• 03 Aug 2021 10:30 AM | Anonymous

    By: Annie Stella, PharmD, BCPS; Centerpoint Medical Center, Independence, MO

    In 2019, the Department of Health and Senior Services rules for hospitals were updated. Under CSR 30-20.100 Pharmacy Services and Medication Management now states that Missouri hospitals and emergency departments can send bulk medications home with patients upon discharge. Any multidose container that was used for or administered to the patient during their hospital stay may be sent with the patient at discharge when ordered by an authorized practitioner. This includes, but is not limited to, inhalers, ointments, creams, medications requiring the original container for dispensing, insulin pens, eye drops, ear drops, and infusions that are currently connected to the patient’s infusion device.

    Written instructions for use shall be provided by a pharmacist, prescriber or a registered nurse at the time of discharge.

    How to implement a send-home program

    Many multidose medications are disposed of upon patient discharge. This provides no continued help to the patient and increases hospital cost for proper waste management of these medications. But what if we could provide transitional care for the patient and reduce hospital waste management costs at the same time? The key is ensuring proper labeling and instructions for use to the patient upon discharge that does not cause an unreasonable increase in workload for staff.

                   The Children’s Hospital and Clinics of Minnesota devised a system that utilizes the initial labeling when sent from the pharmacy as well as a generic supplemental label placed close to discharge. The supplemental label includes the hospital name and address as well as generic directions to “use as directed” with the prescriber’s name inserted and manufacturer of the product. The patient is then instructed to use the medication as directed on their discharge paperwork.

                   Patient Safety & Quality Healthcare (PSQH) published an article in 2009 in which Spectrum Health in Grand Rapids, Michigan, laid out the criteria for an implementation process for sending patients home with the multi-dose products they used while inpatient. If the agreed upon criteria were met, the patient would be provided with the multi-dose medication (inhaler, ophthalmic product, topical preparation or insulin product) upon discharge.  The product had to be labeled according to federal labeling requirements. Hospital information would be printed on the label prior to dispensing for inpatient use, followed by a second label that would be applied to the clear bag containing the inhaler. Finally, the patient was offered counseling if they desired for the particular discharge medication.

    The Big Picture

    We want to provide the best care for our patients while also supporting our own health-systems. This initiative, while seemingly simple, can balance the labeling and counseling services that are required by reducing hospital waste. At the end of the day, a send-home program will improve the care of Missouri patients. There is no better reward than that. Do you provide this service at your hospital? If so, share your ideas with us at mshp@qabs.com
  • 03 Aug 2021 10:22 AM | Anonymous

    By: Sarah Cook, Pharm.D., BCPS; SSM Health St. Joseph’s Hospital – St. Charles

    Although the 2020-2021 year brought many new challenges to MSHP due to the COVID-19 pandemic, the Board of Directors and committees still accomplished a lot!  Read below to hear about all of the accomplishments from the last year.

    Board of Directors and Strategic Plan
    The Board of Directors got several things accomplished this year.  We finalized restructuring our communications by electing our first secretary-elect.  We began working to increase technician involvement in our organization by reinstituting and electing a technician liaison.  We embraced the virtual environment the pandemic created and updated our strategic plan, hosted a midyear reception, held Spring Meeting, and completed a 2 year internal audit – all virtually.  We also increased our advocacy by signing on to numerous initiatives with ASHP.  We ended our year together by fully reviewing and updating the policy and procedures manual.

    Despite approving the Strategic Plan in December 2020, MSHP accomplished many items on the Strategic Plan this year! This is directly attributed to the hard work of our committee chairs and members. The Strategic Plan has three priority areas:

    1. Improving patient care through education and practice advancement
    2. Membership growth and enhancement
    3. Organization and performance

    The Public Policy Committee formed several task forces to advocate for pharmacist provider status in Missouri. A total of 17 MSHP members attended the MSHP Webinar during the 2021 Virtual Legislative Day. The Education and Newsletter Committees implemented a peer review process for Featured Clinical Topics published in the MSHP Newsletter. The Education Committee and New Practitioner Workgroup produced a number of educational webinars for pharmacists and technicians. The Membership Committee established a database to identify gaps in membership and invite new/lapsed members to join MSHP. The Newsletter and Website/Social Media Committees developed a public relations policy to ensure consistent processes and messaging is communicated through media outlets.

    Education/Programming
    The Education and Programming Committees have continued to provide high-quality content for the MSHP membership through hosting webinars for pharmacists and technicians and a successful spring meeting earlier this year. So far, the Education committee has hosted two webinars and is currently working to host a third in August. The committee also partnered with the Newsletter committee to provide peer review for featured clinical articles as of January 2021, which has provided additional support for authors and increased quality of articles for MSHP members. The Programming committee collaborated with ICHP this year to host another successful virtual spring meeting that provided pharmacists and technicians a place to gather, network, and earn CE hours. Looking to the year ahead, the programming committee is excited to partner with KCHP to host the Spring 2022 (in person!) meeting.

    Membership
    The Membership Committee has continued to partner with administrative services to assist in the recruitment of new MSHP members and the retention of current members throughout this past year.  In order to maintain a current membership list for MSHP, the Membership Committee collaborated with affiliate chapter liaisons across the state of Missouri. Recruitment efforts have been a focus this year, with outreach to potential members for active, associate, retired, recent graduates, technician and student categories. Once recruited, each new member was sent a personalized welcome message from the committee. The Membership Committee assisted in the creation, distribution, and the analysis of results of the annual membership survey in Fall 2020. The committee has been working throughout the year on building a database to establish contacts in Missouri hospital pharmacy departments for the purpose of on-site promotion of membership activities. The committee has also been engaged in the evaluation of the diversity of MSHP’s membership, the discussion of avenues to generate revenue for MSHP, and the development of listservs for specialty practice areas to increase opportunities for collaboration. The Membership Committee was excited to experience growth with the addition of 5 new members over the past year and looks forward to strengthening further relations with its membership in the future! 

    Newsletter
    The Newsletter Committee has continued to provide high-quality content for the MSHP membership through collaboration with students, residents, and pharmacists throughout Missouri.  Throughout the issues this year, there were 22 featured clinical articles and 10 pharmacist continuing education articles, as well as various articles regarding public policy, MSHP updates, and other topics.  The committee partnered with the Education Committee to start providing peer review for featured clinical articles in January 2021, which has been successful thus far and well received by authors.  The committee has also been engaged in conversations regarding public relations, and looks forward to further streamlining requests for content included in the newsletter in the following year!

    Public Policy
    2020-2021 was an extremely busy year for the Public Policy Committee, as we saw the culmination of many years of effort.  Missouri is no longer the only state in the nation without a PDMP!  Hospital based Tech Check Tech was approved by the Board of Pharmacy and rules are being written by DHSS.  The Legislative Day was a resounding success, adding to various other advocacy efforts and presentations from throughout the year.  In addition to all of the ‘normal’ work, the committee served the role of disseminating information during the pandemic…everything from regulatory waivers and PPE guidance to staffing discussions and COVID vaccination strategies.  As always, the exceptional, engaged members of the committee proved the value of MSHP again and again. 

    Website/Social Media
    This year, the committee focused on website improvements and increasing social media presence. Significant updates to the website were completed and include a policy section, past presidents’ section, and updated CE program information. Website updates are ongoing and members may see more significant changes over the summer months! The committee also provided extensive social media posts as MSHP celebrated its 50th anniversary, highlighting MSHP’s “50 Favorite Things” and creating a video looking back on the history of the organization. The committee ended the term year with 165 Facebook posts related to member successes, health topics, policy updates, and MSHP events.  This years’ social media efforts increased MSHP’s Facebook member engagement by 67%, and our newly-established Twitter and Instagram accounts have over 100 followers on each platform! Come join us today on Facebook (Missouri Society of Health System Pharmacists), Instagram (missouripharmacists) and Twitter (@Mopharmacists) as we continue to explore new, innovative ways to engage and inform our members.

    MSHP would like to thank all of the board members and committee chairs from 2020-2021 for all of their excellent work, and we look forward to everything MSHP will accomplish in the coming year!  If you would like to get more involved in MSHP through joining a committee, go to http://moshp.com/Committees.


  • 01 Jun 2021 2:21 PM | Anonymous

    By: Sarah Cook, PharmD, BCPS; Clinical Pharmacy Specialist, SSM Health St. Joseph Hospital – St. Charles

    Opioid Use Disorder (OUD) is defined as “a problematic pattern of opioid use leading to problems and distress” according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition.1 Per the American Medical Association, approximately 3-19% of people who take an opioid pain medication will develop OUD, and 45% of those who use heroin first started abusing prescription opioids. Dependence to opioids can develop in as little as 4-8 weeks, and in patients who use opioids chronically, the absence of opioids can lead to withdrawal symptoms (generalized pain, nausea/vomiting, diarrhea, dilated pupils, restlessness, anxiety, insomnia, chills, cravings) which promotes further opioid use to avoid such discomfort.2 Due in part to the significance of withdrawal symptoms, many patients with OUD are unable to effectively cease using opioids without additional assistance. Medication-assisted treatment (MAT) for OUD is a strategy that can increase the likelihood of individuals abstaining from inappropriate opioid use, which can translate into reduced mortality, decreased rates of blood borne illnesses, and other clinical benefits.3

    Since 1999, overdose deaths due to opioids in the United States have increased by approximately 6 times, with over 47,000 deaths due to opioid overdoses occurring in 2018.4 It is estimated that approximately 10.3 million people misused prescription opioids and 2 million people had an OUD in 2018.5 In response to this alarming trend, the U.S. Department of Health and Human Services declared the opioid crisis a public health emergency in 2017 and outlined 5 priorities, two of which were to “improve access to prevention, treatment, and recovery support services” and to “target the availability and distribution of overdose-reversing drugs.”6 One area that has been a focus of these efforts has been emergency departments, as they are often the location where people engage with the medical system following an overdose or when in opioid withdrawal. Although harm-reduction strategies such as distribution of naloxone, an opioid reversal agent, have become more common in emergency departments, initiation of MAT for OUD is far less common and has faced significant barriers and resistance to implementation.7

    Medications for OUD

    Medications that are FDA-approved for the treatment of OUD include methadone, naltrexone, and buprenorphine. Naltrexone is a competitive antagonist of the mu opioid receptor, which is the primary receptor responsible for the pain relieving, euphoric, and respiratory depression effects of opioids. By blocking this receptor, naltrexone prevents patients from experiencing the effects of opioids when they are used (unless they are used in especially high quantities), which may discourage use over time; it may also somewhat decrease cravings for opioids, although the exact mechanism for this is unknown. Naltrexone does not have restrictions on what providers are able to prescribe it, but patients must abstain from opioids for 7-10 day prior to initiating naltrexone therapy to avoid precipitating significant opioid withdrawal symptoms, which makes this medication generally inappropriate for initiation in the emergency department. Methadone, on the other hand, is a long-acting full agonist of the mu opioid receptor with a moderate binding affinity. It effectively reduces cravings, prevents withdrawal symptoms, and does not cause euphoric effects in patients tolerant to it. Unfortunately, however, methadone is quite dangerous if used to overdose, and due to a propensity for inappropriate use, it is only able to be dispensed for OUD in specially designated clinics in the United States. Since it only has moderate binding affinity, it does not effectively block the binding of more potent opioids, such as fentanyl. Due to some of the downfalls of naltrexone and methadone, buprenorphine is the ideal medication to use to initiate MAT for OUD in emergency departments.8

