CASE STUDY
MULTIDISCIPLINARY INITIATIVE
Pharmacist involvement in a multidisciplinary initiative to reduce sepsis-related mortality An audio interview that supplements the information in this article is available on AJHP’s website at www.ajhpvoices.org. Readers can also access this interview through AJHP’s augmented reality (AR) feature by launching the Layar app and scanning this page with their mobile device. James R. Beardsley, Pharm.D., BCPS, Wake Forest Baptist Health, Winston-Salem, NC. Catherine M. Jones, M.D., M.S., University of Missouri Health Sciences Center, Columbia, MO. John Williamson, Pharm.D., BCPS, Wake Forest Baptist Health, WinstonSalem, NC. Jason Chou, Pharm.D., M.S., Ochsner Medical Center, New Orleans, LA. Margaret Currie-Coyoy, M.B.A., Wake Forest Baptist Health, Winston-Salem, NC. Teresa Jackson, R.N., Wake Forest Baptist Health, Winston-Salem, NC.
Purpose. Pharmacy department contributions to a medical center’s broad initiative to improve sepsis care outcomes are described. Summary. Timely and appropriate antimicrobial therapy is a key factor in optimizing treatment outcomes in patients with severe sepsis or septic shock. The inpatient pharmacy at Wake Forest Baptist Health implemented standardized processes to reduce order turnaround time and facilitate prompt antibiotic administration as part of the hospital’s multidisciplinary “Code Sepsis” initiative. The program includes (1) nurse-conducted screening for sepsis using a standard assessment instrument, (2) pager alerts notifying rapid-response, pharmacy, and other personnel of cases of suspected sepsis, (3) activation of an electronic order set including guideline-based antibiotic therapy recommendations based on local pathogen patterns, and (4) a protocol allowing pharmacists to select an antibiotic regimen if providers are busy with other patient care duties. Assessments conducted during and after implementation of the Code Sepsis initiative showed improvements in key program metrics. The mean ± S.D. time from receipt of a Code Sepsis page to antibiotic delivery was reduced to 14.1 ± 13.7 minutes, the mean time from identification of suspected sepsis to antibiotic administration was reduced to 31 minutes in the hospital’s intensive care units and to 51 minutes in non–critical care units, and the institution’s performance on a widely used measure of sepsis-related mortality improved dramatically. Conclusion. Implementation of the Code Sepsis initiative was associated with reductions in order turnaround time, time to antibiotic administration, and sepsis-related mortality. Am J Health-Syst Pharm. 2016; 73:143-9
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DOI 10.2146/ajhp150186
epsis is a serious condition that is commonly encountered in hospitalized patients. Severe sepsis (acute organ dysfunction secondary to documented or suspected infection) and septic shock (severe sepsis accompanied by hypotension that cannot be reversed with fluid resuscitation) are associated with a mortality rate of approximately 25%.1 Studies have demonstrated that the speed of initiating appropriate antibiotic therapy influences treatment outcomes in patients with severe sepsis or septic shock.2-4 Guidelines on the management of sepsis have focused on conducting appropriate diagnostic tests and promptly initiating fluid and antimicrobial therapy.
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Address correspondence to Dr. Beardsley ([email protected]). Copyright © 2016, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/16/0201-0143.
Current Surviving Sepsis Campaign guidelines recommend the administration of effective i.v. antimicrobials within the first hour of recognition of septic shock or severe sepsis.1 Prompt administration of antibiotics is of the utmost importance, since each hour of delay is associated with a measurable increase in mortality for patients in septic shock.2,5-7 Wake Forest Baptist Health is an 885-bed, tertiary academic medical center with over 180 adult intensive care unit (ICU) beds. Data released by the University HealthSystem Consortium (UHC) revealed that the medical center’s sepsis-related mortality index (the observed death rate divided by the expected death rate)
CASE STUDY at the end of 2011 was twice the average value for the 10 best-performing UHC member institutions. This relatively poor performance occurred in spite of the facility’s implementation of an “early warning score” (EWS) screening tool8 (EWS values range from 0 to 20, with higher values indicating an increased risk of death within 24 hours) to help nurses identify unstable patients and a sepsis order set that contained a bundle of guideline-recommended sepsis treatments. These treatment guidelines included antimicrobial recommendations based on results of an institution-specific pathogen analysis.9
Analysis and resolution Understanding the problem. During November and December 2011, an analysis of sepsis episodes in adult non–critical care units was conducted in an attempt to identify causes of suboptimal outcomes. Three areas of concern were revealed by this evaluation. First, although an EWS value of 8 or higher should prompt a call to alert the rapid response team, those calls were occurring in only 39% of cases. Second, the sepsis treatment bundle was being initiated in only 60.9% of patients identified as septic, and bundle initiation was occurring within 1 hour in only 5% of cases. Third, once sepsis was identified, only 5.4% of patients were receiving an antibiotic within 1 hour. The mean time from sepsis onset to antibiotic administration was 6.6 hours. The high mortality index for patients with sepsis prompted the medical center’s leadership to assemble a multidisciplinary task force to lead efforts to reduce sepsis-related mortality. A two-day planning retreat, undertaken in the spirit of kaizen (a business management philosophy aimed at ongoing quality improvement through incremental change), was held in February 2012. Attendees included representatives from the nursing and pharmacy departments
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KEY POINTS • Pharmacists can play important clinical and operational roles in improving the care of patients with sepsis. • Communication and teamwork were foundational to our success. • Allowing pharmacists to select Code Sepsis antibiotics freed physicians to concentrate on other aspects of the patient’s care. • This initiative was very meaningful to our entire organization because we were able to not only improve process metrics but decrease sepsisrelated mortality.
