561782
research-article2014
AOPXXX10.1177/1060028014561782Annals of PharmacotherapyGuarascio et al
Commentary
Ebola Virus Disease: Roles and Considerations for Pharmacists
Annals of Pharmacotherapy 2015, Vol. 49(2) 247–249 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014561782 aop.sagepub.com
Anthony J. Guarascio, PharmD1, Andrew C. Faust, PharmD2, Lyndsay Sheperd, PharmD2, and Lauren A. O’Donnell, PhD1
Abstract Ebola virus disease (EVD) poses significant clinical care implications for pharmacists. Emergency preparedness efforts should be undertaken to ensure vital response to EVD. Pharmacists should consider factors such as enhanced use of resources for front-line EVD patient care along with procurement of investigational medications. Appropriate and timely preparation, distribution, and administration of treatment for patients with EVD in the setting of substantial critical illness as well as infection control measures are essential. Aggressive supportive care and early, goal-directed therapy are cornerstones of therapy, whereas investigational treatments for EVD will likely play a larger, more well-defined role as future clinical trials are conducted. Keywords infectious diseases, viral infections, antivirals, critical care, sepsis, personnel management, pharmaceutical care Ebola virus disease (EVD) has proven to be a devastating epidemic in West Africa. Patients have intermittently arrived on US soil requiring treatment for EVD, and subsequent to caring for these patients, US health care workers have contracted EVD. As pharmacists continue to practice on the front lines of patient care, they must be adequately prepared to encounter patients displaying signs and symptoms of EVD. Pharmacists may serve as the first point of contact in outpatient pharmacies, ambulatory care settings, or the emergency department prior to EVD diagnosis. Controlling the spread of this disease is centered on infection prevention and control methods, and pharmacists should become familiar with standard precautions for prevention of EVD transmission in US hospitals set forth by the Centers for Disease Control and Prevention (CDC).1 At a fundamental level, pharmacists should assume the responsibility of educating patients about EVD, especially those who present with public and socially guided misconceptions. Points to address include an explanation that transmission occurs exclusively by contact with infected bodily fluids and mucous membranes or breaks in the skin, with no evidence of airborne transmission. Additional education regarding the incubation period (2-21 days) in which the virus falls short of limits for both detection and transmission can be helpful. Furthermore, it should be emphasized that transmission of Ebola virus only occurs when patients are in the acute, symptomatic phase of infection, during which time the virus is shed in bodily fluids.2 Emergency preparedness for health care workers in the United States is obligatory because of the significant
mortality associated with EVD. The Ebola preparedness checklist provided by the CDC emphasizes policy development for hospital triage procedures, use of personal protective equipment, and establishment of plans for safe medication administration and supportive care.3 It encourages dialogue within preparatory efforts to detect EVD and respond appropriately while protecting employees. However, little guidance is provided to pharmacists regarding medication preparation and distribution, either for supportive care or investigational therapy. Nevertheless, pharmacists, particularly those in infectious diseases, emergency departments, and critical care subspecialties, will likely be requested as key contributors for preparedness strategies. A considerable demand for pharmacy services and personnel is necessary for the care of a patient with EVD and should be appreciated during preparedness discussions. For example, the pharmacy department caring for the first patient diagnosed with EVD in the United States reallocated resources to designate a critical care pharmacist with the sole duty of EVD patient care. A backup critical care pharmacist was appointed to support all-encompassing 1
Mylan School of Pharmacy at Duquesne University, Pittsburgh, PA, USA Texas Health Presbyterian Hospital, Dallas, TX, USA
2
Corresponding Author: Anthony J. Guarascio, Infectious Diseases Clinical Specialist, Mylan School of Pharmacy at Duquesne University, Bayer Learning Center, 600 Forbes Avenue, Pittsburgh, PA 15282, USA. Email: [email protected]
Downloaded from aop.sagepub.com at UCSF LIBRARY & CKM on April 1, 2015
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Annals of Pharmacotherapy 49(2)
