Trick of the Trade: IV-Push Antibiotics in the ED

IV_arm5 copyLimited intravenous access is a common conundrum in the Emergency Department, with heavy implications for medication administration. Of particular concern, are the profoundly septic patients that necessitate multiple timely therapies, which require tying up a line – fluids, pressors, several antibiotics, etc. The shift away from less central line (i.e. triple lumen) placement for initial resuscitation, may serve to further exacerbate this issue.

The Problem

Since most of these septic patients will require more than one antimicrobial for empiric coverage, the exact timing of therapy and desired order of administration are details that may not be adequately communicated. How many times have you noticed after ordering vancomycin and cefepime, that vancomycin has been administered first, allowing several hours to go by without having received that broad-spectrum, gram-negative coverage with cefepime?

Despite these challenges, the Surviving Sepsis Campaign (SSC) guidelines currently recommend administration of appropriate empiric antibiotics within 1 hour after recognition of severe sepsis [1]. This is largely based upon a retrospective analysis of 2,731 patients with septic shock, which demonstrated that administration of effective antibiotics within the first hour of documented hypotension was independently associated with increased survival to hospital discharge [2]. Currently however, a lack of guidance exists regarding the best way to achieve this important aspect of the resuscitation bundle.

 

Trick of the Trade – IV Push Antibiotics

Administration of antibiotics via intravenous push (IVP) may be one approach to hasten antibiotic administration without tying up lines. Additionally, while communicating the desired order of administration is still important, when faced with limited IV access, nurses may be more inclined to initiate the IVP antibiotic first, due to shorter administration times. Further, IVP administration of antibiotics may be a more economically beneficial alternative as compared to more common methods [3]. Through cost avoidance of both pharmacy preparation and nursing administration time, as well as eliminating the need for minibags and IV tubing, one study estimated savings of $184,000 per year [4].

Listed below are various antibiotics that have been shown to be safe when given as an IVP to adults: [5][6][7][8]

Antibiotic Concentration*, Diluent Rate of Administration Osmolality (mOsm/L)**
Cefazolin 1 g/10 mL, SWFI 1-2 min 340
Cefuroxime 750 mg/10 mL, SWFI 1-2 min 447
Cefoxitin 1 g/10 mL, SWFI 2-4 min 525
Cefotaxime 1 g/10 mL, SWFI 1-2 min 440
Ceftriaxone 1 g/10 mL, SWFI 1-2 min 423
Ceftazidime 1 g/10 mL, SWFI 1-2 min 435
Cefepime 1 g/10 mL, SWFI 2-4 min <400
Meropenem 1 g/10 mL, SWFI 3-5 min <500
Aztreonam 1 g/10 mL, SWFI 2-4 min 487

SWFI, sterile water for injection;

* The concentrations stated above do not necessarily represent recommended doses; these should be used to determine the volume required for higher/lower doses (e.g. cefepime 2 g/20 mL SWFI)

** Substances with an osmolality less than 600 mOsm/L are generally acceptable for administration via a peripheral line [9]

Important Considerations

  • When implementing IVP antibiotics in your ED, standardize the process. This may require substantial changes in nursing practice, updating policies and procedures, departmental education, adjustments to electronic order sets, adjustments to product stocking and inventory, as well as implementing oversight for unforeseen adverse effects
  • It is important to note, that the use of sterile water for injection (SWFI) is to help minimize osmolality; reconstituting with NS or D5W may produce significant phlebitis, and increase the risk for extravasation injury. Read more information (extravasation injuries PDF) on this topic.
  • As with any IV preparation, remember to properly label your syringe. Refer to Dr. Bryan Hayes’ post on The Art of Syringe Labeling in the ED.
  • Beta-lactam antibiotics are often administered as prolonged infusions in order to take advantage of their pharmacokinetic/pharmacodynamic profiles (T > MIC). However, this is usually employed for subsequent maintenance doses, and is also not practical for initiation in the ED. Moreover, time to administration of the initial dose is a more important factor in septic patients.
  • The literature used to support the aforementioned IVP antibiotics did not include pediatric patients. Therefore, the safety and feasibility of implementing this practice within the pediatric population is uncertain.

Take-Home Points

  • Various beta-lactam antibiotics may be safely administered via IVP.
  • IVP administration may be one strategy to help facilitate timely administration of antibiotics, and to prevent tying up multiple lines.
  • To date, no published literature exists to support the potential benefits (i.e. improved time to administration; improved outcomes) of IVP antibiotics in the Emergency Department; future studies are warranted.

