April - Society of Critical Care Medicine

Volume 14 Issue 1
April 2014
Clinical Pharmacy and Pharmacology
Section Newsletter
Society of Critical Care Medicine
Section Officers
Chair
Karen McAllen, PharmD,
FCCM
([email protected])
Past-Chair
Lance Oyen, PharmD, FCCM
([email protected])
Chair-Elect
Ishaq Lat, PharmD, BCPS,
FCCM
([email protected])
Secretary/Treasurer
Russ Roberts, PharmD
(rroberts@tuftsmedicalcenter.
org)
Members-at-Large
Seth Bauer, PharmD
([email protected];
[email protected])
Amy Dzierba, PharmD,
FCCM
([email protected])
Ty Kiser, PharmD, FCCM
([email protected])
MESSAGE FROM THE CHAIR
Karen J. McAllen, PharmD, FCCM
The Annual Congress in San Francisco was full for excellent
programming, and I enjoyed meeting many of our members.
The CPP Section leadership was busy planning this upcoming
year, which should prove to be an exciting one.
I would like to welcome our newly elected leaders to the CPP
Section: Seth Bauer, PharmD, was elected to the position of
Member-at-Large and Russ Roberts, PharmD, was elected to
the position of Secretary/Treasurer. In addition, Sandra KaneGill, PharmD, FCCM, was elected to the open SCCM Council
seat, joining Steve Martin, PharmD, FCCM, as our CPP Section
designated seat.
In addition to myself, the leadership for the CPP Section this
year includes: Immediate Past Chair, Lance Oyen; Chair-Elect,
Ishaq Lat; Secretary/Treasurer, Russ Roberts; and Members-atLarge Amy Dzierba, Ty Kiser, and Seth Bauer.
New Section Committee Chairs and Vice Chairs, respectively,
include Deepali Dixit and Simon Lam (Communications); Jorie
Frasiolas and Jeff Gonzales (Education); Laura Aykroyd and
John Allen (Membership); Lisa Harinstein and Elizabeth Sinclair
(Patient Safety); Moo Sultan and Marilyn Bulloch (Program);
Erin Frazee and Mitch Daley (Research). You may
communicate your interest to the chair of any committee if you
would like to participate. Each committee’s charges can be
found at the CPP website (CPP Section iRoom) and some of the
activities and initiatives of interest will be highlighted during each
issue of the newsletter.
As many of you are aware, late in 2013 critical care was
recognized as a specialty by the Board of Pharmaceutical
Specialties. The first certification exam will occur in October
2015. The CPP Section and SCCM are already hard at work
evaluating how we can help with preparation for the exam and
eventually recertification.
Volume 14 Issue 1
April 2014
Members who wish to apply to one of the SCCM committees can do so on the SCCM website.
Applications for 2015 appointments are due by May 1, 2014.
SCCM has rolled out its eCommunity, a communications platform on the SCCM website. The CPP
Section is exploring this tool to improve communication with the membership. To access the
eCommunity: log in to MySCCM.org; click on SCCM eCommunity (lower right side of page); select
Sections, then Clinical Pharmacy and Pharmacology Section. If you then add the section to your
favorites (right side of page), you will be notified as blogs or messages are posted. You can select
how often you receive these updates.
On behalf of the CPP Section leadership, I would like to thank Lance Oyen and the outgoing
committee chairs for all of their hard work this past year: Xi-Liu DeRyke, Aimee LeClaire, Jenni
Morris, Eric Mueller, Joe Aloi and Seth Bauer. They all did an incredible job throughout the year,
which translated to a successful 2014 Congress.
I look forward to the privilege of serving as Section Chair this year. If you have input or ideas for the
CPP Section, would like to get involved in one of the committees, or can offer any special skills, I
would like to hear from you. Emails can be sent to me at [email protected].
CPP COMMITTEE CORNER
Communications Committee
Deepali Dixit, PharmD (Chair), and Simon Lam, PharmD (Chair-Elect)
The Communications Committee is excited about the new charges for the year. One of the new
charges is to provide monthly CPP Section announcements during the SCCM CPP Journal
Club webcasts, so stay tuned for the upcoming announcements during April 18th webcast. In
addition, the CPP newsletter now features a new Miscellaneous Section (frequently asked
questions and the Critical Care Pharmacotherapy Trials Network updates); both sections are
included below. The committee continues to actively explore new mechanisms to improve CPP
Section visibility, communication with members, and access to our newsletters and other
committee documents.
Congress Reflections
The CPP Communications Committee has highlighted some of the educational sessions from
the 2014 SCCM Congress. Our members attended and compiled brief summaries from the
sessions, which are included in this edition of the newsletter and will be archived in the CPP
Section iRoom. We sincerely thank and appreciate members who contributed their time and
effort.
If you have any questions regarding membership in the Communications Committee or
contributions you would like to make to the CPP Section newsletter, please contact Deepali
Dixit ([email protected]) or Simon Lam ([email protected]).
Education Committee
Jorie Frasiolas, PharmD (Chair), and Jeff Gonzales PharmD (Chair-Elect)
Congratulations to all CPP Section members who presented posters or platforms at the 2014
SCCM Annual Congress in San Francisco. The CPP Education Committee is collecting these
Volume 14 Issue 1
April 2014
posters and presentations to make them available to SCCM members electronically. Please
send a pdf of your poster or slides to Janie Faris at [email protected].
The CPP Education Committee continues to partner with the Society on several key initiatives,
including educational modules, a toolkit for protocol implementation, education for board
certification and recertification in critical care pharmacotherapy, and Journal Club.
Journal Club continues to be held the third Friday of every month at 2 PM EST. Upcoming
dates include April 18, May 16, and June 15. A call for presenters for the 2014-2015 academic
year will be sent out in April. If you would like to receive the monthly notification and link to
access the Journal Club session, please contact Karen Berger at [email protected] or
[email protected].
Membership Committee
Laura Aykroyd, PharmD (Chair), and John Allen, PharmD (Chair-elect)
Clinical Pharmacy and Pharmacology (CPP) Mentor-Mentee Program
Member Packet
The CPP Section Member Packet has been updated for 2014-2015. This material contains a
plethora of information about the section. Please take a moment and fill out the member
survey; the link is located on the first page of the member packet. All members are encouraged
to use this survey to update their demographic information, subspecialties, mentor-mentee
participation, speaking interests, and research interests. The packet can also be located on the
CPP homepage under Committee Documents, Membership Committee.
Mentor-Mentee Program
The Mentor-Mentee Program provides CPP pharmacist members in critical care, emergency
medicine, and pediatrics with guidance in a variety of areas, such as clinical practice, teaching,
and SCCM/CPP involvement. All CPP Section members are welcome to participate in either a
mentor or mentee capacity.
We are currently seeking individuals willing to serve as mentors, particularly those who would
like to mentor PGY2 residents and those who practice in specialty areas, such as pediatrics,
burn, or emergency medicine. If you or anyone you know is interested in serving in this role,
please contact us using the information below or complete the member survey, which can be
found on the first page of the CPP Member Packet.
Section members interested in serving in a mentee capacity are encouraged to contact us as
early as possible. Although many of our mentees in previous years have been relatively new
pharmacists, we would like to emphasize that mentorship is available to those who may be
more experienced but are looking to branch into a new area of practice. If you would like more
information regarding the program or would like to participate, please email either Laura
Aykroyd ([email protected]) or John Allen ([email protected]). We look forward to
working with everyone and to the continued success of this program.
