Outcomes of Hospitalized Patients With Sepsis Before and After Implementation of a Sepsis Care Improvement Initiative at a Community Hospital

Abstract

Purpose: Prompt treatment of sepsis and septic shock is critical as delays increase mortality risk. Various tools, such as electronic alerts, standardized order sets, and rapid response teams, are used to expedite sepsis bundled care, yet their individual effects on outcomes and antimicrobial timing are unclear. This study evaluated the impact of an Inpatient Code Sepsis protocol, featuring an overhead page and order set, on mortality in hospitalized patients with sepsis and septic shock. Methods: A retrospective cohort study was conducted at a 371-bed hospital from July 1, 2020, to July 31, 2023. Hospitalized adults (≥18 years) diagnosed with sepsis and septic shock before and after the Inpatient Code Sepsis protocol implementation were included. The primary outcome was 30-day all-cause mortality; secondary outcomes were hospital length of stay, 30-day readmission, and time to antibiotic administration. Patients were excluded if they were identified for sepsis without infection, had sepsis due to non-bacterial causes, lost to follow-up within 30 days of admission, received empiric antibiotics in an emergency department or outside hospital, or were missing antibiotic administration time. Results: A total of 138 patients were included in the analysis. Mortality within 30 days did not significantly differ preprotocol and postprotocol (p = 0.381). However, a significant reduction in time to antibiotic administration was noted postimplementation (p < 0.05). Hospital length of stay and 30-day readmission showed no significant changes. Conclusion: The Inpatient Code Sepsis protocol did not impact 30-day mortality but did improve the time to antibiotic administration.

Introduction

Sepsis is an inflammatory condition induced by infection that ranks as the leading cause of morbidity and mortality for critically ill patients and the 10th leading cause of death overall in the United States.^1,2 Annually, approximately 1.7 million new cases of sepsis occur with up to 350 000 deaths. ² The economic burden of sepsis on the U.S. healthcare system is estimated at a staggering $38 billion per year, showing an annual escalation of 8% in expenses. ³ The management of this condition often requires additional medical resources and skilled personnel in the intensive care unit (ICU), resulting in a significant financial strain on hospitals.

The Surviving Sepsis Campaign (SSC) guidelines promote early identification of sepsis and septic shock and prompt initiation of fluid resuscitation as well as effective empiric antimicrobial therapy to improve patient outcomes. ⁴ In 2015, the Centers for Medicare and Medicaid Services in collaboration with the SSC, adopted The Severe Sepsis and Septic Shock Management Bundle (SEP-1) to improve adherence to evidence-based treatment bundles. The measure involves implementing bundle elements within 3 and 6 hours of sepsis recognition to ensure sufficient end-organ perfusion and hemodynamic stability. In a retrospective, propensity-score-matched cohort study conducted by Townsend and colleagues, a reduction in the 30-day mortality rate was observed among Medicare beneficiaries whose care adhered to SEP-1 guidelines. ⁵ Each hour of delay in administration of antimicrobial therapy is associated with an increased risk of mortality by 4% to 9%. ⁶

Numerous quality improvement initiatives have emerged to accelerate early goal-directed therapy and enhance outcomes for patients with sepsis and septic shock. As outlined in the Hospital Program Core Elements by the Centers for Disease Prevention and Control, electronic alerts, standardized order sets, and rapid response teams are among the systems and processes designed to streamline the recognition and management of sepsis and septic shock. ⁷ Prior research exploring these interventions indicates their association with intensified resuscitation efforts, expedited initiation of antimicrobial therapy, and improved adherence to guideline-concordant care. ⁸

Current evidence assessing the impact of sepsis improvement initiatives on clinical outcomes, including survival rates and lengths of hospital and ICU stays, has yet to provide conclusive findings. In a multicenter, retrospective cohort study by Seymour and colleagues, the association between the time to completion of the 3-hour sepsis care bundle and hospital mortality was explored among patients presenting with severe sepsis and septic shock who were initiated on a sepsis protocol in the emergency department (ED). Their analysis demonstrated that for every hour of delay in completing the 3-hour bundle and administering broad-spectrum antibiotics, there was an increased likelihood of mortality, particularly evident in patients whose completion exceeded 3 hours compared with those completing it within 3 hours. ⁹ A randomized controlled trial in ICU patients with sepsis by Semler and colleagues found that the use of an electronic sepsis evaluation and management tool did not influence clinical outcomes and compliance with sepsis treatment guidelines. ¹⁰ In a retrospective study by Arabi and colleagues, the introduction of a multifaceted intervention, incorporating a sepsis electronic alert with a sepsis response team, was associated with reductions in hospital mortality and lengths of hospital and ICU stays after adjustment to propensity scores. ¹¹ Finally, a before and after sepsis performance improvement study in an ED of an academic medical center conducted by Schinkel and colleagues showed a decrease in time to antibiotic administrations but failed to show a beneficial change in patient-oriented outcomes such as length of stay or mortality. ¹² Inconsistent findings in the existing literature reflect the heterogeneity in the true effectiveness of these interventions. Moreover, the available studies were predominantly carried out at large academic medical centers, potentially limiting the generalizability of the findings to smaller community hospitals.

