Bupropion Overdose: Factors Associated with Seizures

Background

Bupropion ingestions are one of the scarier poisonings due to a relatively narrow therapeutic index and the numerous adverse effects that may occur. Medical toxicologist Dr. Dan Rusyniak details his hatred of this drug in overdose in a Tox & Hound blog post aptly-titled Illbutrin. When bupropion was first approved in the 1980s, the max dose was 600 mg/day [1]. However, reports of seizures, particularly in patients with bulimia, caused its temporary removal from the market [2]. It was reintroduced a few years later with a max dose of 450 mg/day [3]. Common signs and symptoms noted in overdose include seizures, agitation, sinus tachycardia, and QRS/QTc prolongation. Seizures occur in up to 40% of overdose cases, are often refractory to initial therapy, and can happen as long as 24 hours after an overdose with extended release formulations [4, 5].

Evidence

A study of 256 patients from the Toxicology Investigators Consortium (ToxIC) Registry identified three factors associated with seizure development after bupropion overdose [6, 7].

  1. QTc prolongation > 500 msec (OR = 3.4, 95% CI: 1.3-8.8)
  2. Tachycardia (heart rate > 140) (OR = 1.9, 95% CI: 1-3.6)
  3. Age 13–18 years (OR = 2.4, 95% CI: 1.3-4.3)

Agitation and tremors are more common in patients who develop seizures with bupropion compared to those who do not [4]. Additionally, presence of tachycardia (heart rate >100 bpm) has a sensitivity of 91% and a negative predictive value of 93% for development of seizures [4].

Bottom Line

  • Seizures are common following bupropion overdose and patients who seize are generally tachycardic.
  • Patients should be observed at least 24 hours after a extended release bupropion overdose, as seizures can be significantly delayed.

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Davidson J. Seizures and bupropion: a review. J Clin Psychiatry. 1989;50(7):256-261. PMID: 2500425.
  2. Horne RL, Ferguson JM, Pope HG, et al. Treatment of bulimia with bupropion: a multicenter controlled trial. J Clin Psychiatry. 1988;49(7):262-266. PMID: 3134343.
  3. Huecker MR, Smiley A, Saadabadi A. Bupropion. In: StatPearls. StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470212/.
  4. Starr P, Klein-Schwartz W, Spiller H, Kern P, Ekleberry SE, Kunkel S. Incidence and onset of delayed seizures after overdoses of extended-release bupropion. Am J Emerg Med. 2009;27(8):911-915. doi: 10.1016/j.ajem.2008.07.004. PMID: 19857406.
  5. Al-Abri SA, Orengo JP, Hayashi S, Thoren KL, Benowitz NL, Olson KR. Delayed bupropion cardiotoxicity associated with elevated serum concentrations of bupropion but not hydroxybupropion. Clin Toxicol (Phila). 2013;51(10):1230-1234. doi: 10.3109/15563650.2013.849349. PMID: 24131328.
  6. Wax PM, Kleinschmidt KC, Brent J, ACMT ToxIC Case Registry Investigators. The toxicology investigators consortium (Toxic) registry. J Med Toxicol. 2011;7(4):259-265. doi: 10.1007/s13181-011-0177-z. PMID: 21956161.
  7. Rianprakaisang TN, Prather CT, Lin AL, Murray BP, Hendrickson RG, Toxicology Investigators Consortium (ToxIC). Factors associated with seizure development after bupropion overdose: a review of the toxicology investigators consortium. Clin Toxicol (Phila). Published online April 21, 2021:1-5. doi: 10.1080/15563650.2021.1913180. PMID: 33878992.

ALiEM AIR Series | HEENT 2021 Module

This image has an empty alt attribute; its file name is AIR-logo-2016-transparent-SAEM-CORD-586x650.jpg

Welcome to the AIR HEENT Module! After carefully reviewing all relevant posts from the top 50 sites of the Social Media Index, the ALiEM AIR Team is proud to present the highest quality online content related to head, eyes, ears, nose, and throat emergencies in the Emergency Department. 6 blog posts within the past 12 months (as of March 2021) met our standard of online excellence and were curated and approved for residency training by the AIR Series Board. We identified 2 AIR and 4 Honorable Mentions. We recommend programs give 3 hours (about 30 minutes per article) of III credit for this module.