    Buprenorphine differs from other prescription and non-prescription opioids as it is a partial agonist of the mu opioid receptor rather than a full agonist. As a partial agonist, buprenorphine does have pain-relieving effects, but unlike other opioids, it has a ceiling effect in relation to respiratory depression and euphoria which makes buprenorphine much safer to use. In addition, buprenorphine has much higher affinity for the mu opioid receptor than most other opioids, making it significantly more difficult to overdose with other opioids if buprenorphine is in a person’s system as it will be unable to be displaced from the receptor; however, this high affinity also causes buprenorphine to displace other opioids currently in a person’s system from the receptor which can at times precipitate withdrawal symptoms. Buprenorphine is indicated for use in both acute and chronic pain as well as OUD, and it comes in a variety of formulations, including oral and sublingual tablets, sublingual films, transdermal patches, long-acting injections, and subcutaneous implants. Some of these formulations also contain naloxone, the opioid reversal agent, which is only activated if the medication is not taken via the intended route – this is included to deter patients from abusing buprenorphine.9 In order to prescribe buprenorphine for OUD, providers have to obtain a Drug Addiction Treatment Act 2000 waiver (also known as an X-waiver) – although this is not nearly as restrictive as prescribing methadone, it historically required 8 hours of training for physicians (or 24 hours of training for mid-level providers) and currently restricts providers to having 30 active prescriptions for buprenorphine at a time during the first year, with increased capacity in subsequent years. However, a rule by the DEA also allows buprenorphine to be administered in an emergency department for up to three consecutive days by providers who do not have an X-waiver.10 (Recent changes to X-waiver requirements will be discussed later in this article.)

    Buprenorphine in the Emergency Department

    Although evidence existed for using buprenorphine maintenance therapy for OUD that showed benefits including decreased cravings, reduced all-cause mortality, decreased overdose mortality, improved quality-of-life, and reduced incidence of blood borne illnesses such as HIV and hepatitis C,11 evidence for its use in the emergency department setting did not start accumulating significantly until the past decade. One clinical trial showed that buprenorphine could be safely used in the emergency department for opioid withdrawal and resulted in a fewer emergency department visits when compared to symptomatic treatment alone.12 The ground-breaking study that drew significant attention to buprenorphine’s use in the emergency medicine setting was published by D’Onofrio and colleagues at Yale in 2015. In this study, patients with opioid dependence who reported non-medical use of prescription opioids or heroin use in the last 30 days were randomized into three treatment groups. The first group (“referral group”), which contained 104 patients, received a screening and referral to treatment using a handout containing information on addiction treatment providers arranged according to insurance coverage. The second group (“brief intervention group”), containing 111 patients, received a screening, a 10-15 minute manual-driven brief negotiation interview (BNI), and a coordinated referral including review of insurance eligibility and transportation assistance. The third group (“buprenorphine group”) contained 114 patients who received a screening, a BNI, treatment with buprenorphine if they exhibited moderate-to-severe opioid withdrawal, and a referral to the hospital’s primary care center with an appointment made within 72 hours. A sufficient supply of buprenorphine was prescribed to patients to continue their treatment until follow up. The primary outcome of this study was engagement in addiction treatment at 30 days, with 37% of patients in the referral group, 45% of patients in the brief intervention group, and 78% of patients in the buprenorphine group being engaged in treatment for OUD at 30 days, which was statistically significant. The buprenorphine group also showed a statistically significant reduction in the mean number of days of illicit opioid use per week. The results of this study, with almost double the amount of patients receiving buprenorphine maintained in treatment at 30 days, highlighted the potential for emergency-department initiated buprenorphine to play a key role in improving outcomes for patients struggling with OUD.13

    Since the study by D’Onofrio and colleagues was published, a number of protocols for emergency-department initiated buprenorphine for OUD have been developed and shared. The Yale protocol, which is based off of the treatment strategy for the buprenorphine group in the study led by D’Onofrio, can be seen in Figure 1.14 The CA Bridge initiative which was inspired by the work being done at Yale15 has an extensive library of resources and protocols. This initiative has expanded upon the Yale protocol by expanding the treatment options for patients to include higher total doses of buprenorphine to be given in the emergency department, which has the potential to allow for a longer period of relief from opioid withdrawal symptoms and cravings when an X-waivered provider is not available to write a prescription to bridge patients to their outpatient follow-up appointment. See the Figure 2 for more details.16 Both protocols, as well as others that have been developed, involve screening for inappropriate opioid use as well as an assessment for opioid withdrawal, such as the Clinical Opioid Withdrawal Scale (COWS). If an individual does not yet have notable withdrawal symptoms, buprenorphine should not be administered at that time as it may cause precipitation of worse withdrawal symptoms by displacing other opioids that are bound to the mu opioid receptor. Additionally, naloxone distribution is included as a part of these protocols as a harm-reduction strategy in the event that an individual would continue to use illicit opioids after emergency department discharge. Finally, these protocols are primarily intended to be used by X-waivered providers who will be able to prescribe buprenorphine to be used as an outpatient to bridge patients until their follow-up appointment, but they are written in such a way that they could also be used by non-X-waivered providers in certain situations.14,16 By improving engagement in treatment and therefore increasing the likelihood of long-term abstinence from illicit opioid use, MAT with buprenorphine for OUD being initiated in emergency departments is a key strategy to combating the opioid crisis.

    Figure 1 - Yale Protocol for Buprenorphine Initiation in the Emergency Department14

    (Reprinted from https://medicine.yale.edu/edbup/treatment/.)

    Figure 2 - CA Bridge Buprenorphine Hospital Quick-Start Algorithm16

    (Reprinted from https://cabridge.org/tools/resources/.)

    Addressing Challenges to Buprenorphine Use for OUD

    Despite growing evidence on the benefits of initiating buprenorphine in the emergency department and development of evidence-based protocols that can be translated to a variety of different situations, there remains significant resistance to implementation. A large amount of resistance comes from stigma that is held by healthcare providers, the public, and patients themselves.7 Despite evidence to the contrary, some clinicians still do not see addiction as a medical disease but rather as a moral failing of the individual. Additionally, even those who do understand addiction to be a medical disease may view buprenorphine use as simply replacing one addiction for another. However, when used as directed for the indication of opioid use disorder, buprenorphine is being used as a medication with evidence to support its benefits and not as a substance of abuse.11 Also, as previously described, buprenorphine is generally safer than other opioids as it is a partial agonist with ceiling effects on respiratory depression and as it can block the binding of other opioids which may decrease risk of overdose if illicit opioids are used.10 Other concerns with implementing a program in the emergency department stem from clinicians’ lack of formalized training and knowledge regarding the diagnosis and treatment of OUD, false perceptions that starting MAT for OUD is outside the scope of practice for emergency medicine providers, and actual or perceived lack of resources to effectively implement a program.17 As MAT for OUD is most effective when used as maintenance therapy, prompt connection to treatment post-discharge is especially of concern.8 Fortunately, health system resources, grant funding, and government resources can help address some of these concerns.

    A variety of strategies can be undertaken by health systems to assist with the implementation of buprenorphine programs in emergency departments. Key to any of these strategies, effective programs will have the support of hospital leadership to allocate both educational and administrative resources to the program.17 By increasing clinician’s understating of the science behind addiction and of the diagnosis and treatment of OUD through educational initiatives and advocacy, stigma may slowly be changed to compassion and motivation for some providers, leading to a culture change in the organization.3,7 A variety of educational resources are openly available online, including from Yale, CA Bridge, Project SHOUT: Supporting Hospital Opioid Use Treatment and others, but development of organization-specific materials regarding community treatment resources is also imperative to success.10 Additionally, clinicians who complete X-waiver training have been shown to be more comfortable in providing treatment with buprenorphine,17 so incentivizing providers to obtain this training and obtain an X-waiver can be an effective strategy to help increase participation and bolster the effectiveness of a buprenorphine program by expanding treatment options.18 Having local clinical experts provide guidance and share their expertise can also increase comfort levels with prescribing buprenorphine in the emergency department and can help drive changes in practice. Development of evidence-based, organization-specific protocols and order sets with clinical decision support also increase provider readiness and comfort in initiating buprenorphine.17 Finally, although access to continued treatment for opioid use disorder is of concern and often is reliant on many factors outside an individual health care organization, taking a multidisciplinary approach in implementing buprenorphine in the emergency department, including recovery coaches if possible, may help improve the likelihood of effectively connecting patients to continued treatment.8,18 As implementation of many of these strategies relies on buy-in and support from hospital leadership, presenting evidence on the research-based financial implications of potential cost savings may be beneficial in garnering support; studies show that multiple programs have been initiated with a cost of only approximately $100 per patient and that emergency department programs for treatment of OUD may save from $2000 to $6000 per patient year for patients covered by Medicaid.10 Funds obtained through both government and non-government grants can also alleviate the initial financial burden of program development and implementation for a health care organization.

    Regulatory Issues and the Future of the X-waiver

    Government resources and regulatory changes are also imperative to expansion of MAT programs for OUD in emergency departments. Since the opioid crisis was declared a public health emergency, a large amount of federal grant funding has been made available to states and health organizations to improve access to OUD treatment and services.6 Additionally, it has been shown that Medicaid expansion resulting from the Affordable Care Act of 2008 increased access to care and treatment utilization for OUD,7 with better access to MAT and a 6% decrease in the rate of opioid overdose deaths in expansion states compared to non-expansion states.19,20

    The federal government is currently considering changing the regulatory requirement for providers to have an X-waiver to prescribe buprenorphine. In the meantime, as of April 2021, federal guidelines have been updated to remove the educational requirements for practitioners to obtain an X-waiver if they only desire to treat up to 30 patients at a time. Practitioners still must have a valid DEA registration to prescribe buprenorphine and need to file a Notice of Intent to obtain an X-waiver, but the barrier of completing training has been removed if clinicians do not intend to treat large numbers of patients.21 Further information regarding these changes and answers to frequently asked questions in regards to the new federal guidelines are available on the Substance Abuse and Mental Health Services Administration website.22

    In the future, government agencies will need to continue to consider the implications and efficacy of requiring an X-waiver for prescription of buprenorphine for OUD. Replacing the X-waiver with broad requirements for the inclusion of education regarding diagnosis and treatment for substance use disorders in medical training programs and continuing education requirements for licensure to further improve access to MAT for OUD may be more effective in providing safe, widely-available OUD treatment.7,23 In France, where restrictions on buprenorphine prescribing were removed in 1995, increased use of buprenorphine for treatment of OUD was seen and opioid overdose deaths decreased by 79% within 3 years, which supports the concept of decreased government regulation of buprenorphine.24 Additionally, states and insurance payers that require coverage of buprenorphine to be contingent on concomitant counseling therapy should consider removing this requirement, as it limits access to care and the benefits of buprenorphine can be seen even in the absence of counseling; these restrictions especially impact rural areas where counseling services are less common.7,8

    Conclusion

    It is as important as ever for health systems and government agencies to dedicate resources to effectively implement buprenorphine programs in emergency departments, thereby improving outcomes for individuals struggling with OUD by increasing engagement in treatment. The emergency department is an ideal location to focus resources on as it is a common place for patients to present to following opioid overdose or in opioid withdrawal, and buprenorphine has been shown to be a safe and effective treatment option in this setting as well as for maintenance treatment of OUD. Although there are many barriers to implementation of buprenorphine programs in emergency departments, there are multiple evidence-based strategies to overcoming these barriers, and easing of training requirements to obtain an X-waiver will hopefully ease some of these barriers as well. Especially considering that provisional data from the CDC indicates that overdose deaths increased by over 25% from the previous year as of August 2020,21 there is an urgent need to expand this evidence-based treatment with buprenorphine in emergency departments nationwide.