The investigation team’s primary objective was to show that combining a Code Sepsis overhead page with an order set would synergistically improve patient outcomes and reduce the time to initiation of antibiotic therapy, compared with using the order set alone. The protocol for the inpatient code sepsis can be found in the Supplemental Material.

Methods

Definitions for sepsis, severe sepsis, and septic shock were aligned with the criteria set forth by the third international consensus definitions for sepsis and septic shock and can be found in the Supplemental Material. ¹

This was a single-center, retrospective, observational cohort study that included patients hospitalized at a 371-bed community hospital between July 1, 2020, and July 31, 2023. Adults aged 18 years or older were eligible for inclusion in the study if they were diagnosed with sepsis, severe sepsis, or septic shock. Patients were excluded if they were identified for sepsis or septic shock and deemed to not have an infection at the discretion of the licensed independent practitioner (LIP), if their sepsis or septic shock derived from a non-bacterial cause, if they were lost to follow-up within 30 days of the index admission, if there was missing documented time to antibiotic administration from time zero, or if they received empiric broad-spectrum antimicrobial therapy in an ED or outside hospital, as Code Sepsis is not initiated at this locations. If patients were readmitted multiple times throughout the study period, only their initial encounter was included in the final analysis. Patients were divided into two cohorts based on when the Inpatient Code Sepsis protocol was implemented (preprotocol July 1, 2020, to July 19, 2022 and postprotocol July 20, 2022, to July 31, 2023). The primary objective of this study was to determine the impact of an Inpatient Code Sepsis protocol, incorporating a Code Sepsis overhead page and sepsis order set, on 30-day all-cause mortality among hospitalized adults with sepsis and septic shock. The secondary objectives included comparing the time to administration of empiric antibiotics before and after protocol implementation, as well as assessing the association between the protocol and hospital LOS and 30-day readmission rates. The study was approved by the Institutional Review Board.

Inpatient Code Sepsis Standard Operating Procedure

In July 2022, an Inpatient Code Sepsis Standard Operating Procedure (SOP) was established to guide the assessment and management of hospitalized adult patients suspected of having sepsis, severe sepsis, or septic shock. A sepsis BPA triggered nurses to screen and assess patients. If a known or suspected source of infection was identified by the physician or LIP extender or if there was a change in the patient’s condition, a “Code Sepsis” alert was activated and notified the Code Sepsis Response Team via a hospital pager system. This team included an attending physician or extender, nurse operations manager, clinical pharmacist, phlebotomist, house officer, and quality/assigned nurse. Upon activation, the attending physician or extender entered orders via the “MED Sepsis” order set, including blood cultures, fluid resuscitation, empiric broad-spectrum antimicrobial therapy, serum lactate level, urinalysis, and imaging. The nurse documented the Sepsis Alert Checklist and completed sepsis orders.

Data Collection

Data were retrospectively collected from electronic medical records. Data collected for index admissions included baseline demographics, comorbidities, International Classification of Diseases 10th Revision diagnostic codes, inpatient sepsis BPAs, medication administration, vital signs, laboratory results, ICU admission, mechanical ventilation use, COVID-19 test results, and mortality. Data collected during the follow-up period included mortality status, discharge disposition, and readmission. All data were requested from enterprise analysts in accordance with institutional review board policies.

Outcomes

The primary outcome was 30-day all-cause mortality. Secondary outcomes included time to administration of empiric antibiotic therapy, hospital LOS, and readmission within 30 days of discharge. Time to antibiotic therapy was defined as the time from code sepsis initiation to administration of an antibiotic regimen that was approved for the treatment of sepsis and septic shock according to the National Hospital Inpatient Quality Measures specifications manual. ¹³

Sample Size

A total of 420 patients were needed for 80% power and alpha of 0.05 to detect a 10% absolute difference in mortality. This calculation accounts for an expected 21% mortality at baseline with standard of care per CDC data. ²

Statistical Analysis

Patients admitted during the study period were screened for inclusion in this study. Normality was assessed using the Shapiro-Wilk test. Continuous data were analyzed using the Mann-Whitney U test and presented as a median with an interquartile range (IQR). Categorical data were analyzed using chi-square or Fischer’s exact test with outcomes reported as frequency and percentage. Missing data were excluded from the analyses. All statistical analyses were performed using STATA statistical software version 16.

