New screening tools. For ICU sepsis screening, the Sepsis-3 task force recommended use of the Sequential Organ Failure Assessment (SOFA) score, which had been developed to elucidate the progression of multisystem organ failure and evaluate the effects of various therapies on organ dysfunction and failure.16 For sepsis screening in non-ICU settings, they recommended use of the quick SOFA (qSOFA), an abbreviated version developed in 2016 by Seymour and colleagues.5 In contrast to the SOFA score, the qSOFA requires no laboratory tests and can be repeated frequently, prompting further assessment of organ function, initiation or escalation of treatment, or transfer to intensive care.5 (See The Sequential Organ Failure Assessment (SOFA) Score 16, 17 and The Quick Sequential Organ Failure Assessment (qSOFA) Score.5, 17)
When Seymour and colleagues retrospectively reviewed data from 148,907 hospital patients with suspected infection (15,768 ICU patients and 133,139 non-ICU patients), they found that the predictive validity for in-hospital mortality of SOFA criteria was significantly greater than both the SIRS and qSOFA criteria when applied to ICU patients. Outside of the ICU, however, qSOFA had significantly greater predictive validity for in-hospital mortality than either the SIRS or SOFA criteria.18 Likewise, an international prospective cohort study performed in 30 EDs within four European countries found that the qSOFA score was better at predicting in-hospital mortality than the SIRS criteria, supporting Sepsis-3 recommendations.19
Nursing assessments for sepsis should consider patients’ history, risk factors, and SOFA or qSOFA criteria before determining next steps (see Nursing Assessment for Sepsis).
CLINICAL DECISION SUPPORT TOOLS
Clinical decision support (CDS) encompasses a variety of tools that can be integrated into the EHR to assist health care providers in making timely evidence-based decisions. Because of the need for prompt recognition and treatment of sepsis to prevent life-threatening complications, the integration of sepsis CDS into EHRs is invaluable. When coupled with protocol-driven staff response, the implementation of electronic screening tools has been shown to reduce door-to-bolus and door-to-antibiotics times by 31 and 59 minutes, respectively, in ED patients with suspected sepsis.20 EHR sepsis screening tools have a sensitivity of 93%, a specificity of 98%, and a negative predictive value of up to 100%.21, 22 Like that of other sepsis screening methods, however, the positive predictive value of EHR sepsis screening tools is low, ranging from 21% to 45%, highlighting the importance of clinical judgment in identifying patients with sepsis.21, 22
EARLY GOAL-DIRECTED THERAPY: THE SEPSIS BUNDLES
Bundles are a structured set of interventions that have consistently been shown to improve patient outcomes when performed collectively.23 In 2004, the SSC introduced a six-hour resuscitation bundle and a 24-hour management bundle.24 Data collected on 29,470 patients in 218 hospitals in the United States, South America, and Europe between January 2005 and June 2012 indicated that adherence to the 2004 bundles was associated with a 25% relative risk reduction in sepsis mortality rates.25 In 2012, the SSC revised the 2004 sepsis care bundles, dropping the management bundle and dividing the resuscitation bundle into three- and six-hour time periods to improve adherence to the SSC guidelines.9, 24 In 2015, the SSC revised the bundles again in accordance with new evidence.26 This year, in order to treat sepsis as a medical emergency with the same degree of urgency as trauma and stroke, the SSC combined the three- and six-hour bundles into a one-hour bundle.27 Developed “with the explicit intention of beginning resuscitation and management immediately,” the one-hour bundle comprises the following27:
- Measure lactate level. Remeasure if initial lactate is > 2 mmol/L.
- Obtain blood cultures prior to administration of antibiotics.
- Administer broad-spectrum antibiotics.
- Begin rapid administration of 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L.
- Apply vasopressors if patient is hypotensive during or after fluid resuscitation to maintain MAP ≥ 65 mmHg.