    References

    1. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5 (5th ed.). American Psychiatric Publishing.
    2. American Psychiatric Association. (2018, November). Opioid Use Disorder. American Psychiatric Association (APA). https://www.psychiatry.org/patients-families/addiction/opioid-use-disorder/opioid-use-disorder#:~:text=The%20Diagnostic%20and%20Statistical%20Manual,a%20longer%20period%20than%20intended.
    3. Strugar-Fritsch, D. (2019, August). MAT for Opioid Use Disorder: Overcoming Objections. California Health Care Foundation. https://www.chcf.org/wp-content/uploads/2019/06/MATOpioidOvercomingObjections.pdf
    4. Centers for Disease Control and Prevention. (2020, March 19). Data Overview | Drug Overdose | CDC Injury Center. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/drugoverdose/data/index.html
    5. Assistant Secretary of Public Affairs (ASPA). (2019, September 4). About the Epidemic. HHS.Gov. https://www.hhs.gov/opioids/about-the-epidemic/index.html
    6. U.S. Department of Health and Human Services. (2018, May 23). HHS Acting Secretary Declares Public Health Emergency to Address. HHS.Gov. https://www.hhs.gov/about/news/2017/10/26/hhs-acting-secretary-declares-public-health-emergency-address-national-opioid-crisis.html
    7. Madras, B. K., Ahmad, N. J., Wen, J., Sharfstein, J., & Prevention, Treatment, and Recovery Working Group of the Action Collaborative on Countering the U.S. Opioid Epidemic. (2020). Improving Access to Evidence-Based Medical Treatment for Opioid Use Disorder: Strategies to Address Key Barriers Within the Treatment System. NAM Perspectives, 1–37.
    8. Strayer, R. J., Hawk, K., Hayes, B. D., Herring, A. A., Ketcham, E., LaPietra, A. M., Lynch, J. J., Motov, S., Repanshek, Z., Weiner, S. G., & Nelson, L. S. (2020). Management of Opioid Use Disorder in the Emergency Department: A White Paper Prepared for the American Academy of Emergency Medicine. The Journal of Emergency Medicine, 58(3), 522–546.
    9. Ling, W. (2012). Buprenorphine for opioid addiction. Pain Management, 2(4), 345–350.
    10. Cisewski, D. H., Santos, C., Koyfman, A., & Long, B. (2019). Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting. The American Journal of Emergency Medicine, 37(1), 143–150.
    11. Velander, J. R. (2018). Suboxone: Rationale, Science, Misconceptions. The Oschner Journal, 18(1), 23–29.
    12. Berg, M. L., Idrees, U., Ding, R., Nesbit, S. A., Liang, H. K., & McCarthy, M. L. (2007). Evaluation of the use of buprenorphine for opioid withdrawal in an emergency department. Drug and Alcohol Dependence, 86(2–3), 239–244.
    13. D’Onofrio, G., O’Connor, P. G., Pantalon, M. V., Chawarski, M. C., Busch, S. H., Owens, P. H., Bernstein, S. L., & Fiellin, D. A. (2015). Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence. JAMA, 313(16), 1636.
    14. Yale School of Medicine. (2018, September 24). ED-Initiated Buprenorphine. https://medicine.yale.edu/edbup/treatment/
    15. Goodnough, A. (2018, August 20). This E.R. Treats Opioid Addiction on Demand. That’s Very Rare. New York Times. https://www.nytimes.com/2018/08/18/health/opioid-addiction-treatment.html
    16. CA Bridge. (2021, May). Resources to Treat Substance Use Disorders. https://cabridge.org/tools/resources/
    17. Hawk, K. F., D’Onofrio, G., Chawarski, M. C., O’Connor, P. G., Cowan, E., Lyons, M. S., Richardson, L., Rothman, R. E., Whiteside, L. K., Owens, P. H., Martel, S. H., Coupet, E., Pantalon, M., Curry, L., Fiellin, D. A., & Edelman, E. J. (2020). Barriers and Facilitators to Clinician Readiness to Provide Emergency Department–Initiated Buprenorphine. JAMA Network Open, 3(5), e204561.
    18. Lowenstein, M. (2019, March 13). Starting Opioid Use Disorder Treatment in the Emergency Department. Leonard Davis Institute of Health Economics at the University of Pennsylvania. https://ldi.upenn.edu/healthpolicysense/starting-opioid-use-disorder-treatment-emergency-department
    19. Kravitz-Wirtz, N., Davis, C. S., Ponicki, W. R., Rivera-Aguirre, A., Marshall, B. D. L., Martins, S. S., & Cerdá, M. (2020). Association of Medicaid Expansion With Opioid Overdose Mortality in the United States. JAMA Network Open, 3(1), e1919066.
    20. Sharp, A., Jones, A., Sherwood, J., Kutsa, O., Honermann, B., & Millett, G. (2018). Impact of Medicaid Expansion on Access to Opioid Analgesic Medications and Medication-Assisted Treatment. American Journal of Public Health, 108(5), 642–648.
    21. Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder. Federal Register. (2021, April 28). https://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-buprenorphine-for-treating-opioid-use-disorder.
    22. Become a Buprenorphine Waivered Practitioner. SAMHSA. (2021, May 5). https://www.samhsa.gov/medication-assisted-treatment/become-buprenorphine-waivered-practitioner.
    23. Fiscella, K., Wakeman, S. E., & Beletsky, L. (2019). Buprenorphine Deregulation and Mainstreaming Treatment for Opioid Use Disorder. JAMA Psychiatry, 76(3), 229.
    24. Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède, J.-P., & Tignol, J. (2004). French Field Experience with Buprenorphine. American Journal on Addictions, 13(s1), S17–S28.


  • 18 May 2021 1:56 PM | Anonymous

    By: James Unverferth, PharmD, BCPS; Pharmacist Clinical Specialist

    SSM Health St. Mary’s Hospital – St. Louis

    Background

    Feedback and how to effectively provide feedback is a topic becoming ever more relevant as the years go on mostly due to the “millennial” generation filling the roles of students and residents. Supporting the portrayal of millennials on TV and social media, studies have shown that millennials desire frequent coaching and feedback.3

    Feedback is important because it helps learners to identify areas of weakness in which they can build on foundational skills and knowledge. If done correctly feedback should help students to establish goals and evaluate performance so that over time they become sufficient enough to rely only on themselves for evaluation and motivation. Additionally, preceptor feedback is a topic that is frequently cited on accreditation surveys for residency programs. Accreditation standards specify that this feedback needs to be specific and criteria-based. To lend guidance on how preceptors can help learners achieve this goal, ASHP has developed a 3 part competency-based approach (Figure 1) to evaluate resident performance of a program’s educational goals and objectives, resident self-assessment of their performance, and of the program itself.1 This approach, while effective, is mostly tailored towards residency programs and may not be completely applicable to all learning situations, so I have developed a 6-part approach to establish a process of providing quality feedback to any learner. I hope this process helps you realize the importance of providing constructive feedback and its relationship to growth of a learner.


    Six-part Approach for Providing Effective Feedback

    Part 1: Establishing Expectations

    The first step in my 6-part approach is to establish expectations. This stage of the process of providing quality feedback can begin even before a learner starts on rotation. Knowing past experiences of learners and what stage they are in in their studies or career can help shape expectations for the preceptor. For example — expectations for a rotation are going to be different for a resident on their last rotation compared to an APPE student on their first rotation, compared to an IPPE student on their first ever experiential rotation. Regardless, it is important to involve the learner in the process of establishing expectations. Before a learner starts a rotation have them develop SMART goals for the rotation.


    Having students develop SMART goals will help preceptors when it comes time to evaluate the learner’s performance throughout the rotation AND it is a good exercise to refresh learner’s memory on how to set proper goals to achieve therapeutic outcomes for patients.2 A SMART goal is specific, measurable, achievable, realistic, and timely. In addition to having learner’s create their own goals, studies have shown that physically writing out goals improves the likelihood of achieving those goals.2 Once you have the learners create goals, it is important to meet with them to discuss and hold them accountable for creating quality SMART goals. Once these are documented, criteria needed to meet these goals can be established between the preceptor and the learner so that expectations are clear for both parties at the beginning of the rotation.

    Part 2: Creating Learning Opportunities and Part 3: Observing Learning Experiences

    Parts 2 and 3 of the six-part approach go hand-in-hand. Creating and observing learning opportunities is important because well-developed and well-defined learning activities provide preceptors with the means for directly measuring performance and progress toward fulfilling the learner’s goals. Additionally, this is where learners can apply feedback received by the preceptor after previous experiences. If a student is struggling to grasp a concept or has difficulty applying feedback, this is the opportunity that preceptors can practice the four roles of preceptor to enhance learning; by instructing, modeling, coaching, and facilitating.1


    Part 4: Providing and Documenting Formative Feedback

    During or directly after a learning opportunity it is important to take the time to provide feedback to students. It has been shown that as more time-elapses between learning experience and feedback, the value of the feedback drops, so it is best to provide frequent feedback sessions, even if the sessions are short. On top of feedback immediately after a learning experience, a common practice utilized by preceptors and often appreciated by learners is to schedule a time at least once a week to discuss progress and what things are working or not working. During and after observation and feedback sessions it is beneficial for the preceptor to write down notes on feedback provided to the learner so that it can be followed-up on or relayed to the learner at a later time. This is important because it may help you be more specific and evidence-based, providing more weight to your recommendations to the learner. Additionally, it has been shown that time is one of the major barriers of providing effective feedback to learners so by taking notes in the moment this can help save time on the back end when reflecting on learner’s performance.4

    As mentioned earlier, the goal of feedback is to help learners identify areas of weakness in which they can build on foundational skills and knowledge. It is not meant to degrade, belittle, or embarrass a learner. With this in mind, feedback should be goal-related and actionable. It should be diverse, which means that it should not only be correctional, but should also be affirmative, observational, or even just clarifications. Lastly feedback should focus on the process and not the person. For example – “James you are a quiet person, speak louder next time” instead you can say “It can be hard to hear over skype phone calls, you may want to speak loud and into the microphone next time”. These are just some of the many principles behind providing quality feedback. A quick Google search of “how to provide quality feedback” will result in over a billion hits with links to articles on qualities of effective feedback, but the qualities discussed here are those that appeared most often and found to be worth sharing.

