It is a beautiful Fall day with the temperature reading in the sixties. It is approximately two o'clock in the afternoon, the Emergency Department is slow and you are settled back just wishing you could be out on the golf links.

The nurse disturbs your reverie with the announcement of the arrival of a patient with decreased level of consciousness. As you walk into the room, you note a diaphoretic white male who is currently unresponsive to the nurse's questioning. The EMS crew immediately spits out a bizarre story.

"We were just driving down the road and, as we pulled up to a stop sign, this man staggered out in front of us, falling into the road. We looked for signs of trauma but couldn't find any."

"Was anyone with him?" you ask.

"No," they reply. "And all we could find as far as identity was this card with his name and birth date."

As you begin to examine the patient you become extremely concerned with the warmth of his body.

"Did anyone take his temperature? " you ask. Meanwhile, you begin to assess the basics, apply oxygen and connect the monitor. "Start an intravenous line," you order.

"Vitals are: blood pressure 132/75, respiratory rate 34, pulse 160, oxygen saturation on room air 98%. Axillary temperature is 106.6 Fahrenheit," the nurse reports.

"We'd better work fast," you tell the team.

Physical exam reveals a normocephalic/atraumatic patient with unresponsive and dilated pupils bilaterally. Tympanic membranes are clear and the patient is noted to have an excellent gag reflex. The lung, cardiovascular and abdominal exams are negative except for the pulse rate. Extremity exam reveals profuse diaphoresis; there is no clubbing, cyanosis or edema. Neurological exam reveals a decreased level of consciousness; however, the patient is moving all extremities. No seizure activity is noted.

Initial lab is drawn and pending. The stat portable chest x-ray has been requested and the EKG reveals a supraventricular tachycardia at a rate of 168.

Questions

1. What is the main influence on morbidity and mortality in the hyperthermic patient?
2. What is the appropriate initial management?
3. What are risk factors for developing hyperthermia and what are the signs and symptoms?
4. What is the differential diagnosis?
5. What are the complications to look for with hyperthermia?
6. What are the differences between neuroleptic malignant syndrome and malignant hyperthermia?
7. Bonus Question: You have ordered the dantrolene infusion on this patient and the nurse asks you what the appropriate means of administering dantrolene entails. What is important to remember?

Answers and Discussion

What Is the Main Influence on Morbidity and Mortality in the Hyperthermic Patient?

Morbidity and mortality in the hypothermic patient is generally most closely associated with etiology. In the hyperthermic patient, in contrast, morbidity and mortality are related more to the duration of the hyperpyrexia than to the degree of hyperthermia or etiology.

What Is the Appropriate Initial Management?

As with any patient with decreased mental status, the initial step should be assessment of the Airway, Breathing and Circulation, with appropriate interventions as problems are identified. The specific initial management of hyperthermia consists of vigorous attempts to lower body temperature, by any means available, together with rehydration and circulatory support. The patient should be moved to a cool environment, clothing removed and evaporative cooling of the skin encouraged by spraying tepid water over the body, while electric fans are directed at the patient. If available, bags of ice should be placed over the major vessels in the axillae, groin and neck. Intravenous infusions with 0.9% saline and 100% oxygen administration are of the utmost importance. All of these measures can, and should, be started at the scene by EMTs as soon as the diagnosis is made.

In the ER, these measures can be continued so that fluid and electrolyte abnormalities can be corrected. Other mechanisms of cooling, such as electric cooling blankets, should also be instituted. Some recommend the use of ice water baths as well as cool peritoneal lavage. These modalities of cooling can be difficult, cumbersome and usually are not needed. The prospect of trying to resuscitate a seizing patient, lying in an ice water bath, is not attractive, even though sometimes needed! Antipyretics are useless. The coma protocol of 50mls of 50% dextrose, naloxone (0.01mg/kg IV) and thiamine (100mgs IV) is the next step in a patient with poor mental status.

