Literature research

Running head: SEPSIS LITERATURE REVIEW 1

Sepsis Literature Review

Student at Walden

Walden University

NURS 6052, Section 2, Essentials of Evidence-Based Practice

Please use portrait orientation for the paper, but place your table in landscape. Find directions in doc sharing.

SEPSIS LITERATURE REVIEW 2

Sepsis Literature Review

Conducting a literature review is helpful to become familiar with a topic of interest. The development of a clinical question is

a necessary first step before searching for primary and secondary literature sources (Polit & Beck, 2012, p. 96). Using the databases

provided by the Walden University Library can be a helpful resource while compiling a literature review. The purpose of this project is

to conduct a literature review and, a synthesis of the studies found. From this review, I will draw, and preliminary conclusions about

the following PICOT question: In the adult population diagnosed with severe sepsis or septic shock (P), is utilizing early broad-

spectrum antibiotic therapy (I) superior to awaiting culture results before antibiotic treatment (C), to reduce mortality rate (O) during

inpatient hospitalization (T)?

Current State of Knowledge

The Journal of the American Medical Association (JAMA) recently held a consensus to redefine sepsis and septic shock. The

redefinition of terms stems from advances in diagnostics and the need to clarify and simplify the stages of sepsis. The following are

the definitions proposed by JAMA:

 Sepsis: “Life-threatening organ dysfunction caused by a dysregulated host response to infection” (Singer & et al.,

2016).

 Septic Shock: “Sepsis with circulatory and cellular/metabolic abnormalities profound enough to substantially increase

mortality” (Singer & et al., 2016).

SEPSIS LITERATURE REVIEW 3

Sequential Organ Failure Assessment (SOFA) scores are to be utilized when diagnosing sepsis or septic shock. A SOFA score of two

or greater is considered sepsis. Septic shock also has a SOFA score greater than two, but the patient requires vasoactive medications to

maintain an adequate blood pressure for organ perfusion and has an elevated lactate level (Singer & et al, 2016).

More than one million Americans develop severe sepsis every year. This life-threatening illness is frequently a result of a

bacterial infection that becomes serious enough to cause a systemic inflammatory response syndrome (SIRS). Patients that develop

sepsis are usually debilitated and often have other co-morbidities (NIGHS, 2015). The risk of mortality increases if sepsis is left

untreated. Symptoms of sepsis progress quickly from general malaise to multisystem organ failure as seen in septic shock (Leon, et al.,

2013). Studies suggest that one in four patients diagnosed with sepsis will progress to severe sepsis or septic shock (Capp, et al.,

2015). Early treatment of septic shock is essential to reduce mortality rates (Gaieski, et al., 2010).

The Surviving Sepsis Campaign developed and published in 2013 an international guideline for the treatment of severe sepsis.

The key features of the guidelines recommend that patients receive resuscitative measures via intravenous fluids and vasoactive

medications as necessary. Blood cultures are also to be drawn from needed for patients that who are suspected to have severe sepsis.

Furthermore, empiric antibiotics are to be administered within the first six hours of the onset of the symptoms of sepsis (Dellinger &

et al., 2013). The early administration of an empiric antibiotic can improve the overall mortality rate of patients diagnosed with severe

sepsis or septic shock (Ferrer, et al., 2009). Comment [T1]: Are there more than one study that concludes this? If so, cite them

SEPSIS LITERATURE REVIEW 4

Review of Literature Table

A review of literature table (RLT) is provided that provides information related to the early administration of empiric

antibiotics to patients diagnosed with severe sepsis or septic shock. Siddiqui & Razzak attempted a systematic review of randomized

controlled trials (RCT) revealing no current RCT studies (Siddiqui & Razzak, 2012). The study suggests that RCTs of septic patients

would be unethical and that observational studies would be a more appropriate approach to evaluate the relationship between empiric

antibiotics and the mortality of septic patients (Siddiqui & Razzak, 2012). There are, however, Oobservational studies available that

suggest that the early administration of empiric antibiotics to septic patients can reduce mortality (cite a few of those studies here).

MacArthur, et al. conducted an observational study involving 2634 patients diagnosed with sepsis revealing a 43% mortality

rate of patients that did not receive appropriate empiric antibiotics as compared to a 33% mortality rate for patients that received

appropriate empiric antibiotics (MacArthur, et al., 2004). Ferrer, et al. conducted an observational study of 2,796 patients diagnosed

with sepsis revealing a 41.6% mortality rate of patients that did not receive appropriate empiric antibiotics (Ferrer, et al., 2009). Paul,

et al. conducted a meta-analysis of seventy prospective studies that suggest that the appropriate empiric to septic patients significantly

reduces overall mortality rates (Paul, et al., 2010). Studies with fewer participants diagnosed with sepsis were conducted by Gajeski, et

al., 2010 and Harbarth, et al., 2003 both suggesting that the administration of early empiric antibiotics to septic patients reduces

