13. Thermoregulation

An inherited disorder of skeletal muscle triggered in most instances by inhalation agents and/or succinylcholine, resulting in hypermetabolism, skeletal muscle damage, hyperthermia, and death if untreated

Patients may have up to three exposures to triggering agents prior to having a reaction.

Key Points

Hypercapnia resistant to increasing minute ventilation

Common triggering agents—Inhalational anesthetics (sevoflurane, desflurane, halothane) and succinylcholine

Discontinue all triggering agents if Malignant Hyperthermia (MH) is suspected.

Control airway and ventilation

Call for help and MH cart

Administer dantrolene

Common Symptoms to Remember

Epidemiology

Children: 1:15,000 general anesthetics

Adults: 1:30,000 when general inhalational anesthetics and succinylcholine are used or 1:220,000 when general inhalation anesthetics are used only

Key Pathophysiology

Patients who are susceptible to developing MH have an abnormality in their ryanodine receptor type 1.

This leads to an excessive and sometimes sustained release of calcium from the sarcoplasmic reticulum, causing persistent skeletal muscle contraction in the presence of triggering anesthetic agents.

This contraction causes the downstream effects of rigidity, hyperthermia, excessive carbon dioxide production, and rhabdomyolysis.

Differential Diagnosis

Any condition that impairs elimination of carbon dioxide

Hypoventilation

Pneumothorax

Bronchial obstruction

Intracranial bleed

Traumatic brain injury

Hypoxic encephalopathy

Thyrotoxicosis

Pheochromocytoma

Sepsis

Heat stroke

Serotonin syndrome

Neuroleptic malignant syndrome

CO₂ absorption during laparoscopy

Conditions associated with MH

Central core myopathy—very high risk associated with MH

King–Denborough syndrome

Multicore myopathy

Management and Treatment

Rising end-tidal CO₂ despite increases in minute ventilation along with muscle rigidity.

Exclude other causes: either decreased CO₂ elimination or increased CO₂ production—these should not hinder proceeding with MH treatment.

Communication

Call for MH cart and additional help

Notify surgeon/complete operation if applicable

Call MH Hotline: 1-800-644-9737 (US)

Discontinue offending agents

Inhalational agents and succinylcholine

100% oxygenation with controlled hyperventilation

Administer dantrolene

Binds to ryanodine receptors and directly inhibits sarcoplasmic reticulum calcium release effectively reversing muscle hypermetabolism

Dose: 2.5 mg/kg IV every 5 minutes up to 10 mg/kg

Laboratory values

Assess electrolytes, ETCO₂, blood gases, creatine phosphokinase, serum myoglobin, core temperature, urine output, and color and coagulation studies

Hyperkalemia

Treat with calcium, insulin, glucose, albuterol, bicarbonate, kayexalate, furosemide

Cardiac arrhythmias

Resolves with treatment of acidosis and hyperkalemia

Typical antiarrhythmics may be used if arrhythmias persist but calcium channel blockers are contraindicated because they can worsen hyperkalemia and result in cardiac collapse

Cool the patient

Temperature goal of <38.5°C (101.3°F)—but avoid hypothermia

Continuous monitoring and support of respiratory, cardiovascular, and renal function in the intensive care unit

Recurrence of the signs appeared in 25 patients after initial treatment; dantrolene 1 mg/kg every 6 hours should continue for 48 hours after last sign of MH resolves.

Outcomes

Mortality is estimated at 1% to 20%

Development of Disseminated Intravascular Coagulation (DIC)—greater risk for cardiac arrest and death

Susceptible individuals should avoid anesthesia with triggering agents

Family and relatives should be informed and the susceptibility of MH should be discussed

SUGGESTED READINGS

Burkman JM, Posner KL, Domino KB. Analysis of the clinical variables associated with recrudescence after malignant hyperthermia reactions. Anesthesiology. 2007;106:901.

D’Arcy CE, Bjorksten A, Yiu EM, et al. King-Denborough syndrome caused by a novel mutation in the ryanodine receptor gene. Neurology. 2008;71:776.

Denborough M. Malignant hyperthermia. Lancet. 1998;352:1131.

Guis S, Figarella-Branger D, Monnier N, et al. Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization. Arch Neurol. 2004;61:106.

Larach MG, Brandon BW, Allen GC, et al. Cardiac arrests and deaths associated with malignant hyperthermia in North America from 1987 to 2006: a report from the North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States. Anesthesiology. 2008;108:603.

Larach MG, Gronert GA, Allen GC, et al. Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006. Anesth Analg. 2010;110:498.

Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology. 1994;80:771.

Malignant Hyperthermia Association of the United States. http://www.mhaus.org/

Rosenberg H, Davis M, James D, et al. Malignant hyperthermia. Orphanet J Rare Dis. 2007; 2:21.

Rosero EB, Adesanya AO, Timaran CH, et al. Trends and outcomes of malignant hyperthermia in the United States., 2000 to 2005. Anesthesiology. 2009; 110:89.

Zhang Y, Chen HS, Khanna VK, et al. A mutation in the human ryanodine receptor gene associated with central core disease. Nat Genet. 1993;5:46.

13.2

Neuroleptic Malignant Syndrome

Shamim Nejad

Neuroleptic Malignant Syndrome

A very rare but potentially fatal syndrome associated with the use of dopamine antagonist medications (antiemetics, antipsychotics, etc.) commonly used in critical care medicine.

Characterized by administration of D2-blocking drugs and early development of hyperthermia, muscle rigidity, mental status changes, and autonomic instability (hyper- or hypotension, tachycardia, tachypnea, and diaphoresis). Other drug-induced, systemic, or other neuropsychiatric illnesses should be excluded before making a diagnosis of neuroleptic malignant syndrome (NMS).

Risk Factors

History of NMS or catatonia

Pre-existing organic brain disease, especially involving diminished central brain dopamine activity or receptor function (e.g., Parkinson’s disease, traumatic brain injury)

Use of high-potency antipsychotics

Dehydration

Patients with significant fluid shifts (i.e., postpartum women)

Agitated men under the age of 40 years old

Genetic susceptibility (reports of incidence amongst certain families)

Clinical characteristics: NMS presents as a classic tetrad in the setting of neuroleptic use

fever

rigidity (lead-pipe)

autonomic instability

altered mental status

Early signs include unexpected mental status changes and muscle rigidity developing over the course of a few days (range: hours to weeks) in association with the introduction of D2 blockade or removal of dopamine potentiation.

Mental status changes are nonspecific and typically include confusion and clouding of consciousness, with approximately 50% having abnormal EEGs. Hyperthermia usually develops late. Autonomic dysfunction may develop at any point.