Hospital Pharmacy - June 2018 - 153

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McPheeters et al
in sepsis reported a reduction in mortality associated with
statin users.13 One prospective cohort analysis found that
statin therapy improved 28-day survival in patients with
severe sepsis-associated acute respiratory distress syndrome
(ARDS) with significantly more vasopressor-free days compared with those without statin therapy.14 In contrast,
Zechmeister et al were not able to identify a statistically significant decrease in the duration or dose of vasopressor use
in patients with septic shock. However, a nonsignificant
trend toward decreased mortality was identified.15 Due to
this variability in the literature, the purpose of this study was
to evaluate the implications of statin use on the duration of
vasopressor therapy in the setting of septic shock in patients
exposed to statin therapy prior to admission.

Methods
Study Design and Patient Population
Patients for this multicenter, retrospective cohort analysis
were identified through a medical record query of
International Classification of Diseases, Ninth Revision
(ICD-9) codes for septic shock (785.52/ICD-9). The definition of septic shock used to enroll patients was based on the
2012 "Surviving Sepsis Campaign Guidelines for
Management of Severe Sepsis and Septic Shock."16 The
University of Louisville Hospital is a level I trauma center
and academic medical center, while Jewish Hospital is a
large tertiary referral center. This study was approved by the
institutional review board at both facilities. Patients at both
institutions were included if they were age 18 years or
greater, presented with septic shock, and were treated with a
vasopressor for at least 6 hours. Those who were exposed to
statin therapy prior to admission were compared with those
with no prior exposure. Patients were excluded if they had a
contraindication to statins, were pregnant, or were incarcerated. Each facility utilized a protocol for sepsis management
which specified appropriate antibiotics for administration.
Baseline characteristics included age at admission,
weight, body mass index (BMI), gender, race, smoking history, and presenting source of infection. Certain preexisting
conditions deemed to contribute to inflammation were determined a priori and were also collected: coronary artery disease (CAD), congestive heart failure (CHF), chronic
obstructive pulmonary disease (COPD), stroke, diabetes
mellitus (DM), transplant, human immunodeficiency virus
(HIV), and cancer.

Outcomes
The primary outcome of this study was to compare the duration of vasopressor therapy in patients with and without
statin exposure in the setting of septic shock. Secondary outcomes included intensive care unit (ICU) and hospital lengths
of stay, in-hospital mortality, admission sequential organ

Figure 1. Flowchart of patient population analyzed.

failure assessment (SOFA) scores, number of vasopressors
required, time to first dose of antimicrobials, days of antimicrobial therapy, and steroid use. The number of vasopressors
required and its correlation to hospital mortality were also
examined.

Statistical Analysis
Continuous data were tested for normality. Due to lack of
normality, a nonparametric Wilcoxon 2-sample test was
used. Hospitalization data and mortality were described as
medians and interquartile ranges (IQRs) or counts and percentages, based on the class of data (continuous or categorical, respectively). Differences between groups for
categorical measures were tested using chi-square tests or
Fisher's exact test. Analyses were performed in SAS version
9.4 (SAS Institute, Cary, North Carolina) with a significance
level of P ≤ .05.

Results
A total of 88 statin therapy cases and 205 unexposed controls
were identified from January 2013 through June 2015 and
included for analysis (Figure 1). Testing determined that
stratified analyses were not required for the 2 institutions
included. Statin-exposed patients were older, less likely to be
current smokers, and more likely to have the following preexisting conditions: CAD, stroke, and DM. There were no
differences noted in end-organ dysfunction (Table 1).

Vasopressor Therapy
The duration of vasopressor use did not differ in patients
with septic shock based on prior statin exposure (Table 2).
There were more outliers among patients without exposure
to statins (0-32 vs 0-14 days). The number of vasopressors

Table of Contents for the Digital Edition of Hospital Pharmacy - June 2018