    Now that some of the qualities of effective feedback have been defined, it is time to discuss appropriate methods for delivering feedback to the learner. The first method is called the sandwich method or can also be referred to as pro/con/pro method. This method starts with the preceptor stating something the student did well, then something the student can improve on, and finishing with another thing the student did well. This method leaves the student feeling encouraged instead of down in the dumps. Each comment, both positive and negative, should meet criteria for feedback discussed on the previous paragraph in order to be a “good sandwich”. Some “sandwiches” to avoid include; a “plain sandwich” that offers feedback but lacks any areas for improvement, a “finger sandwich” that offers feedback that is not very informative and is light on comments overall, an “open-faced sandwich” that starts off with just negative comments, and finally a “low-carb sandwich” that does not identify any strengths at all.6

    The next method is the SII method or Strengths, Improvements, Insights method. This method is good to use informally or if no specific criteria are available. As the name implies it involves highlighting strengths of the learner observed during the experience, ways in which performance can improve, and finally insight which involves reviewing relevant new discoveries/understandings that occurred during the experience. It can be sometimes hard to provide insights, so here it may be best to come up with some teaching points that student can use moving forward.6

    The last method to discuss is the Pendleton Method. Anecdotally, this is the most common method used among preceptors as it encourages the student to self-reflect about each learning experience and evaluate their own performance before hearing from the preceptor. Here it is important to facilitate a discussion while remaining positive, making sure to focus again on the process and not the person. In the end the preceptor and learner should agree on an action plan to move forward with.6

    Table 1: Feedback Methods6

    Sandwich Method The assessor provides positive comments first, followed by areas in need of improvement, and ends with another positive statement
    SII Method • Strengths

    o Highlight the positives in the performance

    • Improvements

    o Focus on ways in which the performance could improve

    • Insights

    o Identify new and significant discoveries/understandings that were gained concerning the performance area

    Pendleton Method

    • Student states what was good

    • Evaluator states area of agreement and elaborates on good performance

    • Student states what was poor and could have been improved

    • Teacher states what could have been improved

    • Action plan is agreed upon

    After this formative feedback is provided, the expectation for the learner to apply it to future encounters. Again, if learners struggle to implement feedback this is where preceptors can implement the four roles described earlier to demonstrate ways in which the learner can improve. By repeating this process over and over throughout a rotation, the hope is that the learner’s performance will continuously grow so that they can reach the goals they set at the beginning of the rotation.

    Part 5: Learner Self-Evaluation

    At the end of the rotation when hopefully all the SMART goals set and, the learners should perform a self-evaluation. Here the learner should be encouraged to really spend the time reflecting on their performance to come up with things they have done well and things on which they can improve.

    Part 6: Summative Evaluation with Preceptor

    The summative evaluation should strengthen the message from the formative feedback sessions you have been providing throughout the rotation. Hopefully if you have been meeting with the student regularly to provide feedback after learning experience as was suggested earlier, this should be easy to come up with specific, evidence-based feedback. Several things to keep in mind while wrapping up rotation with the learner: go in with the right intentions. No matter how poorly the learner performed, this should not be a time to condemn/demoralize the student. It should also not be a time to make yourself seem powerful or superior. The purpose of the evaluation is to guide, support, and enhance the learner’s ability to become a successful pharmacist as well as self-evaluator and motivator. Additionally, a final evaluation should not be the first time a learner is hearing constructive feedback. It can be discouraging and unhelpful for a learner to hear that their performance was not up to par without ever getting the chance to remedy or improve. To that point, not every student on their final evaluation should be given an “A”. This can make it difficult to distinguish genuine superior performance and overall good work. So, don’t be afraid to be negative with your feedback as long as it is not the learner’s first time hearing the constructive feedback and it is delivered in a way with the learner’s best interest in mind.

    To wrap up the six-part approach, here are some more tips that can be utilized to enhance both formative feedback and summative evaluation. Many of the things have been touched on before, but a few things not previously mentioned that should be kept in mind: environment – it is best to provide feedback in-person so that a discussion can be had between learner and preceptor. Ideally this should be private, especially if doing a summative evaluation. If on-the-fly feedback is necessary, make sure not to call out the learner but instead wait for a time to take the learner aside and provide instruction on how their performance can improve the next time. Another good tip: always focus on the future. Lastly, feedback is always better if it is individualized. It may be helpful to have a student send you strengths/weaknesses prior to rotation starting.5 This way you can relate feedback to those characteristics.

    References

    1. Buck B, Wilkinson S, Phillips H. Preceptor Development: Providing Effective Feedback, Part 2. Hosp Pharm. 2014; 49 (6): 521-529.
    2. Lawlor KB, Hornyak MJ. SMART Goals: How the Application of SMART Goals can Contributed to Achievement of Student Learning Outcomes. Developments in Business Simulation and Experiential Learning. 2012; 39: 259-267.
    3. Meister J, Willyerd K. Mentoring Millenials. Harvard Business Review, 88(5).
    4. Skrabel MZ, Kaheleh AA, NEmire RE, et al. Preceptors’ Perspectives on benefits of precepting student pharmacists to students, preceptors, and the profession. J Am Pharm Assoc. 2011; 75(1): Article 10.
    5. Wilkinson S, Couldry R, Phillips H, Buck B. Preceptor development: Providing feedback to pharmacy residents: Part 1. Hosp Pharm. 2013;48(1):26–32.
    6. Sarkany D, Deitte L. Providing Feedback: Practical Skills and Strategies. Acad Radiol. 2017l 24 (6): 740-746.
  • 18 May 2021 1:49 PM | Anonymous

    By: Megan Musselman, PharmD, MS, BCPS, BCCCP, MSHP Research & Education Foundation

    At the MSHP/ICHP Spring Meeting, the R&E Foundation presented Kat Lincoln, PharmD, BCPS, BCIDP with the MSHP Best Practice Award for her project entitled “Daptomycin weight-based dose optimization”. Olathe Medical Center implemented a dose optimization intervention that utilized adjusted body weight (AdjBW) for patients ≥ 130% of their ideal body weight (IBW) and actual body weight (ABW) for those < 100% IBW. The primary outcome was to determine if implementation of a weight –based dose optimization intervention was effective for the treatment of severe gram-positive infections infection. Secondary outcomes included adverse effects and costs associated with the new dosing protocol. The goals and specific aims for the program were to determine safety and efficacy of dosing daptomycin using AdjBW, decrease cost associated with this dosing strategy, and to develop criteria for use of daptomycin.

    At the conclusion of the study, the average patient age was 60 years old with an average ABW of 97.25 kg. Of the patients included, 52.5% had a BMI ≥ 30 kg/m2 and 16.6% had a BMI > 40 kg/m2. The infection classification for daptomycin dosing is found in Table 1. In addition, 20% of patients were readmitted within 90 days due to infectious indications. Severity and type of infection attributed to persistence and higher rates of readmission.

    The cost of daptomycin powder for injection is $0.11/mg. Patients with BMI ≥ 30 mg/k2 using AdjBW had a cost savings of $8,000 over 11 months. Patients treated using AdjBW accounted for 53% of orders, but only accounted for 27% of the total cost (Figure 1). The second most common dosing strategy used during the study period was ABW (27.1%) followed by 19.9% of patients being dosed by IBW (Figure 2).

    In conclusion from this research project, patients treated using the dose optimization protocol were adequately dosed for treatment and pathogen eradication with minimal 90 day readmission rates. The following daptomycin dosing protocol maintained effectiveness and safety while reducing costs:

    • ABW < 100% of patient IBW: Daptomycin dosed using ABW

    • ABW ≥ 100-129% of patient IBW: Daptomycin dosed using IBW

    • ABW ≥ 130% of patient IBW: Daptomycin dosed using AdjBW

    If you have any questions about how Dr. Lincoln implemented her project, please email her at Kathryn.burnett@olathehealth.org.



  • 18 May 2021 1:23 PM | Anonymous

    By Nathan Hanson, PharmD, MS, BCPS; Healthtrust Supply Chain

    “The best time to plant a tree is 20 years ago. The second best time to plant a tree is today.”  -Unknown

    The 2021 Missouri Legislative Session has ended.  We could look at that fact and think that we are too late and missed an opportunity.  A more productive mindset is that we are right on time to get started for the 2022 session.  Now is the perfect time to begin learning or continue learning about the various processes that lead to change.  There are many ways to get involved, at the local, state, and Federal level.  This is true for the legislative process, for the regulatory process, and also for the associations in which we participate.  Here are some simple and practical ways that you can increase your ability to get involved for the next year and the next 20 years.

    Local Involvement:

    It is my opinion that you should know your mayor and your city council leaders.  Mark some time on your personal calendar to click around on your local government’s web site to learn who your mayor and City Council members are.  Find out when the meetings are, and consider attending one this year.  This may not have much of an impact on pharmacy, but I have found that the local government often has the biggest impact on our daily lives.  And learning about the government processes at the local level is a good training ground for the next level. 

    State Involvement:

    You should also know your state representative, your state senator, and your governor. The state government won’t be in session until January of 2022, but you can learn about your state representatives and senators right now.  Simply click on this link and type in your home address in the “Find Your Representative” box.  You could also look up the address of your workplace, so that you know the house and senate districts for both locations.  I recommend that you copy and paste this information into the document that you save in a folder marked “Involvement.”  You can use this document to capture information and ideas and keep it all in one place.  Then spend a few minutes clicking on the government web sites of your senator and representative to learn about their background, their committee membership, and the legislation they have sponsored or cosponsored.  If you are feeling very brave, you can spend 5 minutes making a phone call to their office.  In most cases you will speak to a staff member at their front desk or leave a voicemail.  Simply say that you are a hospital pharmacist, and you believe that patients will benefit any time that they are given greater access to the care that pharmacists can provide.  Then offer to be a resource for the senator or representative if they ever have a question about pharmacy related issues.  These small steps will help you to get involved, and they will show our elected officials that pharmacists are interested in the process.

    If you have ideas for ways that the laws need to be changed so that you can take better care of patients, please let us know.  This is the time for brainstorming and information sharing, because bills generally need to be filed by December 1st.  We can be talking with our partners to see what will fit into the priorities for 2022. 