(including antibiotic stewardship pharmacists); respiratory care, rapid response, and performance improvement personnel; and medical staff from the departments of medicine, surgery, neurology, and anesthesiology. Initial efforts focused on adult patients in non–critical care units, with the expectation that the adult critical care units and the emergency department would be addressed at a later time. The task force established the goal of reducing the sepsis-related mortality index to a level equal to or below that of the 10 best-performing UHC member institutions. Implementation of “Code Sepsis” process. Drawing on the concept of a “code” that is called in response to a cardiopulmonary arrest or stroke, the task force developed a standardized process for early identification, communication, and intervention targeting patients with sepsis called “Code Sepsis.” In the Code Sepsis process, the bedside nurse is responsible for notifying the rapid response team and the “first call provider” (the assigned physician or midlevel practitioner) if a patient
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has an EWS value of 8 or higher. The rapid response nurse then performs a sepsis screen; if the screen is positive (defined as an actual or potential infection plus fulfillment of two or more diagnostic criteria for systemic inflammatory response syndrome), the Code Sepsis process is initiated. The nurse calls the hospital’s emergency response system, which generates a text page to the inpatient pharmacy, respiratory therapy department, blood gas laboratory, and ICU triage nurse stating the name and room number of the Code Sepsis patient. All care team members respond to this page to ensure that appropriate care is provided in a timely manner. Of note, the Code Sepsis process identifies patients who might have sepsis. In some cases, other reasons for the patient’s instability (e.g., pulmonary embolus, fluid overload, gastrointestinal bleeding) may be recognized upon in-depth examination of the patient. In these cases, the sepsis bundle (including antibiotics) is not initiated and care is directed toward the patient’s underlying condition. Individual care components. Various task force personnel were assigned to educate nurses on the proper response to an elevated EWS value, instruct providers on the importance of prompt bundle initiation, and increase hospitalwide awareness of sepsis. Pharmacy department representatives on the task force focused on improving the individual components of sepsis care related to timely administration of antibiotics. The process was divided into three stages, as described below. Stage 1: Time from recognition of probable sepsis to antibiotic ordering. In discussing obstacles to timely antibiotic ordering during planning meetings for the Code Sepsis initiative, prescribers acknowledged occasionally losing track of time while doing a workup or performing a procedure (e.g., inserting a central line). To help providers make prompt decisions regarding antimicrobial
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initiation, the pharmacy staff was tasked with calling the nursing unit 15 minutes after a Code Sepsis call to inquire about antibiotics if they had not already been ordered. A protocol that allows pharmacists to select antibiotics for Code Sepsis patients if the prescriber is busy with other aspects of care was implemented. Under this protocol, providers indicate that they want pharmacists to order new antibiotics and specify the probable source of infection. Pharmacists review the patient’s medical record, including information on allergies, prior antibiotic therapy, and previous culture results, and then order the antibiotics. In most cases antibiotics are chosen according to the institution’s antibiotic recommendations for sepsis, but alternative antibiotics may be initiated if characteristics of the patient’s case suggest that a different regimen is more appropriate. Stage 2: Time from antibiotic order to unit delivery. During development of the Code Sepsis program, each aspect of medication order processing was analyzed to remove barriers to the rapid delivery of antibiotics for patients with sepsis. The task force had determined that the main deficiency in pharmacy processes was the lack of a systematic way to elevate those antibiotic orders to the highest priority for all personnel. Therefore, a process to enhance communication regarding Code Sepsis orders was developed. On receiving a Code Sepsis page, a pharmacist announces to the rest of the inpatient pharmacy staff that there is a Code Sepsis on a particular patient (the name and room number are given); this notifies all pharmacists who are verifying orders to be on alert for antibiotic orders for that patient even if they are not stat orders. Once the antibiotic order is verified, each “handoff” in the order process (from the pharmacist verifying the order to the technician preparing the medication to the pharmacist checking the medication to the technician delivering the medication via pneumatic
tube) is accompanied by a verbal acknowledgement: “These are Code Sepsis antibiotics.” The steps of the pharmacy’s Code Sepsis workflow are summarized in Figure 1. Stage 3: Time from unit delivery to administration. The pneumatic tube
system was determined to be the fastest method of delivering medications to a nursing unit, so this was designated as the standard delivery method for Code Sepsis antibiotics. When it was discovered that antibiotics were sometimes inadvertently
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Figure 1. Workflow for antibiotic order processing at the inpatient pharmacy at Wake Forest Baptist Health in cases involving Code Sepsis alerts.
Pharmacy notified of Code Sepsis alert via pager.
Pharmacist announces Code Sepsis alert, with patient’s name and room number, and records time.
Pharmacist reviews patient’s medical record for pertinent information (e.g., allergies, prior and current antibiotic therapy, recent cultures, renal function, relevant progress notes).
If no new antibiotic(s) is ordered within 15 minutes of Code Sepsis alert, pharmacist calls nursing unit to ask if new antibiotic(s) will be needed. If so, pharmacist asks if provider wants pharmacy to select antibiotics and inquires about the presumed source of infection; if antibiotics are not needed, no further action taken.
Order for new antibiotic(s) verified by pharmacist.
Pharmacist communicates to technicians preparing antibiotic(s) that order is for Code Sepsis case.
Antibiotic(s) prepared and handed to pharmacist for checking. Pharmacist informed that antibiotic(s) is for Code Sepsis case.
After final verification, pharmacist hands antibiotic(s) to technician, who is informed of Code Sepsis status. Technician sends antibiotic(s) to nursing station via pneumatic tube.
Pharmacist records in Code Sepsis database patient’s medical record and room numbers, time of Code Sepsis alert page, time antibiotic(s) was sent, and whether or not antibiotic(s) was ordered by pharmacist.