References

  1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for the Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013;41:580-637. PMID: 23361625.
  2. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. PMID: 16625125.
  3. Ambrose PG, Bui KQ, Richerson MA, et al. Pharmacoeconomic analysis of intravenous push vs. slow infusion of beta-lactam antibiotics. Clin Drug Invest. 1999 May;17(5):407-410. PMID: 9161666.
  4. Garrelts JC, Smith DF, Ast D, et al. A comparison of the safety, timing and cost-effectiveness of administering antibiotics by intravenous bolus (push) versus intravenous piggyback (slow infusion) in surgical prophylaxis. Pharmacoeconomics. 1992 Feb;1(2):116-23. PMID: 10172048.
  5. Garrelts JC, Ast D, LaRocca J, et al. Postinfusion phlebitis after intravenous push versus intravenous piggyback administration of antimicrobial agents. Clin Pharm. 1988;7:760-5. PMID: 3233896.
  6. Nowobilski-Vasilios A, Markel Poole S. Development and preliminary outcomes of a program for administering antimicrobials by I.V. push in home care. Am J Health-Syst Pharm. 1999;56:76-9. PMID: 10048883.
  7. Garrelts JC, Wagner DJ. The pharmacokinetics, safety and tolerance of cefepime administered as an intravenous bolus or as a rapid infusion. Ann Pharmacother. 1999;33:1258-61. PMID: 10630824.
  8. Norrby SR, Newell PA, Faulkner KL, et al. Safety profile of meropenem: international clinical experience based on the first 3125 patients treated with meropenem. J Antimicrob Chemother. 1995 Jul; 36 Suppl A:207-23. PMID: 8543496.
  9. Intravenous Nurses Society. Position paper: midline and mid-clavicular catheters. J Intraven Nurs. 1997;20:175-178.
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Author information

Adam Spaulding, PharmD BCPS

Adam Spaulding, PharmD BCPS

Emergency Medicine Pharmacist,

Pharmacy Residency Program Director,

Waterbury Hospital Health Center,

Adjunct Assistant Professor - UCONN School of Pharmacy,

Contributor to Emergency Medicine PharmD Blog

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ALiEM Bookclub: We Need to Talk About Kevin

we-need-to-talk-about-kevinWe Need to Talk About Kevin. Yes we do, I’m afraid. You may have been (like me, for many years) avoiding reading this novel by Lionel Shriver, ducking away from discussions and avoiding reviews, having got wind of the gist of the story through the mass media.

To summarise the book, We Need to Talk About Kevin by Lionel Shriver is written in the form of letters penned by Eva Khatchadourian to her estranged husband Franklin. These missives form a chronological examination of her life before and after the entrance of their son Kevin into their lives (or perhaps, more accurately, the invasion), and they follow the painful path through his childhood, dissecting the family relationships that shape his development along the way. There is no secret about the main event. Kevin, at the tender and cleverly calculated age of 15 years and 362 days, commits mass murder in his school gym.

I need to declare at the outset that I loved this book. It is masterfully written, in my opinion. Any book that can grab you by the throat, shake you until the tears fall and the nausea wells, and every so often cause you to drop the book in shock and surprise, despite knowing the inevitable premise, is a work of consummate skill.

So why are we discussing it in the ALiEM book club? What does this book have to do with critical care and emergency physicians? I would hazard a guess at saying ‘everything.’

When we want to learn about the nuts and bolts of administering the science of critical care, we turn to texts and websites and our colleagues and teachers. But when we want to truly get inside the head of another, and learn about humanity from the inside out, we turn to novels. Books give us windows into the minds of people/characters/good and bad, and allow us to understand and foster empathy. So it is with Kevin. Lionel Shriver tackles an exhaustive list of themes of modern family life in middle America, all of them written with a shrewd intelligence and observation. They are all explored with an almost dispassionate curiosity by Shriver, and never feel like they are falling into polemic.

To list just a smattering of the themes examined:

  • The nature vs nurture debate. Is evil born or made? This is the overarching theme of the book. How much did Eva’s relationship with her son forge the path that he took? If I had one criticism of this book, it would be that the character of Kevin was perhaps unrelentingly evil and malevolent from the start. At times it almost felt like caricature, and detracted from the immersion and faith I had in the importance of the story. Some of the scenes from Kevin’s infant and childhood years seemed impossible to believe. We all have come into contact with antisocial personalities, and seen the spoils of their behaviour. It is difficult to envisage this in somebody so young.
  • Parenting in the modern age. Why do we choose to bear children? The reasons for doing so are often complex, and not always altruistic or venerable. Eva is an ambivalent mother from the start, and this informs much of her interpretation of her relationship with Kevin.
  • The banal and hackneyed wealth of the middle class. Interwoven throughout the book are comments on the choices made from within the luxury of a first world life. These choices bother Eva, and she is quick to speak out about them, peppering the book with her harsh commentary, but they are not enough for her to take any active stand.
  • The phenomena of mass school shootings. This book occurs around the time of Columbine, an event referenced several times, along with others of a similar ilk. There are no answers in here. Like any good novel, it just opens up a space in which you can ask questions of yourself and the world around you. But, particularly as a hopelessly befuddled Australian, where these events seem like they belong to another, crueler, doomed planet, I was left understanding the motivation for these unspeakable horrors no more than when I first picked up the book.

