The impact of a multifaceted intervention including sepsis electronic alert system and sepsis response team on the outcomes of patients with sepsis and septic shock

The study was conducted in a 900-bed tertiary-care academic hospital accredited by Joint Commission International. The ED receives >200,000 patients per year is staffed by board-certified emergency medicine physicians and has 15 resuscitation beds for high-acuity patients and 49 beds for moderate-acuity patients. The Intensive Care Department staffs 5 ICUs on a 24-h/7-day in-house basis [35], has a rapid response team [36] and provides coverage for boarding patients in the ED who meet ICU admission criteria.

This was a pre–post implementation study that consisted of a pre-intervention phase and a 2-step implementation (intervention phases I and II). During the study period, there were no major changes in the hospital admission criteria, nursing or medical care plans, or staffing structure. The study was approved by the Institutional Review Board of Ministry of National Guard-Health affairs, and informed consent requirement was waived.

In this phase (January 01, 2011–September 24, 2012), patients presenting to the ED were triaged based on illness severity according to the Canadian Triage and Acuity Scale [37], evaluated first by the ED nurses and physicians, and then referred to a primary admitting service. Critically ill septic patients were subsequently referred to the intensive care team. Identifying patient as having sepsis and initial resuscitation were based on clinical assessment by the ED physicians, the primary admitting service, the intensive care team or a combination of these services. During this phase, the sepsis bundle had not been implemented.

In this phase (September 25, 2012–March 03, 2013), sepsis e-alert and computerized physician order entry (CPOE) sepsis management order-set (based on the SCC sepsis bundle) were implemented and were accompanied by an educational campaign targeting the ED healthcare providers. A clinical pathway was also generated after multidisciplinary discussions (Additional file 1: Figure S1, Figure S2, Table S1). Additionally, weekly text messages were sent to the phones of the ED and ICU physicians about the bundle compliance rates highlighting the element of the bundle that had the lowest compliance.

This phase required considerable planning, which started in October 2011 as a multidisciplinary quality improvement project aimed at improving sepsis management through the implementation of the SSC bundle. Root-cause analysis was conducted to search for the probable causes of low bundle compliance. In addition, the flow of septic patients from the ED to the ICU was mapped to understand related processes and bottlenecks. After analysis, the low compliance was attributed to multiple factors including delays in sepsis recognition, insufficient awareness of sepsis resuscitation bundle and the complexity of the care processes. For the intervention phase I, the project focused on improving early sepsis recognition through building an electronic sepsis screening tool (e-alert) in the hospital electronic health record (EHR) system (QuadraMed^® Computerized Patient Record System, Reston, VA, USA) and on simplifying the care process by building a CPOE order-set that incorporated the required orders in groups on one platform. The e-alert was based on identifying abnormal vital signs and certain laboratory tests, all captured from the EHR. We used in designing our e-alert the formal definition of sepsis (previously called severe sepsis) with includes a combination of the Systemic Inflammatory Response Syndrome (SIRS) criteria and one organ dysfunction, because this quality improvement project was performed the new definition for sepsis (Sepsis-3) became available [38.] When a patient demonstrated any two SIRS criteria (temperature >38 °C OR <36 °C; heart rate >90 beats/min; respiratory rate >20 breaths/min; WBC count >12,000/mm³ OR <4000/mm³) AND at least one of the following organ dysfunctions (systolic blood pressure 86–90 mmHg with intravenous fluids or <86 mmHg regardless of fluids; blood oxygen saturation of 85–90% with supplemental oxygen or <85% without oxygen; lactate >2 mmol/L) OR two of the above organ dysfunctions, an e-alert was sent to the nursing work-list prompting her/him to contact the treating medical team. The treating physician would then evaluate the patient, confirm the presence or absence of these conditions and use the CPOE order-set if indicated. The development and testing of both the e-alert and the CPOE order-set went through multiple PDSA (plan, do, study, act) cycles with small-scale testing, documentation and learning in the EHR system development (in-production) domain until the activation date. During these PDSA cycles, certain triggers were added to the e-alert (systolic blood pressure 86–90 mmHg with intravenous fluids or <86 mmHg regardless of fluids; blood oxygen saturation of 85–90% with supplemental oxygen or <85% without oxygen) to improve specificity. We could not use reduced level of consciousness in building the e-alert, because it was recorded as a text and not as a numeric value in our EHR.

On March 04, 2013, and through October 30, 2013, a dedicated 24/7 SRT was launched in addition to the interventions already in place from intervention phase I. The SRT consisted of an intensive care registrar physician and a nurse who were trained on sepsis management using didactic lectures and simulation-based learning. The bedside nurse activated the SRT after being prompted by the e-alert or when sepsis was clinically suspected. The SRT assessed the patient for the presence of sepsis, followed the same clinical pathway used in intervention phase I and provided sepsis management as needed in collaboration with the treating team.