CASE STUDY placed in the medication room or left in the tube station, special “stat” stickers were attached to Code Sepsis antibiotics. These stickers helped to alert all team members on the nursing unit that Code Sepsis antibiotics were available and should be given to the appropriate nurse for prompt administration. Since Code Sepsis orders often include more than one antibiotic, pharmacists developed a set of principles to guide the order of antibiotic administration. A compatibility chart for common Code Sepsis antibiotics was also developed to encourage nurses to administer antibiotics simultaneously whenever possible. Expansion to critical care areas. An interim analysis conducted in November 2012 showed that the mean time from arrival of the rapid response nurse to administration of antibiotics was 53 minutes for Code
MULTIDISCIPLINARY INITIATIVE
Sepsis patients, which was a significant improvement over the average of 396 minutes during a specified baseline period (May–July 2012). The institution’s adjusted mortality index for sepsis had decreased by 16%, from 1.65 to 1.39. Based on these encouraging findings, the Code Sepsis initiative was expanded to adult critical care areas and the emergency department. Planning for this expansion was initiated with a second multidisciplinary kaizen event in November 2012 and continued in many subsequent meetings. Due to the unique characteristics of the critical care population, some adjustments were made to the Code Sepsis screening and order-set activation processes. However, pharmacy processes, including the protocol allowing pharmacists to order antibiotics in Code Sepsis cases, remained in
Table 1. Key Dates in Code Sepsis Initiative Planning and Implementationa Date
Event
Feb 2012
Initial kaizen event
Apr 2012
Code Sepsis process implemented in non–critical care units
Nov 2012
Second kaizen event (focused on critical care patients)
Feb 2013
Code Sepsis pilot program implemented in one surgical ICU
Mar 2013
Implementation in emergency department
Apr 2013
Implementation in all surgical ICUs
Jul 2013
Implementation in coronary care unit
Aug 2013
Implementation in medical ICUs
ICU = intensive care unit.
a
Table 2. Antibiotic Ordering Outcomes in Random Sample of Code Sepsis Episodes (n = 50)a Outcome
No. (%) Patients
New antibiotic(s) ordered
32 (64)
By prescriber
23 (46)
By pharmacist per protocol
9 (18)
No new antibiotic(s) ordered
18 (36)
Antibiotic therapy not needed
9 (18)
Patient already receiving broad-spectrum antibiotics
9 (18)
Sampling period was 12 months (April 2013–March 2014).
a
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place. The Code Sepsis initiative was implemented in a stepwise fashion throughout various critical care areas (Table 1). No additional pharmacy personnel were required for Code Sepsis program implementation. Antibiotic treatment recommendations for patients with sepsis did not change throughout the baseline and postimplementation periods, nor were there notable changes in the hospital’s antibiogram or the pharmacy’s i.v. preparation methods or technologies. Impact assessment. Process outcomes. The mean ± S.D. numbers of Code Sepsis episodes per month in the ICUs and non–critical care units were 29 ± 9.3 and 56 ± 15.4, respectively. Table 2 summarizes the results of an analysis of a random sample of 50 Code Sepsis episodes representing 5% of episodes that occurred from April 2013 through March 2014. New antibiotics were ordered in approximately two thirds of Code Sepsis cases. Antibiotics were ordered by pharmacists in 18% of those cases (28% of all Code Sepsis episodes in which new antibiotics were ordered). The mean ± S.D. time from receipt of a Code Sepsis page to delivery of antibiotics to the nursing unit was 14.1 ± 13.7 minutes; since that included time devoted to antibiotic ordering as well as pharmacy processing, it was felt that the average of just over 14 minutes indicated rapid execution of those steps of the Code Sepsis process. After the Code Sepsis initiative was implemented, the mean time from rapid response nurse arrival on the unit to antibiotic administration decreased from 396 minutes to 51 minutes for patients in non–critical care units. The time from a positive sepsis screen to antibiotic administration also decreased in the ICUs as the Code Sepsis rollout was extended to the various critical care units (Figure 2). From September 2013 (i.e., after program implementation in the medical ICUs) through March 2014, the mean value was 31 minutes, as
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Figure 2. Trend in a key Code Sepsis program metric (the mean time from a positive sepsis screen to antibiotic administration) across all intensive care units (ICUs) of Wake Forest Baptist Health (green line) before, during, and after stepwise implementation of the Code Sepsis initiative in relation to the preimplementation goal of 60 minutes (red dashed line). The baseline period was May–July 2012.
450
400
350 Implementation in select surgical ICUs
Mean Time (min)
300
250
Implementation in remainder of surgical ICUs
200
Implementation in medical ICUs
150
100
50
0
Baseline period
Feb 2013
Mar 2013
Apr 2013
May 2013
Jun 2013
Jul 2013
Aug 2013
Sep 2013
Oct 2013
Nov 2013
Dec 2013
Jan 2014
Feb 2014
Mar 2014
Month and Year
compared with the baseline time of 427 minutes. Other aspects of sepsis care also improved after implementation of the Code Sepsis initiative. Rapid response calls for an EWS value of 8 or higher exceeded 80%, and initiation of all aspects of the sepsis bundle within one hour occurred in over 70% of Code Sepsis episodes. Patient outcomes. Figure 3 displays the institution’s sepsis-related mortality index over time in relation to the mean performance of top-performing facilities in the UHC
database. The institution’s sepsisrelated mortality index dropped from a mean value of 1.65 for the five quarters prior to Code Sepsis implementation to 0.8 for the period April 2013–March 2014. The hospital is now considered one of the 10 topperforming UHC institutions for this metric. The reduction in the mortality index translates to over 200 lives saved per year.