AIR Stamp of Approval and Honorable Mentions

 

In an effort to truly emphasize the highest quality posts, we have 2 subsets of recommended resources. The AIR stamp of approval is awarded only to posts scoring above a strict scoring cut-off of ≥30 points (out of 35 total), based on our scoring instrument. The other subset is for “Honorable Mention” posts. These posts have been flagged by and agreed upon by AIR Board members as worthwhile, accurate, unbiased, and appropriately referenced despite an average score.

Interested in taking the HEENT quiz for fun or asynchronous (Individualized Interactive Instruction) credit? Please go to the above link. You will need to create a free, 1-time login account.

Highlighted Quality Posts: HEENT Emergencies

Site Article Author Date Label
EMCrit Epiglottitis Josh Farkas, MD July 2, 2020 AIR
Taming the SRU Jaw Dislocation Kristin Meigh, MD January 13, 2021 AIR
EMDocs Peritonsillar Abscess Ryan Sumpter, MD and Rachel Bridwell, MD Mar 7, 2020 HM
PedEMMorsels Open Globe Injuries in Children Sean Fox, MD August 14, 2020 HM
PedEMMorsels Nasolacrimal Duct Obstruction Sean Fox, MD June 12, 2020 HM
St. Emlyn’s Ludwig’s Angina Pete Hulme, MBChB January 9, 2021 HM

(AIR = Approved Instructional Resource; HM = Honorable Mention)

If you have any questions or comments on the AIR series, or this AIR module, please contact us! More in-depth information regarding the Social Media Index.

Thank you to the Society of Academic Emergency Medicine (SAEM) and the Council of EM Residency Directors (CORD) for jointly sponsoring the AIR Series! We are thrilled to partner with both on shaping the future of medical education.

SplintER Series: What is Wrong With My Daughter?

 

A 16 year-old competitive gymnast presents to the emergency department with left ankle pain for several weeks and missed periods. The mother provides consent to treat the patient and informs you she is concerned that with the patient’s missed periods, she may be pregnant. You obtain x-rays of her ankle (Figure 1).

Figure 1. Case courtesy of Dr Hani Makky ALSALAM, Radiopaedia.org, rID: 8720

 

Stress fracture at the distal tibial metaphysis – note the faint sclerotic line at the tibial metaphysis (Figure 2).

Figure 2. Arrows identifying the stress fracture. Case courtesy of Dr. Hani Makky Al Salam, Radiopaedia.org, rID: 8720

When coupled with the amenorrhea, consider the female athlete triad.

  • PEARL: The female athlete triad is a syndrome consisting of disordered eating, amenorrhea, and low bone mineral density (eg. osteoporosis) – Patients will have a degree of dysfunction from all 3 of the components. This is a fairly common disorder in young female athletes but the actual prevalence is hard to estimate because of the complexity of the three components [1]. Studies have shown a range from 0-16% when encompassing all three but can be as high as 4-18% when using two concurrent components and even 16-54% when only looking for one [2,3].

  • PEARL: Stress fractures in competitive athletes is usually multifactorial – increased activity, poor nutrition, and possible hormone imbalance [4,5].

Plain film ankle views should be obtained. If a stress fracture is acute, sensitivity on plain films can be as low as 10% [6]. MRI can be performed outpatient with a sensitivity approaching 100% [4,5,7,8]. A pregnancy test should be performed as well given the amenorrhea. A standard workup for amenorrhea should be performed as an outpatient. Inquire about eating habits and anxiety/depression.

  • PEARL: Athletes, regardless of competition level and gender, may be pushed into decreasing caloric intake for the sake of performance, appearance, or making weight. This can have serious physical and mental implications.

The three components of the female triad are on a spectrum of severity in the disruption of bone mineral density/osteoporosis, menstrual dysfunction/dysmenorrhea, and low energy with or without an eating disorder [1,9-11]. Patients will have a degree of dysfunction of all three components.

  • PEARL: Risk factors for developing the female athlete triad are participation in sports that emphasize leanness or a specific weight, appearance, or are beneficial if less gravitational forces. These may include gymnastics, ice skating, wrestling, boxing, dance, and track [10,12].

Stress fracture treatment included rest and analgesics. Immobilization is not necessary, but refraining from activity which exacerbates pain is crucial. NSAIDs may be used for pain control [5,7]. Female athlete triad is multifactorial and outpatient follow up should be ensured. Referral to adolescent medicine, sports medicine, or close primary care follow up is important.

