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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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Stopping What You Started: Hemostatic Therapy for Thrombolytic-Associated Hemorrhagic Conversion

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While anticoagulation reversal for anticoagulant-associated bleeding gets a lot of press (see recent publication of ANNEXA-I and the seemingly endless discourse that followed) 1 , the approach to handling bleeding secondary to thrombolysis is arguably more controversial and certainly less clear cut. Entire guidelines and bodies of evidence have explored ideal reversal strategies for warfarin, factor Xa inhibitors, other anticoagulants, and antiplatelets, but discussion surrounding what to do when a patient experiences major bleeding after thrombolysis is generally relegated to a small section of review articles and guidelines with a simple explanation for the brevity – there just isn’t a lot of evidence guiding what to do. A patient who developed significantly worsening level of arousal and worse left-sided facial droop ~2 hours after receiving tenecteplase. She received cryoprecipitate and tranexamic acid and eventually required a decompressive hemicraniectomy. She required inpatient ...
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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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