    Federal Involvement:

    You should know your representative and both of your senators, and you can find this information at the same website.  You can reach out to these leaders as well, but they’re certainly a little less available than the state leaders.  The best way to engage with the Federal centers and representatives is through the ASHP website.  Please take 5 minutes today to enroll on this website so that you can be poised and ready to respond when our responses are needed.

    MHSP Involvement:

    As we are kicking off the 2022 preparation, we would love to have your input.  If you aren’t already active on a committee please reach out.  We have a lot of exciting plans and a lot of goals we want to accomplish this year.  In the public policy committee we have formed task forces to accomplish these aims:

    1.    Work toward obtaining pharmacist prescriptive authority
    2.    Identify and disseminate advocacy topics
    3.    Develop MSHP position statements for pertinent legislation
    4.    Provide professional development

    If you are interested in joining, please contact us! 

    ASHP Involvement:

    Each year the ASHP House of Delegates reviews a variety of policy statements.  You can see these policies here, and you can provide your input to the public policy committee or to the delegates directly.  There are also a lot of other ways to get involved out with your section or at ASHP Connect.

    Plant Today!

    Even if you didn’t get involved with legislative day this year, you can easily get involved next year.  If you missed your opportunity to weigh in on PBM restrictions, the PDMP bill, or various bills that allow patients better access to medications, you can rest assured that there will be plenty of opportunities next year.  Like trees, our progress as professionals can best be measured by the decade.  Make this the year where you begin to grow and change and step outside your comfort zone to make an impact for patients and our profession!  You may be surprised how much you can accomplish if you do. 

    Don’t Miss What the Public Policy Committee Has Done!

    http://www.moshp.com/Public-Policy/
  • 18 May 2021 11:50 AM | Anonymous

    By: Amanda Bernarde, PharmD; PGY-1 Pharmacy Resident

    University of Missouri Health Care

    Abbreviations: RSI = rapid sequence intubation; KPA = ketamine propofol admixture; ED= emergency department; SBP= systolic blood pressure; OR= odds ratio; CI= confidence interval; NEAR= National Emergency Airway Registry; TBI= traumatic brain injury; MAP = mean arterial pressure

    Rapid sequence intubation (RSI) is a mainstay in critical care and emergency medicine to secure a patient’s airway.1,2 Endotracheal intubation may be indicated if the patient: 1) cannot protect his/her airway, 2) has a risk of aspiration, 3) fails to adequately ventilate or oxygenate, or 4) has anticipated further or rapid decompensation leading to any of the other indications. To facilitate endotracheal tube placement, RSI requires use of sedatives and paralytics to minimize consciousness and to blunt the pathophysiologic response of airway manipulation, respectively. Ideal sedatives produce deep anesthesia with a rapid onset of 30 seconds or less.3 The paralytic agent should have a similar duration. Midazolam, propofol, ketamine, and etomidate are among some of the most common sedatives used in RSI. Though the goal of sedative medications is to augment easy manipulation of the airway, they are not without their own adverse effects, including peri-intubation hypotension.

    Concerns for peri-intubation hypotension limit sedative options due to the potential increased risk of cardiac arrest, need for vasopressor support, and in-hospital and post-discharge mortality.3-5 Etomidate, the gold standard sedative, displays hemodynamic neutrality when administered at a dose of 0.2-0.3 mg/kg, whereas midazolam and propofol have known risks of hypotension. Etomidate has potential adverse effects of adrenal suppression and lowering the seizure threshold, which makes it a suboptimal choice during RSI induction in patients presenting with sepsis, epilepsy, or traumatic brain injury (TBI) patients. Increased interest in exploring other RSI sedation options, particularly ketamine only and ketamine-propofol admixture (KPA) regimens, have been analyzed for use in these patient populations.

    Mechanistically, ketamine at doses of 0.5-1 mg/kg increase catecholamine release while prohibiting its reuptake in the synaptic cleft.3,6,7 In patients with sufficient circulating catecholamines, this leads to increased blood pressure. In contrast, patients with autonomic dysfunction, such as in sepsis, diabetic ketoacidosis, and myocardial infarction, exhibit decreased myocardial contraction and heart rate.8 Recent literature of ketamine use for sedation during RSI in hemodynamically unstable patients has shown mixed results (Table 1).

    Table 1. Summary of hemodynamic effects of ketamine alone compared to other sedatives.


    Ischimaru et al was the first study to establish ketamine’s potential hemodynamic neutrality during intubation of hemodynamically unstable patients.6 This prospective observational study from Japan found a statistically significant decrease in ketamine-induced hemodynamic derangement, defined as SBP ≤ 90 mmHg or ≥ 20% decrease in SBP, when compared with the combined comparator of either midazolam or propofol administration. Statistical significance held after adjustments for differences in demographics, primary indication (except in trauma patients), premedication use, and paralytic choice between the two study groups. From this analysis, authors concluded ketamine is superior to midazolam or propofol in maintaining stable hemodynamics during intubation. Of note, etomidate was not compared to ketamine in this study because it is not approved for use in Japan. Due to this difference, additional studies comparing ketamine to etomidate were required to potentially change practice in the United States.

    A single large-scale, prospective, multicenter, observational cohort study was conducted by April et al comparing the incidence of peri-intubation hypotension of ketamine to etomidate for any indication.9 Using the NEAR study dataset, ketamine was found to have a statistically significant increase in peri-intubation hypotension incidence in comparison to etomidate. Doses chosen by the practitioner did not impact this outcome. This indicated that ketamine may not provide hemodynamic neutrality as the above study suggested. There were several challenges that limit this study’s generalizability to all populations, including the propensity to choose ketamine over etomidate for sepsis and traumatic brain injury (TBI) patients.

    A subgroup analysis of NEAR study participants examined current use of etomidate compared to other sedatives and intubation-associated hypotension incidence of etomidate and ketamine.10 Etomidate was the most frequently used sedative in sepsis patients despite the concerns for its potential adrenal suppression. However, etomidate administration decreased and ketamine administration increased in sepsis patients when compared to nonsepsis patients. In this patient population, patients receiving ketamine did experience intubation-related hypotension more often than those administered etomidate. The hypotension was not sustained or significant as there was no statistical difference in need of vasopressor therapy or peri-intubation cardiac arrest between the two medications. The TBI patient cohort had similar findings that showed significant intubation-associated hemodynamic instability with ketamine when compared to other sedatives.11 Unfortunately, analysis of emergency department or in-hospital use of ketamine for RSI in TBI patients is limited. Overall, in the setting of sepsis or TBI, ketamine does not provide beneficial hemodynamic outcomes, with mixed translation to need for vasopressors and incidence of peri-intubation cardiac arrest.

    A novel approach to RSI induction was explored by Smischney et al in the KEEP-PACE trial.12 Reduced dose etomidate (0.15 mg/kg) was compared to a ketamine-propofol admixture (KPA; 0.5 mg/kg of each component) for hemodynamic stability. Because of the novelty of this admixture, the purpose was to establish KPA’s superiority over reduced dose etomidate and reanalyze the mixture against the full etomidate dose if superiority was found. The primary endpoint, the change in mean arterial pressure (MAP) from baseline at 5 minutes post-induction, was not statistically significant (KPA vs etomidate: -3.3 mmHg vs -1.1 mmHg; p= 0.385). Additionally, there was no difference at 10 minutes, 15 minutes, or in average MAP area under the curve. Due to the lack of efficacy, KPA has not been compared to full-dose etomidate.

    Despite the initial positive results suggesting ketamine as an alternative to etomidate for hemodynamically unstable patients during RSI, several multicenter, large-scale observational cohort studies have concluded otherwise. At present, etomidate remains the gold standard for induction, particularly in patients who are hemodynamically unstable or have RSI-indications that could quickly decompensate. Nevertheless, the need remains for a hemodynamically neutral induction agent that does not manipulate the adrenal system or lower the seizure threshold, which continues to be the main concerns with universal etomidate use.

    References

    1. Chong ID, Sandefur BJ, Rimmelin DE, et al. Long-acting neuromuscular paralysis without concurrent sedation in emergency care. Am J Emerg Med. 2014;32(5):452-456.
    2. Driver BE, Klein LR, Prekker ME, et al. Drug order in rapid sequence intubation. Acad Emerg Med. 2019;26(9):1014-1021.
    3. Hamilton JP. Rapid-sequence intubation and the role of the emergency department pharmacist. Am J Health Syst Pharm. 2011;68(14):1320-1330.
    4. Strollings JL, Diedrich DA, Oyen LJ, Brown DR. Rapid-sequence intubation: a review of process and considerations when choosing medications. Ann Pharmacother. 2014;48(1):62-76.
    5. April MD, Arana A, Reynolds JC, et al. Peri-intubation cardiac arrest in the emergency department: a National Emergency Airway Registry (NEAR) study. Resuscitation. 2021;S0300-9571(21)00097-6.
    6. Ishimaru T, Goto T, Takahashi J, et al. Association of ketamine use with lower risks of post-intubation hypotension in hemodynamically-unstable patients in the emergency department. Sci Rep. 2019;9(1):17230.
    7. White PF, Way WL, Trevor AJ. Ketamine—its pharmacology and therapeutic uses. Anesthesiology. 1982;56(2):119-136.
    8. Goldberger JJ, Arora R, Buckley U, Shivkumar K. Autonomic nervous system dysfunction: JACC focus seminar. J Am Coll Cardiol. 2019;73(10):1189-1206.
    9. April MD, Arana A, Schauer SG, et al. Ketamine versus etomidate and peri-intubation hypotension: a National Emergency Airway Registry study. Acad Emerg Med. 2020;27(11):1106-1115.
    10. Mohr NM, Pape SG, Runde D, Kaji AH, Walls RM, Brown CA. Etomidate use is associated with less hypotension than ketamine for emergency department sepsis intubations: a NEAR cohort study. Acad Emerg Med. 2020;27(11):1140-1149.
    11. Fouche PF, Meadley B, St Clair T, et al. The association of ketamine induction with blood pressure changes in paramedic rapid sequence intubation of out-of-hospital traumatic brain injury. Acad Emerg Med. 2021. Epub ahead of print.
    12. Smischney NJ, Nicholson WT, Brown DR, et al. Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE randomized clinical trial. J Trauma Acute Care Surg. 2019;87(4):883-891.
  • 18 May 2021 10:10 AM | Anonymous

    By: Andrew Vogler, PharmD; PGY1 Pharmacy Resident

    Mentor: Daniel Hansen, PharmD; Clinical Pharmacy Specialist

    Mercy Hospital Springfield


    Program Number: 2021-05-0

    Approval Dates: June 1, 2021 – December 1, 2021

    Approved Contact Hours: 1 hour 


    Learning Objectives:

    1.    Define a bacteremia based on infectious pathogen and source of infection
    2.    Identify correct indication and duration of oral antibiotics for gram-negative bacteremia
    3.    Discuss the utility of follow-up blood cultures for gram-negative bacteremia

    Take CE Quiz


    Background

    There are approximately 2 million cases and 250,000 deaths annually from sepsis due to bacteremia with approximately 45% due to a gram-negative pathogen in North America and Europe.1 With the prevalence of gram-negative bacteremia so high and no current guideline discussing proper treatment regimens or duration, it is important to have a clear understanding of bacteremia before one can start a proper treatment regimen.2 Bacteremia is defined as bacteria in the blood and can often be asymptomatic or transient becoming a blood stream infection if the immune system becomes overwhelmed. Bacteremia should be differentiated from sepsis or septicemia. The Surviving Sepsis Campaign defines sepsis as, “life-threatening organ dysfunction caused by a dysregulated host response to infection.”3 Septicemia is a narrower term for sepsis that is caused by bacterial spread into the blood stream. Throughout this article the discussion of sepsis will be kept separate from the discussion of bacteremia, as they are not interchangeable terms.