Laboratory work should be ordered that will detect evidence of end organ damage as a result of hyperthermia. Studies required include: complete blood count, electrolytes, liver profile, blood urea nitrogen, creatinine, calcium, magnesium, PT/PTT, arterial blood gases, urinalysis, urine myoglobin, creatine phosphokinase and a toxicology screen. It is essential to place a foley catheter for monitoring of urine output and a bladder temperature gauge for close monitoring of the core temperature. A chest x-ray and EKG are also important to help determine the etiology as well as complications of hyperthermia.

As the temperature begins to drop, the body begins to shiver and to manufacture heat. Thus, the use of benzodizepines is strongly recommended to alleviate a rebound effect with subsequent rise in the core temperature.

What Are the Risk Factors and What Are the Signs and Symptoms of Hyperthermia?

Risk factors of heat related illnesses include: the extremes of age (elderly and infants), high humidity, military recruits, obesity, previous heat stroke, cystic fibrosis, quadriplegia and recent drinking binge. Roofing workers are a particularly 'at risk' occupational group, as are sportsmen and women (especially tennis players and football players) who exercise in the heat of the day. Thus, a large number of persons are potentially at risk.

Heat related illnesses include heat cramps, heat exhaustion and heat stroke. Heat cramps are deemed the most benign. They are characterized by painful spasms of the skeletal musculature, particularly the legs. The body temperature is usually normal.

Heat exhaustion is characterized by fluid depletion. Patients tend to present sweating profusely. Symptoms include headaches, nausea, vomiting, dizziness and syncope. Treatment includes rest, rehydration (which often needs to be given intravenously) and cooling.

Heat stroke is a life threatening emergency defined as a high core temperature (>40c) accompanied by neurological symptoms. The presentation can range between a patient with minimal to no sweating, to a patient with profuse sweating.

What Is the Differential Diagnosis?

Lab Results

• sodium: 126 mEq/L, potassium: 4.5 mEq/L,. chloride: 96 mEq/L, C02: 12 mEq/L, Blood Urea Nitrogen: 12 mg/dL, Creatinine: 1.6 mg/dL
• White Blood Cell Count: 16.4K/ml, Hemoglobin: 15.5gm/dL, Hematocrit: 44.8%, platelets-288 K/ml
• Arterial Blood Gases pH: 7.44. pCO2: 29mmHg pO2: 123mmHg HCO3: 18.9mmol/L O2 Saturation: 98%
• PT/PTT-12.4/27.8
• Creatine Phosphokinase-364. Creatine Phosphokinase MB Fraction-2.7
• Osmolality-273, Calculated Osmolality-266
• Toxicological Screen-negative (cocaine, amphetamine, opiates, ETOH. acetominophen, salicylates, barbiturates)
• Urinalysis- negative
• SGOT-42, SGPT-18, Lactic Dehydrogenase-215, Alkaline Phosphokinase-86, amylase-30
• Chest X-ray- No Acute Disease

What Are the Complications to Look for with Hyperthermia?

There are many complications that can occur in hyperthermia. These include neurological abnormalities (delirium, seizures, coma), gastrointestinal symptoms (vomiting, diarrhea), hepatocellular necrosis, acute renal failure, electrolyte abnormalities (hypernatremia, hypocalcemia, hypo/hyperkalemia), cardiovascular collapse and rhabdomyolysis.

Rhabdomyolysis is a frequent complication of hyperthermia and can cause renal insufficiency and renal failure. This entity can be treated with large fluid resuscitation and sodium bicarbonate to alkalinize the urine, with close observation of urine output. Furosemide can be used to convert an oliguric form of renal failure into a nonoligouric form, which has a better prognosis.

What Are the Differences Between Neuroleptic Malignant Syndrome and Malignant Hyperthermia?