THE ONE-HOUR SEPSIS BUNDLE
Serum lactate is measured to assess for tissue hypoperfusion in patients who are not yet hypotensive but who are at risk for septic shock (those with tachypnea and altered mentation in the presence of suspected infection, for example). Lactate levels of 4 mmol/L or higher are associated with a mortality rate of 30%.9 Either arterial or venous lactate samples may be used.
Blood cultures. To increase the probability of identifying the causative organism and the specific site of infection, two or more blood cultures, one drawn percutaneously and another through the current vascular access device, and any other indicated cultures (such as urine, cerebrospinal fluid, wound, or sputum) should be collected before broad-spectrum antibiotics are administered, provided it does not delay antibiotic administration by more than 45 minutes.9 It should be noted that cultures are negative in more than half of patients with sepsis who are receiving empiric antimicrobial therapy when blood is drawn.9
Broad-spectrum antimicrobials. Appropriate broad-spectrum antimicrobial therapy has been shown to reduce mortality in patients with gram-positive and gram-negative bacteremia, as well as in those with fungal and viral infections.9
When the causative organism is identified, antimicrobial therapy should be narrowed to reduce the risk of resistant pathogens, toxicity, and costs.9 The Infectious Diseases Society of America (IDSA) recommends that facilities develop clinical practice guidelines that standardize antimicrobial prescribing practices based on local epidemiology.28 Procalcitonin levels can also be used to guide the duration of antibiotic therapy to avoid antimicrobial resistance, reduce length of stay, and lower costs.29
Crystalloid administration. A 30 mL/kg bolus of crystalloid IV fluids should be administered for hypotension (a systolic blood pressure below 90 mmHg) or for a lactate level of 4 mmol/L or higher.9 Patients with sepsis may have ineffective arterial circulation due to vasodilation, resulting in poor tissue perfusion and tissue hypoxia. Administering 30 mL/kg of IV fluids will expand circulating volume and promote adequate perfusion pressure.
Controversy over volume resuscitation. Some have raised concerns that following SSC resuscitation recommendations may result in volume overload, especially in patients with congestive heart failure, end-stage renal disease, or acute respiratory distress syndrome. In one study of more than 400 adult ICU patients receiving treatment for sepsis or septic shock, 67% showed evidence of volume overload on day 1 following initial fluid resuscitation and 48% had persistent fluid overload into day 3.30 The importance of fluid administration, however, is underscored by the fact that the mortality rate of patients with sepsis and hypotension is nearly 37% and increases to more than 46% if combined with a lactate level of 4 mmol/L or higher.31
Vasopressors should be administered to patients with persistent hypotension that does not respond to fluid resuscitation (those who are unable to maintain a MAP of at least 65 mmHg after receiving 30 mL/kg of crystalloid iv fluids).9 If the patient has life-threatening hypotension, vasopressor therapy should not be withheld until delivery of the 30 mL/kg bolus is completed. Norepinephrine is the first-line vasopressor for septic shock. Epinephrine is the second-choice vasopressor and may be used in addition to or instead of norepinephrine at the discretion of the provider.9 Phenylephrine has been found to reduce splanchnic blood flow,32 and therefore is not recommended in the treatment of septic shock unless norepinephrine is triggering serious arrhythmias, cardiac output is elevated, and blood pressure is persistently low, or inotropes or vasopressors and low-dose vasopressin fail to raise MAP sufficiently.9 Vasopressin and dopamine are not considered first-line agents, but may be used as salvage therapy.9 An experimental angiotensin II medication has shown promise in a recent trial after improving blood pressure and reducing doses of concomitant vasopressors within three hours in patients with vasodilatory shock.33
Ongoing critical care assessments. Noninvasive hemodynamic monitoring. The 2012 SSC guidelines called for invasive hemodynamic monitoring to reassess volume status and tissue perfusion. This recommendation was revised in 2015 to include noninvasive measures, such as a repeated focused examination (after initial fluid resuscitation) incorporating vital sign assessment; cardiopulmonary, capillary refill, pulse, and skin findings; or bedside cardiovascular ultrasound and dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge. These changes were made after three trials did not demonstrate the superiority of a central venous catheter to other noninvasive means.26, 34-36
Invasive hemodynamic monitoring. Based on provider discretion, in the presence of persistent hypotension that does not respond to crystalloid iv fluid resuscitation, a central venous catheter may be inserted to monitor both central venous pressure and central venous oxygen saturation. Although invasive hemodynamic monitoring was recommended for patients with a lactate level above 4 mmol/L in earlier SSC guidelines, the 2016 guidelines suggest using dynamic measures instead, which have demonstrated greater accuracy.12 These include passive leg raises, stroke volume measurement, and variations in systolic pressure or pulse pressure on ventilators.