Starting October 2011, we collected patient-level data prospectively by a dedicated data collector using the 2008 SSC data collection tool [39]. Additional data were collected retrospectively for the period January 2011–September 2011, to expand the baseline data of pre-intervention phase. Sepsis (originally severe sepsis) was defined as SIRS with acute organ dysfunction secondary to documented or suspected infection. The organ dysfunctions that were used to build the e-alert were hypotension, hypoxia and increased lactate as defined above. Septic shock was defined as sepsis (originally severe sepsis) with persistent hypotension after fluid resuscitation with at least 20 mL/kg of crystalloid (or equivalent). We recorded the compliance with the following individual elements of the 2008 SSC resuscitation bundle and the time to intervention: [1] serum lactate obtained within 6 h of presentation, [2] blood cultures taken before the administration of broad-spectrum antibiotics, [3] broad-spectrum antibiotics administered within 3 h of ED admission, [4] 20 mL/kg of crystalloid (or equivalent) administered in patients who were hypotensive or had lactate >4 mmol/L; and in patients who remained hypotensive or had lactate >4 mmol/L, [6] achievement of central venous pressure (CVP) ≥8 mmHg and central venous oxygen saturation (ScvO₂) ≥70% and initiation of vasopressors. Based on recent evidence arising from the recent clinical trials on early goal-directed therapy [40‐42], we evaluated bundle compliance with the first 4 elements only and we did not include CVP and ScvO₂. The primary outcome measure was hospital mortality. Secondary outcome measures were the need for mechanical ventilation during this episode of sepsis, ICU and hospital length of stay (LOS) for all patients for survivors.

All statistical analyses were performed using SAS software (version 9.1; SAS Institute, Cary, NC). Continuous variables were presented as means with standard deviations, and categorical variables as absolute and relative frequencies. Mann–Whitney and Chi-square tests were used to compare differences between the phases as appropriate. To account for the differences in baseline characteristics among the three phases, we generated propensity scores using the following variables that were clinically relevant and statistically associated with the different phases (Table 1): pneumonia, hypothermia, acutely altered mental status, hypoxia, leukopenia, increased creatinine, thrombocytopenia, hyperbilirubinemia, coagulopathy and lactate levels. To check the balancing effect of propensity scores, we used the propensity scores as covariates in an analysis of covariance for continuous baseline variables and in multinomial logistic regression for categorical baseline variables. We used multivariate logistic and linear regression analysis to examine the association of implementation phase with mortality and LOS after adjustment to propensity scores. A p value <0.05 was considered to be statistically significant. We constructed control charts with upper and lower control limits for the 4-element bundle compliance and for hospital mortality using CHARTrunner, version 3.6.88 (PQ Systems, Dayton OH, USA).

At the time of identification, patients in the intervention phases I and II were less likely to have hypothermia, altered mental status, hypotension, hypoxemia, leukopenia, elevated creatinine, thrombocytopenia, hyperbilirubinemia and coagulopathy compared to patients in the pre-intervention phase (Table 1). These differences in symptoms and signs, and key laboratory findings between the three phases suggest that the implementation of multifaceted interventions including sepsis e-alert and SRT was associated with earlier identification of sepsis.

The balancing effect of the generated propensity scores is shown in Table 1. When adjusted to propensity scores, all baseline characteristics were balanced.

Intervention phases I and II were associated with improvement in most measured processes of sepsis care. The frequency of measuring lactate (at any time and within 6 h) and the time to obtaining lactate all improved. Similarly the frequency of obtaining blood cultures (at any time and before antibiotics) and the time to blood cultures improved. Antibiotics administration within 3 h and the time to antibiotics followed a similar pattern. In patients with persistent hypotension or lactate >4 mmol/L, CVP ≥8 mmHg and ScvO₂ of ≥70% were achieved more often (Table 2). As a result, the overall compliance with 4-element bundle increased from 19.3 to 44.6 to 69.4% (p values <0.0001 after adjustment to propensity scores) (Table 2; Fig. 1).

Intervention phase II was associated with reduction in crude hospital mortality and ICU LOS (Fig. 1; Table 3). When adjusted to propensity score, intervention phase II was associated with a significant reduction in hospital mortality [adjusted odds ratio (aOR) 0.71, 95% CI 0.58–0.85, p = 0.003] and in the need for mechanical ventilation (aOR 0.45, 95% CI 0.37–0.55, p < 0.0001). In addition, intervention phase II was associated with reduction in ICU LOS and hospital LOS for all patients as well as ICU LOS for survivors (Table 3).