Hyperthermic Syndromes: Types, Causes, Diagnosis, and Treatment Plan

Introduction:

Hyperthermia is referred to as increased body temperature above 40 degrees Celsius and is a serious life-threatening condition that needs to be managed within no time. The failure to compensate for the excess heat generated leads to multiorgan loss, which is usually accompanied by altered neurological function. The hyperthermia associated with fever is caused by endogenous pyrogens, which affect the thermoregulation centers in the brain, whereas hyperthermic syndromes result from excessive heat production and/or inadequate heat dissipation from the body.

What Is A Hyperthermic Syndrome?

Hyperthermia, or extreme elevations in body temperature, is life-threatening and can be caused by prescription drugs or illegal substances acting at a number of different levels of the nervous system. Several psychotropic drug classes and combinations have been associated with hyperthermia, skeletal muscle hyper-metabolism, rigidity or rhabdomyolysis, autonomic dysfunction, and altered mental status ranging from unconsciousness to coma.

What Are the Different Types of Hyperthermic Syndrome?

1. Neuroleptic malignant syndrome (NMS).

2. Malignant hyperthermia.

What Is Neuroleptic Malignant Syndrome (NMS)?

Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency disorder that is linked with the use of antipsychotic (neuroleptic) medications and is associated with a distinctive clinical syndrome of hyperthermia, altered mental status, rigidity, and dysautonomia(impaired non-voluntary neuronal activity).

What Causes Neuroleptic Malignant Syndrome?

NMS is most commonly associated with antipsychotic and antiemetic drugs. Antipsychotic drugs were also called neuroleptic agents. Some of them are as follows:

• Haloperidol.

• Fluphenazine.

• Chlorpromazine.

• Clozapine.

• Risperidone.

• Olanzapine.

• Metoclopramide.

• Promethazine.

• Levosulpiride.

What Are the Clinical Features of Neuroleptic Malignant Syndrome (NMS)?

NMS symptoms typically manifest as a tetrad of symptoms, which include,

1. Hyperthermia: Hyperthermia is a classical finding of NMS. A temperature greater than 40°C is considered hyperthermia.

2. Muscular Rigidity:

• Muscular rigidity is often severe and generalized.

• Motor abnormalities are seen in tremors, dystonia, opisthotonus, trismus, chorea, and dyskinesias.

Altered Mental Status:

• Mental status change is the initial symptom in most of the patients.

• This may lead to marked encephalopathy with loss of consciousness and eventually lead to coma.

Autonomic Instability:

• Autonomic instability presents as tachycardia, labile or high blood pressure, and tachypnea with profuse sweating.

• Dysrhythmias may also occur.

How Is Neuroleptic Malignant Syndrome Diagnosed?

1. Elevated creatinine kinase (CK) levels.

2. Leukocytosis, with a white blood cell count of 10,000 to 40,000/mm3.

3. Elevated lactate dehydrogenase, alkaline phosphatase, and liver transaminase levels.

4. Electrolyte abnormalities like hypocalcemia, hypomagnesemia, hypo- and hypernatremia, hyperkalemia, and metabolic acidosis give a clue to the diagnosis.

5. A low serum iron concentration of 5.71 micromol/L is commonly seen in NMS patients (normal ranges from 11 to 32 micromol/L).

How Is Neuroleptic Malignant Syndrome Treated?

Stopping The Causative Agent:

• Removal of the causative agent is the single most important treatment in NMS.

• Other potential contributing psychotropic drugs like lithium, anticholinergic therapy, and serotonergic agents also should be stopped if possible.

Supportive Care:

• Cardiorespiratory stability is maintained by mechanical ventilation, antiarrhythmic agents, or pacemakers.

• The euvolemic state is maintained using intravenous fluids.

• If creatine kinase (CK) is elevated, high-volume intravenous fluids with urine alkalinization can prevent renal failure from rhabdomyolysis.

• Hyperthermia is controlled using cooling blankets.

• Elevated blood pressure is monitored by giving Clonidine.

• Nitroprusside is beneficial as it acts by cutaneous vasodilation.

• Benzodiazepines like Lorazepam are given about 0.5 to 1 mg to control anxiety.

What Is Malignant Hyperthermia (MH)?

Malignant hyperthermia (MH) is a hypermetabolic response to potent anesthetic agents and is also caused due to stressful conditions like vigorous exercise and heat. It is a life-threatening condition that is often treatable with the help of timely diagnosis and management.

What Causes Malignant Hyperthermia?

• People susceptible to malignant hyperthermia have a genetic mutation that causes abnormal proteins in the muscle cells of the body.

• The mutation causes no problems in everyday life, but when exposed to certain anesthetics like Halothane, Sevoflurane, and Desflurane and to depolarizing muscle relaxants such as Succinylcholine or, in rare cases of high heat or strenuous activity, chances are more that the person can undergo hyperthermia, which causes the abnormal release of calcium from the muscle cells.

• This leads to sustained muscle contraction (tense or rigid muscles) and an abnormal increase in metabolism and body heat (temperature). Muscle cells eventually die and release large amounts of potassium into the bloodstream, leading to additional symptoms and complications.

What Are the Clinical Features of Malignant Hyperthermia?

Early signs of malignant hyperthermia include,

• Unexplained increase in heart rate (tachycardia).

• Unexplained increase in carbon dioxide produced by the body.

• Rapid breathing (tachypnea).

• Muscle rigidity.

• Rapid elevation in temperature.

Later signs of malignant hyperthermia include,

• Increase in body temperature.

• Dark pee.

• Muscle breakdown shows up on blood tests.

• Heart rhythm problems.

• Bleeding.

• Seizures.

How Is Malignant Hyperthermia Diagnosed?

For some, malignant hyperthermia runs in families, and they are more prone to have an attack while undergoing anesthetic intervention during a surgical procedure. Hence, a detailed family and personal history should be taken to assess the risks, and further complications can be avoided. The following investigations are beneficial in diagnosing malignant hyperthermia to avoid potential complications which include:

• Caffeine Halothane Contracture Test (CHCT): This is done by exposing the biopsied liver muscle tissue to Halothane and caffeine to check for any reaction.

• Genetic Testing: Genetic testing reveals mutations in RYR1, STAC3, and CACNA1S locations on DNA. There are over 45 mutations that are recognized as diagnostic for malignant hyperthermia.

How Is Malignant Hyperthermia Managed?

The drug of choice for managing malignant hyperthermia is Dantrolene. Anesthesiologists administer the drug as soon as they suspect the signs of malignant hyperthermia during a surgical procedure and also stop administering the triggering anesthetic, and the surgeon ends the surgery as soon as possible. The signs and symptoms that occur during a procedure have to be managed immediately by taking the following measures:

• Body cooling measures, such as cold IV fluids and ice packs for hyperthermia, should be provided.

• Oxygen is to be provided through a face mask or a tube placed into the trachea.

• Arrhythmia (abnormal or irregular heartbeat) needs to be treated with medications.

• Once the patient becomes stable, they will be shifted to an ICU (Intensive care unit) for at least a day.

Conclusion

The importance of prevention lies in reducing modifiable risk factors, early recognition of the impending risk at the onset of fever, and apt diagnosis. Treatment is best provided in emergency medicine. Initial treatment must focus on patency of the airway, breathing, and maintenance of circulation. The key to successful treatment and good outcomes lies in the rapid withdrawal of the offending drug and initiation of supportive therapies.