousness and death.

Signs & Symptoms

Heat Cramps Heat Exhaustion Heat Stroke

Pain
Muscle rigidity Red, Sweaty, Hot Skin

Nausea, Vomiting
Muscle Cramps Pale, Cool, Clammy Skin Weak, Rapid Pulse Breathing Faintness, Dizziness Headache Confusion

Nausea, Vomiting
Irritable Hot, Red, Dry Skin Pounding, Rapid Pulse that gradually weakens Breathing Dizziness, Delirium Headache Altered consciousness leading to convulsions and unconsciousness

Thirst

Heat Stroke
Core body temperature > 40.5C (105F) with associated CNS dysfunction in the setting of a large environmental heat load that cannot be dissipated Complications include:
ARDS DIC Renal or hepatic failure Hypoglycemia Rhabdomyolysis Seizures

Classic (nonexertional) heat stroke

Affects individuals with underlying chronic medical conditions that either impair thermoregulation or prevent removal from a hot environment. Conditions include:
Cardiovascular disease Neurologic or psychiatric disorders Obesity Anhidrosis Extremes of age Anticholinergic agents or diuretics

Exertional heat stroke

Occurs in young, otherwise healthy individuals engaged in heavy exercise during periods of high ambient temperature and humidity Findings include cutaneous vasodilation, tachypnea, rales due to noncardiogenic pulmonary edema, excessive bleeding due to DIC, altered mentation or seizures Labs: coagulopathy, ARF, elevated LFTs due to acute hepatic necrosis, respiratory alkalosis, and a leukocytosis as high as 30,000 to 40,000/mm3 One series of 58 patients with heat stroke found an acute mortality rate of 21 percent (Ann Intern Med 1998 Aug 1;129(3):173-81)

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Hipertermia - Murdin Amit

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Menerangkan pengendalian hipertermia

Hipertermia - Murdin Amit

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Heat stroke
Classical Occurs due to exposure to a high environmental temperature Exertional Occurs in the setting of strenuous exercise

Pathophysiology
Oxidative phosphorylation stops at temperatures > 42 C Cell damage Loss of thermoregulatory compensatory mechanisms Hypoxia, increased metabolic demands, circulatory failure, coagulopathies and inflammatory response

CVS Effects
Tachyarrythmias and hypotension Two types exist with exertional heat stroke
Hyperdynamic group high cardiac output and tachycardia Hypodynamic group Low cardiac output, increase peripheral vascular resistance

Neurological Effects
Cardinal features of heat stroke Delirium, lethargy, coma and seizures Can be permanent (up to 33%)

Rhabdomyolysis
Injured cells leak phosphate and calcium Hypercalcaemia and Hyperphosphataemia Hypokalaemia is seen early

Secondary to heat induce hyperventilation leading to respiratory alkalosis Sweat and renal losses Potassium losses from damaged cells and renal failure

Hyperkalaemia is seen later

Hyperuricaemia develops secondary to the release of purines from injured muscle

Renal Effects
ARF in approx 30%
Direct thermal injury to kidneys Pre-renal insult of volume depletion and renal hypoperfusion Rhabdomyolysis

Haematological
Exertional heat stroke is associated with haemorrhagic complications Petechial haemorrhages or eccyhmosis secondary to direct thermal injury or DIC

Immunological
Similar to sepsis The actions of inflammatory mediators account for the multi organ dysfunction

Assessment
Consider in patients with altered mental state and exposure to heat Classic triad of hyperthermia, neurological abnormalities and dry skin Measure temp with rectal/oesophageal probe Sweating can still be present Hypotension and shock 25%
Hypovolaemia, peripheral vasodilatation and cardiac dysfunction

Sinus tachy Hyperventilation a universal finding in heat stroke

Investigations
UEC
Hypokalaemia Hyperphosphataemia and hypercalcaemia Hyperkalaemia and hypocalcaemia may be present if rhabdomyolysis has occurred Renal impairment

Investigations
Urate is frequently high and may play a role in the development of acute renal failure Glucose elevated in up to 70% LFT Almost always seen in exertional heat stroke (AST and LDH most commonly elevated) CK 10000 to 1000000 in rhabdomyolysis

Investigation
FBC WCC as high as 30 -40,000 Coag routinely abnormal and DIC may occur Acid Base:
Lactic acidosis Compensatory respiratory alkalosis

Myoglobin serum or urine myoglobin may be elevated

Investigation
ECG
Rhythm disturbances (sinus tachy, SVT + AF) Conduction defects (RBBB and intraventricular conduction defects) QT prolongation (most common secondary to low K+ , Ca 2+ and Mg 2+) ST changes (secondary to myocardial ischaemia)

Investigations
CXR:
ARDS Aspiration

Management of Heat Stroke

If prompt effective treatment not undertaken mortality approaches 80% A
ETT if needed Consider early Avoid suxamaethonium

