Evaluation of recombinant activated protein C for severe sepsis at a tertiary academic medical center

Kevin E Anger,1 Jeremy R DeGrado,1 Bonnie C Greenwood,1 Steven A Cohen,2 Paul M Szumita1 1Department of Pharmacy, Brigham and Women&rsquo;s Hospital, Boston, MA, USA; 2Department of Family Medicine and Population Health, Division of Epidemiology, Virginia Commonwealth University, Richmond, VA, USA Purpose: Early clinical trials of recombinant human activated protein C (rhAPC) for severe sepsis excluded patients at high risk of bleeding. Recent literature suggests bleeding rates are higher in clinical practice and may be associated with worsened outcomes. Our objective was to evaluate baseline demographics; incidence, and risk factors for major bleeding; and mortality of patients receiving rhAPC for severe sepsis at our institution. Methods: A retrospective study was performed for all patients receiving rhAPC for treatment of severe sepsis at a tertiary academic medical center from January 2002 to June 2009. Demographic information, clinical variables, intensive care unit, and hospital outcomes were recorded. Results: Of the 156 patients that received rhAPC, 54 (34.6%) did not meet institutional criteria for safe use at baseline due to bleeding precaution or contraindication. Twenty-three (14.7%) patients experienced a major bleeding event. Multivariate analysis demonstrated baseline International Normalized Ratio &ge;2.5 (odds ratio [OR] 3.68, 95% confidence interval [CI]: 1.28&ndash;10.56; P = 0.03) and platelet count &le;100 &times; 103/mm3 (OR 2.86, 95% CI: 1.07&ndash;7.67; P = 0.01) as significant predictors of a major bleed. Overall hospital mortality was 57.7%. Multivariate analysis demonstrated the presence of &ge;3 organ dysfunctions (OR 2.46, 95% CI: 1.19&ndash;5.09; P < 0.05) and medical intensive care unit admission (OR 1.99, 95% CI: 1.00&ndash;3.98; P = 0.05) were independent variables associated with hospital mortality. Conclusion: Patients receiving rhAPC at our institution had higher APACHE II scores, mortality, and major bleeding events than published postmarketing studies. Risk factors for major bleeding other than package-labeling contraindications and bleeding precautions were identified in our patient population. Keywords: severe sepsis, activated protein C, drotrecogin alfa, Xigri

Evaluation of the maximum beyond-use-date stability of regular human insulin extemporaneously prepared in 0.9% sodium chloride in a polyvinyl chloride bag

Megan A Rocchio, Caryn D Belisle, Bonnie C Greenwood, Michael C Cotugno, Paul M SzumitaDepartment of Pharmacy, Brigham and Women&#39;s Hospital, Boston, MA, USABackground: Regular human insulin 100 units added to a sufficient quantity of 0.9% sodium chloride, to yield a total volume of 100 mL within a polyvinylchloride bag, is accepted to be stable for 24 hours due to physical denaturation and chemical modification. The objective of this study was to evaluate the extended stability of such extemporaneously prepared regular human insulin, stored under refrigeration, to the maximum beyond-use-date allowed by United States Pharmacopeia chapter 797.Methods: At time &ldquo;0&rdquo; three admixtures of regular human insulin were prepared by withdrawing 1 mL of regular human insulin with a concentration of 100 units/mL and adding it to a sufficient quantity of 0.9% sodium chloride for injection in a polyvinylchloride bag to yield a total volume of 100 mL. The three admixtures were stored under refrigeration (2&deg;C&ndash;8&deg;C [36&deg;F&ndash;46&deg;F]), and one sample of each admixture was withdrawn and tested in duplicate at 0, 6, 24, 48, 72, 144, 168, 192, 216, 240, 312, and 336 hours. Utilizing high performance liquid chromatography, each sample underwent immediate testing. The time points were stable if the mean concentration of the samples exceeded 90% of the equilibrium concentration at 6 hours.Results: The equilibrium concentration was 0.89 units/mL. Time points were stable if the mean concentration was at least 0.80 units/mL. All time points retained at least 90% of the equilibrium concentration, with the exception of hour 168 (0.79 &plusmn; 0.03 units/mL). At 192 hours the mean concentration was 0.88 &plusmn; 0.03 units/mL. At 336 hours the mean concentration was 0.91 &plusmn; 0.02 units/mL.Conclusion: Based on these results, regular human insulin 100 units added to 0.9% sodium chloride for injection in a polyvinylchloride bag to yield a total volume of 100 mL is stable for up to 336 hours when stored at 2&deg;C&ndash;8&deg;C (36&deg;F&ndash;46&deg;F).Keywords: insulin, stability, storage, temperature, USP 797, sodium chloride, polyvinylchlorid

Implementation of a guideline for the treatment of pain, sedation, agitation and neuromuscular blockade in the mechanically ventilated adult patient in the emergency department

Kristin E White1, Paul M Szumita1, Nicki Gilboy2, Hillary A Keenan3, Christian Arbelaez21Department of Pharmacy Services, 2Department of Emergency Medicine, 3Center for Clinical Investigation, Brigham and Women&amp;#39;s Hospital, Boston, MA, USAPurpose: When emergency department (ED) overcrowding includes admitted mechanically ventilated (MV) critically-ill patients without an open intensive care unit (ICU) bed, emergency providers must deliver ICU level care in the ED. Implementing standardized hospital based clinical guidelines may help providers achieve uniform care standards for assessing and managing pain and sedation for the MV patient.Objective: This paper is a description of a hospital performance improvement project that was implemented in the ED. The objective of this study was to measure the degree of adoption of a hospital-wide clinical guideline for the management of pain, sedation and neuromuscular blockade in MV patients into clinical practice in the ED.Methods: A retrospective analysis was performed for all mechanically ventilated patients who were admitted from ED to an Intensive Care Unit (ICU). Patient charts were reviewed before (December 2005) and after the implementation of the guideline (June, August, and December 2006). Data was collected and analyzed for the ED visit only and no ICU data was used. The primary outcome was the degree of adoption of the guideline by emergency providers into their daily clinical practice.Results: A convenience sample of 170 adult MV patients who were admitted to the ICU during the preselected time period was analyzed. There were no demographic differences between groups of patients observed during each month interval, age (P = 0.34), gender (P = 0.40), race (P = 0.14), and Hispanic ethnicity (P = 0.84). Overall, there was an increase in the provider use of propofol (P &amp;lt; 0.01), RASS sedation scale (P &amp;lt; 0.01), and a decrease in the use of a paralytic agent (P &amp;lt; 0.01).Conclusion: There was partial adoption of a guideline into their clinical practice by emergency providers in a busy urban emergency department. Across the 12-month implementation period, there was improvement in the assessment of and use of analgesia and sedation for MV patients.Keywords: clinical guideline, critical care, ICU, emergency department, sedation, pain, neuromuscular blocke