Patient Safety Committee
Lisa Harinstein, PharmD (Chair), and Elizabeth Sinclair, PharmD (Chair-Elect)
The Patient Safety Committee would like to thank Eric Mueller (Past-Chair) and Amy Dzierba
(Member-at-Large) for their leadership and guidance over the past year. We also would like to
Volume 14 Issue 1
April 2014
thank our dedicated members who contributed to our charges.
The Patient Safety Committee is currently working on three research projects and anticipates
starting a new project this year. The first ongoing project is a national survey to evaluate
standard cardiovascular medication infusion concentrations and rates. Revisions to the survey
are being finalized, and then the project will move into the data collection phase. The second
project is a multicenter study evaluating drug-related admissions to the ICU. Additional sites
are needed to participate in this study. If interested, please contact Jaclyn LeBlanc
([email protected]). Lastly, a group continues to work on a systematic review of
adverse drug events occurring in the ICU versus those related to ICU admission or transfer.
During this upcoming year, we will formalize a survey-based research project evaluating the
use and performance characteristics of triggers for adverse drug event detection. Please email
Lisa Harinstein ([email protected]) for more information regarding any of the projects.
Save the date: In July, the Patient Safety Committee will be seeking nominations and
submissions for the Excellence in Using Technology to Improve ICU Medication Safety Award
and Innovations in ICU Medication Safety Award. Please check the CPP Section iRoom for
more information regarding the travel awards.
Program Committee
Moo Sultan, PharmD (Chair), and Marilyn Bulloch, PharmD (Chair-Elect)
The SCCM CPP Programming Committee has been working to get the ball rolling on our
charges for the year. The first order of business is to get the Year in Review: Pharmacy ready
for submission. As a group, we submitted many topics and are in the process of finalizing the
three topics for the session. Soon we will be reaching out to section members to determine
speakers for the program. Also, the Visiting Clinical Professor (VCP) Program applications are
due on April 1, 2014. We are working with Vidant Medical Center, which was awarded the VCP
scholarship last year to help reach the goals requested by the organization. As for the other
charges, we are developing subcommittees to begin working on the Pre-Congress
Symposium, CPP Member Reception, and the Recruitment Exchange. If you have any
questions, please email Moo Sultan ([email protected]) or Marilyn Bulloch
([email protected]).
Research Committee
Erin Frazee, PharmD (Chair), and Mitch Daley, PharmD (Chair-Elect)
It’s another exciting year for the CPP Research Committee! We have several established
charges, including facilitating CPP member-initiated research; providing peer review of
manuscripts, grant proposals, and strategic documents for the section; and maintaining a list of
funding opportunities appropriate for critical care pharmacists looking to do research. We also
provide monthly summaries of recently released critical care pharmacotherapy literature, which
are available for review in the section iRoom. Looking ahead to the 2014-2015 year, several
new charges will also be explored by our committee. We will lay the foundation for a new
research consult service and invest additional efforts to elevate our collaborative work to
scientific publication.
Upcoming deadline: Critical Care Pharmacotherapy Trials Network (CCPTN) proposal
submission deadline is April 18, 2014.
 If you’re considering submitting a research proposal to the CCPTN now or in the future,
take advantage of the peer pre-review service offered by the CPP Research
Committee. This great service connects proposal, grant, and manuscript authors with a
Volume 14 Issue 1
April 2014
senior content expert who provides feedback on the material prior to submission. You
may submit your proposal any time, but we encourage anyone interested to do so no
later than mid-March, to allow enough time for review prior to the April 18 CCPTN
deadline. Please contact the CPP Research Committee chair, Erin Frazee
([email protected]) with your materials and any questions.
If you would like further information about any of these activities or would like to get involved in
the Research Committee, please do not hesitate to contact the Chair, Erin Frazee
([email protected]), or Chair-Elect, Mitch Daley ([email protected]).
Congress Reflections: 43th Annual Critical Care Congress
Drug Shortages: Lessons Learned
(by Andrea Passarelli, PharmD, BCPS)
Patient Outcomes from Drug Shortages
Speaker: John Lewin, PharmD, MBA, FASHP, FCCM
New drug shortages are on the decline, but the current number of shortages remains
unchanged. The primary drivers for shortages are generic injectable quality manufacturing
issues. Generic injectables compete on price rather than quality because good manufacturing
practices are assumed by purchasers. Several publications have shown that shortages
contribute to medication errors and patient harm due to unavailability of medications or the
substitution with an unfamiliar or suboptimal medication. Some institutions have resorted to
outsourcing to compounding pharmacies, which are not subject to the same regulations as
manufacturers, leading to quality issues.
Recent legislation has led to a decline in new drug shortages. The Food and Drug
Administration Safety and Innovation Act (FDASIA) of 2011 requires manufacturers to notify the
FDA 6 months in advance of interrupting the manufacture of medications that are lifesupporting/sustaining, used in prevention of a debilitating disease, sterile injectable products, or
used in emergency care/surgery. FDASIA also enables the FDA to provide expedited reviews
for products that may prevent a shortage and to consider drug shortages when implementing
regulatory actions. The FDA can import drugs, encourage production, and extend expiration
dates but cannot require continuing the manufacture of a product. The Drug Quality and
Security Act of 2013 created “outsourcing facilities,” a voluntary registration for compounding
pharmacies, subjecting them to CGMP and FDA inspections.
Strategies to Deal with Shortages at the Local Level
Speaker: Stephanie Mallow Corbett, PharmD, FCCM
Sterile product shortages have had a significant impact on our practice for the past 3 years.
Antibiotics, autonomic agents, cardiovascular drugs, central nervous system agents, and
electrolytes are most commonly affected. Branded products coming off patent have led to an
increasing need for generic products; however, generics do not offer the same profit margin for
manufacturers, and production is often shifted to less efficient facilities with fewer resources.
Substantial hospital pharmacy resources are dedicated to managing drug shortages, including
increases in pharmacist and pharmacy technician time.
Shortage preparedness plans have been implemented by many institutions. These include:
o Identification of shortages. The ASHP, FDA, CDC and SCCM Drug Shortage Task
Force websites are excellent resources for keeping up with current drug shortages.
Volume 14 Issue 1
April 2014
o
Operational assessment to determine drug on hand, anticipated shortage duration,
purchase history, and estimated time to institutional impact.
o Therapeutic assessment to determine the patient population affected, therapeutic
alternatives, and potential restrictions or allocations to certain patient populations.
o Shortage impact analysis to devise prescribing, distribution, and administration
processes, as well as assessing financial ramifications.
o Communication of the plan to frontline staff and implementation. This can be
accomplished through emails, conversations, newsletters, and dashboards.
Administrators, clinical staff, and informatics specialists should be involved in shortage
preparedness. Risk management and ethics committees may also be helpful. Collaboration
between institutions and advocacy through local, state, and national government and
professional organizations are essential to minimize the impact of drugs shortages on patient
care.