  • PEARL: The patient will need education on good eating habits and nutrition, decrease in activity, and counseling [1,10,12]. The best way to treat the female athlete triad is to prevent it.

Check out ALiEM’s SplintER Series to brush up on other can’t miss diagnoses of ankle pain.

References

  1.  Weiss Kelly AK, Hecht S; COUNCIL ON SPORTS MEDICINE AND FITNESS. The Female Athlete Triad. Pediatrics. 2016;138(2):e20160922. PMID: 27432852.
  2. Nichols JF, Rauh MJ, Lawson MJ, Ji M, Barkai HS. Prevalence of the female athlete triad syndrome among high school athletes. Arch Pediatr Adolesc Med. 2006;160(2):137-142. doi:10.1001/archpedi.160.2.137. PMID: 16461868.
  3. Hoch AZ, Pajewski NM, Moraski L, et al. Prevalence of the female athlete triad in high school athletes and sedentary students. Clin J Sport Med. 2009;19(5):421-428. doi:10.1097/JSM.0b013e3181b8c136. PMID: 19741317.
  4. Matcuk GR Jr, Mahanty SR, Skalski MR, Patel DB, White EA, Gottsegen CJ. Stress fractures: pathophysiology, clinical presentation, imaging features, and treatment options. Emerg Radiol. 2016;23(4):365-375. PMID: 27002328.
  5. Saunier J, Chapurlat R. Stress fracture in athletes. Joint Bone Spine. 2018;85(3):307-310. PMID: 28512006.
  6. Matheson GO, Clement DB, McKenzie DC, Taunton JE, Lloyd-Smith DR, MacIntyre JG. Stress fractures in athletes. A study of 320 cases. Am J Sports Med. 1987;15(1):46-58. doi:10.1177/036354658701500107. PMID: 3812860.
  7. Denay KL. Stress Fractures. Curr Sports Med Rep. 2017;16(1):7-8. PMID: 28067732.
  8. McInnis KC, Ramey LN. High-Risk Stress Fractures: Diagnosis and Management. PM R. 2016;8(3 Suppl):S113-S124. PMID: 26972260.
  9. Otis CL, Drinkwater B, Johnson M, Loucks A, Wilmore J. American College of Sports Medicine position stand. The Female Athlete Triad. Med Sci Sports Exerc. 1997;29(5):i-ix. PMID: 9140913.
  10. Nattiv A, Loucks AB, Manore MM, et al. American College of Sports Medicine position stand. The female athlete triad. Med Sci Sports Exerc. 2007;39(10):1867-1882. PMID: 17909417.
  11. Sundgot-Borgen J. Risk and trigger factors for the development of eating disorders in female elite athletes. Med Sci Sports Exerc. 1994;26(4):414-419.PMID: 8201895.
  12. Scofield KL, Hecht S. Bone health in endurance athletes: runners, cyclists, and swimmers. Curr Sports Med Rep. 2012;11(6):328-334. PMID: 23147022.

One-Time Vancomycin Doses in the Emergency Department

Background

A previous ALiEM post from 2013 by an EM pharmacist colleague argued the case against one-time vancomycin doses in the ED prior to discharge. The take-home points from this post were:

    1. No evidence that a one-time vancomycin has any benefit
    2. This practice is not recommended by the Infectious Diseases Society of America (IDSA)
    3. May extend the patient’s ED stay by at least an hour for the IV infusion, depending on the dose
    4. Increases the cost of the ED visit (e.g., IV line, medication, RN time)
    5. Pharmacokinetically 1 dose of vancomycin doesn’t make sense
      • Vancomycin 1 gm IV x1 provides sub-therapeutic levels for patients with normal renal function
      • Efficacy is based on overall exposure (e.g., AUC/MIC) achieved with repeated dosing over several days
    6. Subtherapeutic vancomycin concentrations lead to development of resistance

Despite the above points, a one-time dose of vancomycin prior to the patient being discharged on an oral regimen is a common practice [1].