Even the pervasive desire for fifteen minutes of fame in today’s celebrity bedeviled world gets the treatment, with the incarcerated Kevin bemoaning other mass murderer’s substandard methods whilst they hog the limelight.

There are so very many other subplots and themes in this book, that I don’t feel I can do them justice, such as the influence of the American presidential race, the personality of the All-American ‘Gee-Whiz’ husband and his contribution to the unfolding of the story, the civil courts, the responsibilities of the school system, and many more. My recommendation? Go read the book. And be prepared for a surprise.

Discussion Questions

It is customary to conclude a review like this with some questions.  Some of these I have already alluded to. The answers, however, are unlikely to be found in the book. What this extraordinary novel does, is open up the door into further fundamental questions, that we should all be asking of ourselves, and of our society to which we contribute.

  1. What is evil? Is it born, or made?
  2. Why are school shootings, although nominally present in other countries, vastly more frequent in the U.S.? Are there behaviour patterns, individual characteristics, or societal issues, that specifically predispose to these events, and if so, how can they be identified and prevented?
  3. Is the love of a parent for a child unconditional?

We Need to Talk About Kevin was also released in movie format in 2012 staring Tilda Swinton and Ezra Miller. (Rotten Tomatoes Review)

* Disclaimer: We have no affiliations financial or otherwise with the authors, the books, Amazon, or Rotten Tomatoes

 

Author information

Michelle Johnston, MBBS FACEM

Michelle Johnston, MBBS FACEM

Specialist Emergency Physician

Royal Perth Hospital

Perth, Australia

The post ALiEM Bookclub: We Need to Talk About Kevin appeared first on ALiEM.

Vancomycin Loading Doses in Pediatric Patients: A Missed Opportunity?

Pediatric Syringe Pump

In January 2014, ALiEM featured a must-read post by Bryan Hayes regarding proper dosing of vancomycin in the emergency department, including a special note related to the recommendations regarding consideration of loading doses of vancomycin ranging from 25 to 30 mg/kg in adult patients who are critically ill with a high suspicion for MRSA infection.

Recommended pediatric dosing of vancomycin

In pediatric patients with serious and/or invasive infection, the recommended dosing regimen of vancomycin is [1]:

15 mg/kg/dose administered every 6 hours

Challenges associated with aggressive empiric dosing of vancomycin in pediatrics

Although a number pharmacokinetic models have established that such a dosing scheme may achieve a desired area under the curve/minimum inhibitory concentration (AUC:MIC) ratio of at least 400 mcg • hr/mL [2][3], several studies in pediatric patients have demonstrated that even this aggressive regimen does not lead to desired associated serum concentrations of 15 to 20 mcg/mL for serious infections when measured at steady state [4][5].

Is more aggressive empiric dosing necessary?

Results of the recently published Pediatric Assessment of Vancomycin Empiric Dosing (PAVED) study suggest that empiric dosing of vancomycin in pediatric patients may need to be more aggressive based on age and desired therapeutic concentration [6]:

Desired Therapeutic Concentration Age
1 to 6 years >6 years
10 to 15 mcg/mL 70 mg/kg/day divided q6h 60 mg/kg/day divided q8h
15 to 20 mcg/mL 90 mg/kg/day divided q6h 70 mg/kg/day divided q6h

 

Pharmacokinetic considerations in pediatrics

Pharmacokinetic parameters to be considered in pediatric patients related to vancomycin include the following:

  • Volume of distribution (Vd): Neonates and young infants tend to possess higher apparent volumes of distribution. As a result, these patients may exhibit lower plasma concentrations following the administration of hydrophilic medications such as vancomycin [7].
  • Clearance: Age-dependent variations in clearance of occur in the early stages of life, with peak clearance generally occurring between 2 and 6 years of age before decreasing and ultimately reaching the adult plateau by puberty [8]

Is a loading dose of vancomycin the answer in pediatrics?

Given the physiological and pharmacokinetic challenges of vancomycin in pediatric patients, can these be overcome with a loading dose of vancomycin in pediatric patients? That is, does a loading dose of 25-30 mg/kg of vancomycin hold any benefit in critically ill pediatric patients in achieving therapeutic concentrations without posing a serious risk for toxicity?