clinical care responsibilities while highly experienced IV room staff were organized. Additionally, an investigational drug pharmacist was assigned to assist the primary EVD pharmacist with obtaining and storing investigational agents for EVD while serving as a liaison between attending physicians, a local investigational review board, pharmaceutical companies, and the FDA. An essential role of the pharmacist in EVD patient care is ensuring safe, timely, and appropriate procurement and administration of all prescribed treatments. The presence of isolation areas should be considered, and methods of drug delivery, such as automatic dispensing cabinets and pneumatic tube systems, should be favored if possible to limit unnecessary traffic to isolation areas, so long as these systems reside in nonisolation or “clean” areas. High-quality, goal-directed therapy for sepsis and shock, electrolyte replacement, and supportive care should be primary focuses. Patients with gastrointestinal disease may lose copious amounts of fluid (up to 8-10 L daily) and electrolytes (eg, potassium, magnesium, calcium). Frequent laboratory values, preferably by wireless point-of-care testing, should be determined, interpreted, and promptly corrected. Patients with septic shock caused by EVD should be monitored for secondary bacterial infections as well because this complication has been recently described.4 The potential for use of nutrition support, investigational drug administration, and continuous renal replacement therapy are likely, and each should be discussed in planning processes. In this issue of The Annals of Pharmacotherapy, Bishop highlights potential and investigational treatments for EVD. An impressive study of various agents for both treatment and prevention of EVD is under way, along with recent advances in vaccine development. Unfortunately, these agents are all mutually in early phases of development, and this poses both ethical and scientific dilemmas. We likely will not know true comparative effectiveness until largescale clinical trials are performed. Although pharmacists should pay attention to preliminary treatment outcomes observed with these agents, it is important to note that factors for treatment success are largely multifactorial, and these medications do not subvert the need for early, aggressive supportive care. Whereas estimates of mortality during this epidemic are 50% to 70%, fatality rates for patients treated within the robust US health care system have proved to be lower to date (1 of 7, 14%). The extent that EVD fatality rates may be influenced by timely supportive and investigational care is unknown, although anecdotal findings suggest that patients who receive this type of care fare better. In EVD patients, survivors develop neutralizing antibodies against the virus, whereas patients who succumb to the infection lack a neutralizing humoral response.5 Supportive therapy during the acute phase of the infection may provide the necessary time for a patient to generate an effective antibody
response against the virus. Moreover, time to effective therapy is shown to be a key factor, influencing outcomes and mortality in many bacterial, fungal, and viral illnesses.6,7 For example, influenza virus is most effectively treated with antiviral therapy early in the course of infection (within 12-36 hours) to maximize treatment efficacy and reduce illness duration.8,9 Though no specific antiviral agents are broadly available for Ebola viruses, lessons learned from other viral illnesses such as influenza may be important to guide our clinical mindset for treatment of EVD. Hence, early and effective antiviral therapy could prove similarly meaningful for EVD patient outcomes. It goes without mention that any health care facility tasked with caring for a patient with EVD will face significant challenges. Viable efforts directed toward preparedness will likely prove advantageous in this rare circumstance. Unfortunately, optimal Ebola virus–targeted regimens are unknown at this time, and we are left to infer effectiveness from a few clinical cases, many of which have exhibited both treatment successes and failures. The first EVD clinical trial with currently unidentified investigational drug candidates is set to commence in November during this ongoing epidemic and brings promise of meaningful data.10 For now, pharmacists must implement common principles that hold true for critical illness, such as early, goal-directed therapy along with appropriate and timely medication administration. As we gain further information regarding optimization of both supportive and investigational drug regimens for EVD, we must remain dynamic in our approach to patient care. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Centers for Disease Control and Prevention. Infection prevention and control recommendations for hospitalized patients with known or suspected Ebola virus disease in U.S. hospitals. http://www.cdc.gov/vhf/ebola/hcp/infection-preventionand-control-recommendations.html. Accessed November 12, 2014. 2. Bausch DG, Towner JS, Dowell SF, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007;196(suppl 2):S142-S147. 3. Centers for Disease Control and Prevention. Detailed hospital checklist for Ebola preparedness. http://www.cdc.gov/ vhf/ebola/pdf/hospital-checklist-ebola-preparedness.pdf. Accessed November 12, 2014.