Evidence

As stated above, a single dose of vancomycin is unlikely to provide a therapeutic benefit and may only serve to reassure clinicians. The 2020 consensus guidelines regarding vancomycin monitoring for serious MRSA infections reinforce the recommendation of achieving an AUC0-24/MIC ratio of ≥400, as a ratio <400 increases resistance and has inferior efficacy [2]. Since the AUC is dependent on overall time of exposure plus concentration, a single dose for an average patient with normal renal function is not adequate (Figure 1). The graph below also demonstrates how long it generally takes for vancomycin to reach steady state when patients receive a dose every 8 hours.

 

*The estimated AUC above assumes a 30 yo male that weights 70kg and is 6′ tall with a serum creatinine of 1.0 mg/dL.

A randomized trial conducted at Christiane Care Health System compared patients who received a vancomycin loading dose of 30 mg/kg or 15 mg/kg [3]. Just twelve hours after this initial dose, 34.6% of patients who received 30 mg/kg had vancomycin levels in the therapeutic range (trough >15 mg/L) vs. 3% of patients who received 15 mg/kg (p < 0.01).

Bottom Line

Even large vancomycin loading doses rarely achieve therapeutic levels after one dose. Therefore, if the plan is to discharge, skip the one-time dose altogether and choose an antimicrobial regimen that will be continued in the outpatient setting (e.g., doxycycline or sulfamethoxazole/trimethoprim if concerned for MRSA or cephalexin for most other patients).

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Mueller K, McCammon C, Skrupky L, Fuller BM. Vancomycin use in patients discharged from the emergency department: a retrospective observational cohort study. J Emerg Med. 2015;49(1):50-57. doi: 10.1016/j.jemermed.2015.01.001. PMID: 25802166.
  2. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant staphylococcus aureus infections: a revised consensus guideline and review by the american society of health-system pharmacists, the infectious diseases society of america, the pediatric infectious diseases society, and the society of infectious diseases pharmacists. Am J Health Syst Pharm. 2020;77(11):835-864. doi: 10.1093/ajhp/zxaa036. PMID: 32191793.
  3. Rosini JM, Laughner J, Levine BJ, Papas MA, Reinhardt JF, Jasani NB. A randomized trial of loading vancomycin in the emergency department. Ann Pharmacother. 2015;49(1):6-13. doi: 10.1177/1060028014556813. PMID: 25358330.

Reading from the Silver Linings Playbook: The ALiEM Connect Project

ALiEM Connect graduation

It feels like yesterday that we were sheltered-in-place, staring at our computers, wondering, “So now what?” 

As COVID-19 paused all in-person educational sessions, the early morning residency conference we used to begrudgingly join quickly became something that we profoundly missed. While we can now be “present” while wearing sweatpants and a button-down shirt, we miss the human connection. Many of us would gladly even suffer through traffic just to be a part of this morning conference tradition.

As educators and innovators, we know what a disruptive force the COVID-19 pandemic has been to the medical community. It has strained our medical and healthcare systems and has irrevocably altered our day-to-day lives. Without a doubt, the pandemic also changed how we delivered educational content to our learners over the past year.

Scholars have written about how likely this pandemic will likely precipitate the much-needed digital transformation of healthcare and health professions education that many of us have expected and hoped for. But while some of these innovations are born out of necessity, they may also inadvertently isolate us from the experiential aspects of education and human interaction that provide meaning to our work. For the ALiEM team, we cherish the opportunity to be part of some of these significant innovative and positive “disruptions,” further aligning our goal of creating an impactful and fulfilling academic life in emergency medicine. 

The Backstory

As a remote team working across continents, the ALiEM team has thrived on digital connection for over a decade. With excellent collaborators and volunteers representing different parts of the world, our daily operations require us to stay connected and work asynchronously to achieve our goals and deliverables. When the lockdowns hit, we leveraged its impact on physical distancing and leaned into connecting with each other even more! They say “chance favors the prepared mind,” and there we were, already on Slack and yearning for the opportunity to harness the power of teamwork using our shared passions, individual creative strengths, and enthusiastic and supportive emojis. There were moments of creating, moments of celebration, and moments of simply being with each other – often through an evening #WifiAndWine.

By the Ides of March 2020, an auspicious time indeed, we knew we were at a turning point. Our friends and work families had been working on the front lines combating the pandemic locally, gathering PPE, and studying the effects of a virus we knew next to nothing about. New information was coming in daily, and the signal-to-noise ratio was low. In some ways, to escape the disruptions going on all around us, we banded together to focus our unique energies toward creating something as novel as the virus itself in the realm of free open-access medical education.

