SCCM Resource Library-18-Evaluation of Intravenous Push Levetiracetam in a Neurospine Intensive Care Unit

Video Transcription

Hi, everybody. Thank you so much for listening in today. I'm Tori Adams, a current critical care pharmacist at University of Iowa Hospital and Clinics  and a former PGY2 in critical care at Northwestern Memorial Hospital. I will be speaking on the evaluation of intravenous push levotriacetam in a neurospine ICU.  My co-investigators and myself have nothing to disclose. Historically speaking, over the past 10 years or so, levotriacetam has gotten a lot of attention  with how we are administering it. Wheelis and colleagues first looked at a rapid infusion with minimal dilution back in 2009  in this pediatric study of 45 children, although the age range was 4 to 32 years old, requiring urgent treatment with levotriacetam as the anti-epileptic medication.  They broke their groups out by a milligram per kilogram basis, so 20 milligrams per kilogram  and 40 milligrams per kilogram were administered over 5 minutes and 60 milligrams per kilogram were administered over 6.  Now the key here is that at this point in time, the manufactured vials were prepared in a 100 milligram per milliliter fashion and in this study they diluted that to a one-to-one  fashion with normal saline or D5W. The only adverse effects reported were in the 60 milligram per kilogram group with one  experiencing a rash and two experiencing injection site pain.  However, they did report that maximum plasma concentrations were achieved within 15 minutes. More recently, in 2019, Morgan and Menenwald looked at rapid infusion of levotriacetam  without any dilution and this was a rather larger study, almost 200 adults that received  anywhere, any dose up to 1 gram of levotriacetam and this dose was again infused, administered without further dilution over 2 to 5 minutes.  They reported zero concentration-related adverse effects like the ones that we saw in the previous study, however, they did note that three patients experienced behavioral-related  effects that were deemed to be caused by levotriacetam ultimately resulting in levotriacetam discontinuation.  The three specific behaviors that they reported on was agitation, delirium, and confusion.  So based upon both of these studies at Northwestern Memorial Hospital in Chicago, Illinois, which  is an 894-bed academic medical center with 108 ICU beds, 23 of those specifically designated to the neurospine ICU, we had a policy change that prior to the policy change, once the  order of levotriacetam was verified, the label printed to the clean room, the pharmacy technician  prepared the dose, diluting it to 100 milliliters of normal saline, that dose was checked, verified  by a pharmacist, tubed to this respective unit, the nurse retrieved it, and gave the dose as an IV piggyback infusion over 15 minutes.  With our policy change, this allowed us to stock the manufactured vials in our automated dispensing systems.  Thus, upon order verification, the nurse could simply obtain those vials from the automated dispensing system and give that dose in an undiluted manner as an IV push over 2 to 5  minutes. So the purpose of this study was to evaluate the operational and clinical effects of the levotriacetam administration policy change.  This was a retrospective observational study where our groups were based on the timing. So our go-live date for this policy approval was September 26th of 2019.  So our IV piggyback group was based on administrations from March 25th, 2019 to September 25th, 2019,  and then our IV push group started on that go-live date, September 26th through January 26th of 2020.  We did include adults admitted to our neurospine ICU that received at least one dose of at least 1,000 milligrams of levotriacetam.  And again, we based this off of the prior data that I was previously presenting on. We of course did exclude patients that had documented allergy to levotriacetam, or if  a dose of IV push was ordered but then subsequently discontinued and not administered, and prisoners in pregnancy. Our outcomes of investigation were threefold.  In relation to efficacy, this was of course centered on efficiency of this policy change,  looking at the time to administration of levotriacetam, so comparing the time of order verification to the time of dose administration based upon nurse scanning at bedside.  Clinically, we were wanting to evaluate whether this, the anticipated time to administration change would result in a change in administration of benzodiazepines within that window.  Additionally, looking for any change in orders for a non-benzodiazepine anti-epileptic that were ordered while the team was waiting for the levotriacetam dose to arrive.  And then of course, looking at safety outcomes related to those concentration-based reactions and behavioral reactions that were attributed to the levotriacetam administration.  And this was reliant upon reporting within our patient safety incident reporting system,  which was the NETS reports, or if it was documented that the levotriacetam dose was decreased  or it was discontinued altogether, transitioned back to an IV piggyback, if that was deemed due to the route of administration.  So in our entire study period, we had about 2,000 doses to look at after our exclusion criteria was applied.  That left us with 100 doses in the IV piggyback group and 60 doses in the IV push group to be evaluated.  Looking at our patient demographics, there was no baseline differences in relation to weight, age, sex, or degree of renal dysfunction.  And lastly, with seizure etiology, you'll note quite a variety of deemed etiologies of the seizures with malignancy, traumatic brain injury, and ischemic events being the  main three deemed etiologies.  With our outcomes, our first one in relation to our efficiency, we looked at, again, the  time to administration from order verification, and we did see a significant decrease in time  to administration when transitioning from IV piggyback, which had a median of 80 minutes, to IV push, which had a median of 28 minutes to administration from order verification.  Clinically, what did this correlate to? Well, we saw a decrease in administration of benzodiazepines in that order verification administration window.  So, patients that received it as an IV piggyback received more benzodiazepines in that interim than those that received it as an IV push.  And secondly, with the clinical outcome, we also saw a significant decrease in orders for non-benzodiazepine anti-epileptic agents, additionally, within that window.  Lastly, in regards to our safety outcomes, we did not have any reports of injection site reactions across the board.  And there was no significant difference seen in the deemed necessity to decrease the dose of levotriazetam based upon safety consideration or concern.  So, safety-wise, there was no concerns that there was any significant difference between methods of administration.  Of course, limitations of this study, we do have to talk about specifics in relation to  the retrospective nature, bringing into consideration shift personnel efficiency differences, whether that be day shift where we're fully staffed versus overnight.  Those might look very different, as well as the pneumatic tube system functioning, specifically with our IV piggyback group, and then, of course, patient-related factors in delay of  administration, whether that patient was transferring or we didn't have access at that point in  As always, with safety considerations for retrospective data, that really does rely upon staff reporting  for adverse effects, so you always have to consider an under-reporting bias introduction.  And lastly, the elephant in the room is the ESET trial was published directly in the middle of this research.  However, we did not feel that this introduced bias in the results that we saw, but we felt that it really just perhaps increased the amount of IV push doses that we were being  able to evaluate.  So, in conclusion, administration of undiluted levotriazetam doses up to 2,000 milligrams via IV push over two to five minutes is a very important step in the process of evaluating  whether or not undiluted levotriazetam doses up to two to five minutes is not only a safe  method of drug administration, but it reduces time to drug administration, optimizing patient  care, and it reduces utilization of benzodiazepines, which could potentially mitigate the risk of negative sequelae that have been correlated with administration of such agents.  I'd like to acknowledge my research advisors, Drs. Casey Greathouse and Ahmed Mahmoud, and please email me with any questions, and I will look forward to hopefully meeting you  guys in the future at another conference.