mortality rates. Comment [T2]: Excellent synthesis

SEPSIS LITERATURE REVIEW 5

Preliminary Conclusions

Systematic reviews or meta-analysis of RCTs summarize and provide a high-quality synthesis of multiple RCTs and are

considered a gold standard in research (Polit & Beck, 2012, p. 30). Observational studies and reviews lack the randomization of

groups found in RCTs. and They are prospective in design thus decreasing the risk of unethical research. The utilization of a

prospective design was consistent with all the studies in the RLT. The observational studies provided in the RLT represent a small

group of patients, but there are significant findings suggest that the administration of early empiric antibiotics to septic patients can

reduce overall mortality (cite all studies that support this conclusion). Continued research regarding the timing of empiric antibiotics

can provide standards for evidenced based practice that can reduce the mortality rates of patients diagnosed with severe sepsis.

Summary

The purpose of this project was to conduct a literature review addressing the PICOT question regarding the administration of

early empiric- antibiotics effects on the mortality rate of adults diagnosed with severe sepsis. The findings of the literature review

suggest that overall mortality is decreased when an appropriate early antibiotic treatment is utilized for patients with severe sepsis. The

main limitation of the studies is that RCTs is unethical. All studies resorted to observational reviews of other RCTs that included septic

patients who received antibiotics. Further study of the type and timing of the administration of broad-spectrum antibiotics to septic

patients’ needs to be evaluated. Comment [T3]: patients

SEPSIS LITERATURE REVIEW 6

References

Capp, R., Horton, C., Takhar, S., Ginde, A., Peak, D., Zane, R., & Marill, K. (2015). Predictors of patients who present to the

emergency department with sepsis and progress to septic shock between 4 and 48 hours of emergency department arrival.

Critical Care Medicine, 43(5), 983-988. Retrieved from

http://web.b.ebscohost.com.ezp.waldenulibrary.org/ehost/detail/detail?vid=7&sid=ae3fe6e6-bd00-4cd7-b645-

27af89d436eb%40sessionmgr111&hid=125&bdata=JnNjb3BlPXNpdGU%3d#AN=25668750&db=mnh

Dellinger, P., & et al. (2013). International guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine

Journal, 41(2), 580-637. doi:10.1097/CCM.0b013e31827e83af

Ferrer, R., Artigas, A., Suarez, D., Palencia, E., Levy, M., Arenzana, A., . . . Sirvent, J. (2009). Effectiveness of treatments for severe

sepsis. American Journal of Respiratory and Critical Care Medicine, 180(9), 861-866. doi:10.1164/rccm.200812-19120C

Gaieski, D., Mikkelsen, M., Band, R., Pines, J., Massone, R., Furia, F., . . . Goyal, M. (2010). Impact of time to antibiotics on survival

in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department.

Society of Critical Care Medicine, 38(4), 1045-1053. doi:10.1097/CCM.0b013e3181cc4824

Harbarth, S., Garbino, J., Pugin, J., Romand, J., Lew, D., & Pittet, D. (2003). Inappropriate initial antimicrobial therapy and its effect

on survival in a clinical trial of immunomodulating therapy for severe sepsis. The American Journal of Medicine, 115(7), 529-

535. doi:http://dx.doi.org/10.1016/j.amjmed.2003.07.005

SEPSIS LITERATURE REVIEW 7

Leon, A., Hoyos, N., Barrera, L., Rosa, G., Dennis, R., Duenas, C., . . . Jaimes, F. (2013). Clinical course of sepsis, severe sepsis, and

septic shock in a cohort of infected patients from ten Colombian hospitals. BMC Infectious Diseases, 1-9. Retrieved from

http://web.b.ebscohost.com.ezp.waldenulibrary.org/ehost/pdfviewer/pdfviewer?vid=9&sid=8d0ed0c2-8f30-431c-8884-

77b4d709fa82%40sessionmgr102&hid=125

MacArthur, R., miller, M., Albertson, T., Panacek, E., Johnson, D., Teoh, L., & Barchuk, W. (2004). Adequacy of early empiric

antibiotic treatment and survival in severe sepsis: Experience from the MONARCS trial. Clinical Infectious Diseases, 38(2),

284-288. doi:10.1086/379825

NIGHS. (2015). Sepsis fact sheet. Retrieved from National Institute of General Medical Sciences:

https://www.nigms.nih.gov/Education/pages/factsheet_sepsis.aspx

Paul, M., Shani, V., Muchtar, E., Kariv, G., Eyal, R., & Leibovici, L. (2010). Systematic review and meta-analysis of the efficacy of

appropriate empiric antibiotic therapy of sepsis. Antimicrobial Agents and Chemotherapy, 54(11), 4851-4863.

doi:10.1128.AAC.00627-10

Polit, D., & Beck, C. (2012). Nursing research: Generating and assessing evidence for nursing practice (Laureate Education, Inc.,

custom ed.). Philidelphia, PA: Lippincott Williams & Wilkins.