    Bacteremia can vary in source of infection and infectious pathogen. Though bacteremia can occur due to direct inoculation into the blood stream, it typically occurs as the result of an infectious pathogen spreading to the blood from another source. Bacteremia is classified by 3 main criteria: infectious pathogen, the source of infection, and whether the bacteremia is complicated or uncomplicated. The source of infection can either be primary or secondary. A primary bacteremia is caused from direct inoculation of pathogen into the bloodstream. A secondary bacteremia is caused by a pathogen entering the body from a site other than direct inoculation such as bacteremia secondary to pneumonia or urinary tract infection.4

    During the initial Gram-stain phase, pathogen-based classification of bacteremia is typically either Gram-positive or Gram-negative. The most common cause of gram-positive bacteremia is Staphylococcus aureus (S. aureus), which is due to the organism’s ability to produce the enzyme coagulase, which can convert fibrinogen in the blood to fibrin causing the blood to clot.1 The infectious emboli then stick to different areas of the body like blood vessels or heart valves, making a bacteremia very difficult to clear. Other Gram-positive bacteria such as enterococcus and coagulase-negative staphylococcus can form biofilms making them difficult to treat, as well. In comparison to Gram-positive bacteria, Gram-negative bacteria do not produce coagulase and are often easier to treat, with patients often being able to clear infection with oral antibiotics and shorter durations of therapy.

    The severity of bacteremia is classified as either complicated or uncomplicated based on the likelihood of a timely resolution of infection. To be considered an uncomplicated bacteremia, the patient must be afebrile within 72 hours of initial treatment, have a negative repeat blood cultures obtained 2-4 days after initial set, and not have endocarditis or metastatic infection. Complicated bacteremia is often treated for longer durations with IV antibiotics due to severity of illness, high inoculum of infection, lack of treatment response, seeding of infection, or a combination there of. Morpeth and colleagues looked at the rate of endocarditis in 2761 patient cases with species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species (non-HACEK) Gram-negative bacteremia. The study determined the risk of complicated bacteremia due to Gram-negative endocarditis is extremely low at approximately 1.8% with a high percentage of those patients having some sort of implanted endovascular device (29%).6

    The Infectious Disease Society of America (IDSA) for the treatment of Methicillin-Resistant S. aureus (MRSA) bacteremia. They do not address bacteremia due to organisms other than MRSA. The rate of mortality for MRSA bacteremia with endocarditis (upwards of 37%) is higher than that of gram-negative bacteremia (12.5%).7 For MRSA bacteremia, IDSA recommends at least 14 days of IV anti-MRSA antibiotics following negative blood cultures. Historically Gram-negative bacteremia has been treated using IV antibiotics for 7 to 14 days, primarily based on expert opinion. The following discussion of the evidence supporting shorter treatment durations and opportunities for oral antibiotic therapy for uncomplicated Gram-negative bacteremia will better prepare the pharmacists in managing patients and in antibiotic stewardship.

    Prevalence of Infectious Pathogen

    Gram-negative bacteremia is most often secondary to another source of infection. Likely pathogens for secondary bacteremia are variable based on source of infection and location of onset. From the results of three studies, Table 2 depicts the likely pathogens for community, hospital, and ICU acquired Gram-negative bacteremia.8-10 Manzoni and colleagues looked at 2,924 different microorganisms from 16 different hospitals in northern Italy over the course of 2 years for community acquired gram-negative bacteremia.8 The study found that the majority of community acquired Gram-negative bacteremia were caused by cephalosporin susceptible Escherichia coli in this study population. The most likely source for bacteremia with this organism is a urinary-tract infection, although the study did not report sources of infection.8 There is an increase in more drug-resistant organisms when infection onset occurs in the hospital and intensive care unit setting setting.9,10 Shorr and colleagues looked at data from 6,697 patient from 59 different hospitals in the United States with hospital acquired Gram-negative bacteremia defined as a first positive blood cultures drawn >2 days after admission.9 The study found a wider variety of infectious pathogens than was found in the study  of community acquired bacteremia with only 18% of infections due to Escherichia coli and 56% being from various spp. For ICU acquired Gram-negative bacteremia, 2 studies by Sligl and colleagues looked at 18,146 admissions over a 5-year period from 1999 to 2003 and an 8-year period from 2004 to 2012 seeing consistent occurrence rates of infectious pathogen, over the 13 year period.5,10 Swamy and colleagues looked at 406 cases of Gram-negative bacteremia and broke down source of infection by percent, the results can be found in figure 1.17 Swamy and colleagues found the majority of gram-negative bacteremia were due to a urinary source, which remains consistent to the other studies discussed. They found the majority of community acquired Gram-negative bacteremia were due to Escherichia coli. Based on prevalence data presented, the majority (up to 90% in community acquired) of Gram-negative bacteremia is the result of bacteria from the Enterobacterales (formerly Enterobacteriaceae) family such as E. coli, Klebsiella, Enterobacter, and Citrobacter.8

    Intravenous vs Oral Treatment

    Once an infection is suspected, empiric therapy is initiated, and cultures should be obtained. As blood cultures begin to result, one may begin targeting therapy to treat the source of infection. A clinician often does not know they are treating a bacteremia until the blood cultures result. Once a causative pathogen is identified, treatment considerations such as de-escalation to oral therapy can be considered. The transition of a patient’s antibiotic therapy from IV to oral is not only a cost avoidance measure for the hospital system and the patient, provided it is done appropriately. Conversion to oral antibiotics lowers the number IV administrations decreasing a patient’s risk for infection and often allows for earlier discharge. There is evidence to support patients transitioning to highly bioavailable antibiotics after 1 to 5 days of IV therapy for gram-negative bacteremia. Listed in table 3 are common highly bioavailable antibiotics listed from highest to lowest:


    *IV dosing 400mg vs PO dosing 500mg accounts for decreased bioavailability

    Uncomplicated MRSA bacteremia treatment must be IV for a duration of at least 14 days per IDSA guidelines.1 The transition to oral therapy for Gram-negative bacteremia can be considered for the treatment of Enterobacteriaceae. Two different studies found treatment failure for highly bioavailable antibiotics was 2% or less when evaluating uncomplicated Enterobacterales bacteremia of urinary source.12,13 One of the studies by Kutob and colleagues looked at the rate of treatment failure for 362 patients being treated with high, moderate, and low bioavailable oral antibiotics. The study showed treatment failure rates of 2% (n=106), 12% (n=179), and 14% (n=77), respectively. Treatment failure for the purpose of this study was defined as all-cause mortality or recurrent infection within 90 days of the initial episode of bacteremia. Levofloxacin was the only highly bioavailable antibiotics investigated, and all 3 groups received an average of 4.7 days IV therapy prior to oral conversion. These results are further bolstered by 2019 meta-analysis from Punjabi and colleagues, which investigated 2289 patients from 14 studies.16 The studies evaluated oral vs IV step-down therapy for Enterobacterales bacteremia. The analysis found 65% of patients transitioned to oral fluoroquinolone, 7.7% to TMP-SMX, and 27.2% to oral beta-lactam, and again showed overall treatment failure for transitioning patients to oral antibiotic was low when using a highly bioavailable antibiotic. The results did find that recurrence of infection occurred more often when transitioned to oral beta-lactam than fluoroquinolone (OR 2.15; 95% CI, 0.93-4.99), however inadequate dosing was cited as a possible reason for this finding. All of these studies evaluated transitioning patients to oral after day 3-4 of IV therapy. While these studies show positive results for fluoroquinolone efficacy in this setting, it is noteworthy that resistance amongst Enterobacterales to fluoroquinolones is increasing limiting their use. In addition, black box warnings around toxicities of these drugs make them less than optimal choices in many patients. Fortunately, newer data have shown positive results for alternative agents as well. Two retrospective studies found that the rate of treatment failure for oral beta-lactams were similar to oral fluoroquinolones.13,14 The first study by Rieger and colleagues, looked at 241 patients with uncomplicated urinary Enterobacterales bacteremia treated with oral antibiotics. The study found no statistically significant difference in treatment failure between IV only and IV to oral treatment (3.8% vs 8.2%; p=0.19). Treatment failure was defined as a change in antibiotic regimen due to worsening clinical status, escalation back to IV antibiotics from oral, or readmission for the same infection within 30 days of discharge. The primary oral regimens used were, ciprofloxacin (65.3%), oral beta-lactams (19%) and trimethoprim-sulfamethoxazole (9.1%).13 The second study was by Mercuro and colleagues.14 The study reviewed 224 patients with uncomplicated urinary Enterobacterales bacteremia comparing clinical success of oral beta-lactam step-down therapy vs oral fluoroquinolone. Rates of clinical success were found to be similar among both groups (86.9% vs 87.1%; p>0.05) with higher rates of therapy completion in the beta-lactam group (91.7% vs 82.1%; p=0.049).14 A prospective study by Sutton and colleagues released in 2020 was much larger and evaluated 4089 patients who received an oral beta-lactam compared with a highly bioavailable fluoroquinolone or trimethoprim-sulfamethoxazole (TMP-SMX). The study found a 30-day mortality rate of 3% (n=29) vs 2.6% (n=82) and a recurrence rate of 1.5% (n=14) vs 0.4% (n=12), respectively.15 Based on the findings of these studies, a highly bioavailable fluoroquinolone should be considered an adequate choice for step-down therapy for an uncomplicated Enterobacterales bacteremia of urinary source after at least 2-days IV therapy. In addition, it appears that in many cases an oral beta-lactam can be considered an acceptable, side-effect minimizing substitution to a highly bioavailable fluoroquinolone provided the dosing regimen is optimized based on pharmacokinetic parameters and the patient has completed 3-4 days of IV therapy.