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Discussion The ongoing Code Sepsis initia-
tive has highlighted the important operational and clinical roles that pharmacists can play in improving sepsis care. In both the planning and execution phases, the Code Sepsis program enhanced cooperation among prescribers, pharmacy staff, and nursing personnel. Pharmacy personnel worked with representatives of the medical and nursing staffs to analyze all aspects of the medication-use process relating to antibiotics for sepsis. Processes were then improved, and antibiotic turn-
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Figure 3. Trend of reduced sepsis-related mortality index at Wake Forest Baptist Health (green), as measured by the University HealthSystem Consortium (UHC) sepsis-related mortality index, relative to Code Sepsis program implementation landmarks. The (purple) trend line depicts the mean performance of 10 top-performing UHC member institutions.
1.9 Implementation in non–critical care units
Sepsis-Related Mortality Index
1.7
1.5 Implementation in ICUs begins
1.3
1.1
0.9
0.7
0.5
Q1 2011
Q2 2011
Q3 2011
Q4 2011
Q1 2012
Q2 2012
Q3 2012
Q4 2012
Q1 2013
Q2 2013
Q3 2013
Q4 2013
Q1 2014
Quarter and Year
around time decreased to a point that exceeded the expectations of most program participants. A challenge in all studies of the timeliness of sepsis treatment is to define “time 0” (i.e., the point at which sepsis is recognized); this is especially true with regard to patients who are already admitted to the hospital. In our study, values for time to antibiotic administration were reported separately for ICUs and non– critical care units to account for the slightly different screening processes used. The best documented time value for purposes of calculating baseline data in non–critical care units was the time to rapid-response nurse arrival on the unit; this was usually within a couple minutes of recognition of a patient’s unstable condition and was considered to be time 0 for those units. In the ICUs, we were able to assess the time at which vital signs
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met sepsis screening criteria, and the resulting time value was used to calculate baseline and postimplementation data for all critical care units. An important aspect of the Code Sepsis initiative was the implementation of a protocol that allows pharmacists to choose sepsis antibiotics. The idea of allowing pharmacists to choose Code Sepsis antibiotics came from the chief medical officer, who recognized pharmacists’ ability to perform this clinical task. Allowing pharmacists to take on this responsibility freed up physicians to focus on other critical aspects of the patient’s care without delaying the administration of antimicrobial therapy. It appears that this type of protocol is fairly unique, as we are unaware of the existence of similar protocols at other institutions. Flynn and colleagues10 recently published data from a study that
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also demonstrated the important role that pharmacists can play in improving the care provided to patients with sepsis. As part of their institution’s Coordinated Response to Sepsis (CaRTS) initiative, pharmacists are paged to the patient’s bedside when the sepsis order set is activated. These pharmacists help facilitate appropriate sepsis care, including the selection and delivery of antibiotics. After implementation of the CaRTS program, there were significant increases in the number of patients receiving antibiotics within one hour and the number of septic patients with a central venous pressure of at least 8 mm Hg at six hours. Our institution achieved the goal set at the introduction of the Code Sepsis initiative; the institution is now one of the top 10 UHC performers in terms of sepsis-related mortality. However, because the program
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was implemented as part of a process improvement initiative rather than a controlled study, we acknowledge that factors other than the Code Sepsis initiative might also have had a favorable impact on that metric. Likewise, although we are pleased that the time from sepsis recognition to antibiotic administration is now under one hour in most cases, it is impossible to precisely determine the degree to which this improvement affected sepsis mortality. However, given the data linking reduced mortality and the prompt administration of antimicrobial therapy to patients with severe sepsis and septic shock, it is likely that process improvements instituted through the Code Sepsis initiative have had a significant impact on patient outcomes.
Conclusion Implementation of the Code Sepsis initiative was associated with improvements in order turnaround time, time to antibiotic administration, and sepsis-related mortality.
Disclosures The authors have declared no potential conflicts of interest.
Previous affiliations At the time of Code Sepsis program implementation, Dr. Jones and Dr. Chou were affiliated with Wake Forest Baptist Health, Winston-Salem, NC.
Additional information The authors won a 2014 ASHP Best Practices Award for the program described here.
References 1. Dellinger RP, Levy MM, Rhodes A et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41:580-637. 2. Gaieski DF, Mikkelsen ME, Band RA et al. Impact of time of antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010; 38:1045-53. 3. Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345:1368-77. 4. Levy MM, Dellinger RP, Townsend SR et al. The Surviving Sepsis Campaign: results of an international guidelinebased performance improvement program targeting severe sepsis. Crit Care Med. 2010; 38:367-74. 5. Kumar A, Roberts D, Wood KE et al. Duration of hypotension before
initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006; 34:1589-96. 6. Puskarich MA, Trzeciak S, Shapiro NI et al. Emergency Medicine Shock Research Network (EMSHOCKNET): association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med. 2011; 39:206671. 7. Ferrer R, Martin-Loeches I, Phillips F et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guidelinebased performance improvement program. Crit Care Med. 2014; 42:1749-55. 8. Prytherch DR, Smith GB, Schmidt PE, Featherstone PI. ViEWS—towards a national early warning score for detecting adult inpatient deterioration. Resuscitation. 2010; 81:932-7. 9. Hanzelka KM, Pierce CA, Beardsley JR et al. Influence of an institutionspecific sepsis protocol on the adequacy of empiric antimicrobial therapy. Hosp Pharm. 2010; 45:53844. 10. Flynn JD, McConeghy KW, Fannery AH et al. Utilization of pharmacist responders as a component of a multidisciplinary sepsis bundle. Ann Pharmacother. 2014; 48:1145-51.