They are very different entities, often mistaken for one another. The misunderstanding probably stems from the fact that these two conditions have very similar symptoms. The differentiating point is that one is associated with neuroroleptics while the other is associated with certain anesthetics. Neuroleptic malignant syndrome is a life-threatening reaction to a neuroroleptic medication which may occur at any time during therapy. Features include: hyperthermia, muscular rigidity (often of the 'lead-pipe' type), altered level of consciousness and autonomic instability. The incidence is reported to be 0.02-3.2 percent and is most commonly reported with haloperidol. An anti-dopaminergic theory is favored.

Treatment for neuromuscular malignant syndrome includes IV benzodiazepines as a first line medication. Bromocriptine and dantrolene, a direct skeletal muscle relaxant, have both been reported to be effective. However, their lack of rapid effect probably precludes their use for immediate therapy.

Malignant hyperthermia is an autosomal dominant syndrome. It was first described in 1969 in a patient who was afraid of anaesthetics. When this patient's family history was examined, it was found that 10 of 24 family members had died during anaesthesia!(1) The genetics of the condition were confirmed by a statistical analysis of the numerous case reports that followed this original article.(2) Generally, malignant hyperthermia occurs after use of a depolarizing agent such as succinylcholine. Pathophysiology involves the flux of calcium ions from the skeletal muscle sarcoplasmic reticulum. This, in turn, activates an ATPase which produces the large amount of heat. This syndrome can occur peri-operatively as well as several hours after surgery. The treatment of malignant hyperthermia includes cessation of anesthesia, rapid cooling and dantrolene. It should be noted that, prior to the introduction of dantrolene, mortality was approximately 50 percent. However, mortality has dropped dramatically with its use.

Note: Always check for recent surgical scars/wounds in hyperthermic patients. With the increasing use of day surgery, and early discharge from hospital, there is a chance that emergency physicians may encounter hyperthemia in the post-operative patient.

Bonus Question: You Have Ordered the Dantrolene Infusion on This Patient and the Nurse Asks You What the Appropriate Means of Administering Dantrolene Entails. What Is Important to Note?

Always remember that during the reconstitution of dantrolene it must be mixed with sterile water. The use of normal saline or dextrose containing solutions will create an ineffective form of dantrolene which could hinder the treatment of this patient.

Conclusion

The patient was stabilized and his temperature corrected in the ER. The patient received benzodiazepines, thiamine, third generation cephalosporin and hydrocortisone. The patient was also begun on dantrolene while in the department. The decision was made not to intubate the patient secondary to patient maintaining an adequate airway.

Patient was subsequently transferred to the Intensive Care Unit, where the head CT was negative. The Iumbar puncture and blood cultures were also negative. Creatine Phosphokinase was noted to rise significantly and thus the patient was treated for rhabdomyolysis.

During the hospital stay, records from previous psychiatric treatment revealed a history of schizophrenia. The records also revealed that the patient was last treated two weeks prior to this ER visit with prolixin 50 mg IM. Dantrolene, thiamine and benzodiazepines were continued. Upon discharge five days later, friends noted a normal baseline mental status. Discharge diagnosis included hyperthermia (presumbablysecondary to NMS, though never actually proven), schizophrenia and rhabdomyolysis.

It should be noted that even at the time of discharge, the etiology behind this case of hyperthermia was still in question. The take home point is the fact that, when treating a patient with hyperthermia, the key is to cool the patient as rapidly as possible with close attention to supportive care.

Other Web Resources and Further Reading

For discussion on management of malignant hyperthermia, the following web site is excellent:

http://auryn.ibme.utoronto.ca/casweb/mhp.htm

A site with a good information page on prevention is:

http://www.doconline.com/heatstroke.html

And prevention tips for the elderly can be found on:

http://www.dhfs.state.wi.us/Aging/Age_News/newsteps.html

A general, short, discussion on hyperthermia is on:

http://www.mediscene.com/medpub/heat.htm

A 'layperson' perspective on prevention and first aid is on:

http://www.healthy.net/scr/article.asp?PageType=article&ID=1291