Results

A total of 1126 were screened in the initial cohort, and 988 patients were eventually excluded (Figure 1). Reasons for exclusion included receiving empiric antibiotics in an ED or outside hospital (n = 924), missing inpatient sepsis BPA (n = 25), sepsis and septic shock from non-bacterial etiology (n = 21), and missing time to antibiotic administration after time zero (n = 18). A total of 138 patients were included in the final analysis, with 84 patients in the preprotocol cohort and 54 patients in the postprotocol cohort.

Baseline demographics and clinical characteristics were generally similar between cohorts (Table 1). The median age was 71 years (IQR 61-81), 51% were male, and 59% were Black. The most common comorbidities were diabetes mellitus (n = 62, 45%), chronic kidney disease (n = 62, 45%), and congestive heart failure (n = 55, 40%). Septic shock occurred in 22% of included patients and 30% required mechanical ventilation during admission.

Table 1.

Baseline Characteristics.

Variable	Total (N = 138)	Preprotocol (n = 84)	Postprotocol (n=54)	P value
Age (years), median [IQR]	71 [61-81]	71 [63-83]	70 [56-79]	0.106
Gender, female, no. (%)	68 (49)	42 (50)	26 (48)	0.832
Race, no. (%)				0.370
White	53 (38)	29 (35)	24 (44)
Black	81 (59)	53 (63)	28 (52)
Other	4 (3)	2 (2)	2 (4)
Ethnicity, Hispanic/Latino, no. (%)	2 (1)	1 (1)	1 (1)	1.000
Weight (kg), median [IQR] a N = 132	166 [131-207]	175 [137-216]	149 [125-266]	0.112
Comorbidities, no. (%)
Cancer
Cerebrovascular disease	11 (8)	6 (7)	5 (9)	0.751
Chronic kidney disease	35 (25)	24 (29)	11 (20)	0.280
Cirrhosis	62 (45)	40 (48)	22 (41)	0.428
Congestive heart failure	18 (13)	10 (12)	8 (15)	0.620
Chronic obstructive pulmonary	55 (40)	32 (38)	23 (43)	0.598
disease	26 (19)	17 (20)	9 (17)	0.601
Ischemic heart disease	36 (26)	25 (30)	11 (20)	0.220
Diabetes mellitus	62 (45)	42 (50)	20 (37)	0.135
Human immunodeficiency virus	3 (2)	1 (1)	2 (4)	0.561
ICU admission, no. (%)	19 (14)	15 (18)	4 (7)	0.082
Septic shock, no. (%) a N = 116	25 (22)	14 (21)	11 (22)	0.919
Lactate level, median [IQR] a N = 116	2 [1.3-2.8]	2.1 [1.3-3]	1.75 [1.2-2.5]	0.195
Vasopressor/inotrope use, no. (%) a N = 136	52 (38)	33 (40)	19 (35)	0.553
COVID-19 positive, no. (%) a N = 93	18 (19)	15 (25)	3 (9)	0.051
Mechanical ventilation use, no. (%)	42 (30)	29 (35)	13 (24)	0.193

^aNumber of patients included in analysis without missing data.

An absolute decrease of 7% was observed in 30-day mortality postprotocol (24% vs 31%; RR 0.78, 95% CI 0.44-1.38, p = 0.381); however, this was not a significant result. There was also no difference in median hospital LOS between the preprotocol and postprotocol cohorts, 8 (IQR 4-14) vs 7 (IQR 4-12) days; p = 0.067, or 30-day readmission (57% vs 48%; RR 1.2, 95% CI 0.87-1.66, p = 0.262). A reduction in time to antibiotic administration from time zero was observed after the protocol was implemented, which was statistically significant, 378 (IQR 144-1,192) vs 191 (IQR 89-552) minutes; p = 0.008. All results can be found in Table 2.

Table 2.

Analyses of Primary and Secondary Outcomes.

Outcome	Preprotocol (n = 84)	Postprotocol (n = 54)	P value	Relative Risk (95% CI)
Primary outcome
30-day mortality, no. (%)	26 (31)	13 (24)	0.381	0.78 (0.44-1.38)
Secondary outcomes
Hospital LOS (days), median [IQR]	8 [5-16]	7 [4-12]	0.067	–
Discharge disposition, no. (%)			0.320	–
Home	17 (20)	14 (26)
Expired	13 (15)	3 (6)
Hospice	5 (6)	5 (9)
Skilled nursing facility	30 (36)	15 (28)
Transfer to another facility	18 (21)	16 (30)
Other	1 (1)	1 (2)
30-day readmission, no. (%)	40 (48)	31 (57)	0.262	1.2 (0.87-1.66)
Time to antibiotics from time zero (min), median [IQR]	378 [144-1,192]	191 [89-552]	0.008*	–

^*P < 0.05 deemed to be statistically significant.