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Pharmacist involvement in a multidisciplinary initiative to reduce sepsis-related mortality An audio interview that supplements the information in this article is available on AJHP’s website at www.ajhpvoices.org. Readers can also access this interview through AJHP’s augmented reality (AR) feature by launching the Layar app and scanning this page with their mobile device. James R. Beardsley, Pharm.D., BCPS, Wake Forest Baptist Health, Winston-Salem, NC. Catherine M. Jones, M.D., M.S., University of Missouri Health Sciences Center, Columbia, MO. John Williamson, Pharm.D., BCPS, Wake Forest Baptist Health, WinstonSalem, NC. Jason Chou, Pharm.D., M.S., Ochsner Medical Center, New Orleans, LA. Margaret Currie-Coyoy, M.B.A., Wake Forest Baptist Health, Winston-Salem, NC. Teresa Jackson, R.N., Wake Forest Baptist Health, Winston-Salem, NC.
Purpose. Pharmacy department contributions to a medical center’s broad initiative to improve sepsis care outcomes are described. Summary. Timely and appropriate antimicrobial therapy is a key factor in optimizing treatment outcomes in patients with severe sepsis or septic shock. The inpatient pharmacy at Wake Forest Baptist Health implemented standardized processes to reduce order turnaround time and facilitate prompt antibiotic administration as part of the hospital’s multidisciplinary “Code Sepsis” initiative. The program includes (1) nurse-conducted screening for sepsis using a standard assessment instrument, (2) pager alerts notifying rapid-response, pharmacy, and other personnel of cases of suspected sepsis, (3) activation of an electronic order set including guideline-based antibiotic therapy recommendations based on local pathogen patterns, and (4) a protocol allowing pharmacists to select an antibiotic regimen if providers are busy with other patient care duties. Assessments conducted during and after implementation of the Code Sepsis initiative showed improvements in key program metrics. The mean ± S.D. time from receipt of a Code Sepsis page to antibiotic delivery was reduced to 14.1 ± 13.7 minutes, the mean time from identification of suspected sepsis to antibiotic administration was reduced to 31 minutes in the hospital’s intensive care units and to 51 minutes in non–critical care units, and the institution’s performance on a widely used measure of sepsis-related mortality improved dramatically. Conclusion. Implementation of the Code Sepsis initiative was associated with reductions in order turnaround time, time to antibiotic administration, and sepsis-related mortality. Am J Health-Syst Pharm. 2016; 73:143-9
S
DOI 10.2146/ajhp150186
epsis is a serious condition that is commonly encountered in hospitalized patients. Severe sepsis (acute organ dysfunction secondary to documented or suspected infection) and septic shock (severe sepsis accompanied by hypotension that cannot be reversed with fluid resuscitation) are associated with a mortality rate of approximately 25%.1 Studies have demonstrated that the speed of initiating appropriate antibiotic therapy influences treatment outcomes in patients with severe sepsis or septic shock.2-4 Guidelines on the management of sepsis have focused on conducting appropriate diagnostic tests and promptly initiating fluid and antimicrobial therapy.
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Address correspondence to Dr. Beardsley ([email protected]). Copyright © 2016, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/16/0201-0143.
Current Surviving Sepsis Campaign guidelines recommend the administration of effective i.v. antimicrobials within the first hour of recognition of septic shock or severe sepsis.1 Prompt administration of antibiotics is of the utmost importance, since each hour of delay is associated with a measurable increase in mortality for patients in septic shock.2,5-7 Wake Forest Baptist Health is an 885-bed, tertiary academic medical center with over 180 adult intensive care unit (ICU) beds. Data released by the University HealthSystem Consortium (UHC) revealed that the medical center’s sepsis-related mortality index (the observed death rate divided by the expected death rate)
CASE STUDY at the end of 2011 was twice the average value for the 10 best-performing UHC member institutions. This relatively poor performance occurred in spite of the facility’s implementation of an “early warning score” (EWS) screening tool8 (EWS values range from 0 to 20, with higher values indicating an increased risk of death within 24 hours) to help nurses identify unstable patients and a sepsis order set that contained a bundle of guideline-recommended sepsis treatments. These treatment guidelines included antimicrobial recommendations based on results of an institution-specific pathogen analysis.9
Analysis and resolution Understanding the problem. During November and December 2011, an analysis of sepsis episodes in adult non–critical care units was conducted in an attempt to identify causes of suboptimal outcomes. Three areas of concern were revealed by this evaluation. First, although an EWS value of 8 or higher should prompt a call to alert the rapid response team, those calls were occurring in only 39% of cases. Second, the sepsis treatment bundle was being initiated in only 60.9% of patients identified as septic, and bundle initiation was occurring within 1 hour in only 5% of cases. Third, once sepsis was identified, only 5.4% of patients were receiving an antibiotic within 1 hour. The mean time from sepsis onset to antibiotic administration was 6.6 hours. The high mortality index for patients with sepsis prompted the medical center’s leadership to assemble a multidisciplinary task force to lead efforts to reduce sepsis-related mortality. A two-day planning retreat, undertaken in the spirit of kaizen (a business management philosophy aimed at ongoing quality improvement through incremental change), was held in February 2012. Attendees included representatives from the nursing and pharmacy departments
144
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KEY POINTS • Pharmacists can play important clinical and operational roles in improving the care of patients with sepsis. • Communication and teamwork were foundational to our success. • Allowing pharmacists to select Code Sepsis antibiotics freed physicians to concentrate on other aspects of the patient’s care. • This initiative was very meaningful to our entire organization because we were able to not only improve process metrics but decrease sepsisrelated mortality.
