Neurocritical care
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Randomized Controlled Trial
The effects of fluid balance and colloid administration on outcomes in patients with aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.
Delayed ischemic neurological deficit (DIND) following aneurysmal subarachnoid hemorrhage (SAH) remains a significant cause of mortality and disability. The administration of colloids and the induction of a positive fluid balance during the vasospasm risk period remain controversial. Here, we compared DIND and outcomes among propensity score-matched cohorts who did and did not receive colloids and also tested the effect of a positive fluid balance on these endpoints. ⋯ Colloid administration and induction of a positive fluid balance during the vasospasm risk period may be associated with poor outcomes in specific patient groups. Patient selection is of utmost importance when managing the fluid status of patients with aneurysmal SAH.
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Randomized Controlled Trial Multicenter Study
High Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF) Trial: Rationale, Design, and Methods.
Hemoglobin degradation products, in particular iron, have been implicated in secondary neuronal injury following intracerebral hemorrhage (ICH). The iron chelator Deferoxamine Mesylate (DFO) exerts diverse neuroprotective effects, reduces perihematoma edema (PHE) and neuronal damage, and improves functional recovery after experimental ICH. We hypothesize that treatment with DFO could minimize neuronal injury and improve outcome in ICH patients. As a prelude to test this hypothesis, we conducted a Phase I, open-label study to determine the tolerability, safety, and maximum tolerated dose (MTD) of DFO in patients with ICH. Intravenous infusions of DFO in doses up to 62 mg/kg/day (up to a maximum of 6000 mg/day) were well-tolerated and did not seem to increase serious adverse events (SAEs) or mortality. We have initiated a multi-center, double-blind, randomized, placebo-controlled, Phase II clinical trial (High Dose Deferoxamine [HI-DEF] in Intracerebral Hemorrhage) to determine if it is futile to move DFO forward to Phase III efficacy evaluation. ⋯ The Hi-Def trial is expected to advance our understanding of the pathopgysiology of secondary neuronal injury in ICH and will provide a crucial "Go/No Go" signal as to whether a Phase III trial to investigate the efficacy of DFO is warranted.
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The core challenge of pain management in neurocritical care is to keep the patient comfortable without masking or overlooking any neurological deterioration. Clearly in patients with a neurological problem there is a conflict of clinical judgement and adequate pain relief. Here we review the presentation, assessment, and development of pain in the clinical spectrum of patients with associated neurological problems seen in a general intensive care setting. ⋯ There is evidence that swift and targeted pain management may improve the outcome. Importantly pain management is multidisciplinary. The available non-invasive, pharmacological, and invasive treatment strategies are discussed.
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As important mediators of solute transport at the blood-brain and blood-cerebrospinal fluid barriers, ATP-binding cassette (ABC) transporters (including ABCB1, ABCC1, and ABCC2), impact the bioavailability of drugs and endogenous substrates in the brain. While several ABCB1, ABCC1, and ABCC2 single nucleotide polymorphisms (SNPs) have been identified, their impact on outcome after traumatic brain injury (TBI) is unknown. ⋯ In this single-center study, patients homozygous for the T allele of ABCB1 rs1045642 or the G allele of ABCC1 rs4148382 were found to have better outcome after severe TBI. Further study is necessary to replicate these very preliminary findings and to determine whether these associations are due to central nervous system bioavailability of ABC transporter drug substrates commonly used in the management of TBI, brain efflux of endogenous solutes, or both.
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Case Reports
Augmented renal clearance of vancomycin and levetiracetam in a traumatic brain injury patient.
Increased creatinine clearance and subsequent elevated antimicrobial clearance is evident in many traumatic brain injury (TBI) patients due to augmented renal clearance (ARC). Little is known about the effects of ARC on other renally-eliminated medications, such as the anti-epileptic drug levetiracetam. ⋯ Vancomycin and levetiracetam both appear to be subject to ARC after TBI. Clinicians should be mindful that standard dosing of these agents may not achieve typical target concentrations in this clinical scenario.