Clinical studies

Surprisingly, the evidence for loading doses of vancomycin is relatively scarce in the pediatric population.

  • STUDY 1: In a prospective, double-blind study conducted by Demirjian and colleagues [9], 59 patients between the ages of 2 and 18 years of age were randomized to receive either a loading dose of vancomycin of 30 mg/kg or a standard dose of 20 mg/kg, both followed by a standard dose of 20 mg/kg administered every 8 hours.
    • At 8 hours post-infusion of the first dose, 11% of patients in the loading dose group (2/19) attained a serum concentration of 15 to 20 mcg/mL compared to none of the 27 patients in conventional dosing group (p = 0.17).
    • Yet, pharmacokinetic analyses demonstrated no measurable differences in achievement of AUC:MIC, as both groups reached levels greater than 400 mcg • hr/mL (p = 0.79).
    • In terms of adverse effects:
      • Red man syndrome occurred in 48% and 24% of patients in the loading dose and conventional dosing groups, respectively (p = 0.06).
      • In addition, serum creatinine doubled from baseline values within 7 days of initiation of vancomycin in 4 patients in the loading dose group (13%) versus 1 patient in the conventional dosing group (3%) (p = 0.14).
    • Conclusion: A loading dose did not necessarily lead to rapid achievement of therapeutic concentrations, and systemic exposure to vancomycin was sufficient, based on observed AUC:MIC, in both treatment arms.
  • STUDY 2: Bartlett and colleagues evaluated the effects of vancomycin loading doses based on subsequent trough concentrations in a single center retrospective study [10].
    • 54 pediatric patients who were at least 3 months in age were included in the analysis.
    • 11 patients who received a loading dose of vancomycin had higher initial median steady state concentrations relative to those who received conventional dosing of vancomycin (10.5 mcg/mL versus 9.8 mcg/mL).
    • Loading doses of vancomycin ranged from 18 to 27 mg/kg, and none of these patients experienced nephrotoxicity.
    • Conclusion: Loading doses of vancomycin are associated with higher initial trough concentrations, and that more aggressive dosing strategies for vancomycin may be of benefit in pediatric patients.

Application to clinical practice

Clinical outcomes such as eradication of confirmed infection, length of stay, and mortality remain to be observed in this patient population. With the limited and inconsistent data associated with loading doses of vancomycin in pediatric patients, it is somewhat challenging to validate or contest its use as a standard practice in this population.

Take home point

Until we have more investigations to validate the results of the PAVED study related to more aggressive dosing of vancomycin, pediatric patients should still be prescribed a vancomycin dose of 15 mg/kg/dose every 6 hours. Loading doses of vancomycin of 25-30 mg/kg may be considered on a case-by-case basis in critically ill pediatric patients.

References

  1. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18-55. PMID: 21208910
  2. Frymoyer A, Guglielmo BJ, Wilson SD, et al. Impact of a hospitalwide increase in empiric pediatric vancomycin dosing on initial trough concentrations. Pharmacotherapy 2011; 31:871-876. PMID: 21923588
  3. Le J, Bradley JS, Murray W, et al. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J 2013; 32:e155-1563. PMID: 23340565
  4. Eiland LS, English TM, Eiland EH 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother 2011; 45:582-589. PMID: 21521865
  5. Frymoyer A, Hersh AL, Benet LZ, et al. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J 2009; 28:398-402. PMID: 19295465
  6. Rainkie D, Ensom MH, Carr R. Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review. Paediatr Drugs 2015 March 27 [Epub ahead of print]. PMID: 25813682
  7. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology: Drug disposition, action, and therapy in infants and children. N Engl J Med 2003; 349:1157-1167. PMID: 13679531
  8. Neuman G, Nulman I, Adeli K, et al. Implications of serum creatinine measurements on GFR estimation and vancomycin dosing in children. J Clin Pharmacol 2014; 54:785-791. PMID: 24596064
  9. Demirjian A, Finkelstein Y, Nava-Ocampo A, et al. A randomized controlled trial of a vancomycin loading dose in children. Pediatr Infect Dis J 2013; 32:1217-1223. PMID: 23817340
  10. Bartlett A, Brown-Alm D, Landon E, et al. Vancomycin loading dose in pediatric patients receiving intermittent vancomycin dosing. Abstract 162. Presented at ID Week; October 2-6, 2013; San Francisco, CA.
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Author information

Nadia Awad, PharmD, BCPS

Pediatric Pharmacist

Robert Wood Johnson University Hospital

Staff Blogger at Emergency Medicine PharmD

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