Remeasure lactate. To evaluate peripheral tissue perfusion, serum lactate should be remeasured after delivery of the 30 mL/kg bolus of crystalloid iv fluids. A serum lactate level > 2 mmol/L despite adequate volume resuscitation, combined with vasopressor requirements to maintain a MAP of at least 65 mmHg, is associated with a hospital mortality rate above 40% and should prompt further diagnostic evaluation and therapeutic intervention to improve tissue perfusion.5
GOVERNMENTAL MEASURES TO PREVENT SEPSIS
Health care providers and hospitals are held accountable for patient outcomes. The Centers for Medicare and Medicaid Services (CMS) provide greater reimbursement for better performers, assessing a 1% payment reduction to hospitals ranking in the lowest quartile with respect to preventable hospital-acquired infections, including sepsis.37 In October 2015, sepsis became a Joint Commission core measure; hospital reimbursement is now tied to adherence to the SSC sepsis bundles.38 All of the SSC bundle elements must be met to ensure adherence and improve patient outcomes. The Institutes of Medicine (IOM)—now known as the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine—Joint Commission, CMS, and Institute for Healthcare Improvement have called for increased transparency regarding practice outcomes.39 The New York State Department of Health has mandated public reporting of sepsis survival and bundle compliance since 2013, and the subsequent reductions in in-hospital mortality40 should lead other states to follow suit. By implementing evidence-based practice guidelines and standards to improve patient safety and clinical outcomes, hospitals can provide clinically effective care, thereby minimizing the incidence of sepsis and readmissions, while increasing reimbursement.
LEADING THROUGH EVIDENCE-BASED PRACTICE
The IOM has called for 90% of clinical decisions and interventions to be evidence based by the year 2020.41 Achieving this goal will require health care providers to identify gaps in translating research to clinical practice and to implement proven decision-making tools, protocols, and policies. Integrating sepsis CDS tools into EHRs promotes prompt recognition and treatment of sepsis.
The Modified Early Warning Score (MEWS) was developed in 2001 to identify hospitalized patients at risk for clinical deterioration. The MEWS takes into account all components of the qSOFA (systolic blood pressure, respiratory rate, and mental status), as well as heart rate and temperature.42 Points are assigned based on values for each physiologic parameter. Scores of 5 or higher are associated with an increased risk of death and ICU admission.42 The MEWS has been adapted at many facilities to help nurses evaluate subtle signs of deterioration, increase use of rapid response teams, and increase nurses’ confidence in their patient assessments.43 The score can be calculated by the EHR system or manually on every shift by nursing staff. A rising MEWS should prompt nurses to consider possible sources of infection. When used appropriately in the hospital setting, the MEWS has been shown to reduce the number of code blues by as much as 50%.43
Customized sepsis screening tools can be incorporated into EHRs, using best practice advisories or components of the SOFA, qSOFA, and SIRS criteria, based on facility preferences. As nurses are at the forefront of patient care, it is important to couple such screening tools with nurse-initiated provider notification (see Putting It All Together: When Sepsis Is Suspected). The Society for Healthcare Epidemiology of America, in association with the IDSA, American Hospital Association, and Joint Commission, has compiled a Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals. All sections are available for download at www.shea-online.org/index.php/practice-resources/priority-topics/compendium-of-strategies-to-prevent-hais.