Video Summary

In this video, Tori Adams discusses the evaluation of intravenous push levotriacetam in a neurospine ICU. She presents two studies on the administration of levotriacetam, one involving pediatric patients and the other involving adult patients. Based on these studies, a policy change was implemented at Northwestern Memorial Hospital to administer undiluted levotriacetam doses via IV push over 2 to 5 minutes. A retrospective observational study was conducted to evaluate the operational and clinical effects of this policy change. The results showed that the policy change resulted in a decrease in time to administration, a decrease in administration of benzodiazepines, and a decrease in orders for non-benzodiazepine anti-epileptic agents. No significant safety concerns were identified. Overall, the administration of undiluted levotriacetam doses via IV push was found to be safe and efficient.

Asset Subtitle

Pharmacology, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Tori Adams

Introduction/Hypothesis: The purpose of this study was to evaluate the time to therapy, the clinical effect and safety of a recent Pharmacy and Therapeutics (P&T) Committee approved change in the administration of levetiracetam from intravenous piggy back (IVPB) over 15 minutes to undiluted intravenous push (IVP) over 2-5 minutes at a large academic medical center.

Methods: The primary outcome was the time from order verification to administration of IVP levetiracetam versus IVPB levetiracetam. The secondary outcome was any benzodiazepine administered in the time between levetiracetam order verification and administration in both groups. Adult patients admitted to the Neuro-Spine Intensive Care Unit (NSICU) in the 6 months prior to and after the policy change who received at least 1 dose of â‰¥ 1000 mg of IVP or IVPB levetiracetam for active seizures were included in this retrospective, observational, IRB approved study. Data was analyzed using descriptive statistics, Chi-square and Mann-Whitney U as appropriate.

Results: Of the 2,055 levetiracetam doses ordered in the study period, 316 were screened for enrollment, and 160 were enrolled with 60 and 100 patients assigned to the IVP and IVPB groups, respectively. There were no differences between groups at baseline. The majority of the population was male, 57 years old, without significant renal dysfunction (CrCl <60ml/min), and a seizure etiology of malignancy or traumatic brain injury. A significant reduction in time to administration of levetiracetam was found with IVP compared to IVPB administration (28 vs 80 minutes, p<0.0001). A subsequent reduction in patients who received benzodiazepines in the interim of levetiracetam order verification and administration was also associated with IVP compared to IVPB (2% vs 13%, p=0.042). There were no differences found in rates of adverse effects between groups.

Conclusions: Administration of levetiracetam doses up to 2000mg via IVP is a safe method of administration that results in reduction of time to medication administration and a consequent reduction of benzodiazepine use.

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Level Advanced

Membership Level Select

Tag Seizure

Year 2021

Keywords

Tori Adams

intravenous push levotriacetam

neurospine ICU

pediatric patients

adult patients

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