Management of Cerebral Edema
(by Adam Linstedt, PharmD, BCPS)
Osmotic Approach
Speaker: Jeff Fletcher, MD
 Should osmotic agents be used at all?
o No level 1 evidence
o Bolus dose for herniation syndrome or as a bridge to other therapy is typically
agreed upon, but continuous infusion is controversial due to potential for
rebound edema and intracranial hypertension
o Conclusion: osmotic agents should be used to decrease intracranial pressure
(ICP) and raise cerebral perfusion pressure, cerebral blood flow, and brain
tissue oxygenation
 Which agent is preferred?
o Mannitol is more standardized and hypertonic saline has higher quality studies,
but no large class I trials
o Current data do not support a meaningful clinical difference
 It depends on patient characteristics
 Should continuous infusions be used?
o Potential for rebound edema, but limited data
o Bulk of literature says that hypertonic saline controls ICP regardless of method
and doesn’t report rebound edema
o Conclusion: initially, intermittent boluses seem preferred over continuous
infusions
Oncotic Approach
Speaker: Michel Torbey, MD
 Types of cerebral edema
o Cytotoxic (ischemia) or vasogenic (disrupts blood-brain barrier)
 Role of colloids
o If low molecular weight, such as albumin, will seep into blood-brain barrier
o If high molecular weight, may cause hemorrhage
o Safe study showed that albumin associated with increased mortality rate and
ICP compared to normal saline in traumatic brain injury patients
o Comparison of hetastarch and normal saline showed no difference in mortality,
but more patients required renal replacement therapy with hetastarch
o Hypertonic saline with hetastarch decreased ICP quicker than mannitol and
cerebral perfusion pressure increased
 Why don’t we use this approach clinically?
Volume 14 Issue 1
o
April 2014
Potential for combination therapy (osmotic and oncotic), but side effects are the
limiting factor
Surgical Approach
Speaker: Mark Cipolle, MD
 Decompressive craniectomy
o Not recommended in textbooks, used as damage control for the brain
o When adjusted for injury severity, craniectomy was not associated with worse
survival
o Summary: could be used to manage edema after severe traumatic brain injury
and middle cerebral artery infarct; recent studies showed reasonably good longterm functional outcomes, but questionable benefit to cost and long-term
outcome ratio
Therapeutic Drug Monitoring: A Modern Day Approach
(by: Amanda Giancarelli, PharmD)
Anticoagulants: More than INR and Partial Thromboplastin Time
Speaker: Farooq A. Bandali, PharmD, BCPS
Over 200 articles have been published on this topic in the past year, but many questions
remain unanswered. The optimal patient population for monitoring and values for efficacy and
bleeding risk have not been established.
 Dabigatran: An activated partial thromboplastin time greater than two times the upper
limit of normal may indicate excessive risk of bleeding. Dilute thrombin time and ecarin
clotting time both have linear relationships and excellent correlation for quantifying
dabigatran levels; however, they are not approved for commercial use in the United
States and are not available at most institutions. The thromboelastogram has a high
negative predictive value, but its sensitivity for dabigatran monitoring is limited.
 Rivaroxaban: There is no role for thromboelastogram monitoring at this time. A
prolonged prothrombin time may indicate excess bleeding risk. Anti-factor Xa
chromogenic assays provide a quantitative test, but reference values have not been
established.
 Apixaban: There are no data for anti-factor Xa chromogenic assay monitoring.
Beta-Lactams: It’s Not Just Minimum Inhibitory Concentration
Speaker: Scott Micek, PharmD
It is well known that critically ill patients have altered pharmacokinetics. Augmented renal
clearance occurs in about 50% of critically ill patients with normal serum creatinine during the
first 7 days. Variability in the volume of distribution of beta-lactams in critically ill patients is also
common. In patients with severe sepsis or septic shock, after a single dose of cefepime,
ceftazidime, meropenem or piperacillin/tazobactam, only 34%, 45%, 57%, and 33%,
respectively, achieved a serum concentration greater than four times the minimum inhibitory
concentration (MIC). Many studies have shown that mortality is increased with higher MICs
compared to lower MICs. This may be due to failure to achieve target serum concentrations. In
a study by Roberts and colleagues, only 25.8% of patients achieved the target concentration
based on initial dosing.
Although there appears to be a role for beta-lactam monitoring in this population, especially for
pathogens with higher MICs, it is not available in most institutions. Available beta-lactam
assays are labor intensive and do not take into account antibiotic-protein binding. Another
Volume 14 Issue 1
April 2014
limitation to beta-lactam therapeutic drug monitoring is the lack of studies evaluating clinical
outcomes.
Antifungal TDM: I Need to Get a Level?
Speaker: Simon Lam, PharmD
The Early Pseudomonas Infection Control (EPIC) 2 study found that 19% of critically ill patients
had fungal infections. Candida species was the most common pathogen isolated and had an
associated mortality of 30%. Aspergillosis was uncommon, but was associated with 70%
mortality.
 Invasive Candidiasis: The Infectious Diseases Society of America (IDSA) recommends
an echinocandin or fluconazole for treatment. Therapeutic drug monitoring (TDM) is not
necessary for echinocandins. Fluconazole does have an established target area under
the curve/minimum inhibitory concentration (AUC/MIC) ratio of >25-50, but with no
exposure to safety concerns and linear pharmacokinetics, TDM is likely not necessary.
The dose of fluconazole administered is approximately equal to the AUC achieved, and
therefore dose adjustments can be made based on MIC to achieve the target AUC/MIC
ratio.
 Invasive Aspergillosis: Voriconazole is the IDSA recommended first-line agent.
Liposomal amphotericin is an alternative for primary therapy, and posaconazole is
recommended for salvage therapy. TDM is recommended for voriconazole and
posaconazole. Voriconazole undergoes nonlinear pharmacokinetics due to saturable
metabolism and is also subject to many drug-drug interactions. Established target
levels are 1-2 mcg/mL for efficacy and <5 mcg/mL for safety, and one randomized
controlled clinical trial found increased treatment success with the use of TDM.
Posaconazole is only available in an oral formulation and has saturable absorption.
The absorption is increased by fatty meals and gastric acidity. TDM is recommended
with the following established targets for efficacy: >0.7 mg/L for prophylactic dosing and
>1.25 mg/L for treatment. Liposomal amphotericin does not have established levels for
efficacy or safety; therefore, TDM is not recommended.