Downloaded from aop.sagepub.com at UCSF LIBRARY & CKM on April 1, 2015
249
Guarascio et al 4. Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by Gram-negative septicemia [published online October 22, 2014]. N Engl J Med. doi:10.1056/NEJMoa1411677. 5. Sobarzo A, Ochayon DE, Lutwama JJ, et al. Persistent immune responses after Ebola virus infection. N Engl J Med. 2013;369:492-493. 6. Ogilvie MM. Antiviral prophylaxis and treatment in chickenpox: a review prepared for the UK Advisory Group on chickenpox on behalf of the British Society for the Study of Infection. J Infect. 1998;36(suppl 1):31-38. 7. Wood MJ, Shukla S, Fiddian AP, Crooks RJ. Treatment of acute herpes zoster: effect of early (
research-article2014
AOPXXX10.1177/1060028014561782Annals of PharmacotherapyGuarascio et al
Commentary
Ebola Virus Disease: Roles and Considerations for Pharmacists
Annals of Pharmacotherapy 2015, Vol. 49(2) 247–249 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014561782 aop.sagepub.com
Anthony J. Guarascio, PharmD1, Andrew C. Faust, PharmD2, Lyndsay Sheperd, PharmD2, and Lauren A. O’Donnell, PhD1
Abstract Ebola virus disease (EVD) poses significant clinical care implications for pharmacists. Emergency preparedness efforts should be undertaken to ensure vital response to EVD. Pharmacists should consider factors such as enhanced use of resources for front-line EVD patient care along with procurement of investigational medications. Appropriate and timely preparation, distribution, and administration of treatment for patients with EVD in the setting of substantial critical illness as well as infection control measures are essential. Aggressive supportive care and early, goal-directed therapy are cornerstones of therapy, whereas investigational treatments for EVD will likely play a larger, more well-defined role as future clinical trials are conducted. Keywords infectious diseases, viral infections, antivirals, critical care, sepsis, personnel management, pharmaceutical care Ebola virus disease (EVD) has proven to be a devastating epidemic in West Africa. Patients have intermittently arrived on US soil requiring treatment for EVD, and subsequent to caring for these patients, US health care workers have contracted EVD. As pharmacists continue to practice on the front lines of patient care, they must be adequately prepared to encounter patients displaying signs and symptoms of EVD. Pharmacists may serve as the first point of contact in outpatient pharmacies, ambulatory care settings, or the emergency department prior to EVD diagnosis. Controlling the spread of this disease is centered on infection prevention and control methods, and pharmacists should become familiar with standard precautions for prevention of EVD transmission in US hospitals set forth by the Centers for Disease Control and Prevention (CDC).1 At a fundamental level, pharmacists should assume the responsibility of educating patients about EVD, especially those who present with public and socially guided misconceptions. Points to address include an explanation that transmission occurs exclusively by contact with infected bodily fluids and mucous membranes or breaks in the skin, with no evidence of airborne transmission. Additional education regarding the incubation period (2-21 days) in which the virus falls short of limits for both detection and transmission can be helpful. Furthermore, it should be emphasized that transmission of Ebola virus only occurs when patients are in the acute, symptomatic phase of infection, during which time the virus is shed in bodily fluids.2 Emergency preparedness for health care workers in the United States is obligatory because of the significant
mortality associated with EVD. The Ebola preparedness checklist provided by the CDC emphasizes policy development for hospital triage procedures, use of personal protective equipment, and establishment of plans for safe medication administration and supportive care.3 It encourages dialogue within preparatory efforts to detect EVD and respond appropriately while protecting employees. However, little guidance is provided to pharmacists regarding medication preparation and distribution, either for supportive care or investigational therapy. Nevertheless, pharmacists, particularly those in infectious diseases, emergency departments, and critical care subspecialties, will likely be requested as key contributors for preparedness strategies. A considerable demand for pharmacy services and personnel is necessary for the care of a patient with EVD and should be appreciated during preparedness discussions. For example, the pharmacy department caring for the first patient diagnosed with EVD in the United States reallocated resources to designate a critical care pharmacist with the sole duty of EVD patient care. A backup critical care pharmacist was appointed to support all-encompassing 1
Mylan School of Pharmacy at Duquesne University, Pittsburgh, PA, USA Texas Health Presbyterian Hospital, Dallas, TX, USA
2
Corresponding Author: Anthony J. Guarascio, Infectious Diseases Clinical Specialist, Mylan School of Pharmacy at Duquesne University, Bayer Learning Center, 600 Forbes Avenue, Pittsburgh, PA 15282, USA. Email: [email protected]
Downloaded from aop.sagepub.com at UCSF LIBRARY & CKM on April 1, 2015
248
Annals of Pharmacotherapy 49(2)