The quest to determine best practices in the areas of fluid resuscitation, screening tools, and early goal-directed therapy continues to provide numerous research opportunities in the areas of fluid resuscitation, screening tool validation, and efficacy of early goal-directed therapy on mortality and adverse events.
Although more conservative fluid resuscitation than that recommended by the SSC has been shown to increase the number of ventilator-free days and to decrease ICU days, there have been no significant findings regarding reduced mortality rates.44 Large randomized trials are needed to determine the fluid resuscitation measures that optimally affect mortality rates.
The validation of the screening tools used to identify sepsis provides another opportunity for future research. When Churpek and colleagues compared the qSOFA, SIRS criteria, MEWS, and National Early Warning Score (NEWS) in predicting in-hospital mortality and critical care transfer in non-ICU patients, they found that the qSOFA was more accurate than the SIRS criteria but less accurate than the MEWS or NEWS.45 As this study was performed in only one academic institution, further investigation and validation is needed to increase the external validity of these screening tools.
Finally, what is the effect of early goal-directed therapy on mortality and adverse events? The Australasian Resuscitation in Sepsis Evaluation trial, as well as a meta-analysis by Rusconi and colleagues, found that early goal-directed therapy did not decrease mortality but caused no significant adverse events.34, 46 Additionally, Rusconi and colleagues found no difference in hospital mortality rates, length of required organ support, or length of hospital stay. A limitation of this meta-analysis is that the therapies administered, especially IV fluid volume, varied widely across the studies evaluated, and early antibiotic administration, which is both common practice and part of bundled early goal-directed therapy, was noted in all trials.46
2. Fleischmann C, et al Assessment of global incidence and mortality of hospital-treated sepsis
: current estimates and limitations Am J Respir Crit Care Med 2016 193 3 259–72
5. Singer M, et al The Third International Consensus Definitions for Sepsis and Septic Shock
-3) JAMA 2016 315 8 801–10
6. Gaieski DF, et al Benchmarking the incidence and mortality of severe sepsis
in the United States Crit Care Med 2013 41 5 1167–74
8. Hotchkiss RS, et al Immunosuppression in sepsis
: a novel understanding of the disorder and a new therapeutic approach Lancet Infect Dis 2013 13 3 260–8
9. Dellinger RP, et al Surviving Sepsis Campaign
: international guidelines for management of severe sepsis
and septic shock
: 2012 Crit Care Med 2013 41 2 580–637
10. Rivers E, et al Early goal-directed therapy in the treatment of severe sepsis
and septic shock
N Engl J Med 2001 345 19 1368–77
11. Gu WJ, et al The effect of goal-directed therapy on mortality in patients with sepsis
—earlier is better: a meta-analysis of randomized controlled trials Crit Care 2014 18 5 570
12. Rhodes A, et al Surviving Sepsis Campaign
: international guidelines for management of sepsis
and septic shock
: 2016 Crit Care Med 2017 45 3 486–552
13. Bone RC, et al Definitions for sepsis
and organ failure and guidelines for the use of innovative therapies in sepsis
. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest
14. Sprung CL, et al An evaluation of systemic inflammatory response syndrome signs in the Sepsis
Occurrence in Acutely Ill Patients (SOAP) study Intensive Care Med 2006 32 3 421–7
15. Churpek MM, et al Incidence and prognostic value of the systemic inflammatory response syndrome and organ dysfunctions in ward patients Am J Respir Crit Care Med 2015 192 8 958–64
16. Vincent JL, et al The SOFA (Sepsis
-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the Working Group on Sepsis