(including antibiotic stewardship pharmacists); respiratory care, rapid response, and performance improvement personnel; and medical staff from the departments of medicine, surgery, neurology, and anesthesiology. Initial efforts focused on adult patients in non–critical care units, with the expectation that the adult critical care units and the emergency department would be addressed at a later time. The task force established the goal of reducing the sepsis-related mortality index to a level equal to or below that of the 10 best-performing UHC member institutions. Implementation of “Code Sepsis” process. Drawing on the concept of a “code” that is called in response to a cardiopulmonary arrest or stroke, the task force developed a standardized process for early identification, communication, and intervention targeting patients with sepsis called “Code Sepsis.” In the Code Sepsis process, the bedside nurse is responsible for notifying the rapid response team and the “first call provider” (the assigned physician or midlevel practitioner) if a patient
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has an EWS value of 8 or higher. The rapid response nurse then performs a sepsis screen; if the screen is positive (defined as an actual or potential infection plus fulfillment of two or more diagnostic criteria for systemic inflammatory response syndrome), the Code Sepsis process is initiated. The nurse calls the hospital’s emergency response system, which generates a text page to the inpatient pharmacy, respiratory therapy department, blood gas laboratory, and ICU triage nurse stating the name and room number of the Code Sepsis patient. All care team members respond to this page to ensure that appropriate care is provided in a timely manner. Of note, the Code Sepsis process identifies patients who might have sepsis. In some cases, other reasons for the patient’s instability (e.g., pulmonary embolus, fluid overload, gastrointestinal bleeding) may be recognized upon in-depth examination of the patient. In these cases, the sepsis bundle (including antibiotics) is not initiated and care is directed toward the patient’s underlying condition. Individual care components. Various task force personnel were assigned to educate nurses on the proper response to an elevated EWS value, instruct providers on the importance of prompt bundle initiation, and increase hospitalwide awareness of sepsis. Pharmacy department representatives on the task force focused on improving the individual components of sepsis care related to timely administration of antibiotics. The process was divided into three stages, as described below. Stage 1: Time from recognition of probable sepsis to antibiotic ordering. In discussing obstacles to timely antibiotic ordering during planning meetings for the Code Sepsis initiative, prescribers acknowledged occasionally losing track of time while doing a workup or performing a procedure (e.g., inserting a central line). To help providers make prompt decisions regarding antimicrobial
CASE STUDY
MULTIDISCIPLINARY INITIATIVE
initiation, the pharmacy staff was tasked with calling the nursing unit 15 minutes after a Code Sepsis call to inquire about antibiotics if they had not already been ordered. A protocol that allows pharmacists to select antibiotics for Code Sepsis patients if the prescriber is busy with other aspects of care was implemented. Under this protocol, providers indicate that they want pharmacists to order new antibiotics and specify the probable source of infection. Pharmacists review the patient’s medical record, including information on allergies, prior antibiotic therapy, and previous culture results, and then order the antibiotics. In most cases antibiotics are chosen according to the institution’s antibiotic recommendations for sepsis, but alternative antibiotics may be initiated if characteristics of the patient’s case suggest that a different regimen is more appropriate. Stage 2: Time from antibiotic order to unit delivery. During development of the Code Sepsis program, each aspect of medication order processing was analyzed to remove barriers to the rapid delivery of antibiotics for patients with sepsis. The task force had determined that the main deficiency in pharmacy processes was the lack of a systematic way to elevate those antibiotic orders to the highest priority for all personnel. Therefore, a process to enhance communication regarding Code Sepsis orders was developed. On receiving a Code Sepsis page, a pharmacist announces to the rest of the inpatient pharmacy staff that there is a Code Sepsis on a particular patient (the name and room number are given); this notifies all pharmacists who are verifying orders to be on alert for antibiotic orders for that patient even if they are not stat orders. Once the antibiotic order is verified, each “handoff” in the order process (from the pharmacist verifying the order to the technician preparing the medication to the pharmacist checking the medication to the technician delivering the medication via pneumatic
tube) is accompanied by a verbal acknowledgement: “These are Code Sepsis antibiotics.” The steps of the pharmacy’s Code Sepsis workflow are summarized in Figure 1. Stage 3: Time from unit delivery to administration. The pneumatic tube
system was determined to be the fastest method of delivering medications to a nursing unit, so this was designated as the standard delivery method for Code Sepsis antibiotics. When it was discovered that antibiotics were sometimes inadvertently
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Figure 1. Workflow for antibiotic order processing at the inpatient pharmacy at Wake Forest Baptist Health in cases involving Code Sepsis alerts.
Pharmacy notified of Code Sepsis alert via pager.
Pharmacist announces Code Sepsis alert, with patient’s name and room number, and records time.
Pharmacist reviews patient’s medical record for pertinent information (e.g., allergies, prior and current antibiotic therapy, recent cultures, renal function, relevant progress notes).
If no new antibiotic(s) is ordered within 15 minutes of Code Sepsis alert, pharmacist calls nursing unit to ask if new antibiotic(s) will be needed. If so, pharmacist asks if provider wants pharmacy to select antibiotics and inquires about the presumed source of infection; if antibiotics are not needed, no further action taken.
Order for new antibiotic(s) verified by pharmacist.
Pharmacist communicates to technicians preparing antibiotic(s) that order is for Code Sepsis case.
Antibiotic(s) prepared and handed to pharmacist for checking. Pharmacist informed that antibiotic(s) is for Code Sepsis case.
After final verification, pharmacist hands antibiotic(s) to technician, who is informed of Code Sepsis status. Technician sends antibiotic(s) to nursing station via pneumatic tube.
Pharmacist records in Code Sepsis database patient’s medical record and room numbers, time of Code Sepsis alert page, time antibiotic(s) was sent, and whether or not antibiotic(s) was ordered by pharmacist.