Discussion

In this study, we found no difference in 30-day all-cause mortality in our cohort after the implementation of an Inpatient Code Sepsis protocol involving an overhead page and order set. A significant reduction in time to antibiotic administration was found with an approximate 50% seen after protocol implementation, although there was no difference seen in other secondary outcomes.

Our research contributes to the existing literature by examining the impact of individual hospital sepsis program elements on process and patient-related outcomes within a community hospital setting. Unlike tertiary academic medical centers, community hospitals often encounter challenges such as limited resources, including staffing shortages and a deficiency in specialists trained in sepsis care. These challenges may affect the delivery of consistent, high-quality care for patients with sepsis and septic shock. Although the implementation of the Inpatient Code Sepsis SOP did not lead to improvements in mortality, hospital LOS, and readmission rates, the enhanced timing of antibiotic administration may be attributed, in part, to an interdisciplinary team approach that facilitated the more rapid identification and assessment of sepsis.

Other studies have investigated the impact of a Code Sepsis protocol on process and patient-related outcomes in patients with sepsis and septic shock. In a single-center, retrospective cohort study by Whitfield and colleagues, the effect of an Adult Code Sepsis protocol on SEP-1 perfect score attainment (PSA) rates was evaluated among patients with severe sepsis and septic shock in the ED (preprotocol, n = 300; postprotocol, n = 150). ¹⁴ SEP-1 PSA rates were significantly higher postprotocol (71.3%) than preprotocol (30.7%). ¹⁴ They also found a significant reduction in time-to-antimicrobials postprotocol (78 min vs 126 min) and no significant differences in hospital mortality, overall and ICU LOS, or 30-day readmission, which aligns with the results of our research. ¹⁴ A second study assessing mortality and time to 3- and 6-hour sepsis bundle compliance among patients with sepsis, severe sepsis, and septic shock in the ED before and after implementation of an interdisciplinary code sepsis team with the use of a sepsis order set. ¹⁵ Significant improvements were observed in the completion of bundle elements, except for antibiotics and blood cultures within 3 hours, with a decline in mortality rate from 12.8% to 4.9% during the postintervention phase. ¹⁵ Studies of this nature predominantly occurred in prehospital settings with the implementation of code sepsis protocols that differ from the one used at our hospital.

Several limitations should be acknowledged in this study. First, due to its single-center, retrospective, observational design, our findings may not generalize to other institutions, especially large academic medical centers. Second, a significant proportion of patients were excluded from our analysis, primarily due to receiving empiric antibiotics in an ED or at an outside hospital, which affected our study’s statistical power. Our study primarily focused on a Code Sepsis protocol for hospitalized patients, as there is no equivalent protocol for patients presenting with sepsis or septic shock in the ED. Considering patients who were initiated with Code Sepsis during admission and received an escalation of antibiotics previously administered in the ED or at an outside hospital could have increased the study’s sample size. Thirdly, we did not assess overall and individual compliance with the SEP-1 bundle elements, which could have influenced our findings. SEP-1, an “all-or-none” quality measure, necessitates the administration of all bundle components within a specific timeframe, posing challenges for hospitals and providers to demonstrate compliance. Moreover, the association between overall SEP-1 compliance and patient outcomes remains inconclusive, with variations observed among patient populations and study designs.^{5,16 -18} Fourthly, our study solely focused on the Code Sepsis overhead page, inpatient sepsis order set use, and antibiotic administration components of the protocol; however, other bundled sepsis care elements, such as fluid resuscitation and vasopressors for fluid-refractory hypotension, are pivotal for improving survival. Although an interdisciplinary response team is crucial, it is challenging to ascertain the presence of all team members in a retrospective study. Finally, while not statistically significant, there were numerically more patients with COVID-19 in the preimplementation group (15) compared with postimplementation group (3). Having more patients infected with COVID-19 in the preimplementation group could have impacted the results.

Conclusion

This study found no difference in 30-day all-cause mortality, hospital LOS, and 30-day readmission rates after implementing an Inpatient Code Sepsis protocol featuring an overhead page and order set; however, a significant reduction in time to antibiotic therapy was observed. Further large, prospective, randomized controlled studies are warranted to clarify the true effectiveness of individual SEP-1 bundle elements in hospitalized patients with sepsis and septic shock.