-Related Problems of the European Society of Intensive Care Medicine Intensive Care Med 1996 22 7 707–10
17. Makic MBF, Bridges E Managing sepsis
and septic shock
: current guidelines and definitions Am J Nurs 2018 118 2 34–9
18. Seymour CW, et al Assessment of clinical criteria for sepsis
: for the Third International Consensus Definitions for Sepsis and Septic Shock
-3) JAMA 2016 315 8 762–74
19. Freund Y, et al Prognostic accuracy of Sepsis
-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department JAMA 2017 317 3 301–8
20. Hayden GE, et al Triage sepsis
alert and sepsis
protocol lower times to fluids and antibiotics in the ED Am J Emerg Med 2016 34 1 1–9
21. Alsolamy S, et al Diagnostic accuracy of a screening electronic alert tool for severe sepsis
and septic shock
in the emergency department BMC Med Inform Decis Mak 2014 14 105
22. Nguyen SQ, et al Automated electronic medical record sepsis
detection in the emergency department PeerJ 2014 2 e343
24. Jozwiak M, et al Implementing sepsis
bundles Ann Transl Med 2016 4 17 332
25. Levy MM, et al Surviving Sepsis Campaign
: association between performance metrics and outcomes in a 7.5-year study Intensive Care Med 2014 40 11 1623–33
27. Levy MM, et al The Surviving Sepsis Campaign
bundle: 2018 update Crit Care Med 2018 46 6 997–1000
28. Barlam TF, et al Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Clin Infect Dis 2016 62 10 e51–e77
29. Thayer S A procalcitonin-guided algorithm to reduce antibiotic duration. Nursing2016 Critical Care
30. Kelm DJ, et al Fluid overload in patients with severe sepsis
and septic shock
treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death Shock 2015 43 1 68–73
31. Levy MM, et al The Surviving Sepsis Campaign
: results of an international guideline-based performance improvement program targeting severe sepsis
Intensive Care Med 2010 36 2 222–31
32. Reinelt H, et al Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock
Crit Care Med 1999 27 2 325–31
33. Khanna A, et al Angiotensin II for the treatment of vasodilatory shock N Engl J Med 2017 377 5 419–430
34. ARISE investigators, ANZICS Clinical Trials Group, et al. Goal-directed resuscitation for patients with early septic shock
. N Engl J Med
35. Mouncey PR, et al Trial of early, goal-directed resuscitation for septic shock
N Engl J Med 2015 372 14 1301–11
36. ProCESS Investigators, et al A randomized trial of protocol-based care for early septic shock
N Engl J Med 2014 370 18 1683–93
39. Wurmser T The financial case for EBP Nurs Manage 2009 40 2 12–4
40. Seymour CW, et al Time to treatment and mortality during mandated emergency care for sepsis
N Engl J Med 2017 376 23 2235–44
42. Subbe CP, et al Validation of a modified early warning score in medical admissions QJM 2001 94 10 521–6
43. Maupin JM, et al Use of the modified early warning score decreases code blue events Jt Comm J Qual Patient Saf 2009 35 12 598–603
44. Silversides JA, et al Conservative fluid management or deresuscitation for patients with sepsis
or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis Intensive Care Med 2017 43 2 155–70
45. Churpek MM, et al Quick sepsis
-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores for detecting clinical deterioration in infected patients outside the intensive care unit Am J Respir Crit Care Med 2017 195 7 906–11
46. Rusconi AM, et al Early goal-directed therapy vs usual care in the treatment of severe sepsis
and septic shock
: a systematic review and meta-analysis Intern Emerg Med 2015 10 6 731–43
For eight additional continuing nursing education activities on the topic of sepsis, go to www.nursingcenter.com/ce.
Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
quick Sequential Organ Failure Assessment (qSOFA); sepsis; sepsis care bundles; sepsis treatment guidelines; septic shock; Sequential Organ Failure Assessment (SOFA); Surviving Sepsis Campaign; Third International Consensus Definitions for Sepsis and Septic Shock