phenobarbital use have increased risk for steven johnson syndrome

This patient is experiencing the early symptoms of a severe, adverse drug reaction due to phenobarbital, and the most important next step is to discontinue the medication causing the reaction.

This patient’s presentation is consistent with the onset of a reaction along the Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) continuum (steven johnson syndrome). The early features of SJS/TEN include high fever, malaise, and myalgia with symptoms attributed to early mucous membrane involvement, including photophobia, conjunctival dryness and burning, orodynia, and odynophagia. Another prominent feature of early SJS/TEN is diffuse skin pain. This prodrome is typically present 1 to 3 days prior to the onset of observable cutaneous and/or mucous membrane findings. The onset of SJS/TEN is most often between 5 and 28 days from the initiation of the medication but can be seen as early as 1 to 2 days.

Phenobarbital has a well-documented association with SJS/TEN. With the recent increase in use of this medication for the treatment of alcohol withdrawal syndromes, it is important that critical care physicians are aware of this potential adverse reaction. Early discontinuation of the medication causing SJS/TEN is associated with improved mortality.

In this patient who is recovering from an alcohol withdrawal syndrome, another consideration is recurrence of alcohol withdrawal symptoms. However, several features of this case make alcohol withdrawal a less likely explanation. First, the patient is alert, oriented, and with a normal neurologic exam, with a notable absence of hypertension, tremor, and hyperreflexia. While alcohol hallucinosis can present as tactile and involving the skin, these hallucinations are not typically described as severe skin pain and are not typically associated with fever. Therefore, escalating the treatment of alcohol withdrawal in this patient is not the most important next step in management.

Adverse drug reactions other than SJS/TEN should also be considered in critically ill patients who develop acute onset, high fevers in the ICU. One example is serotonin syndrome, and this patient is currently taking a selective serotonin reuptake inhibitor, escitalopram. Serotonin syndrome is characterized by high fever and hyperreflexia, tremor, hypertonia, clonus, and diaphoresis in the context of exposure to serotonergic medications. Serotonin syndrome is treated with discontinuation of the serotonergic medications, administration of benzodiazepines, and consideration of cyproheptadine in severe or refractory cases. However, this patient has a normal neurologic exam, no diaphoresis, and absence of tremor, making the diagnosis of serotonin syndrome very unlikely. She would not meet the Hunter Serotonin Toxicity Criteria decision rules for serotonin syndrome, which require exposure to a serotonergic agent and satisfying at least one of five conditions: (1) spontaneous clonus, (2) inducible clonus + agitation or diaphoresis, (3) ocular clonus + agitation or diaphoresis, (4) tremor + hyperreflexia, and/or (5) hypertonia + temperature >39.0°C + clonus. Furthermore, her symptoms are more suggestive of an adverse drug reaction such as SJS/TEN.1234567

A 32-year-old woman with a history of alcohol use disorder is admitted to the ICU with severe alcohol withdrawal syndrome. Her symptoms are eventually controlled with escalating doses of lorazepam and adjunctive treatment with phenobarbital, and she requires intubation due to respiratory depression. Her prior to admission dosing of escitalopram is continued. On ICU day 5, she is extubated, and her withdrawal symptoms have not recurred while receiving tapering doses of phenobarbital. Suddenly, she develops a temperature of 39.0°C and tachycardia, and she reports photophobia and severe, diffuse skin pain and myalgia.

What is the most important next step in management?

Footnotes

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