    Evidence for the use of oral antibiotics outside of treating Enterobacterales is lacking. Fluoroquinolones are the only oral agents with reliable activity against Pseudomonas aeruginosa due to high intrinsic resistance to oral beta-lactams. This means there are significantly less options for oral step-down therapy.16 As a result, there is an overall lack of evidence to support routine transition to oral therapy for MDR-bacteremia including Pseudomonas aeruginosa.16 However, in a study by Fabre and colleagues of 249 patients treated for uncomplicated urinary Pseudomonal bacteremia, 17 (6.8%) transitioned to an oral fluoroquinolone.17 A reported median time to transition was 5 days after initiating therapy. All 17 patients had source control, defined as the removal of infected hardware or devices, resolution of biliary or urinary obstruction, or drainage of infected fluid collections, and no difference in outcomes were reported. Thus, while routine transition of all patients with Pseudomonas bacteremia would not be recommended, the high bioavailability of fluoroquinolones along with the small retrospective study by Fabre and colleagues does support consideration of oral fluoroquinolones in uncomplicated urinary pseudomonal bacteremia where source control is achieved, and the patient has a rapid clinical response to antibiotics. The use of oral fluoroquinolone step-down therapy for pseudomonal bacteremia should be made on a case-by-case basis. There is also a lack of evidence to support the use of oral antibiotics for non-urinary source uncomplicated Gram-negative bacteremia. The meta-analysis by Punjabi and colleagues cited 6 studies which evaluated non-urinary sources of bacteremia in addition to urinary sources. These studies reported positive outcomes supporting the use of oral therapy for bacteremia of any source, but the results of these studies are likely skewed as the majority (>60%) of cases were secondary to a urinary tract infection.18

    Considerations for Duration of Treatment

    Once targeted therapy has been chosen for an infection, a proper duration of therapy must be determined to reduce excessive use of antibiotics and risk of adverse events. Whether a bacteremia is complicated or uncomplicated as well as the source of infection are the primary factors in determining treatment duration. If the infection is complicated, an extended duration of treatment of up to 14 days or more should be considered following resolution of complicating signs and symptoms.19 For uncomplicated Gram-negative bacteremia, the majority of cases are derived from a urinary infection with a catheter related source the second most common, and then unidentified source.19 In the study by Swamy and colleagues discussed above in which the majority of Gram-negative bacteremia cases were the result of a urinary tract infection, the achievement of clinical response at the end of therapy for short (7 days or less), intermediate (8 to 14 days) and long (more than 14 days) courses of treatment for gram-negative bacteremia showed no difference in clinical responses. (78.6% vs 89% vs 80.6%, respectively; p=0.2). In addition, the study failed to find a correlation between identified pathogen type, source of infection (urinary vs non-urinary), and time to defervescence (≤72 hours, >72 hours) with clinical failure at the end of therapy. However, the study was underpowered and patients with delayed clinical response may require longer durations of treatment.19 Another study by Yahav and colleagues compared 7 vs 14 days for uncomplicated Gram-negative bacteremia.20 The study, which looked at a 90 days composite of all-cause mortality, relapse, suppurative, or distant complications, found a 7 day duration to be non-inferior to a 14 day duration of treatment (45.8% vs 48.3%). The majority of patients had a urinary sourced infection (68%) caused by a Enterobacterales (90%).20


    Unlike data surrounding IV to oral conversion, treatment durations for multi-drug resistant pathogens such as Pseudomonas aeruginosa or Acinetobacter baumannii may be reduced. Of the studies cited above recommending a reduced duration of 7 days for uncomplicated bacteremia, there was a relatively low percent of patients included with multi-drug resistant pathogens.19,20 The study by Yahav and colleagues only evaluated 28 (4.6%) patients with pseudomonal bacteremia and 2 (0.3%) patients with Acinetobacter bacteremia.20 The study by Swamy and colleagues only included 7% of patients treated for a pseudomonal bacteremia and 4% of patients treated with an Acinetobacter bacteremia.19 A retrospective study by Fabre and colleagues of 249 patients with uncomplicated Pseudomonas bacteremia found patients treated for approximately 10 days had similar outcomes to those treated with longer durations.17 There are too few patients in these studies with MDR Gram-negative bacteremia to recommend a reduced duration of therapy for this patient population.

    The Use of Follow-up Cultures

    Follow-up cultures are necessary for adequate treatment duration for Gram-positive bacteremia. In GNB, the utility of follow-up cultures is more ambiguous. Canzoneri and colleagues looked at 383 cases of GNB where follow-up cultures had been drawn and found positive follow-up cultures for a Gram-negative bacteria in 8 cases.21 Only one of the positive cultures was indicative of a possible treatment failure, suggesting follow-up cultures for uncomplicated GNB are not needed.

    Conclusion

    The treatment of a GNB can range from 7 to 14 days. For complicated GNB a full 14-day duration following resolution of complicating factors would be ideal, as the risk for recurrence is likely high. For MDR pathogens such as Pseudomonas or Acinetobacter, there is evidence to support a reduced duration of 10-days IV antibiotics for uncomplicated bacteremia. Enterobacterales can be treated with a short 7-day course of either IV treatment for non-urinary sourced bacteremia or oral step-down therapy for urinary sourced bacteremia. Provided the patient sees clinical improvement, the use of follow-up blood cultures is not needed for GNB. The flow sheet in figure 2 depicts when to consider treatment duration reductions and IV to oral conversion for Gram-negative bacteremia based on infectious pathogen, source of infection, and complications of bacteremia. The use of shorter oral antibiotic regimens when appropriate will aid in better antibiotic stewardship and patient care.

    Figure 2: Treatment Duration Flowsheet


    *Recommendations should be considered on a case-by-case basis

    Take CE Quiz

    References

    1. Liu C, Bayer A, Cosgrove SE, and colleagues. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children [published correction appears in Clin Infect Dis. 2011 Aug 1;53(3):319]. Clin Infect Dis. 2011;52(3):e18-e55. doi:10.1093/cid/ciq146
    2. Biedenbach DJ, Moet GJ, Jones RN. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002). Diagn Microbiol Infect Dis. 2004;50(1):59-69. doi:10.1016/j.diagmicrobio.2004.05.003
    3. Smith DA, Nehring SM. Bacteremia. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441979/
    4. Harald Seifert, The Clinical Importance of Microbiological Findings in the Diagnosis and Management of Bloodstream Infections, Clinical Infectious Diseases, Volume 48, Issue Supplement_4, May 2009, Pages S238–S245, https://doi.org/10.1086/598188
    5. Sligl WI, Dragan T, Smith SW. Nosocomial Gram-negative bacteremia in intensive care: epidemiology, antimicrobial susceptibilities, and outcomes. Int J Infect Dis. 2015;37:129-134. doi:10.1016/j.ijid.2015.06.024
    6. Morpeth S, Murdoch D, Cabell CH, and colleagues. Non-HACEK gram-negative bacillus endocarditis. Ann Intern Med. 2007;147(12):829-835. doi:10.7326/0003-4819-147-12-200712180-00002
    7. Singer M, Deutschman CS, Seymour CW, and colleagues. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
    8. Luzzaro F, Viganò EF, Fossati D, and colleagues. Prevalence and drug susceptibility of pathogens causing bloodstream infections in northern Italy: a two-year study in 16 hospitals. Eur J Clin Microbiol Infect Dis. 2002;21(12):849-855. doi:10.1007/s10096-002-0837-7
    9. Shorr AF, Tabak YP, Killian AD, Gupta V, Liu LZ, Kollef MH. Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database. Crit Care Med. 2006;34(10):2588-2595. doi:10.1097/01.CCM.0000239121.09533.09
    10. Sligl W, Taylor G, Brindley PG. Five years of nosocomial Gram-negative bacteremia in a general intensive care unit: epidemiology, antimicrobial susceptibility patterns, and outcomes. Int J Infect Dis. 2006;10(4):320-325. doi:10.1016/j.ijid.2005.07.003
    11. Michael Smith, MD, MSCE, Samir Shah, MD, MSCE, Matthew Kronman, MD, MSCE, Sameer Patel, MD, MPH, Cary Thurm, PhD, Adam L Hersh, MD, PhD, Route of Administration for Highly Orally Bioavailable Antibiotics, Open Forum Infectious Diseases, Volume 4, Issue suppl_1, Fall 2017, Pages S498–S499, https://doi.org/10.1093/ofid/ofx163.1291
    12. Kutob LF, Justo JA, Bookstaver PB, Kohn J, Albrecht H, Al-Hasan MN. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. Int J Antimicrob Agents. 2016;48(5):498-503. doi:10.1016/j.ijantimicag.2016.07.013
    13. Rieger KL, Bosso JA, MacVane SH, Temple Z, Wahlquist A, Bohm N. Intravenous-only or Intravenous Transitioned to Oral Antimicrobials for Enterobacteriaceae-Associated Bacteremic Urinary Tract Infection. Pharmacotherapy. 2017;37(11):1479-1483. doi:10.1002/phar.2024
    14. Mercuro NJ, Stogsdill P, Wungwattana M. Retrospective analysis comparing oral stepdown therapy for enterobacteriaceae bloodstream infections: fluoroquinolones versus β-lactams. Int J Antimicrob Agents. 2018;51(5):687-692. doi:10.1016/j.ijantimicag.2017.12.007
    15. Sutton JD, Stevens VW, Chang NN, Khader K, Timbrook TT, Spivak ES. Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source. JAMA Netw Open. 2020;3(10):e2020166. Published 2020 Oct 1. doi:10.1001/jamanetworkopen.2020.20166
    16. Hale AJ, Snyder GM, Ahern JW, Eliopoulos G, Ricotta D, Alston WK. When are Oral Antibiotics a Safe and Effective Choice for Bacterial Bloodstream Infections? An Evidence-Based Narrative Review. J Hosp Med. 2018;13(5):328-335. doi:10.12788/jhm.2949
    17. Fabre V, Amoah J, Cosgrove SE, Tamma PD. Antibiotic Therapy for Pseudomonas aeruginosa Bloodstream Infections: How Long Is Long Enough?. Clin Infect Dis. 2019;69(11):2011-2014. doi:10.1093/cid/ciz223
    18. Punjabi C, Tien V, Meng L, Deresinski S, Holubar M. Oral Fluoroquinolone or Trimethoprim-sulfamethoxazole vs. ß-lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis [published online ahead of print, 2019 Aug 14]. Open Forum Infect Dis. 2019;6(10):ofz364. doi:10.1093/ofid/ofz364
    19. Swamy, Siddharth PharmD; Sharma, Roopali BS, PharmD, AAHIVP, BCPS(AQ-ID) Duration of Treatment of Gram-Negative Bacteremia, Infectious Diseases in Clinical Practice: May 2016 - Volume 24 - Issue 3 - p 155-160 doi: 10.1097/IPC.0000000000000362
    20. Yahav D, Franceschini E, Koppel F, and colleagues. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019;69(7):1091-1098. doi:10.1093/cid/ciy1054
    21. Canzoneri CN, Akhavan BJ, Tosur Z, Andrade PEA, Aisenberg GM. Follow-up Blood Cultures in Gram-Negative Bacteremia: Are They Needed?. Clin Infect Dis. 2017;65(11):1776-1779. doi:10.1093/cid/cix648


  • 26 Mar 2021 5:00 PM | Anonymous

    By: Jacklyn Harris, PharmD, BCPS, Christian Hospital/St. Louis College of Pharmacy

    We had another great virtual Spring Meeting this year! We hope that you enjoyed the programming as much as we did and hope that you were able to view this year’s posters. Our poster presenters did not disappoint- they did a great job completing their research and recording a short 5-minute video review of their poster. Our poster winners this year are listed below.

