Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non–vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of clinicaltrials.gov, we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with “indications” including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.
We report a case of pharmacologic management of pediatric paroxysmal sympathetic hyperactivity (PSH) in a patient who experienced symptomatic resolution with dexmedetomidine and propranolol. Following a blunt traumatic subdural hematoma and diffuse axonal injury, an 8-year-old male developed PSH on approximately day 5 of the hospitalization. PSH symptoms identified in this patient were hyperthermia, tachycardia, posturing, and hypertension with associated elevations in intracranial pressure. Episodes of PSH continued to be observed despite appropriate titration of opiates, sedatives, and traditional blood pressure management. Dexmedetomidine and propranolol were subsequently initiated to attenuate acute episodes of PSH. A reduction in sedative requirements and improvement in symptoms followed, which facilitated successful extubation. The combination of propranolol and dexmedetomidine was followed by a decrease in the frequency and severity of acute episodes of PSH. After utilization of multiple treatment modalities to control PSH episodes in our patient, propranolol and dexmedetomidine may have helped attenuate PSH signs and symptoms.
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