Management of Heat Stroke

B
Monitor Resp Rate and O2 sats Look for evidence of aspiration if GCS decreased Check for ARDS and ventilate as per lung injury protocol
May be a large fluid deficit N saline is probably best (CSL lactate and avoid K+ containing fluids) Monitor heart rate, BP, CVP and urine output Picco/Swan-Ganz pulmonary artery catheter may be indicated Pressors may be needed but avoid adrenergic agents as they can impair heat dissipation by causing peripheral vasoconstriction (dopamine)

Management of Heat Stroke

D Intubate if needed E Temperature should be measured by oesophageal or rectal probe

Cooling Methods
Mainstay of therapy and must be initiated from the onset Use prehospital may be lifesaving Initially remove patient from heat source and remove all clothing Evaporative cooling tepid water on the skin with fans Ice water immersion most effective method but practically difficult and cant use monitors/equipment and uncomfortable for the patient

Cooling Methods
Ice packs to axilla, groin and neck Cooling blankets and wet towels Peritoneal lavage and cardiopulmonary bypass can be considered in severe resistant cases Shivering may occur in rapid cooling this will increase oxygen consumption and heat production
Sedate paralyse

Paracetamol and aspirin are ineffective and

Outcome
Mortality should be less than 10% with prompt treatment Most recover without sequalae Residual neurological defects are reported

Heat Exhaustion
Heat exhaustion mild heat stroke Same physiological process Patients can still have the capacity to dissipate heat and the CNS is not impaired Volume depletion is still a problem

Heat Cramps
Painful involuntary spasms of major muscles Usually in heavily exercised muscle groups Dehydration and salt loss also thought to plat a role Rest rehydrate and replace salts

OBJECTIVES FOR MALIGNNANT HYPERTHERMIA

Describe the pathophysiology associated with malignant hyperthermia. Discuss the signs and symptoms of malignant hyperthermia. List triggering agents for malignant hyperthermia. Describe the malignant hyperthermia treatment protocol. Discuss the testing available to identify malignant hyperthermia patient. List differential diagnosis for malignant hyperthermia. Identify the population at risk for developing malignant hyperthermia. Describe the plan of care for a known malignant hyperthermia patient.

Malignant Hyperthermia
Uncommon, life-threatening, hypermetabolic disorder of the skeletal muscle triggered by inhalation agents and succinylcholine. First case was of an Australian family over 40 years ago. Inherited in some families as a autosomal dominant pattern with variable penetrance. 52% of cases occur under the age of 15, with the mean age 18.3 years. Incidence- 1:50,000 adults and 1:15,000 children. High incidence states-Wisconsin, West Virginia, and Michigan

MALIGNANT HYPERTHERMIA
PATHOPHYSIOLOGY Cause of MH is not yet known with certainty. MH is an inherited disorder of the skeletal muscle system in which a defect in the calcium regulation is expressed by exposure to triggering anesthetic agents; intracellular hypercalcemia results.

MALIGNANT HYPERTHERMIA
PATHOPHYSIOLOGY The ryanodine receptor modulate calcium release from the channels in the sarcoplasmic reticulum, and much attention has been focused on this receptor as a site of the MH defect. There is no evidence of primary defect in cardiac or smooth muscle cells.

MALIGNANT HYPERTHERMIA
PATHOPHYSIOLOGY When MH is initiated-the concentration of calcium in the muscle cells increase. Actomysin cross-bridging, sustain muscle contraction, and rigidity results. Energy-dependent reuptake mechanisms attempt to remove excess calcium from the muscle cells, increasing muscle metabolism twofold to threefold.

MALIGNANT HYPERTHERMIA
PATHOPHYSIOLOGY Increased oxygen consumption, augment carbon dioxide and heat production, deplete ATPstores, and generate lactic acid. Resulting in acidosis, hyperthermia, ATP depletion, marked increase of myoglobin, creatine kinase and potassium.

MALIGNANT HYPERTHERMAI
TRIGGERING AGENTS ALL VOLITILE ANESTHETICS SUCCINYLCHOLINE NON TRIGGERING AGENTS- EVERYTHING ELSE

MALIGNANT HYPERHTERMIA
CLINICAL EVENTS OF MH: TACHYCARDIA TACHYPNEA LIABILE B/P, ARRHYTHMIAS RISE ETCO2, ABRUPT OR GRADUAL MASSETER MUSCLE OR GENERALIZED MUSCLE RIGIDITY (75%) UNANTICIPATED RESPIRATORY OR METABOLIC ACIDOSIS RISING PATIENT TEMPERATURE COLA-COLORED URINE MOTTLED, CYANOTIC SKIN, DECREASED SaO2

MALIGNANT HYPERTHERMIA
LABORATORY FINDINGS: ARTERIAL BLOOD GAS:PCO2>60mmHg BASE EXCESS MORE NEGATIVE THAN8mEq/L,Ph<7.25 POTASSIUM ION >6mEq/L CK>10,000 IU/L, AFTER ANESTHETIC WITHOUT SUCCINYLCHOLINE SERUM MYOGLOBIN >170mcg/L URINE MYOGLOBIN >60mcg/L

MALIGNANT HYPERTHERMIA
Hyperthermia may climb 1 degree to 2 degrees C every 5 minutes and exceed 43.3 C (110 degrees F). Often a late but confirming sign of MH. Late complications: cerebral edema, myoglobinuric renal failure, consumptive coagulopathy, hepatic dysfunction, and pulmonary edema.