    • Original Research: Kennedy Moore, Pharm.D, Susan Burros, Pharm.D, BCACP, Amy Cummings, Pharm.D, BCACP, Lauren Wilde, Pharm.D, Sarah Will, Pharm.D., BC-ADM for “Integration of Patient-Aligned Care Team (PACT) Clinical Pharmacy Specialist (CPS) Involvement in the Interdisciplinary Management of COPD”
    • Encore Research: Lavinia Salama, Pharm.D for “Evaluation of Cost Savings, Safety and Barriers to Implementing a Biosimilar Interchange Policy in a Community Infusion Center”
    • Student Research: Danielle Murdock, Pharm.D Candidate, Heather Lyons-Burney, Pharm.D for “Assessing the impact of a pharmacist-led diabetes prevention program at a clinic for uninsured, medically underserved patients”

    If you were not able to view the posters, check them out here http://www.moshp.org/mshp-posters-2021/.

    This year’s MSHP R&E Foundation Best Practice theme was ‘Adapting to New Circumstances’. This year’s Best Practice award was presented to Kat Lincoln for her project entitled “Daptomycin-weight-based dose optimization”. Look for a review of her project in the next newsletter!

    This year’s Best Residency Project Award was presented to Sara Lauterwasser for her project entitled “Safety comparison of heparin and enoxaparin for venous thrombosis prophylaxis in traumatic brain injury”. We will be scheduling a special webinar for Dr. Lauterwasser to present her project.

    The 2nd annual Tonnies Preceptor Award was given out at this year’s meeting. The Tonnies awards was established in honor of Fred Tonnies, Jr for his longstanding support of MSHP, MMSHP, and numerous professional and academic contributions to Pharmacy, including over 35 years of dedicated service to student learners. The award recognizes a pharmacist for their sustained contribution to precepting learners in health-system pharmacy, mentoring students/residents in the research process, activity with pharmacy students throughout the state, and service to the profession through ASHP, MSHP, and/or local affiliates. This year’s Tonnies Preceptor Award was presented to Austin Campbell. Dr. Campbell is Clinical Pharmacy Specialist in Psychiatry at the Missouri Psychiatric Center at the University of Missouri Health Care. His investment in developing future practitioners has been evident for many years.

    Our final award was the Garrison Award. The Garrison Award recognizes an individual who demonstrates outstanding accomplishments in health-system pharmacy practice, demonstrates teaching through involvement with pharmacy students and contributions to the professional of pharmacy through involvement with MSHP, ASHP, or local affiliates. This year’s award was presented to Diane McClaskey. Diane is the Assistant Director of Experiential Education and Clinical Assistant Professor for the University of Missouri Kansas City, School of Pharmacy at MSU. She embodies the spirit of the Garrison Award in her continuous efforts in student involvement, research and publications, and leadership. We were honored to award this year’s Garrison Award to Diane! Congratulations!!

    Please congratulate each of our award winners!! We look forward to when we can present these awards to each of you in person. Thanks for another great Spring Meeting and continue to push the practice of pharmacy in Missouri!

  • 19 Mar 2021 5:54 PM | Anonymous

    By: Amanda Bernarde, PharmD; PGY1 Pharmacy Resident, University of Missouri Health Care

    Uncontrolled pain in the trauma patient population can lead to a variety of long-term, debilitating effects.1,2 Most prominently, patients experience impaired healing due to additional production of inflammatory factors, increased risk of infection, and psychological disorders persisting well past the initial injury.3 Due to the subjectivity of pain assessments and confounding factors, including sedating medications that can mask uncontrolled pain, recent exposure to opioids, and chronic versus acute pain etiologies, pain management remains a challenge in all patient populations.

    Opioids continue to be the mainstay in pain management for trauma patients. However, due to their adverse effect profile, potential for misuse and abuse, and the ever-evolving drug shortage issues facing health care institutions, additional approaches to medication management are necessary to adequately control patients’ pain.2 Multimodal analgesia (MMA) is the concomitant use of both opioid and non-opioid pain medications for synergistic mechanisms of action in an effort to minimize opioid-related adverse effects. This approach combats the two sides of pain patients experience: nociceptive and neuropathic.2,4 Nociceptive pain is caused by mechanical harm to the body, which is the traditional sense of trauma-related pain and commonly managed by opioids, while neuropathic pain is an effect of inappropriate stimuli to the sensory system and not well controlled by opioids.

    In a quasi-experimental study completed by Hamrick et al., investigators demonstrated the positive effects of MMA on cumulative oral morphine equivalents (OME) in critically ill trauma patients.5 Patients with three or more mechanisms of medication pain management had an average OME of 116.3 mg, while patients without MMA had an average OME of 479 mg spanning the first five days after injury. Beyond the overall reduction of opioid requirements when using a multimodal pain approach, use of non-opioids in addition to traditional regimens have significantly reduced intubation time and intensive care unit length of stay with a reduction of 2.64 and 4.25 days, respectively.6 This impact on both short-term and long-term outcomes can drastically alter a patient’s disease course and management beyond the acute setting.

    There are a number of specific medication classes that have been explored in conjunction with opioids, including traditional over-the-counter pain medications, gabapentinoids, α-adrenergic agonists, and ketamine. Trauma patients given scheduled oral acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) in addition to opioids had an average OME reduction 6.34 mg and 10.18 mg, respectively, in the 24-hour period post-MMA.4 Though reduction in opioid requirements may have been a natural disease progression, several studies have found similar results in non-trauma patients.2,7,8 Gabapentin and pregabalin mitigate neuropathic pain and help prevent chronic pain, while α-adrenergic agonists, like dexmedetomidine and clonidine, work both peripherally and centrally to provide analgesia, anxiolysis, and sedation.2 Both medication classes have demonstrated effective reduction of OME and coinciding pain scores in non-trauma surgical patients, yet no studies have been conducted in critically ill trauma patients to illustrate the effects in this patient population. Lastly, in a recent systematic review and meta-analysis, ketamine administration in the pre-hospital setting was not found to be less effective at managing pain compared to opioids.9 This non-opioid analgesic has proven efficacious in decreasing pain scores and OME for both intranasal administration and intravenous administration in a variety of trauma population subsets.10,11 Each MMA approach, though successfully protocolized at many institutions, should be individualized to the patient, including end organ function, comorbid conditions precluding use, and baseline use of these medications which may reduce their efficacy in treating the acute pain needs of the patient.

    In addition to the non-opioid medication therapies, there are nonpharmacologic approaches that can facilitate to both the physical progress and emotional aspects for trauma patients. One such nonpharmacologic therapy is early initiation of physical therapy. From a physical standpoint, assisted movement restores range of motion, promotes healing of injured tissues, and decreases long-term activation of inflammatory responses.12 Early mobilization has demonstrated a reduction of pulmonary, vascular, and cardiovascular complications, including pneumonia, pulmonary embolism, acute respiratory distress syndrome, deep vein thromboses, myocardial infarctions, and cardiovascular shock.12,13 Additionally, a statistically significant decrease in hospital length of stay by 2.4 days was shown when comparing early mobility to the control group (p=0.02). Though ICU length of stay was reduced by 1.5 days, these findings were not statistically significant, attributing the decrease in total length of stay to fewer complications when patients reached the general care floors. The positive effect of early physical therapy have prompted additional research in nonpharmacologic approaches to pain management, including mobilization in the emergency department and use of virtual reality.

    The limitations and risks associated with long-term, high-dose opioid use remain a concern in practitioners’ minds in treating critically ill trauma patients. Despite the limited data in this patient population, literature from other non-traumatic surgeries has been extrapolated to trauma patients due to their similar pain management needs. In the studies available and those extrapolated, MMA has shown to significantly decrease opioid and overall analgesic requirements, intubated days, and intensive care unit and hospital length of stay, in addition to minimizing misuse and abuse of opioids by setting the same precedent in the outpatient world.

    References:

    1. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263-306.
    2. Wampole CR, Smith KE. Beyond opioids for pain management in adult critically ill patients. J Pharm Pract. 2019;32(3):256-270.
    3. Karamchandani K, Klick JC, Linseky Dougherty M, Bonavia A, Allen SR, Carr ZJ. Pain management in trauma patients affected by the opioid epidemic: a narrative review. J Trauma Acute Care Surg. 2019;87(2):430-439.
    4. Gross JL, Perate AR, Elkassabany NM. Pain management in trauma in the age of the opioid crisis. Anesthesiol Clin. 2019;37(1):79-91.
    5. Hamrick KL, Beyer CA, Lee JA, Cocanour CS, Duby JJ. Multimodal analgesia and opioid use in critically ill trauma patients. J Am Coll Surg. 2019;228(5):769-775.e1
    6. Zhao H, Yang S, Wang H, Zhang H, An Y. Non-opioid analgesics as adjuvants to opioid for pain management in adult patients in the ICU: A systematic review and meta-analysis. J Crit Care. 2019;54:136-144.
    7. Polomano RC, Fillman M, Giordano NA, Vallerand AH, Nicely KL, Jungquist CR. Multimodal analgesia for acute postoperative and trauma-related pain. Am J Nurs. 2017;117(3 Suppl 1):S12-S26.
    8. Jibril F, Sharaby S, Mohamed A, Wibly KJ. Intravenous versus oral acetaminophen for pain: systematic review of current evidence to support clinical decision-making. Can J Hosp Pharm. 2015;68(3):238-247.
    9. Yousefifard M, Askarian-Amiri S, Rafiei Alavi SN, et al. The efficacy of ketamine administration in prehospital pain management of trauma patients: a systematic review and meta-analysis. Arch Acad Emerg Med. 2020;8(1):e1.
    10. Carver, TW, Kugler NW, Juul J, et al. Ketamine infusion for pain control in adult patients with multiple rib fractures: results of a randomized control trial. J Trauma Acute Care Surg. 2019;86(2):181-188.
    11. Bouida W, Bel Haj Ali K, Ben Soltane H, et al. Effect on opioids requirement of early administration of intranasal ketamine for acute traumatic pain. Clin J Pain. 2020;36(6):458-462.
    12. Chimenti RL, Frey-Law LA, Sluka KA. A mechanism-based approach to physical therapist management of pain. Phys Ther. 2018;98(5):302-314.
    13. Clark DE, Lowman JD, Griffin RL, Matthews HM, Reiff DA. Effectiveness of an early mobilization protocol in a trauma and burns intensive care unit: a retrospective cohort study. Phys Ther. 2013:93(2):186-196.

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