At a time where everyone was feeling alone, we asked ourselves how we could support the joy of learning from and with each other? In truly whirlwind fashion, the first ALiEM Connect conference went from idea to execution in less than 2 weeks, a record-breaking time even for ALiEM. Thank especially to the American Board of Emergency Medicine for sponsoring these events.

We recently made it to the semi-finals at the CORD/ACEP Innovator of the Year competition, where we shared the below video capturing the fun, collaboration, and innovative outcome of our efforts. Oh, and the familiar ratatat of Slack.

Making this a Multiple Win

The secret sauce of the ALiEM team is that we have a diverse group of people, each of whom brings their own perspective and that we are able to share with one another liberally. Dr. Michelle Lin encouraged an environment that is psychologically safe and supportive since the inception of the ALiEM enterprise. It is out of this space that our diverse team was able to successfully bring a massively successful project to fruition amid a global pandemic. What started as a small brainstorming session blossomed into ALiEM Connect – 3 distinct remote conferences featuring nationally-recognized educators and thought leaders enjoyed by residents across the country.

It’s difficult to express as a linear narrative, but looking back, it seems as though our team divided into unique roles without a second thought. Just like a production company, we had the front and back of the house. Those in the front made sure to help get people in the seats to watch; stage managers and coordinators ensured that every part of each of the ALiEM Connect experiences was phenomenally smooth. We had talented individuals who acted as hosts and speakers to ensure that each of these experiences was top-notch and engaging. In the back, Drs. Mary Haas, Yusuf Yilmaz, and Teresa Chan sprung quickly into action to create a program evaluation strategy for our ALiEM Connect program, including a formal institutional review board exemption! All the while, testing and vetting platforms and methods to distribute the material were ongoing. We built upon each technological skill, learned new platforms, and trialed different features. We had barely decided on an open, free, and accessible platform (which was, in fact, no individual platform but an amalgamation of many!) before sending out the invites.

But the fun didn’t stop there! We’re the “academic” life in emergency medicine! How could we not also share our results with the traditional academic community? Within days of finishing our first ALiEM Connect experience, our program evaluation team generated the scaffolding of a manuscript to put together our thoughts and analyze the evaluation data collected. We harnessed the power of metrics from social media platforms (YouTube, Slack, Twitter), website analytics, and end-user experiences. Harnessing all of these analytics and communicating the right message with our academic medicine community was important to inform and help others to replicate similar approaches to their residents. Our team used ready to use metrics which came from YouTube analytics. But we did not stop there as we needed more reports of how the residents and programs interacted during the Connect events in the backchannel, Slack. We developed Python supported software to export and analyze all the messages happening in separate channels. We developed a “Emoji Cloud” to see how the reactions happened, and closely analyzed the messages during the event.

Given the true novelty of the experience, we figured we might as well shoot for the moon, as they say, by submitting our innovation description paper to Academic Medicine. After all, even if they didn’t accept it, we might get some constructive reviews, to say the least. As innovators, we are comfortable with the possibility of failure. We understand the value of the saying, “You miss 100% of the shots you don’t take,” and were prepared to accept “no” as an answer. With that, we took a calculated risk, making use of the same collaborative strategy to craft a manuscript, and clicked submit.

…And we’re glad we took that shot! We are excited to share that what we sent was indeed accepted and express our gratitude for the chance to share our low-cost approach to a large-scale, nationwide residency conference! You may read the Published Ahead-of-Print version of our paper.

Moral of the story…

You might be asking yourself, “What’s the moral of the story here? Of course, with enough academics and experts, yeah, you got a paper published. Cool…” But the papers aren’t the point. In fact, during the COVID-19 pandemic, more papers have been published than ever before – more research is being done, and our whole field is changing. The point is… this is how we got to ENJOY the academic life during a pandemic! We made lemonade (and several other desserts!) out of the lemons we were handed. New knowledge comes from thinking big and trying new things. Turns out, sometimes you also have to write about those experiences and share them with others.