Siddiqui, S., & Razzak, J. (2012). Early versus late pre-intensive care unit admission broad spectrum antibiotics for severe sepsis in

adults. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd. doi:10.1002/14651858.CD007081.pub2

Comment [T4]: I know this physician

SEPSIS LITERATURE REVIEW 8

Singer, M., & et al. (2016). The third international consensus definitions for sepsis and septic shock (Sepsis-3). The Journal of the

American Medical Association, 315(8), 801-810. doi:10.1001/jama.2016.0287

Review of Literature Table

Citation Type of Study

Design Type

Framework/Theory

Setting Key Concepts/Variables

Findings Hierarchy of Evidence Level

(Ferrer, et al., 2009) Type of Study:

Observational Design Type:

Prospective,

multicenter Framework/Theory:

Setting: 2,796 adult septic patients in 77 intensive care units were studied to determine the

Concepts: Independent Variable: Early administration of broad-spectrum antibiotics Dependent Variable: mortality

Findings of this study show that 41.6% of the patients analyzed died before hospital discharge. The study suggests that there is a decreased risk of mortality with the use of the early administration of broad-spectrum antibiotics.

Level IV

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None listed effectiveness of treatments recommende d by sepsis guidelines.

Controlled Variable: Patients diagnosed with severe sepsis or septic shock

(Gaieski, et al., 2010) Type of Study: Observational

Design Type: Single-center cohort study

Framework/Theory: None listed

261 patients diagnosed with severe sepsis or septic shock in one emergency department from 2005- 2006

Concepts: Effects of the timing of antibiotics on mortality.

Independent Variable: EGDT, timing of antibiotics

Dependent Variable: Mortality

Controlled Variable: Patient with severe sepsis or septic shock

There were significant findings to suggest that the early administration of appropriate antibiotics reduces the incidence of mortality. Patients receiving appropriate antibiotics under I hour had a mortality rate of 25% vs. 38.5% mortality rate for septic patients that did not receive an appropriate antibiotic within 1 hour.

Level IV

(Harbarth, et al., 2003) Type of Study:

Observational

Design Type:

Cohort

Framework/Theory: None listed

Setting: 904 patients diagnosed with sepsis were evaluated for the effect of inappropriate versus appropriate antibiotic administratio n related to mortality.

Concepts: Evaluate the effectiveness of the administration of inappropriate antibiotics related to the prognosis of septic patients. Independent Variable: Adequate antibiotics, inadequate antibiotics Dependent Variable: Mortality

Controlled Variable: Patients diagnosed

Findings of this study suggest that septic patients who received inadequate antibiotics had increased rates of mortality. The mortality rate of septic patients who received adequate antibiotics was 24% versus 39% mortality for patients who did not receive adequate antibiotics.

Level IV

SEPSIS LITERATURE REVIEW 10

with sepsis

(MacArthur, et al., 2004) Type of Study: Observational Design Type: Prospective Framework/Theory: None listed

Setting: 2634 patients were enrolled to determine mortality rate of patients receiving adequate antibiotics versus inadequate antibiotics

Concepts: Evaluation of the effectiveness of the administration of appropriate antibiotics in patients with severe sepsis or septic shock on the mortality rate within twenty-eight days

Independent Variable: adequate antibiotics, inadequate antibiotics Dependent Variable: Mortality at twenty- eight days Controlled Variable: Patients diagnosed with sepsis

Septic patients who received appropriate antibiotic treatment was 33% and a 43% mortality rate in septic patients who received inadequate antibiotics The significant findings of this trial conclude that the use of appropriate antibiotic therapy decreases the mortality rate in patients with suspected sepsis.

Level IV

(Paul, et al., 2010) Type of Study: Systematic Review

Design Type: Prospective, cohort

Framework/Theory: None listed

Setting: Meta- analysis of seventy prospective studies

Concepts: Analysis of the effects of appropriate timing of empirical antibiotics on the mortality in septic patients. Independent Variable: Appropriate empirical antibiotics, inappropriate antibiotics Dependent Variable: Mortality

The findings of this study suggest that the use of appropriate empirical antibiotics can significantly reduce mortality among patients with severe sepsis or septic shock. Mortality rate was found to be 34% in septic patients that did not receive adequate antibiotics.

Level III

SEPSIS LITERATURE REVIEW 11

Controlled Variable:

Patients diagnosed with severe sepsis or septic shock.

(Siddiqui & Razzak, 2012)

Type of Study: Systematic Review

Design Type: Review of RCTs

Framework/Theory: None listed

Review of RCTs for patients with severe sepsis of septic shock, timing of broad- spectrum antibiotics

Concepts: The outcome assessment of patients receiving early versus late antibiotic administration.

Independent Variable: Timing of antibiotic administration

Dependent Variable: Mortality

Controlled Variable: Patient diagnosed with severe sepsis or septic shock

There were no studies that fit the criteria to satisfy this study. The authors of this study do, however, feel that randomizing critically ill patients can be unethical and that observational cohort studies would be more appropriate.

Level I

Comment [T5]: This sentence is unclear