The overall goal of the Neuro-CPK lab is to translate benchside and bedside observations into clinical practice protocols that will potentially improve outcomes in patients with neurological illnesses including neurocritical care population. This is being achieved through a myriad of research techniques such as critical appraisal of clinical trials, systematic reviews and meta-analyses, design and conduct of retrospective and prospective observational studies, pharmacokinetic studies and clinical trials. This is in addition to development of lab techniques to support clinical research.
Current Research Projects
Pharmacotherapy optimization in patients with aneurysmal subarachnoid hemorrhage
Subarachnoid hemorrhage (SAH) is a neurological emergency characterized by the extravasation of blood into the subarachnoid space. Although SAH accounts for 5% of all strokes, given the relatively younger age at onset, it has a significant burden on productive-life years. The average mortality rate for SAH has been reported to range from 30-50%, with a significant proportion of survivors left with disability. Neurological and medical complications are common after SAH and contribute significantly to the overall prognosis. Cerebral vasospasm and delayed cerebral ischemia are significant contributors to disability in SAH patients who survive the initial bleed. Several agents have been proposed to target vasospasm or provide neuroprotection in animal models; however, when tested in randomized controlled trials those agents failed to provide significant improvement in patient outcomes. The only agent that provided clinical benefit in trials is nimodipine. Nimodipine has been shown to improve outcomes following SAH. Guidelines recommend that all patients receive nimodipine fixed doses for 21 days. However, pharmacokinetic studies reported extensive variability of nimodipine concentrations. It is not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening outcomes. The aim of this research is individualization of nimodipine treatment for the sake improving patient outcomes.
Pharmacotherapy optimization in neurocritical care patients exhibiting augmented renal clearance
Stroke, severe brain injury, status epilepticus and bacterial meningitis are the most common life-threatening neurological illnesses in the world with an estimated combined annual hospital management cost of up to 44 billion dollars. Seizures and infections are common complications following acute neurological illnesses and contribute significantly to poor outcomes if not promptly treated with appropriately dosed anti-seizure medications and antimicrobials, respectively. Many of the commonly administered medications used to treat such complications are renally eliminated and the patient’s kidney function should be taken into consideration to allow appropriate dosing. Therefore, clinicians are vigilant in adjusting drug dosage regimens in patients with various degrees of kidney impairment to avoid potential toxicities. On the other hand, little attention is given if patients exhibit an augmented renal clearance (ARC) or, in other words, enhanced kidney function. ARC has a significant influence on how medications are removed from the body potentially resulting in insufficient doses and treatment failure subsequently leading to poor patient outcomes and increased health care cost. Therefore, patients with ARC require higher medication doses; however, ARC is largely undetected using kidney assessment methods currently used in practice. In addition, it is not clear how medications should be dosed in those with ARC. The majority of ARC research has not focused on neurocritical care patients where ARC predominantly exists. Thus, clinicians are likely under-dosing vital medications in those patients, and completely unaware. There is an immediate need to address the gap in knowledge. Therefore, our research aims to characterize the phenomenon of ARC in patients with life-threatening neurological illnesses through identifying the prevalence, risk factors and clinical impact of ARC.
Optimization of epilepsy management in patients with comorbid conditions
Epilepsy affects more than 50 million people worldwide and is characterized by recurrent unprovoked seizures. One of the main goals of treatment is to improve patient quality of life by optimizing the balance between seizure control and side effects of the antiepileptic drugs (AEDs). Although the majority of patients can be adequately controlled with AEDs, a significant number, estimated to be as high as 30 % stay uncontrolled with conventional medical treatment. This can be further complicated if a patient has other comorbidities contributing to poor control. The aim of this research is pharmacotherapy optimization of AEDs in epilepsy patients with superimposing comorbidities.