As emergency physicians, we know we’re good in a crisis. But this experience reminded us that by surrounding ourselves with amazing people, we could get a surprising amount of work done (at record speed) and have a fantastically memorable time along the way. The moral of this story is that when you bring great people together and give them a chance to get to know each other, magic happens. ALiEM Connect happens. And we impact more people than we can possibly meet at the touch of our keyboards. We are so grateful for the chance to work alongside all the wonderful people at each of our institutions every day. Still, also, we are indebted to those who are our digital family. Thank you to all of you who make initiatives like ALiEM Connect possible. Academic life in emergency medicine is all about bringing a great team together.

So is the ALiEM team.

Safety and Efficacy of Clevidipine for Acute Blood Pressure Control

Background

Rapid and precise control of blood pressure is vital for patients with a hypertensive emergency or an acute stroke. Commonly, nicardipine is utilized in these situations, with nitroprusside being a less appealing alternative. The most recent AHA/ASA Acute Ischemic Stroke Guidelines, updated in 2019, also recommend clevidipine as a first-line antihypertensive option [1]. Clevidipine is a dihydropyridine calcium channel blockers, similar in mechanism to nicardipine and amlodipine. The main advantage of clevidipine over nicardipine is related to its pharmacokinetics (Table 1). Given its shorter half-life of elimination, clevidipine can be titrated every 1-2 minutes. Additionally, if hypotension does occur, stopping the clevidipine infusion allows blood pressure to rebound quickly.

Medication Onset Duration Half-Life
Clevidipine 2-4 mins 5-15 mins 1-15 mins
Nicardipine 10-20 mins 1-2 hours 2-4 hours
Nitroprusside 1-2 mins 1-10 mins 2 mins

Table 1: Pharmacokinetics of Common Antihypertensive Infusions [Micromedex; Lexicomp]

Evidence

Most studies demonstrate equivalent outcomes between clevidipine and other agents (e.g., nicardipine, nitroprusside, nitroglycerin) [2-5]. The ECLIPSE trial is the largest to assess the safety and efficacy of clevidipine [6]. The authors randomized cardiac surgery patients to clevidipine, nicardipine, nitroprusside, or nitroglycerin and found no difference in the incidence of myocardial infarction, stroke, or renal dysfunction. They noted that mortality was higher in patients receiving nitroprusside vs clevidipine, but equivalent compared to the the other medications. Additionally, clevidipine treated patients had significantly fewer excursions outside the prespecified blood pressure range than patients treated with any of the other agents.

Safety

Clevidipine is formulated in a 20% lipid emulsion and packaged in a glass vial. This causes clevidipine to appear similar to propofol, which could lead to safety issues. Also, care should be taken when using both clevidipine and propofol concomitantly, especially at high doses, as both provide clinically significant amounts of lipids, so triglycerides should be monitored.

Bottom Line

Clevidipine is a safe and effective antihypertensive to use in patients that require rapid and strict blood pressure control, specifically in patients with an aortic dissection or an acute ischemic/hemorrhagic stroke.

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2019;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. PMID: 31662037.
  2. Allison TA, Bowman S, Gulbis B, Hartman H, Schepcoff S, Lee K. Comparison of clevidipine and nicardipine for acute blood pressure reduction in patients with stroke. J Intensive Care Med. 2019;34(11-12):990-995. doi: 10.1177/0885066617724340. PMID: 28820038.
  3. Rosenfeldt Z, Conklen K, Jones B, Ferrill D, Deshpande M, Siddiqui FM. Comparison of nicardipine with clevidipine in the management of hypertension in acute cerebrovascular diseases. J Stroke Cerebrovasc Dis. 2018;27(8):2067-2073. doi: 10.1016/j.jstrokecerebrovasdis.2018.03.001. PMID: 29627171.
  4. Ulici A, Jancik J, Lam TS, Reidt S, Calcaterra D, Cole JB. Clevidipine versus sodium nitroprusside in acute aortic dissection: A retrospective chart review. Am J Emerg Med. 2017;35(10):1514-1518. doi: 10.1016/j.ajem.2017.06.030. PMID: 28669696.
  5. Brehaut SS, Roche AM. Abstract W P65: Clevidipine Outperforms Other Agents in Emergent Acute Hypertension Treatment in Ischemic Stroke Pre-rt-PA. 2015;46:AWP65. doi: 10.1161/str.46.suppl_1.wp65.
  6. Aronson S, Dyke CM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008;107(4):1110-1121. doi:10.1213/ane.0b013e31818240db. PMID: 18806012.
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