MALIGNANT HYPERTHERMIA
Manifestations that mimic MH TACHYCARDIA-hypoxia, hypercarbia, hypovolemia, light anesthesia, anticholinergics, sympathomimetics, cocaine, pheochromocytoma. HYPERPYREXIA-heatstroke, blood transfusion reaction, infection, drug reaction, neuroleptic malignant syndrome, serontonin syndrome, hypermetabolic states-sepsis, thyroid storm, pheochromocytoma.

MALIGNANT HYPERTHERMIA
Manifestations that mimic MH Tachypnea, Hypercapnia-CHF, pulmonary edema, hypermetabolic states, intraperitoneal CO2 insuflation, airway obstruction, pneumothorax, excessive dead space, low minute volume. Masseter Muscle Rigidity-insufficient neuromuscular blockade, temporomandibular joint syndrome, neuroleptic malignant syndrome, myotonia.

MALIGNANT HYPERTHERMIA
IN ADDITION TO BEING A TRIGGERING AGENT FOR MH, SUCCINYLCHOLINE MAY ALSO INDUCE A HYPERKALEMIC MEDIATED CARDIAC ARREST IN CHILDREN WITH OCCULT MYOPATHIES. PACKAGE INSERT WAS MODIFIED TO WARN AGAINST THE ROUTINE USE OF SUCCINYLCHOLINE IN CHILDREN.

MALIGNANT HYPERTHERMIA
PREOP ASSESMENT Family history of muscle disorders Unexpected intraoperative deaths Family or personal muscle rigidity/stiffness or high fever under anesthesia History of heat stroke Personal history of dark cola-colored urine following surgery Absence of positive history does not preclude MH susceptability MH is linked to Duchennes and Beckers muscular dystrophy 50% of patients with unexplained CK elevation test positive for MH on biopsy

MALIGNANT HYPERTHERMIA
TREATMENT CALL FOR HELP-tell surgeon to conclude procedure Discontinue volitile agent and succinylcholine Hyperventilate 100% O2 at 10 L/min Dantrolene 2.5mg/kg up to 10mg/kg (175mg in 70kg up to700mg) each vial 20mg mix in 60 cc of sterile water Dysrhythmias treat acidosis and hyperkalemia, standard antiarrhythmic drugs. Avoid calcium channel blockers

MALIGNANT HYPERTHERMIA
FEVER- cooling lavage orogastric, bladder, open cavities, chilled IV fluid, ice packs, hypothermia blanket ACIDOSIS- NA bicarbonate, send ABGs, lytes, glucose every 15minutes. Base line coagulation studies, CK, myoglobin, liver enzymes HYPRERKALEMA-hyperventilation, 10 units regular insulin in 50 ml 50% glucose titrated to potassium level Maintain urine output 2ml/kg/hr by hydration and mannitol (300mg/kg) and/or furosemide (.5 to 1.0mg/kg) Consider CVP/PA arterial monitoring

MALIGNANT HYPERTHERMIA
Anesthesia for the MH-susceptible patient Standard monitoring equipment Cooling blanket under patient at start of procedure Preop anxiolytic Local or regional if possible Triggering agents removed from OR Anesthesia machine- change soda lime, circuit, removing or inactivating vaporizers, flush 10L O2 for 20 minutes 3000 ml cold IV solution available Ice available ABG analysis available 36 VIAL OF DANTROLENE AVAILABLE

MALIGNANT HYPERTHERMIA
DIAGNOSTIC TESTING CAFFEINE HALOTHANE TEST THIGH MUSCLE BIOPSY MEASURES THE CONTRACTILE RESPONSE TO CAFFEINE, HALOTHANE, OR BOTH. THIS IS AUGMENT IN THE PATIENT WITH MH. 92% SENSITIVITY AND 78%SPECIFICITY

MALIGNANT HYPERTHERMIA
GENETIC DIAGNOSTIC TESTING RYR-1 gene Has 28 mutations that are causal for MH Blood test can be shipped to the lab Limitation is sensitivity of approximately 25%

MALIGNANT HYPERTHERMIA
GENETIC DIAGNOSTIC TESTING Patients should consider genetic testing if: a) they have a positive contracture test, b) a family member has had a positive contracture test, c)they suffered a MH episode, d) a family member has been found to have a causal mutation

MALIGNANT HYPERTHERMIA
POSTOP CARE DANTROLENE TREATMENT NEEDS TO BE CONTINUED FOR A MINIMUM OF 24 HOURS AFTER CONTROL OF THE EPISODE. MASSETER MUSCLE RIGIDITY-STUDIES INDICATE IF THE CK IS GREATER THAN 20,000 IU AND A CONCOMITANT MYOPATHY IS NOT PRESENT THE DIAGNOSIS OF MH IS LIKELY