Pravin George

Calling our #NCSPharmacy #PharmICU colleagues to weigh in on #NCSVJC discussion!

@neurocritical 4) long term functional outcomes of surviving patients 5) more data from etiologies of ABI, other than TBI, from MIC /4

@neurocritical 1) the use of additional agents, i.e. opiates and ketamine 2) sedative dosing ranges and titration in response to clinical events 3) additional clinical variables including ICP and/or PbTO2 values and seizures, with associated sedative changes /3

#NCSVJC Q5: Recognizing the observational nature of this analysis, what would be your ideal design for a future trial comparing sedation strategies in ABI patients? Where should we go from here rdcu.be/efSic

We've concluded the questions for today's journal club! Feel free to continue to respond to the questions posted today and engage with colleagues throughout the day. Read the article here: rdcu.be/efSic

#NCSVJC Q4: Given the independently associated longer ICU stay with midazolam, but no difference in mortality, what are the practical and ethical implications of using midazolam as a first-line agent in resource-limited settings? Should ICU LOS be prioritized over mortality in these decisions? rdcu.be/efSic

@neurocritical I'd also appreciate input from medical personnel, or even patients, with experience in resource-limited areas as to what limits sedation/medication choice and what other constraints inherent to these settings that are not routinely encountered in high-income countries./6

@neurocritical Ultimately, data on long-term outcome measures, and additional clinical outcomes, mentioned previously, would be helpful in answering this question.  /5

@neurocritical if patients were on higher doses of midazolam for seizure suppression, sedation interruptions would have been intentionally withheld for approximately 48hrs.  However, we can't definitely confirm this given the constraints of the data, and cannot rule out confounding variables./2

@neurocritical This is probably due to decreased daily awakening trials and likely prolonged clearance compared to propofol.  VAP rates were also higher in the propofol + midazolam and sodium thiopental group, which would support this.  /1

#NCSVJC Q3: Patients sedated with midazolam had significantly higher rates of VAP. Could this be a reflection of the pharmacokinetics of midazolam impeding daily sedation interruption, or might there be confounding variables such as weaning protocols or ICU nurse-to-patient ratios? rdcu.be/efSic

#NCSVJC Q1: Given that there were no statistically significant differences in IMV duration between sedation strategies after adjustment, how should clinicians interpret these findings in light of prior studies suggesting potential benefits of propofol? Could the lack of difference reflect appropriate titration in neurocritical care settings or limitations in the dataset’s granularity (e.g., sedation depth, dosing protocols)? rdcu.be/efSic

#NCSVJC Q2: The study highlights substantial differences in sedative choice between high-income and middle-income countries. How do you think international guidelines should adapt to these realities—especially considering cost, drug availability, and storage logistics—without inadvertently promoting inequities in care? rdcu.be/efSic

@neurocritical similar long-term outcomes in resource limited settings.  If/when studies emerge indicating an agent that is currently limited is truly superior, hopefully there would be international support to facilitate increasing availability in resource limited settings. /8

@neurocritical Without more definitive studies, especially on long term outcomes between use of different sedatives, international guidelines should include sedative options and combinations that are feasible and likely as effective in controlling the above parameters and achieving /7