SCCM Resource Library-17-Safety of Intravenous Push Levetiracetam Administration at a Tertiary Academic Medical Center

Video Transcription

Hello everyone, I'm Akrael Kazemi, a Clinical Research Pharmacy Fellow at Brigham and Women's Hospital in Boston.  Welcome to this presentation on the safety of intravenous push levitiracetam administration at a tertiary academic medical center. The authors and I report no disclosures.  I'd like to begin with a brief background. Levitiracetam, an anti-epileptic drug, is a favorable treatment option given its broad  spectrum anti-epileptic activity, safe profile, and minimum drug interactions. While manufacturer labeling recommends diluting all intravenous or IV doses in 100 ml compatible  diluent and administering as a 15 minute IV infusion, studies suggest that small volume dilutions in a one-to-one ratio in doses up to 4,500 mg are well tolerated in patients  for urgent indications. In a subsequent study, undiluted IV push levitiracetam in doses of 1,000 mg or less was not associated with IV site or concentration related reactions.  However, to our knowledge, limited data is available on the safety of IV push levitiracetam in doses greater than 1,000 mg.  Recent fluid shortages resulted in many health care systems shifting medication administration from traditionally IV piggyback or IVPB to IV push or IVP.  Additionally, administering medication as IV push presents multiple advantages, such as reduced drug and material cost, improved workflow, and shorter time to first dose.  However, there may be a risk of increased adverse drug reaction, thus evaluating the safety of this transition is crucial.  In 2020, Brigham and Women's Hospital revised the levitiracetam administration protocol for all IV doses from IV piggyback to IV push for the potential advantages mentioned.  The purpose of this analysis was to compare the safety profile of IV push to IV piggyback levitiracetam in doses greater than 1,000 mg.  This was a single-center, retrospective, pre- and post-cohort IRB-approved analysis. The patient's electronic health records at Brigham and Women's Hospital were used to  identify all patients who received IV levitiracetam in doses greater than 1,000 mg between November 1, 2019 and May 30, 2020.  Administered doses were grouped and presented as either less than 2,000 mg, equal to 2,000 mg, or greater than 2,000 mg.  All patients aged 18 years or older who received at least one dose of IV levitiracetam greater than 1,000 mg were included.  Patients were excluded if they received levitiracetam peri- or intraoperatively, or if they had  a baseline systolic blood pressure less than 90 millimeters of mercury, or a baseline heart rate less than 50 beats per minute.  The primary safety outcome includes the incidence of post-administration hypotension or bradycardia  event, medication-related sedation event, and peripheral IV site reactions, such as phlebitis and infiltration, in addition to the number of events requiring a therapeutic  intervention, such as fluid bolus, or an increase or new-onset vasopressor or inotrop support, or dose resuscitation or reduction, among others.  For statistical analysis, the Chi-square or Fisher's exact test was used as appropriate for nominal data, and the Mann-Whitney U-test was used for continuous data.  Definition of events used included hypotension, defined as a systolic blood pressure less than 90 millimeters of mercury, or a 30% or more reduction from baseline.  Bradycardia was defined as a heart rate less than 50 beats per minute, or a 30% or more reduction from baseline.  The closest measured blood pressure and heart rate values before and after therapy within a two-hour window were used.  Sedation was defined as a decrease in score of one or more from baseline on the Richmond Agitation and Sedation Scale, or RAS, or the Glasgow Coma Scale, or GCS.  The closest measured score value before and after therapy within a six-hour window were used.  Peripheral IV site reactions was defined as any documented phlebitis or infiltration noted in a peripheral line per our institutional grading system here on the right.  The Naranjo Nomogram, a validated probability scale, was utilized to assess the probability of levotiracetam administration resulting in a safety event rather than other factors  such as concomitant medications. There were a total of 531 administrations greater than 1,000 milligram during the study time frame between IV push and IV piggyback.  Of the 275 administrations that were IV push, 23 were excluded for the reasons listed here, and 252 administrations in 84 patients were included in the final analysis.  Of the 256 administrations that were IV piggyback, 10 were excluded for the reasons listed here, and 246 administrations in 78 patients were included in the final analysis.  Baseline patient demographics were similar between the two groups, with the exception of baseline older-aged patients in the IV piggyback cohort.  The overall mean age was 58 years, and the majority of patients were Caucasian. Diabetes were comparable between the two groups, except for more patients with diabetes mellitus  in the IV piggyback cohort. Doses were balanced between the two cohorts. The majority of administrations were in doses of 2,000 milligram.  The mean dose was similar between both groups. The maximum dose in the IV push and IV piggyback group were 4,000 milligram and 4,500 milligrams, respectively.  Based on the documented RAS and GCS scores available in the patient's chart of the accessible  administrations analyzed, there were no differences between the two groups for post-administration-related sedation events.  An overall per-administration sedation event rate of 19.3% and 27.9% was observed in the IV push and IV piggyback cohort, respectively.  There were no differences among the dose categories. Levotirostam dose reduction or cessation of treatment was not noted in either group.  Based on the documented heart rate available in the patient's chart, bradycardia post-levotirostam  administration was noted in 3.2% of the IV push administrations assessed and 1.5% of the IV piggyback administration.  Two of the seven patients received a fluid bolus after the observed bradycardia event in the IV push group, while all three of the bradycardia events were self-resolved in the  IV piggyback group. Based on the documented blood pressure available in the patient's chart, post-medication-related  hypotension was noted in 5.2% of IV push administrations assessed and 3.5% of IV piggyback administrations assessed. There were no differences among the dose categories.  Each cohort resulted in three hypotensive events requiring a clinical intervention. In the IV push group, one patient required a fluid bolus and two required an increase  in vasopressor requirements. While in the IV piggyback group, one patient required a fluid bolus, one required an increase  in vasopressor requirements, and one was started on vasopressors. Based on the documented peripheral IV infusion reactions available in the patient's chart,  only one peripheral infusion site reaction was documented in the IV piggyback group, resulting in a grade-free infiltration with no filobitis based on our institution's IV  infusion reaction grading system. Using the Naranjo probability scale, 42.1% and 69.6% were deemed possible in the IV push  and IV piggyback group, respectively, while 7.9% versus 10.9% were deemed probable in the IV push and IV piggyback group, respectively.  The remaining were unlikely related to IV levotiracetam administration. For limitations, this was a single-center analysis that evaluated our institutional  experience and safety with IV push levotiracetam compared to IV piggyback. Results were dependent on accurate and complete documentation in the electronic medical record.  There is a potential for confounders not captured that may impact hemodynamic and sedation events.  Also, the clinical efficacy or operational benefit were not assessed in our analysis. In summary, this was the largest analysis to examine the safety of IV push levotiracetam  compared to IV piggyback in doses greater than 1,000 milligram. There were no difference in all predefined safety outcome when transitioning from IV piggyback to IV push.  IV push levotiracetam was not associated with IV site reactions and had low incidence of hemodynamic and sedation events relative to IV piggyback, and very few administrations  warranted clinical interventions.  Thank you for listening, and I would be happy to take any questions you may have. ♪♪♪