Optimizing Antimicrobial Therapy in the ICU
(by Krystina Geiger, PharmD, BCPS)
Source Control
Speaker: John Marshall, MD
 Drainage
o Converts an abscess to an open infection
o Percutaneous imaging techniques usually utilized
 Debridement
o Used to removed necrotic tissue
o Consider risks vs. benefits approach
 Removal of foreign bodies
Antibiotic Resistance
Speaker: Jorge Hidalgo, MD
 Antimicrobial resistance increasing
o Negative impact on clinical outcomes
 Risk factors for development of resistance:
Volume 14 Issue 1
April 2014
o


Age, duration of hospitalization, ICU admission, renal insufficiency,
immunosuppression, neutropenia, hematologic malignancy, solid organ/bone
marrow transplant, AIDS, prior surgery
o Number and duration of antibiotics used, diarrhea/Clostridium difficile, use of
catheters, prior colonization, exposure to vancomycin-resistant enterococci
source
Mechanisms of resistance
o Mutation
o Destruction or inactivation
o Efflux
Judicious use of current agents necessary to preserve future use
Biomarkers as a Guide for De-escalation
Speaker: Steven Opal, MD
 2012 Surviving Sepsis Campaign guidelines recommend use of low procalcitonin (PCT)
levels or other biomarkers to assist clinician in discontinuation of empiric antibiotics
(grade 2C)
o PCT most studied biomarker in sepsis
 PCT may be useful as a guide in discontinuation of potentially unnecessary empiric
antibiotics when clinical situation has stabilized
o Healthy adults <0.05 ng/mL
o Localized bacterial or viral infections >0.5 ng/mL
o Possible bacterial or other systemic infection 0.5-2.0 ng/mL
o Probable bacterial sepsis >2-10 ng/ml
o High risk of bacterial sepsis >10 ng/mL
 Overall, majority of evidence shows PCT can be used to de-escalate therapy for empiric
treatment
o No effect on mortality or length of stay, but may help cost savings
o Safety is still a potential concern
 Risk of relapse or re-infection
Post-Intensive Care Syndrome
(By Daryl Glick, PharmD)
Post-Intensive Care Syndrome Survivors and Families
Speaker: Ramona Hopkins, PhD
 For patients and families, return to normal function after ICU discharge is one of the
most important endpoints
 Post-intensive care syndrome impacts functional abilities, ability to return to work,
and/or quality of life in ICU survivors
 It is defined as new or worsening impairment in physical, cognitive, or mental health that
persists beyond hospitalization for critical illness
 Prevention strategies include reducing the use of sedatives to allow patients to be more
alert, initiating an early mobility strategy, helping family members keep an ICU diary,
and developing post-ICU cognitive and physical rehabilitation programs
Costs of Post-Intensive Care Syndrome to Families and Societies
Speaker: Theodore Iwashyna, MD, PhD
 Post-traumatic stress disorder, anxiety, and depression occur in over 50% of individuals
who experience the death of a family member in the ICU
 Up to 50% of family members and surrogate decision makers of patients in the ICU
exhibit learned helplessness
Volume 14 Issue 1


April 2014
Interventions to help decrease post-intensive care syndrome in family members include
improved family meetings and increased family involvement and support
Survivors of severe sepsis experience higher rates of rehospitalization and healthcare
utilization, and costs up to $150,000 in the 5 years after discharge
Recovering from the ICU: A Physician-Survivor’s Story
Speaker: Alison Clay, MD
 Intubation, noise, restraints, delirium/cognitive dysfunction, and isolation contribute to
the development of post-intensive care syndrome
 Post-traumatic stress disorder may develop secondary to uncontrolled pain, noise,
restraints, immobility, and isolation
 Access to home healthcare and assistive devices, appropriate nutrition, physical
therapy, and psychiatric services/support groups is important following ICU discharge
Understanding Sleep in Critically Ill Patients
(By Robert Witcher, PharmD)
Impact of Medication, Delirium, and Mechanical Ventilation on Sleep in the ICU
Speakers: John Devlin, PharmD, Brian Gehlbach, MD, Paula Watson, MD








Sleep is a time of increased metabolic clearance, demonstrated by increase in
interstitial space and increased clearance of metabolites from the cerebrospinal fluid
compared to an awake state
Majority of ICU sleep occurs in atypical patterns
o Survivors of ICU stays report long-lasting difficulty with sleep up to 4 to 12
months after ICU stay
o Up to 60% of patients report insomnia after ICU stay
o Delusions, post-traumatic stress disorder, anxiety, and depression occur
disproportionally more often in patients who experience sleep disturbances in
the ICU
Patients who experience sleep disturbances in the ICU experience long-lasting deficits,
with up to 40% of patients having 1.5 standard deviations below mean global cognition
scores; on a similar level of the development of mild Alzheimer’s disease or moderate
traumatic brain injury
Opioids have been shown to decrease total sleep time, and steroids have also been
associated with an increase in non-REM sleep
Benzodiazepines have been shown to increase stage 1 and 2 sleep while decreasing
slow wave sleep and REM sleep
In case reports, an increase in slow-wave sleep has been described with
dexmedetomidine, while other reports show no increase in slow-wave or REM sleep
Interestingly, studies have not shown that time in delirium, benzodiazepine dose,
Sequential Organ Failure Assessment score, or coma duration is associated with total
sleep time, sleep efficiency, or waking after sleep onset
ICU-wide initiatives should address circadian misalignment by focusing on medical and
environmental factors
Stop Stressing Over Stress Ulcers
(By Michael Vertin)
Stress ulcer prophylaxis remains a controversial topic for ICU practitioners, both in the
selection of agents to use and the population in which they should be used.
Volume 14 Issue 1
April 2014
The SCCM Congress seminar featured ICU practitioners commenting on the populations most
at risk for stress-related mucosal bleeding, as well as considerations in choosing the
appropriate agent.
 The incidence of clinically significant gastrointestinal bleeding related to stress ulcers
has been reported to be up to 5% of patients.
 The highest incidence of clinically significant bleeding included patients with a
coagulopathy and those who were mechanically ventilated for >48 hours.
 In the absence of these two risk factors, the incidence of clinically important bleeding
was decreased dramatically.
 Therefore, practitioners should have a relatively high threshold for stress ulcer
prophylaxis if their patients do not fit into one of these two categories. Achievement of
multiple simultaneous risk factors may still warrant stress ulcer prophylaxis; however,
the careful consideration of what types of patients should receive prophylaxis was
emphasized.
Decision regarding the choice of agent to use for stress ulcer prophylaxis:
 After identification of the appropriate patient for prophylaxis, the question remains which
agent provides the best benefit.
 The evidence for selection of a proton-pump inhibitor (PPI) or histamine-2 receptor
antagonist (H2RA) is wide-ranging and often conflicting.
 Each agent provides its own benefit potential and risk profile, making efficacy a deciding
factor.
 Consensus is difficult to achieve on this topic. In the meta-analyses reviewed, the
recommendations were weak and often conflicting.
 In a recent meta-analysis reviewed extensively, the authors seemed to favor PPI over
the H2RA class, citing decreased clinically significant bleeding events and superior
efficacy at maintaining prophylaxis stomach pH.
 While these authors made a strong case for PPIs in their analysis, closer examination
reveals the differences may not be so profound.
 The meta-analysis included a study by Levy in 1996, which showed increased rates of
bleeding in those patients treated with an H2RA. These results greatly skewed the data
in favor of the PPI group; in the meta-analysis, it was the only trial to achieve statistical
significance favoring PPIs.
 The presenter went into great deal about how this singular trial may greatly influence
the outcomes of the analysis, and stressed the importance of critically evaluating the
results of these meta-analyses. In addition to the efficacy of each agent, the presenter
also stressed the importance of considering the adverse events associated with
widespread stress ulcer prophylaxis.
 Rates of secondary infection were discussed, including C. difficile and nosocomial
pneumonias. In addition, acute side effects, such as thrombocytopenia and aspiration
pneumonia, were discussed.
 The take-home message was that these drugs are not without significant side effects,
necessitating judicious use in the ICU setting.
 The resounding conclusion for intensive care providers is to critically evaluate patients
for the need to prescribe stress ulcer prophylaxis.
 Great emphasis was placed on the realization that not all ICU patients qualify or should
receive stress ulcer prophylaxis.
 Both PPIs and H2RAs have adverse events associated with their use, and exposing
patients to excessive or unneeded therapy may cause more harm than good. While the
seminar did not determine the best agent to use, it did stress the importance of frequent
and in-depth review of the patients most at risk for bleeding events and the use of
stress ulcer prophylaxis in this population.
Volume 14 Issue 1
April 2014
Delirium and Encephalopathy in the ICU
(by Olusola O. Apena, PharmD)
Physiology of Delirium
Speaker: Gregory Kopinos, MD
Delirium was defined as a neurobiological derangement which culminates a syndrome of
cerebral insufficiency.
