Internal Medicine Correlations and Clinical Scenarios (CCS) USMLE Step 3

CASE 10: Neuroleptic Malignant Syndrome

Setting: ICU

CC: Unexpectedly high carbon dioxide level during surgery

VS: BP: 94/62 mm Hg; P: 120 beats/minute; T: 98°F; R: 30 breaths/minute

HPI: A 34-year-old woman with a history of Crohn disease, who has just been in the operating room for her third surgery to relieve obstruction, is now brought to the ICU because of a rise in PCO2 to 65 mm Hg that cannot be explained. The patient had induction of anesthesia with midazolam then an inhalational anesthetic by face mask. Despite increasing the respiratory rate on the ventilator to 30 breaths per minute, the increased PCO2 persists.

PMHX:

Image Crohn disease

Image Surgery to relieve obstruction from stricture in past

Image Nephrolithiasis

Medications:

Image Mesalamine (Pentasa)

Image Infliximab intermittently

PE:

Image General: muscle rigidity

Image Chest: clear to auscultation; normal lung examination

Image Cardiovascular: normal

Image HEENT: normal

Initial Orders:

Image ABG

Image Chest x-ray

Image CHEM-20

Image Creatine kinase (CK)

CCS sometimes gives unexpected “Nurses Notes” that have updates on the patient’s condition. The updates can be either positive or negative in terms of improvement or worsening of the patient’s condition.

While moving the clock forward on CCS to get the results of ABG, you get a “Nurses Note,” which says, “The patient’s muscles have become more rigid.” You think that the increased carbon dioxide is from muscular rigidity and decide to give a neuromuscular blocking agent to relax the muscles and decrease carbon dioxide production.

Order:

Image Succinylcholine administration IV

On CCS, medications are considered administered instantly, but you cannot see the effects of them until you move the clock forward.

What is the mechanism of succinylcholine?

a. It inhibits the release of ACh.

b. It blocks nicotinic receptor depolarization.

c. It prevents repolarization of the nicotinic receptors.

d. It cleaves ACh prematurely.

e. It prevents the release of calcium from the sarcoplasmic reticulum.

Answer c. It prevents repolarization of the nicotinic receptors.

Succinylcholine causes persistent depolarization of the nicotinic receptors, which results in neuromuscular blockade. It works exclusively at nicotinic receptors. Succinylcholine is not hydrolyzed by acetylcholinesterase, so its effect cannot be ended. Flaccidity of the muscles occurs because intramuscular calcium is taken up by the calcium ATPase of the muscle into the sarcoplasmic-endoplasmic reticulum calcium adenosine triphosphatase (SERCA). When all the calcium is removed from the cytoplasm, muscle contraction ends.

Succinylcholine prevents repolarization of the neuromuscular junction.

No Repolarization = Block of Next Depolarization

You move the clock forward 5 minutes to see the effects of the neuromuscular blocking agent.

PE:

Image Markedly increased muscle rigidity; masseter rigidity is severe.

Reports:

Image ABG: pH 7.24; PCO2 64 mm Hg; PO2 74 mm Hg

Image Chest x-ray: normal

Image CHEM-20: potassium 5.4 mEq/L (elevated)

Image CK: 7400 units/L (normal 40–175 units/L)

Anesthesia + Unexpected Rise in PCO2 = Malignant Hyperthermia

Malignant Hyperthermia (MH)

• Genetic predisposition

• Third or fourth exposure

• Inhalational anesthetics plus succinylcholine

Move the clock forward to recheck the laboratory test results and confirm MH.

Repeat Laboratory Tests:

Image ABG: pH 7.22; PCO2 68 mm Hg; PO2 74 mm Hg

Image Potassium 6.0 mEq/L (elevated)

Image CK: 16,300 units/L (normal 40–175 units/L)

Succinylcholine makes MH worse.

Depolarizing blockade massively increases CO2 production by the muscles.

The patient’s muscular rigidity persists.

VS: P: 112 beats/minute; T: 104°F

Increased PCO2 precedes temperature elevation in MH.

Which of the following is most effective for MH?

a. Dantrolene

b. Cooling blanket

c. Iced IV fluids

d. Bromocriptine

e. Spraying with water and evaporation

Answer a. Dantrolene

Dantrolene reorders the heat-generating mechanisms of skeletal muscle in both MH and neuroleptic malignant syndrome (NMS). NMS is specifically treated with bromocriptine because we think NMS has to do with the antidopaminergic qualities of neuroleptics.

Cooling blankets and especially the power of heat removal through evaporation are what is used in heat stroke. Heat stroke is entirely a problem of exertion of the body with high outside temperatures. MH and NMS have nothing to do with the outside temperature. They have to do with an idiosyncratic reaction of the body to either inhalational anesthetics and succinylcholine (MH) or neuroleptics. Iced IV fluids are always wrong. Iced IV fluids can stop the heart.

Orders:

Image Dantrolene

Image Stop anesthetics and stop succinylcholine if not already done

Image IV normal saline

Image UA

Image Urine myoglobin

Massive CO2 overproduction is always first in MH!

It cannot be compensated by hyperventilation.

After administering dantrolene and stopping exposure to anesthetics, the treatment of MH is similar to management of rhabdomyolysis with fluids and monitoring potassium, CK, calcium, and phosphate levels.

Rhabdomyolysis

• Potassium (K) level increased

• Phosphate level increased from muscles

• Calcium level down

Damaged muscles bind calcium.

Masseter Muscle Rigidity = Succinylcholine-Induced Malignant Hyperthermia

Report:

Image UA: dipstick positive blood, no red blood cells seen

Image Urine myoglobin: elevated

CK and urine myoglobin levels peak at about 24 hours after the use of inhalational anesthetics and neuromuscular blockers.

MH Mechanism

• Abnormal calcium release from SERCA

• Abnormal muscle contraction and rigidity

Dantrolene Mechanism

• Binds ryanodine receptors

• Inhibits calcium release from SERCA

Expect dark urine in MH.

If your case describes severe hyperkalemia and rhabdomyolysis, move the clock forward 30 to 60 minutes after administering insulin and glucose and recheck the potassium level. If your case describes only rhabdomyolysis with a normal potassium level, move the clock forward 4 to 6 hours and recheck the CK and potassium. Vital signs in an ICU are measured every 2 hours.

MH kills by

• Hyperkalemia

• Seizures from high temperature

VS: at 2-hour intervals

Image T: 104°F, 103°F, 102.8°F, 103.4°F

You should not expect CK and temperature to peak for 24 hours. Both will come down after that.

Orders:

Image Dantrolene—continue for 48 hours

Image IV saline

Image Repeat potassium, calcium, and CK levels at 6- to 12-hour intervals in ICU

Image Repeat ABG

On CCS, you can get notes saying, “Are you sure you want to continue?” on any case. It does not mean you did anything wrong or made a mistake. It is simply giving you an opportunity to cancel orders or make changes.

The patient should stay in the ICU until mental status and temperature have normalized. If the hydration and correction of ventilatory support and potassium and calcium levels are well monitored, the patient will leave the ICU in 48 hours.



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