CASE STUDY placed in the medication room or left in the tube station, special “stat” stickers were attached to Code Sepsis antibiotics. These stickers helped to alert all team members on the nursing unit that Code Sepsis antibiotics were available and should be given to the appropriate nurse for prompt administration. Since Code Sepsis orders often include more than one antibiotic, pharmacists developed a set of principles to guide the order of antibiotic administration. A compatibility chart for common Code Sepsis antibiotics was also developed to encourage nurses to administer antibiotics simultaneously whenever possible. Expansion to critical care areas. An interim analysis conducted in November 2012 showed that the mean time from arrival of the rapid response nurse to administration of antibiotics was 53 minutes for Code
MULTIDISCIPLINARY INITIATIVE
Sepsis patients, which was a significant improvement over the average of 396 minutes during a specified baseline period (May–July 2012). The institution’s adjusted mortality index for sepsis had decreased by 16%, from 1.65 to 1.39. Based on these encouraging findings, the Code Sepsis initiative was expanded to adult critical care areas and the emergency department. Planning for this expansion was initiated with a second multidisciplinary kaizen event in November 2012 and continued in many subsequent meetings. Due to the unique characteristics of the critical care population, some adjustments were made to the Code Sepsis screening and order-set activation processes. However, pharmacy processes, including the protocol allowing pharmacists to order antibiotics in Code Sepsis cases, remained in
Table 1. Key Dates in Code Sepsis Initiative Planning and Implementationa Date
Event
Feb 2012
Initial kaizen event
Apr 2012
Code Sepsis process implemented in non–critical care units
Nov 2012
Second kaizen event (focused on critical care patients)
Feb 2013
Code Sepsis pilot program implemented in one surgical ICU
Mar 2013
Implementation in emergency department
Apr 2013
Implementation in all surgical ICUs
Jul 2013
Implementation in coronary care unit
Aug 2013
Implementation in medical ICUs
ICU = intensive care unit.
a
Table 2. Antibiotic Ordering Outcomes in Random Sample of Code Sepsis Episodes (n = 50)a Outcome
No. (%) Patients
New antibiotic(s) ordered
32 (64)
By prescriber
23 (46)
By pharmacist per protocol
9 (18)
No new antibiotic(s) ordered
18 (36)
Antibiotic therapy not needed
9 (18)
Patient already receiving broad-spectrum antibiotics
9 (18)
Sampling period was 12 months (April 2013–March 2014).
a
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place. The Code Sepsis initiative was implemented in a stepwise fashion throughout various critical care areas (Table 1). No additional pharmacy personnel were required for Code Sepsis program implementation. Antibiotic treatment recommendations for patients with sepsis did not change throughout the baseline and postimplementation periods, nor were there notable changes in the hospital’s antibiogram or the pharmacy’s i.v. preparation methods or technologies. Impact assessment. Process outcomes. The mean ± S.D. numbers of Code Sepsis episodes per month in the ICUs and non–critical care units were 29 ± 9.3 and 56 ± 15.4, respectively. Table 2 summarizes the results of an analysis of a random sample of 50 Code Sepsis episodes representing 5% of episodes that occurred from April 2013 through March 2014. New antibiotics were ordered in approximately two thirds of Code Sepsis cases. Antibiotics were ordered by pharmacists in 18% of those cases (28% of all Code Sepsis episodes in which new antibiotics were ordered). The mean ± S.D. time from receipt of a Code Sepsis page to delivery of antibiotics to the nursing unit was 14.1 ± 13.7 minutes; since that included time devoted to antibiotic ordering as well as pharmacy processing, it was felt that the average of just over 14 minutes indicated rapid execution of those steps of the Code Sepsis process. After the Code Sepsis initiative was implemented, the mean time from rapid response nurse arrival on the unit to antibiotic administration decreased from 396 minutes to 51 minutes for patients in non–critical care units. The time from a positive sepsis screen to antibiotic administration also decreased in the ICUs as the Code Sepsis rollout was extended to the various critical care units (Figure 2). From September 2013 (i.e., after program implementation in the medical ICUs) through March 2014, the mean value was 31 minutes, as
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Figure 2. Trend in a key Code Sepsis program metric (the mean time from a positive sepsis screen to antibiotic administration) across all intensive care units (ICUs) of Wake Forest Baptist Health (green line) before, during, and after stepwise implementation of the Code Sepsis initiative in relation to the preimplementation goal of 60 minutes (red dashed line). The baseline period was May–July 2012.
450
400
350 Implementation in select surgical ICUs
Mean Time (min)
300
250
Implementation in remainder of surgical ICUs
200
Implementation in medical ICUs
150
100
50
0
Baseline period
Feb 2013
Mar 2013
Apr 2013
May 2013
Jun 2013
Jul 2013
Aug 2013
Sep 2013
Oct 2013
Nov 2013
Dec 2013
Jan 2014
Feb 2014
Mar 2014
Month and Year
compared with the baseline time of 427 minutes. Other aspects of sepsis care also improved after implementation of the Code Sepsis initiative. Rapid response calls for an EWS value of 8 or higher exceeded 80%, and initiation of all aspects of the sepsis bundle within one hour occurred in over 70% of Code Sepsis episodes. Patient outcomes. Figure 3 displays the institution’s sepsis-related mortality index over time in relation to the mean performance of top-performing facilities in the UHC
database. The institution’s sepsisrelated mortality index dropped from a mean value of 1.65 for the five quarters prior to Code Sepsis implementation to 0.8 for the period April 2013–March 2014. The hospital is now considered one of the 10 topperforming UHC institutions for this metric. The reduction in the mortality index translates to over 200 lives saved per year.