 Kopinos pointed out that there are many factors that contribute to delirium.
 Etiology cannot be pinpointed to a single cause; rather, many theories have been used
to explain the myriad of factors that lead to delirium.
o Global hypoperfusion has been evidenced by several recurring factors in
patients with delirium, such as hypoxia, anemia, and cerebral ischemia.
o Neuroimaging has revealed encephalopathy in patients with prolonged severe
delirium. In concert, certain values, such as high Acute Physiology and Chronic
Health Evaluation scores, low hemoglobin, and low hematocrit, have been
explored for use in predicting delirium.
o Researchers have hypothesized that excess glutamate and depletion of
serotonin may contribute to the physiology of delirium.
o Other suggestions linked to neurotransmitter imbalances include aging,
inflammation, stress, trauma, surgery, and systemic inflammation.
o Certain medications have been classified as high risk for causing delirium.
These include opioid analgesics, antiparkinsonian agents (particularly
anticholinergic agents), antidepressants, benzodiazepines, centrally acting
agents, corticosteroids, and lithium.
Prevention of Delirium
Speaker: Timothy Girard, MD
The prevention of delirium was geared towards addressing benzodiazepines and pushing for
the ABCDE bundle.
 Studies have shown a direct correlation associated effect between benzodiazepine
doses and the incidence of delirium.
o Pandiharipande et al showed that as higher doses of lorazepam were given to
ICU patients, there was a proportional increase in the incidence of delirium.
o The ABC trial showed no difference in delirium between patients in the control
arm and in the intervention arm (spontaneous awakening group, who received
fewer doses of benzodiazepines), although limitations were noted.
o The second modality to prevent delirium is implementing the Awake and
Breathing Controlled Delirium Early mobilization bundle.
o This advocates for implementing the findings of the ABC trial by using
spontaneous awakening and breathing trials and sedation holidays in ICU
protocols. Also, this calls for taking active steps to control delirium by reorienting
patients to their normal sleep-wake cycle.
o Early mobilization is encouraged because it has been associated with a
decreased ICU length of stay.
Workup and treatment of the delirious patient focused on the tools that we have available and
the agents that may be beneficial.
 The Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care
Delirium Screening Checklist (ICDSC) are tools that can be used along with physical
exams and etiological assessments (such as electroencephalography and magnetic
resonance imaging) to work up patients for delirium.
Volume 14 Issue 1



April 2014
Neuroimaging may reveal areas of hypoperfusion, and in combination with the other
tools, guide towards an earlier diagnosis of delirium.
Treatment should be multifaceted by gearing towards all potential causes of delirium.
For precipitating factors of organ dysfunction, infection, sleep disturbance, mechanical
ventilation, drugs restraints, and restraints, the integrated interventions of organ
resuscitation, antimicrobial source control, sleep promotion, ventilator liberation,
rationalize sedation, and physical therapy mobilization, respectively, should be
implemented.
Apart from these modalities, antipsychotics have been shown to reduce the severity of
delirium in patients. Novel areas of research for brain-directed interventions to treat
delirium include anti-inflammatory agents, immune modulators, and neurotransmitter
cocktails.
All in all, there is no single cause of delirium. It is a subacute mental syndrome, and efforts
should be made to restore the sleep-wake cycle. Untreated delirium is associated with poor
cognitive outcomes. Treatment must involve knowledge of the delirium biology.
Year in Review: Pharmacology
(by Andrea Passarelli, PharmD, BCPS)
Substance Withdrawal
Speaker: Russel Roberts, PharmD
Nicotine withdrawal in critically ill patients can be difficult to identify due to other pathologic
processes. The onset typically occurs within 2 days and peaks within 1 week. Nicotine
replacement therapy (NRT) increases abstinence from nicotine at 6 months in non-ICU
patients; however, its effect on withdrawal symptoms is poorly characterized. Risks of NRT
include increased myocardial oxygen demand leading to myocardial ischemia. A study
published in Circulation in 2013 showed no increase in cardiovascular events in patients
receiving NRT, but an increase in tachycardia and palpitations. Another study published in
Respiratory Care in 2013 showed a nonsignificant decrease in the need for analgesia, days of
mechanical ventilation, and ICU length of stay in patients randomized to NRT vs. placebo,
although this study was limited by a small sample size and potential confounders.
Reviews of alcohol withdrawal syndrome are plagued with lack of standard definitions and ICUvalidated alcohol withdrawal scales. Risks of using benzodiazepines as monotherapy include
poor dose-response relationship, oversedation, and respiratory depression. A study in The
American Journal of Critical Care showed no difference in ICU complications and an increased
risk of disorientation in patients randomized to ethanol compared to those randomized to
lorazepam. A study in the Journal of Emergency Medicine showed that patients randomized to
phenobarbital (10 mg/kg) plus symptom-triggered benzodiazepine had a lower benzodiazepine
requirements and fewer ICU admissions with no difference in withdrawal symptoms or adverse
events compared to patients receiving symptom-triggered benzodiazepine alone. A study
published by Mueller et al in Critical Care Medicine demonstrated decreased benzodiazepine
requirements and no difference in adverse events in patients randomized to dexmedetomidine
vs. placebo with symptom-triggered lorazepam.
Care of the Critically Ill Transplant Patient
Speaker: Heather Personett, PharmD, BCPS
Donor-derived infections remain a significant problem in solid-organ transplant recipients with
an associated mortality rate of up to 30%. Risk assessment includes donor history and clinical
Volume 14 Issue 1
April 2014
status as well as recipient illness severity and serology. Guideline recommendations published
in 2013 suggest that infected organ donors should be treated with antimicrobials for 24-48
hours prior to donation, and recipients of organs from infected donors should be treated for 714 days post-transplant regardless of confirmed infection. Antimicrobials should be narrowed
according to culture and susceptibility data.
Changing patterns of invasive fungal infections, including increasing non-albicans species and
Aspergillus infection, have led to an increasing reliance on voriconazole and posaconazole. A
study published in Antimicrobial Agents and Chemotherapy in 2013 assessed 163 drug levels
in patients with infection and found that patients failing drug therapy had lower troughs. A
trough >1.7 was associated with a decreased risk of treatment failure and troughs >5 were
associated with an increased risk of neurotoxicity. Factors influencing pharmacokinetic
variability included age, dose, and proton pump inhibitor use. Therapeutic drug monitoring
should be performed in patients on voriconazole (target trough >1.5) and posaconazole (target
trough >0.5), especially those on more than 7-14 days of therapy and patients using enteral
formulations to ensure adequate absorption.
The Molecular Adsorbent Recirculating System (MARS) is an extracorporeal albumin dialysis
system approved for hepatic encephalopathy and poisonings. It includes an albumin pump and
charcoal filter and can remove lipophilic and protein-bound molecules, as well as hydrophilic
compounds. In a case published in Transplant Infectious Diseases in 2013, a patient with
acetaminophen-induced acute liver failure receiving MARS, the half-life of
piperacillin/tazobactam was 3.7 hours shorter compared to patients on continuous venovenous
hemodiafiltration. Another study published in Acta Anesthesiology Scandinavia in 2013 showed
that MARS removed meropenem and moxifloxacin despite the low protein-binding of these
agents.
