This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.

We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.

At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.

At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

Prognosis and disposition among older emergency department (ED) patients with suspected infection remains challenging. Frailty is increasingly recognized as a predictor of poor prognosis among critically ill patients; however, its association with clinical outcomes among older ED patients with suspected infection is unknown.

We conducted a multicenter prospective cohort study at two tertiary care EDs. We included older ED patients (≥75 years) with suspected infection. Frailty at baseline (before index illness) was explicitly measured for all patients by the treating physicians using the Clinical Frailty Scale (CFS). We defined frailty as a CFS 5–8. The primary outcome was 30-day mortality. We used multivariable logistic regression to adjust for known confounders. We also compared the prognostic accuracy of frailty with the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) criteria.

We enrolled 203 patients, of whom 117 (57.6%) were frail. Frail patients were more likely to develop septic shock (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.08–2.51) and more likely to die within 30 days of ED presentation (aOR 2.05; 95% CI, 1.02–5.24). Sensitivity for mortality was highest among the CFS (73.1%; 95% CI, 52.2–88.4), compared with SIRS ≥ 2 (65.4%; 95% CI, 44.3–82.8) or qSOFA ≥ 2 (38.4; 95% CI, 20.2–59.4).

Frailty is a highly prevalent prognostic factor that can be used to risk-stratify older ED patients with suspected infection. ED clinicians should consider screening for frailty to optimize disposition in this population.

In 2008–2009, the Canadian Institute for Health Information reported over 30,000 cases of sepsis hospitalizations in Canada, an increase of almost 4,000 from 2005. Mortality rates from severe sepsis and septic shock continue to remain greater than 30% in Canada and are significantly higher than other critical conditions treated in the emergency department (ED). Our group formed a multidisciplinary sepsis committee, conducted an ED process of care analysis, and developed a quality improvement protocol. The objective of this study was to evaluate the effects of this sepsis management bundle on patient mortality.

This before and after study was conducted in two large Canadian tertiary care EDs and included adult patients with suspected severe infection that met at least two systemic inflammatory response syndrome (SIRS) criteria. We studied the implementation of a sepsis bundle including triage flagging, RN medical directive, education campaign, and a modified sepsis protocol. The primary outcomes were 30-day all-cause mortality and sepsis protocol use.

We included a total of 167 and 185 patients in the pre- and post-intervention analysis, respectively. Compared to the pre-intervention group, mortality was significantly lower in the post-intervention group (30.7% versus 17.3%; absolute difference, 13.4%; 95% CI 9.8–17.0; p=0.006). There was also a higher rate of sepsis protocol use in the post-intervention group (20.3% versus 80.5%, absolute difference 60.2%; 95% CI 55.1–65.3; p<0.001). Additionally, we found shorter time-intervals from triage to MD assessment, fluid resuscitation, and antibiotic administration as well as lower rates of vasopressor requirements and ICU admission.

The implementation of our multidisciplinary ED sepsis bundle, including improved early identification and protocolized medical care, was associated with improved time to achieve key therapeutic interventions and a reduction in 30-day mortality. Similar low-cost initiatives could be implemented in other EDs to potentially improve outcomes for this high-risk group of patients.

Does early goal-directed therapy decrease mortality when compared with usual care?

Angus DC, Barnato AE, Bell D, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med 2015;41(9):1549-60. doi:10.1007/s00134-015-3822-1.

We sought to determine whether the implementation of a sepsis protocol in a Canadian emergency department (ED) improves care for the subset of patients admitted to the intensive care unit (ICU).

After implementing a sepsis protocol in our ED we used an ICU database and chart review to compare various time-dependent end points and outcomes between a historical control year and the first year after implementation. We reviewed the charts of all patients admitted to the ICU within 24 hours of ED admission with a primary or other diagnosis of sepsis, severe sepsis or septic shock, who met criteria for early goal-directed therapy within the first 6 hours of their ED stay.

We compared 29 patients from the control year with 30 patients from the year after implementation of our sepsis protocol. We found that patients treated during the postintervention year had improvements in time to antibiotics (4.2 v. 1.0 h, difference = –3.2 h, 95% CI –4.8 to –2.0), time to central line placement (above the diaphragm) (11.6 v. 3.2 h, difference = –8.4 h, 95% CI –12.1 to –4.7), time to arterial line placement (7.5 v. 2.3 h, difference = –5.2 h, 95% CI –7.4 to –3.0), and achievement of central venous pressure and central venous oxygen saturation goals (11.1 v. 5.1 h, difference = –6.0 h, 95% CI –11.03 to –1.71, and 13.1 v. 5.5 h, difference = –7.6 h, 95% CI –11.97 to –3.16, respectively). There were no statistically significant differences in ICU length of stay, hospital length of stay or mortality (31.0% v. 20.0%, difference = –11.0%, 95% CI –33.1% to 11.1%).

Implementation of an ED sepsis protocol improves care for patients with severe sepsis and septic shock.

We sought to evaluate the time to antibiotics for emergency department (ED) patients meeting criteria for severe sepsis before and after the implementation of an ED sepsis protocol. Compliance with published guidelines for time to antibiotics and initial empiric therapy in sepsis was also assessed.

A retrospective chart review was conducted. Emergency department patient encounters with International Classification of Diseases codes related to severe infections were screened during a 3-month period before and after the implementation of a sepsis protocol. Encounters meeting criteria for severe sepsis were further assessed. The time to initiation of antibiotics was determined as well as the initial choice of antimicrobial therapy based on the presumed source of infection.

We reviewed 213 unique ED patient encounters meeting criteria for severe sepsis. Analysis of the period before implementation showed a median time from the time criteria for severe sepsis were met to delivery of antibiotics of 163 minutes (95% confidence interval [CI] 124 to 210 min). Analysis of the period after implementation of the protocol revealed a median time of 79 minutes (95% CI 64 to 94 min), representing an overall reduction of 84 minutes (95% CI 42 to 126 min). Before the implementation of the protocol, 47% of patients received correct antibiotic coverage for the presumed source of infection in compliance with locally published guidelines. After the initiation of the protocol, 73% received appropriate initial antibiotics, for an overall improvement of 26%.

A guideline-based ED sepsis protocol for the evaluation and treatment of the septic patient appears to improve the time to administration of antibiotics as well as the appropriateness of initial antibiotic therapy in patients with severe sepsis.

Optimal management of severe sepsis in the ED has evolved rapidly. The purpose of these guidelines is to review key management principles for Canadian emergency physicians, utilizing an evidence-based grading system.

Key areas in the management of septic patents were determined by members of the CAEP Critical Care Interest Group (C4). Members of C4 were assigned a question to be answered after literature review, based on the Oxford grading system. After completion, each section underwent a secondary review by another member of C4. A tertiary review was conducted by additional external experts, and modifications were determined by consensus. Grading was based on peer-reviewed publications only, and where evidence was insufficient to address an important topic, a “practice point” was provided based on group opinion.

The project was initiated in 2005 and completed in December 2007. Key areas which were reviewed include the definition of sepsis, the use of invasive procedures, fluid resuscitation, vasopressor/inotrope use, the importance of culture acquisition in the ED, antimicrobial therapy and source control. Other areas reviewed included the use of corticosteroids, activated protein C, transfusions and mechanical ventilation.

Early sepsis management in the ED is paramount for optimal patient outcomes. The CAEP Critical Care Interest Group Sepsis Position Statement provides a framework to improve the ED care of this patient population.