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Discussion The ongoing Code Sepsis initia-
tive has highlighted the important operational and clinical roles that pharmacists can play in improving sepsis care. In both the planning and execution phases, the Code Sepsis program enhanced cooperation among prescribers, pharmacy staff, and nursing personnel. Pharmacy personnel worked with representatives of the medical and nursing staffs to analyze all aspects of the medication-use process relating to antibiotics for sepsis. Processes were then improved, and antibiotic turn-
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Figure 3. Trend of reduced sepsis-related mortality index at Wake Forest Baptist Health (green), as measured by the University HealthSystem Consortium (UHC) sepsis-related mortality index, relative to Code Sepsis program implementation landmarks. The (purple) trend line depicts the mean performance of 10 top-performing UHC member institutions.
1.9 Implementation in non–critical care units
Sepsis-Related Mortality Index
1.7
1.5 Implementation in ICUs begins
1.3
1.1
0.9
0.7
0.5
Q1 2011
Q2 2011
Q3 2011
Q4 2011
Q1 2012
Q2 2012
Q3 2012
Q4 2012
Q1 2013
Q2 2013
Q3 2013
Q4 2013
Q1 2014
Quarter and Year
around time decreased to a point that exceeded the expectations of most program participants. A challenge in all studies of the timeliness of sepsis treatment is to define “time 0” (i.e., the point at which sepsis is recognized); this is especially true with regard to patients who are already admitted to the hospital. In our study, values for time to antibiotic administration were reported separately for ICUs and non– critical care units to account for the slightly different screening processes used. The best documented time value for purposes of calculating baseline data in non–critical care units was the time to rapid-response nurse arrival on the unit; this was usually within a couple minutes of recognition of a patient’s unstable condition and was considered to be time 0 for those units. In the ICUs, we were able to assess the time at which vital signs
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met sepsis screening criteria, and the resulting time value was used to calculate baseline and postimplementation data for all critical care units. An important aspect of the Code Sepsis initiative was the implementation of a protocol that allows pharmacists to choose sepsis antibiotics. The idea of allowing pharmacists to choose Code Sepsis antibiotics came from the chief medical officer, who recognized pharmacists’ ability to perform this clinical task. Allowing pharmacists to take on this responsibility freed up physicians to focus on other critical aspects of the patient’s care without delaying the administration of antimicrobial therapy. It appears that this type of protocol is fairly unique, as we are unaware of the existence of similar protocols at other institutions. Flynn and colleagues10 recently published data from a study that
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also demonstrated the important role that pharmacists can play in improving the care provided to patients with sepsis. As part of their institution’s Coordinated Response to Sepsis (CaRTS) initiative, pharmacists are paged to the patient’s bedside when the sepsis order set is activated. These pharmacists help facilitate appropriate sepsis care, including the selection and delivery of antibiotics. After implementation of the CaRTS program, there were significant increases in the number of patients receiving antibiotics within one hour and the number of septic patients with a central venous pressure of at least 8 mm Hg at six hours. Our institution achieved the goal set at the introduction of the Code Sepsis initiative; the institution is now one of the top 10 UHC performers in terms of sepsis-related mortality. However, because the program
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was implemented as part of a process improvement initiative rather than a controlled study, we acknowledge that factors other than the Code Sepsis initiative might also have had a favorable impact on that metric. Likewise, although we are pleased that the time from sepsis recognition to antibiotic administration is now under one hour in most cases, it is impossible to precisely determine the degree to which this improvement affected sepsis mortality. However, given the data linking reduced mortality and the prompt administration of antimicrobial therapy to patients with severe sepsis and septic shock, it is likely that process improvements instituted through the Code Sepsis initiative have had a significant impact on patient outcomes.
Conclusion Implementation of the Code Sepsis initiative was associated with improvements in order turnaround time, time to antibiotic administration, and sepsis-related mortality.
Disclosures The authors have declared no potential conflicts of interest.
Previous affiliations At the time of Code Sepsis program implementation, Dr. Jones and Dr. Chou were affiliated with Wake Forest Baptist Health, Winston-Salem, NC.
Additional information The authors won a 2014 ASHP Best Practices Award for the program described here.
References 1. Dellinger RP, Levy MM, Rhodes A et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41:580-637. 2. Gaieski DF, Mikkelsen ME, Band RA et al. Impact of time of antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010; 38:1045-53. 3. Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345:1368-77. 4. Levy MM, Dellinger RP, Townsend SR et al. The Surviving Sepsis Campaign: results of an international guidelinebased performance improvement program targeting severe sepsis. Crit Care Med. 2010; 38:367-74. 5. Kumar A, Roberts D, Wood KE et al. Duration of hypotension before
initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006; 34:1589-96. 6. Puskarich MA, Trzeciak S, Shapiro NI et al. Emergency Medicine Shock Research Network (EMSHOCKNET): association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med. 2011; 39:206671. 7. Ferrer R, Martin-Loeches I, Phillips F et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guidelinebased performance improvement program. Crit Care Med. 2014; 42:1749-55. 8. Prytherch DR, Smith GB, Schmidt PE, Featherstone PI. ViEWS—towards a national early warning score for detecting adult inpatient deterioration. Resuscitation. 2010; 81:932-7. 9. Hanzelka KM, Pierce CA, Beardsley JR et al. Influence of an institutionspecific sepsis protocol on the adequacy of empiric antimicrobial therapy. Hosp Pharm. 2010; 45:53844. 10. Flynn JD, McConeghy KW, Fannery AH et al. Utilization of pharmacist responders as a component of a multidisciplinary sepsis bundle. Ann Pharmacother. 2014; 48:1145-51.
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