Video Summary

The presenter discusses the safety profile of intravenous push (IV push) administration of levitiracetam, an anti-epileptic drug, at Brigham and Women's Hospital. Traditionally, levitiracetam is administered as an IV piggyback (IVPB) infusion, but due to fluid shortages, the hospital transitioned to IV push administration. The study compared the safety outcomes of IV push versus IVPB levitiracetam doses greater than 1,000 mg. The analysis found that IV push levitiracetam was not associated with IV site reactions and had a low incidence of hemodynamic and sedation events. The study suggests that IV push administration may be a safe alternative to IVPB for levitiracetam.

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.

Afrah Alkazemi

Introduction/Hypothesis: Recent shortages of intravenous (IV) fluids has resulted in many health care systems converting medications from IV piggyback (IVPB) to IV push (IVP). In 2019, Brigham and Women's Hospital changed several medications to IVP; which included levetiracetam. Administering medications via IVP presents multiple advantages such as reduced drug/material cost, improved workflow, and shorter time to first dose, however there may be a risk of increased adverse drug reactions. The purpose of this analysis was to compare the safety profile including both systemic side effects and IV site reactions of IVP to IVPB levetiracetam.

Methods: This IRB approved, single-center, pre-post analysis was performed between November 1, 2019 and May 30, 2020 at Brigham and Women's Hospital in Boston, Massachusetts. The electronic health record was used to identify all administrations of IV levetiracetam greater than 1 g in patients â‰¥ 18 years old. The primary endpoints included hypotension, bradycardia, drug-induced sedation and IV site reactions such as phlebitis and infiltration. The Naranjo Nomogram was utilized to evaluate all drug reactions to determine the likelihood of whether the event was due to levetiracetam rather than other factors, such as concomitant medications.

Results: A total of 522 administrations in 165 patients were included in the analysis: 267 administrations in 86 patients in the IVP group and 255 administrations in 79 patients in the IVPB group. The median dose administered in both groups was 2 g. The incidence of hypotension in the IVP vs. IVPB groups was 10 vs. 7 (3.8% vs. 2.7%, p=0.075); bradycardia 13 vs. 4 (4.9% vs. 1.6%, p=0.054); sedation 21 vs. 37 (7.9% vs. 14.5%, p=0.039); and IV site reactions 0 vs. 2 (0% vs. 0.8%, p=0.238), respectively. Sixteen of the 44 (36.4%) events in the IVP group were deemed 'possible' with 3 assessed as 'probable' per the Naranjo Nomogram. In the IVPB group, 33 (66%) were found to be 'possible' on the Naranjo Nomogram while 5 were assessed as 'probable'.

Conclusions: The administration of levetiracetam via IVP had a similar safety profile compared to IVPB. Intravenous levetiracetam in doses as high as 4 g may be considered safe for IV push administration with appropriate monitoring.

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Level Advanced

Membership Level Select

Tag Seizure

Year 2021

Keywords

intravenous push

levitiracetam

anti-epileptic drug

safety profile

Brigham and Women's Hospital

	Society of Critical Care Medicine 500 Midway Drive Mount Prospect, IL 60056 USA Phone: +1 847 827-6888 Fax: +1 847 439-7226 Email: support@sccm.org	Contact Us About SCCM Newsroom Advertising & Sponsorship DONATE	MySCCM LearnICU Patients & Families Surviving Sepsis Campaign Critical Care Societies Collaborative	GET OUR NEWSLETTER
© Society of Critical Care Medicine. All rights reserved. \| Privacy Statement \| Terms & Conditions The Society of Critical Care Medicine, SCCM, and Critical Care Congress are registered trademarks of the Society of Critical Care Medicine.