Toxicology
Speaker: Cassie Barton, PharmD
Methylene blue has been studied in septic shock and was shown to increase mean arterial
pressure, decrease vasopressor requirements, and maintain oxygen delivery. The role of
methylene blue in treatment-resistant anaphylaxis continues to be elucidated. One case series
from 1997, in which patients received methylene blue at a dose of 1.5 mg/kg, demonstrated
recovery of anaphylaxis, with one patient developing a junctional rhythm and one developing
angina. A case series published by Del Duca et al described the use of methylene blue in two
patients with anaphylaxis after receiving protamine and aprotinin during cardiovascular surgery,
both of whom had resolution of symptoms in 20 minutes. A case report published by Bauer et
al in 2013 showed that anaphylaxis resolved within 15 minutes of methylene blue
administration without the need for intubation. Many patients included in these case reports did
not receive the standard of care for anaphylaxis treatment (epinephrine, corticosteroids, and
histamine receptor antagonists) prior to methylene blue administration.
Methylene blue—1.5 mg/kg over 20 minutes, followed by an optional 1.5 mg/kg bolus—can be
considered as salvage therapy for anaphylaxis. Patients should be monitored for serotonin
syndrome, cardiovascular effects, nausea, vomiting, and abdominal pain. Methylene blue
administration also interferes with pulse oximetry, so an alternative method should be used to
monitor oxygenation.
Volume 14 Issue 1
April 2014
Novel Approaches in Sepsis
(By Julie Kalabalik, PharmD, BCPS)
Micronutrients and Therapies
Speaker: Hector Wong, MD
 Selenium has antioxidant and anti-inflammatory effects. It plays an important role in
glutathione, iodine, and thyroid metabolism. Recent evidence shows that seleniumdependent glutathione peroxidase activity correlates inversely with sepsis severity and
patients with sepsis commonly have low selenium levels.
 In a meta-analysis of randomized controlled trials comparing selenium supplementation
(in doses above the daily requirement) to placebo in patients with sepsis syndrome,
Alhazzani and colleagues found that selenium supplementation was associated with
lower mortality. There was no difference in ICU length of stay or nosocomial
pneumonia. In one study, mechanically ventilated adult patients with multiorgan failure
who received antioxidant supplementation (selenium, zinc, beta carotene, vitamin E,
and vitamin C) did not have a reduced mortality rate, but this trial was not sepsisspecific.
 Zinc plays a role in glucose homeostasis, antioxidant responses, and adaptive and
innate immunity. Liu and colleagues showed that the zinc transporter (ZIP8) is a
negative regulator of the NF-κB signaling pathway and identified a negative feedback
loop that regulates innate immunity through zinc metabolism. In one pediatric ICU
study, plasma zinc levels correlated inversely with C-reactive protein levels and
interleukin-6 levels. Patients with ≥2 organ failures had lower zinc concentrations
compared with patients with ≤1 organ failure. In a murine model, zinc supplementation
delayed onset of death and improved survival compared to a zinc-deficient group of
mice with bacterial sepsis. The National Heart, Lung, and Blood Institute and the
University of Vermont are conducting an ongoing study evaluating the role of zinc
therapy in critically ill patients.
Endotoxin Removal in Sepsis
Speaker: R. Phillip Dellinger, MD, MCCM
 Sources of endotoxins include local bacterial infection and translocation from the
gastrointestinal tract. Studies have demonstrated the link between the presence of
endotoxin in the blood and mortality in septic patients. Patients with higher endotoxin
concentrations had significantly higher 28-day mortality compared to those with lower
endotoxin activity assay levels.
 The Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock (EUPHAS)
Trial evaluated whether adding polymyxin B hemoperfusion to conventional medical
therapy improved clinical outcomes and mortality compared with conventional therapy
alone. The mortality rate was 32% in the polymyxin B group and 53% in the
conventional therapy group. The EUPHRATES trial (Evaluating the Use of Polymyxin B
Hemoperfusion in a Randomized Controlled Trial of Adults Treated for Endotoxemia
and Septic Shock) is ongoing. This blinded, randomized trial will compare the safety
and efficacy of the polymyxin cartridge based on 28-day mortality in subjects with septic
shock who have high levels of endotoxin.
Vitamin D and Sepsis
Speaker: Greg Martin, MD

Vitamin D regulates both innate and adaptive immune systems. Vitamin D deficiency is
common in ICU patients. In a retrospective study of 437 patients, 25(OH)D deficiency
was identified in 77.8%. Hospital mortality was higher in patients with this deficiency. In
Volume 14 Issue 1

April 2014
one study, length of stay, surgical ICU cost, and mortality were significantly associated
with vitamin D deficiency.
Patients with sepsis have lower 25(OH) D levels compared to those with systemic
inflammatory response syndrome. Patients with vitamin D deficiency had increases in
30-day mortality, mechanical ventilation days, and total ICU and hospitalization days. In
a recent study, multivariable adjusted risk of 90-day mortality was 1.6-fold higher in
those with preadmission 25(OH) D values in the insufficient and deficient range,
compared with those with preadmission vitamin D sufficiency. Amrein and colleagues
evaluated 25 patients with vitamin D deficiency and an expected ICU stay of <48 hours
who randomly received either 540,000 IU of cholecalciferol or placebo. Oral high-dose
vitamin D3 corrected vitamin D deficiency within 2 days in most patients. The question
of whether vitamin D influences outcomes in ICU patients is yet to be seen. Some
ongoing trials include the Correction of Vitamin D Deficiency in Critically Ill Patients: a
Randomized, Double-blind, Placebo-controlled trial and High-Dose Vitamin D and
Antimicrobial Peptide Expression in Lung Failure trial.
Probiotics for the Treatment and Prevention of Clostridium difficile Infection
Stephanie Davis, PharmD, BCPS; Jessica Crow, PharmD, BCPS, CNSC; Darlene Chaykosky,
PharmD, BCPS
Introduction
Clostridium difficile infection (CDI) is the most common cause of healthcare-associated
diarrhea, accounting for 20% to 30% of cases.1 CDI is defined as the presence of diarrhea (>3
unformed stools in <24 hours) and either a positive stool test result or colonoscopic or
histopathologic findings of pseudomembranous colitis. In 2009, CDI-related hospital stays
accounted for 0.9% of all hospitalizations, with a four-fold increase in mortality compared to
other hospitalized patients.2 In recent years, significant efforts have been made to identify
interventions that decrease the incidence, severity, and recurrence of disease, including the
use of biologic methods such as probiotics.
Probiotics are defined by the World Health Organization as live microorganisms that confer a
health benefit on the host when administered in adequate amounts.3 Probiotics may contain
various strains and colony-forming units (CFU) of microorganisms, but the most commonly
utilized strains include lactobacilli, bifidobacteria, and the yeast Saccharomyces boulardii.4
Probiotics are hypothesized to be effective in the prevention and treatment of CDI through a
number of mechanisms, including maintenance of normal gastrointestinal flora, secretion of
antimicrobial molecules, immunomodulatory effects, and inhibition of pathogenic bacterial
colonization via adhesion sites.5 S. boulardii has also been shown to increase host titers of antitoxin A IgA and secretion of a protease that hydrolyzes C. difficile toxins A and B.4,5
Safety
Probiotics are marketed in the United States as dietary supplements and manufacturers can
make health claims based on data in a healthy population, but supportive data are not
evaluated by the Food and Drug Administration.6,7 Probiotics are generally regarded as safe,
but the administration to patients at high risk of opportunistic infections has not been
adequately studied. The PROPATRIA trial raised questions regarding the safety of probiotics
after use in patients with severe acute pancreatitis was associated with a significant increase in
mortality and bowel ischemia.8 Multiple case reports of endocarditis, bacteremia, and fungemia
have been associated with probiotic supplementation. In addition, reports have suggested
transmission of infection to hospitalized patients not receiving probiotics, possibly via
contamination of vascular catheters among neighboring patients.9 Resistance determinants
Volume 14 Issue 1
April 2014
carried on mobile genetic elements in probiotics potentially can confer resistance to
gastrointestinal pathogens.10
Boyle and colleagues proposed risk factors for probiotic use, warranting caution in patients with
a single major or more than one minor risk factor. 9 Major risk factors include
immunocompromise and prematurity. Minor risk factors include the presence of a central
venous catheter (contraindicated with S. boulardii), impaired intestinal epithelial barrier,
administration of probiotic by jejunostomy, or cardiac valvular disease (Lactobacillus probiotics
only).
