A 29-year-old woman is evaluated in the post-anesthesia care unit (PACU) due to severe agi… — USMLE Step 2 CK

A 29-year-old woman is evaluated in the post-anesthesia care unit (PACU) due to severe agitation and a rapidly rising temperature. She just underwent an emergency laparoscopic appendectomy for a perforated appendix. Her medical history is significant for major depressive disorder, for which she takes sertraline daily. Intraoperative medications included propofol, succinylcholine, desflurane, fentanyl, and ondansetron. Reversal of neuromuscular blockade was achieved with sugammadex. Her temperature is $39.6^\circ\text{C}$ ( $103.3^\circ\text{F}$ ), blood pressure is $168/96\text{ mmHg}$ , pulse is $138/\text{min}$ , and respiratory rate is $24/\text{min}$ . On physical examination, she is diaphoretic, flushed, and disoriented. Neurologic examination reveals marked hyperreflexia in the bilateral lower extremities, spontaneous myoclonus, and inducible ocular clonus. Her muscle tone is increased, particularly in the lower extremities, but there is no "lead-pipe" rigidity. An arterial blood gas analysis shows a normal partial pressure of carbon dioxide ( $PaCO_2$ ). Administration of a medication with which of the following mechanisms of action is the most appropriate targeted therapy for this patient's current condition?

Antagonism of $5-\text{HT}_{2A}$ receptorsCevap
B
Inhibition of ryanodine receptor type 1 ( $\text{RyR1}$ )
C
Agonism of dopamine $D_2$ receptors
D
Inhibition of acetylcholinesterase
E
Inhibition of bacterial peptidoglycan cross-linking

Cevap

Antagonism of 5-HT2A receptors (such as Cyproheptadine)

The correct answer describes the mechanism of action of cyproheptadine. This patient is suffering from classic Serotonin Syndrome (SS), precipitated by the combination of her home SSRI (sertraline) and serotonergic intraoperative medications (fentanyl and ondansetron). SS is characterized by the triad of autonomic hyperactivity (tachycardia, hyperthermia, diaphoresis), altered mental status, and neuromuscular irritability. The presence of hyperreflexia, spontaneous myoclonus, and inducible ocular clonus is highly specific for SS. The specific targeted antidote for moderate-to-severe SS is cyproheptadine, which exerts its primary therapeutic effect through the antagonism of

5-\text{HT}_{1A}

and

5-\text{HT}_{2A}

receptors.

Adım Adım Çözüm

Analyze the patient's medication history.

The patient takes a home SSRI (sertraline) and received fentanyl and ondansetron intraoperatively. All three medications possess strong serotonergic activity.

Identifying potential drug interactions is critical in the immediate postoperative period.

Correlate medications with the physical examination findings.

The combination of autonomic hyperactivity (tachycardia, hyperthermia, diaphoresis), altered mental status, and profound neuromuscular irritability (hyperreflexia, myoclonus, ocular clonus) definitively establishes a diagnosis of Serotonin Syndrome.

Neuromuscular findings are key to distinguishing toxidromes.

Differentiate the presentation from Malignant Hyperthermia (MH).

Although the patient received succinylcholine and desflurane (classic MH triggers), MH presents with hyporeflexia, lead-pipe rigidity (often masseter spasm), and severe hypercapnia (elevated PaCO2). The patient's hyperreflexia, clonus, and normal PaCO2 rule out MH.

MH and Serotonin Syndrome are both life-threatening PACU emergencies that cause hyperthermia but require completely different antidotes.

Determine the targeted pharmacologic therapy.

For moderate-to-severe Serotonin Syndrome that does not respond to supportive care and benzodiazepines, the antidote of choice is cyproheptadine, which works primarily via antagonism of 5-HT2A receptors.

To reverse the specific neuroreceptor overstimulation causing the crisis.

Anahtar Kavram

Differentiating perioperative toxidromes (Serotonin Syndrome vs. Malignant Hyperthermia) and applying the correct mechanism-specific antidote.

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Cevap

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