Pharmacokinetic/Pharmacodynamic, Neuro-Specific Physiologic and Safety Effects of Propofol, Dexmedetomidine, Midazolam, and Ketamine in Adult Neurocritical Care: A Scoping Review
Abstract
Sedation is a cornerstone of care in the neurocritical care unit (NCCU). Non-procedural sedation is given for therapeutic reasons such as pain control, anxiety, agitation, and ventilator synchrony. Moreover, the benefit of non-procedural sedation in NCCN expands to include reducing cerebral metabolic demand (CMRO₂), improving brain tolerance to ischemia, and serving as a direct tool for intracranial pressure (ICP) control, seizure control, and targeted temperature management. The criticality of nonprocedural sedation in the NCCU stems from the imperative to balance sedation maintenance with the conduct of a thorough neurological assessment, essential for monitoring disease progression. Daily sedation interruptions for neurologic wake-up testing (NWT) are the standard of care for repeated neurologic assessment of patients with severe traumatic brain injury. However, this procedure may cause a transient physiological stress response, as demonstrated by the increase in intracranial pressure and elevated levels of ACTH, cortisol, epinephrine, and norepinephrine. In clinical practice, the most frequently used agents are propofol, dexmedetomidine, midazolam, and ketamine. Studies in general ICU populations support light sedation strategies that preferentially use non-benzodiazepine agents. These trials largely excluded patients with acute brain injury. Thus, there is limited evidence-based practice informing sedation practice in the neurocritical care setting, and it is largely based on expert consensus, physiologic evidence, and small observational studies. Studies of sedative and analgesic agents in neurocritical care cover a diverse spectrum of neurological populations and various choices of drug, dosing regimen, titration approach, and concurrent analgesic therapy. Reported outcomes are also quite varied and include quality of sedation, time to awakening, intracranial and systemic physiologic measures, biomarkers, adverse events, and clinical outcomes assessed at different time points. Pharmacodynamic and clinical outcomes are often assessed separately from pharmacokinetic factors, which may affect drug accumulation and recovery, such as critical illness, organ dysfunction, inflammation, therapeutic hypothermia, and concomitant medications. This heterogeneity supports the need for further research to standardize evidence-based practice. We are conducting a scoping review to map the evidence for propofol, dexmedetomidine, midazolam, and ketamine in adults admitted to neurocritical care units who receive non-procedural sedation. It will describe the populations studied, the sedation strategies used, pharmacokinetic and pharmacodynamic outcomes, neurophysiological effects, and drug safety outcomes. Because of the differences in study design, interventions, and outcome reporting in the literature, the review will not identify a single best agent for sedation but will clarify how outcomes have been assessed. The goal is to describe the current evidence base, identify gaps relevant to neurocritical care practice, and guide the design of future research.
Topics & conditions
Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.
Psychedelic Commons aggregates metadata from open sources and links back to the original. Rights remain with the authors and publishers. Something wrong with this record? Report a problem.