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Can't Catch Your Breath? Calcium Channel Blockers and Pulmonary Shunting - A Deep Dive

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  Periodically, a patient on the unit on a nicardipine or clevidipine infusion develops what appears to be unexplainable hypoxia. The situations are inevitably multifactorial, but often end with a workup for pneumonia, PE, or volume overload turning up dry and a question to me about whether it could have been the nicardipine all along. Despite the frequency in which continuous infusion CCBs are used in the NeuroICU this doesn't come all that often, so my answer often boils down to "well, theoretically" - vasodilators, including CCBs and nitroprusside 1 (see also here 2 ), have been demonstrated to be capable of reversing hypoxia-induced pulmonary vasoconstriction, so it is perfectly within the realm of possibility that nicardipine could contribute to pulmonary shunting and thus new-onset hypoxia. The adverse effects are only briefly mentioned in the package inserts of either nicardipine or clevidipine, with major Phase III trials not reporting it at all. Because of t...
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Unbound and Uncharted - Therapeutic Drug Monitoring of Free Valproic Acid in ICU Patients

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  I'm sorry to break this to you, but your ICU patient’s valproate (VPA) level may be lying to you. Hidden within the total valproate concentration you checked is the concentration that matters – the free concentration, which is pharmacologically active and primarily responsible for the CNS exposure to VPA 1,2 – but without peeking under the hood and directly measuring that free concentration, it is nearly impossible to predict exactly how much VPA your patient is exposed to. Because of this, dose adjustments made based on total concentrations have the risk of widely missing the mark. While altered protein binding with valproic acid is a well-known phenomenon especially in the setting of drug interactions like co-therapy with phenytoin, the extent to which protein binding can be altered in ICU patients is criminally underrecognized. Here we'll talk a bit about how VPA’s pharmacokinetics are unique, what factors influence its binding to albumin, why those factors matter...
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To Lyse or Not to Lyse: The Great tPA Debate

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It’s been a few months since I’ve posted (a little over six, whoops), but as they say – new year new me. I’m planning on trying to stick to a once a month or so posting schedule so hopefully that goes well! I’m kicking 2024 off with a real doozy – does thrombolysis really work in stroke? Got your attention, maybe? Yes, this debate is withered and old and the same arguments from both sides get circulated routinely about the putative risks and benefits of providing a guideline-supported therapy with decades of supporting evidence to patients who are experiencing a neurologic emergency which has the potential to permanently alter their entire life. Ok, ok – that is the only bit of sass I’ll allow myself. Key Points Thrombolysis for eligible acute ischemic stroke patients is guideline-recommended and backed by strong evidence, but controversy remains over the merits of the evidence Objection #1: There is No Positive Data for Thrombolysis Re-analyses of positive...
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