Probiotics for Primary Prevention of CDI
The use of probiotics for primary prevention of CDI remains controversial. Several studies
have investigated this topic, but results have been conflicting due to variability in study
methodology.11 The Infectious Diseases Society of America/Society for Hospital Epidemiology
of America 2010 guidelines recommend against the use of probiotics for the primary prevention
of CDI based on limited data and possible adverse effects.1
In 2013, Goldenberg and colleagues published a meta-analysis of randomized controlled trials
investigating the use of various probiotics for the prevention of C. difficile-associated diarrhea
(CDAD) or CDI in adults or children receiving antibiotic therapy.12 The risk of CDAD was
evaluated in 23 randomized controlled trials (n=4213) and was shown to be significantly
reduced with probiotics (relative risk [RR] 0.36, 0.26 to 0.51). Additionally, the authors
evaluated the incidence of CDI in 13 trials (n=961) and found it not significantly different
between groups. The authors concluded that probiotics appeared to be effective in preventing
CDAD, but the optimal probiotic product, dosage, and length of treatment, as well as related
adverse events, needed to be studied further.3
To further investigate the relationship between probiotics and CDAD, Allen and colleagues
conducted the PLACIDE trial, a large-scale multicenter, randomized, double-blind, placebocontrolled study in elderly (≥65 years) hospitalized patients exposed to at least one antibiotic.13
Patients received a multistrain preparation of lactobacilli and bifidobacteria (n=1470) or placebo
(n=1471) for 21 days. There was no difference between study groups in the occurrence of
antibiotic-associated diarrhea or C. difficile diarrhea.
In 2012, Pozzoni and colleagues published a single-center, randomized, double-blind, placebocontrolled, parallel group trial in older hospitalized patients (>50 years).14 Patients received S.
boulardii (n=141) or placebo (n=134) within 48 hours of beginning antibiotic therapy and
continued treatment for 7 days after antibiotic cessation. S. boulardii was not effective in
preventing antibiotic associated diarrhea or CDAD.
Although a meta-analysis evaluating multiple products and doses in varied populations
demonstrated that probiotics may be effective in preventing CDAD, recent prospective studies
have been unable to demonstrate similar results. The role of probiotics in the primary
prevention of CDI remains unclear, and the risks and potential benefits of probiotic therapy
must be evaluated on a patient-specific basis.
Probiotics for Treatment and Secondary Prevention of CDI
Despite highly effective antibiotics available for the treatment of CDI, the rate of recurrence has
been estimated at 6% to 25% in the general population, with frequency in patients ≥65 years of
age reaching 50%.1,15 Current American and European guidelines do not support the use of
probiotics in the treatment of primary CDI or prevention of recurrent CDI due to lack of sufficient
and compelling evidence.15,16
Volume 14 Issue 1
April 2014
McFarland and colleagues conducted a double-blind, placebo-controlled trial to evaluate the
efficacy of S. boulardii in reducing the incidence of recurrence in patients with active CDI (initial
or recurrent disease) who were receiving metronidazole or vancomycin.17 Patients were
randomized to receive S. boulardii or placebo for 4 weeks. Overall, those treated with S.
boulardii had a lower rate of CDI recurrence (adjusted RR 0.43, 0.20-0.97). This result was
largely influenced by the subgroup of 60 patients (48.3%) with recurrent disease who had a
reduction in recurrence from 64.7% to 34.6% (P=0.04). There was no significant reduction in
recurrence for patients with their initial episode of CDI; however, treatment failure in this group
was low overall.
Focusing on secondary prevention of CDI, Surawicz and colleagues conducted a double-blind,
placebo-controlled, multicenter trial of 32 patients randomized to receive S. boulardii beginning
on day 7 of a 10-day high-dose oral vancomycin regimen and continued for 28 days.18 When
combined with high-dose vancomycin, those receiving S. boulardii had a significantly reduced
incidence of recurrent CDI compared to patients receiving placebo (16.7% vs. 50%, P=0.05).
In 2003, Wullt et al conducted a prospective, placebo-controlled multicenter trial of 21 patients
who were randomized to receive metronidazole for 10 days in combination with a fruit drink
containing oats fermented with Lactobacillus plantarum 299v or placebo for an additional 28
days.19 The majority of patients in each group had clinical and bacteriologic cure of CDI with no
difference between groups. Thirty-six percent of patients in the treatment group and 67% of
patients in the placebo group had recurrence of CDAD at 70 days; however, these results did
not reach statistical significance and the study was underpowered due to slow enrollment.
A meta-analysis of the trials cited and other pilot studies showed combined results favored
probiotics (RR 0.59, 0.41-0.85); however, post hoc analysis contributed this effect largely to
patients with recurrent CDI.20 A Cochrane review of the same studies concluded that there was
insufficient evidence to recommend probiotics in the treatment of CDAD.21
Large scale trials addressing the treatment and secondary prevention of recurrent CDI have
provided varied results. Further evidence will be needed to evaluate the usefulness of
probiotics, including determination of the appropriate strain, dose, and duration of therapy.
Conclusions
Probiotics are not recommended for the treatment or prevention of CDI based on lack of
conclusive supporting evidence, as well as the risk of adverse events. 1 While some small trials
and meta-analyses have shown probiotics to be effective, large-scale trials utilizing a single
dose and product in specific populations have failed to demonstrate benefit. The potential
complications of bacteremia, fungemia, endocarditis, and possible mortality currently outweigh
any benefit.
References
1. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium
difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of
America and the Infectious Disease Society of America. Infect Control Hosp Epidemiol.
2010;31:431-455.
2. Healthcare Utilization and Cost Project. Clostridium difficile infections (CDI) in hospital
stays, 2009: Statistical Brief #124. January 2012. www.hcupus.ahrq.gov/reports/statbriefs/sb124.pdf. Accessed February 15, 2014.
3. World Health Organization and Food and Agriculture Organization of the United Nations.
Health and nutritional properties of probiotics in food including powder milk with live lactic
acid bacteria. October 2011.
www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf.
Volume 14 Issue 1
April 2014
Accessed February 15, 2014.
4. Parkes GC, Sanderson JD, Whelan K. The mechanisms and efficacy of probiotics in the
prevention of Clostridium difficile-associated diarrhea. Lancet Infect Dis. 2009;9:237-244.
5. Varughese CA, Vakil NH, Phillips KM. Antibiotic-associated diarrhea: a refresher on
causes and possible prevention with probiotics. J Pharm Pract. 2013;26:476-482.