clinical care responsibilities while highly experienced IV room staff were organized. Additionally, an investigational drug pharmacist was assigned to assist the primary EVD pharmacist with obtaining and storing investigational agents for EVD while serving as a liaison between attending physicians, a local investigational review board, pharmaceutical companies, and the FDA. An essential role of the pharmacist in EVD patient care is ensuring safe, timely, and appropriate procurement and administration of all prescribed treatments. The presence of isolation areas should be considered, and methods of drug delivery, such as automatic dispensing cabinets and pneumatic tube systems, should be favored if possible to limit unnecessary traffic to isolation areas, so long as these systems reside in nonisolation or “clean” areas. High-quality, goal-directed therapy for sepsis and shock, electrolyte replacement, and supportive care should be primary focuses. Patients with gastrointestinal disease may lose copious amounts of fluid (up to 8-10 L daily) and electrolytes (eg, potassium, magnesium, calcium). Frequent laboratory values, preferably by wireless point-of-care testing, should be determined, interpreted, and promptly corrected. Patients with septic shock caused by EVD should be monitored for secondary bacterial infections as well because this complication has been recently described.4 The potential for use of nutrition support, investigational drug administration, and continuous renal replacement therapy are likely, and each should be discussed in planning processes. In this issue of The Annals of Pharmacotherapy, Bishop highlights potential and investigational treatments for EVD. An impressive study of various agents for both treatment and prevention of EVD is under way, along with recent advances in vaccine development. Unfortunately, these agents are all mutually in early phases of development, and this poses both ethical and scientific dilemmas. We likely will not know true comparative effectiveness until largescale clinical trials are performed. Although pharmacists should pay attention to preliminary treatment outcomes observed with these agents, it is important to note that factors for treatment success are largely multifactorial, and these medications do not subvert the need for early, aggressive supportive care. Whereas estimates of mortality during this epidemic are 50% to 70%, fatality rates for patients treated within the robust US health care system have proved to be lower to date (1 of 7, 14%). The extent that EVD fatality rates may be influenced by timely supportive and investigational care is unknown, although anecdotal findings suggest that patients who receive this type of care fare better. In EVD patients, survivors develop neutralizing antibodies against the virus, whereas patients who succumb to the infection lack a neutralizing humoral response.5 Supportive therapy during the acute phase of the infection may provide the necessary time for a patient to generate an effective antibody
response against the virus. Moreover, time to effective therapy is shown to be a key factor, influencing outcomes and mortality in many bacterial, fungal, and viral illnesses.6,7 For example, influenza virus is most effectively treated with antiviral therapy early in the course of infection (within 12-36 hours) to maximize treatment efficacy and reduce illness duration.8,9 Though no specific antiviral agents are broadly available for Ebola viruses, lessons learned from other viral illnesses such as influenza may be important to guide our clinical mindset for treatment of EVD. Hence, early and effective antiviral therapy could prove similarly meaningful for EVD patient outcomes. It goes without mention that any health care facility tasked with caring for a patient with EVD will face significant challenges. Viable efforts directed toward preparedness will likely prove advantageous in this rare circumstance. Unfortunately, optimal Ebola virus–targeted regimens are unknown at this time, and we are left to infer effectiveness from a few clinical cases, many of which have exhibited both treatment successes and failures. The first EVD clinical trial with currently unidentified investigational drug candidates is set to commence in November during this ongoing epidemic and brings promise of meaningful data.10 For now, pharmacists must implement common principles that hold true for critical illness, such as early, goal-directed therapy along with appropriate and timely medication administration. As we gain further information regarding optimization of both supportive and investigational drug regimens for EVD, we must remain dynamic in our approach to patient care. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Centers for Disease Control and Prevention. Infection prevention and control recommendations for hospitalized patients with known or suspected Ebola virus disease in U.S. hospitals. http://www.cdc.gov/vhf/ebola/hcp/infection-preventionand-control-recommendations.html. Accessed November 12, 2014. 2. Bausch DG, Towner JS, Dowell SF, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007;196(suppl 2):S142-S147. 3. Centers for Disease Control and Prevention. Detailed hospital checklist for Ebola preparedness. http://www.cdc.gov/ vhf/ebola/pdf/hospital-checklist-ebola-preparedness.pdf. Accessed November 12, 2014.
Downloaded from aop.sagepub.com at UCSF LIBRARY & CKM on April 1, 2015
249
Guarascio et al 4. Kreuels B, Wichmann D, Emmerich P, et al. A case of severe Ebola virus infection complicated by Gram-negative septicemia [published online October 22, 2014]. N Engl J Med. doi:10.1056/NEJMoa1411677. 5. Sobarzo A, Ochayon DE, Lutwama JJ, et al. Persistent immune responses after Ebola virus infection. N Engl J Med. 2013;369:492-493. 6. Ogilvie MM. Antiviral prophylaxis and treatment in chickenpox: a review prepared for the UK Advisory Group on chickenpox on behalf of the British Society for the Study of Infection. J Infect. 1998;36(suppl 1):31-38. 7. Wood MJ, Shukla S, Fiddian AP, Crooks RJ. Treatment of acute herpes zoster: effect of early (
