Pharmacotherapy of residual excessive sleepiness among continuous positive airway pressure (CPAP) treated patients with sleep apnea.

INTRODUCTION: Patients with persistent sleepiness after adequate treatment of obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (nCPAP) experience impaired cognition, reduced productivity, and worse quality of life. Although the mechanisms responsible for this phenomenon are not completely understood, neuroimaging studies have identified reduced gray matter in the frontal cortex and alterations in white matter integrity suggestive of axonal and myelin damage. The intermittent hypoxia with resulting oxidative injury is considered a prime culprit behind the loss of wake-promoting catecholaminergic neurons. AREAS COVERED: This narrative review gives an overview of the pathophysiology and approaches to managing patients with residual sleepiness. The authors explore different targeted strategies aimed at improving selection of appropriate pharmacotherapy. EXPERT OPINION: Wake-stimulant medications (modafinil and armodafinil) have demonstrated efficacy in reducing sleepiness in adequately treated OSA. The recent FDA approval of pitolisant and solriamfetol complements the use of modafinil by substituting for direct sympathomimetic agents. The distinctive pharmacologic profile and mode of action of each of these agents offer the opportunity of a personalized approach to the management of this disorder. Further studies should be conducted on the long-term effect of these agents alone or in combination on brain structural and functional changes.

Dantrolene-Induced Hepatitis: A Rare Culprit in the PICU.

Dantrolene is used for reversal of malignant hyperthermia and for improvement in spasticity following stroke which are Food and Drug Administration-approved indications. It is an infrequently used medication in the pediatric intensive care unit and is usually continued from the operating room or sedation suite after suspicion for malignant hyperthermia, secondary to other medications and anesthetic agents. Hepatitis has been described as a side effect of the medication after prolonged use and at doses of more than 100 mg/d mainly in adults. We described in this case report a patient in which the drug was used for sympathetic overactivity in the PICU and development of asymptomatic hepatitis on day 3 after starting the medication at a dose much lower than previously described.