6. U.S. Food and Drug administration. Dietary supplements.
www.fda.gov/food/dietarysupplements/. Accessed February 15, 2014.
7. Venugopalan V, Shriner KA, Wong-Beringer A. Regulatory oversight and safety of probiotic
use. Emerg Infect Dis. 2010;11:1661-1665.
8. Besselink MG, van Santvoort HC, Buskens E, et al. Probiotic prophylaxis in predicted
severe acute pancreatitis: a randomized, double-blind, placebo-controlled trial. Lancet.
2008;371:651-659.
9. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the
risks? Am J Clin Nutr. 2006;83:1256-1264.
10. Gueimonde M, Sanchez B, de los Reyes-Gavilan CG, Margolles A. Antibiotic resistance in
probiotic bacteria. Front Microbiol. 2013;4:1-6.
11. Johnson S, Maziade PJ, McFarland LV, et al. Is primary prevention of Clostridium difficile
infection possible with specific probiotics? Int J Infect Dis. 2012;16:e786-e792.
12. Goldenberg JZ, Ma SS, Saxton JD, et al. Probiotics for the prevention of Clostridium
difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev.
2013;5:CD006095.
13. Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of
antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients
(PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet.
2013;382:1249-1257.
14. Pozzoni P, Riva A, Bellatorre AG, et al. Saccharomyces boulardii for the prevention of
antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized,
double-blind, placebo-controlled trial. Am J Gastroenterol. 2012;107:922-931.
15. Kee VR. Clostridium difficile infections in older adults: a review and update on its
management. Am J Geriatr Pharmacother. 2012;10(1):14-24.
16. Debast SB, Bauer MP, Kuilper EJ. European Society of Clinical Microbiology and Infectious
Disease: update of the treatment guidance document for Clostridium difficile infection. Clin
Microbiol Infect. 2014;20(S2):1-26.
17. McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of
Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile
disease. JAMA. 1994;271(24):1913-1918.
18. Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for
recurrent Clostridium difficile disease: use of high-dose vancomycin combined with
Saccharomyces boulardii. Clin Infect Dis. 2000;31:1012-1017.
19. Wullt M, Hagslatt Johansson ML, Odenholt I. Lactobacillus plantarum 299v for treatment of
recurrent Clostridium difficile-associated diarrhea: a double-blind, placebo-controlled trial.
Scand J Infect Dis. 2003;35:365-367.
20. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated
diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol.
2006;101:812-822.
21. Pillai A, Nelson RL. Probiotics for the treatment of Clostridium difficile-associated colitis in
adults. Cochrane Database of Systematic Reviews. 2008;1:1-16.
Volume 14 Issue 1
April 2014
CPP Member Spotlight
by Drayton Hammond, PharmD, MBA, BCPS
Calvin Tucker, PharmD, BCPS, serves as one of the
adult critical care clinical pharmacy specialists at St.
Vincent’s Medical Center Riverside in Jacksonville, FL.
St. Vincent’s Medical Center Riverside is part of the St.
Vincent’s HealthCare health system, which includes two
tertiary, acute-care hospitals containing 1,081 beds in
addition to a long-term skilled nursing facility. It is home
to the largest cardiovascular program between Orlando,
FL, and Atlanta, GA, performing over 20,000
cardiovascular procedures annually. The Riverside campus has over 60 ICU beds with
dedicated areas to medicine, cardiology, cardiothoracic surgery, surgery, and neurology. In
2011, Calvin began practicing in the mixed medical-surgical intensive care unit. He is an
assistant professor at the University of Florida College of Pharmacy and is the President-elect
for the Northeast Florida Society of Health-system Pharmacists (NEFSHP).
As soon as you meet Calvin, you realize he is an exceptionally professional, visionary and
(self-described) intense critical care pharmacist. His passion for the betterment of patient care
is evident through his involvement in interprofessional committees and healthcare teams at his
hospital. One of his greatest traits is the ability to motivate and articulate concepts and
successful practices to residents and students he encounters through his classes and rotation.
Calvin’s aunt actually introduced him to the idea of pursuing clinical pharmacy because of his
passion for helping others. He completed his education at the University of Florida College of
Pharmacy, where he became interested in the care pharmacists can provide for critically ill
patients. During his PGY1 residency at Shands Jacksonville Medical Center (now University of
Florida Health Jacksonville), his proclivity for critical care grew exponentially. This led Calvin to
pursue a PGY2 in critical care at Jackson Healthcare in the Miami Florida. He obtained his BCPS
certification and plans to sit for the critical care certification exam in 2015. He spends the majority
of his time in the mixed medical-surgical intensive care unit, as well as coordinating and leading
many committees and initiatives in the residency program. He is especially proud of the growth in
research endeavors and the impact the residents have on patient care within the medical center.
Calvin is actively involved in clinical research with a variety of healthcare practitioners,
including pharmacy residents, students and colleagues from other institutions, as well as
physicians and nurses. He is the coordinator for pharmacy resident research at his institution.
His research areas of interest include sedation and analgesia, infectious diseases in critically ill
patients, and medication dosing in obesity.
Calvin is actively involved in professional organizations as well as his institution’s residency
program and local colleges of pharmacy. In addition to his involvement in NEFSHP, he is active
in committees for the Society of Critical Care Medicine and Florida Society of Health-system
Pharmacists. He is a preceptor for pharmacy students from the six colleges of pharmacy in
Florida and the PGY1 residents at St. Vincent’s Medical Center Riverside. He coordinates and
teaches in elective classes at the University of Florida College of Pharmacy. Calvin possesses
Volume 14 Issue 1
April 2014
a unique ability to explain complex critical care concepts to learners and models effective and
professional interactions with all members of the healthcare team.
We can all congratulate Calvin for his recent marriage to the love of his life, Lyn. In his free
time, Calvin enjoys outdoor sports, weight training, reading; documentaries are his guilty
pleasure.
Miscellaneous Sections
Frequently Asked Question
How do I get into the CPP iRoom?
Click on Using the SCCM CPP I-room, the section "how to" guide.
The Critical Care Pharmacotherapy Trials Network (CCPTN)
CCPTN will be issuing a call for proposals in June for submission before a November deadline.
More information will be contained in an upcoming newsletter item. For more information
regarding the CCPTN, please refer to: http://www.pharmacy.vcu.edu/ccptn/.
Communications Committee members are charged with publishing the newsletter.
Thanks to the following members:
Deepali Dixit (Chair)
Simon Lam (Chair-Elect)
Amy L. Dzierba (MAL)
Kate Adamczyk
Farooq Bandali
Kim Berger
Aida Rebecca Bickley
Marilyn Bulloch
Darlene Chaykosky
Jessica Crow
Garrett Curtis
Stephanie Davis
Hammond Drayton
Chris Droege
Michaelia Dunn
Diana Esaian
Stacey Folse
Amanda Giancarelli
Daryl Glick
Payal K Gurnani
Susan Hamblin
John Hammer
Angela Haskell
Tudy Hodgman
Julie Kalabalik
Kirstin Kooda
Jim Landzinski
Xi Liu-Deryke
Jason Makii
Tom Moran
Justin Muir
Aljuhani Ohoud
Mona K. Patel
Tom Smooth
Joanna Stollings
Ed Sypniewski
Calvin Tucker
Upcoming SCCM Congress Meetings – Save the Date!
2015
2016
2017
January 17-21
February 20-24
January 21-25
Phoenix, Arizona
Orlando, Florida
Honolulu, Hawaii