Current RecGOROommendations for Diagnosis and Management of Sepsis and Septic Shock

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Early goal-directed therapy (EGDT) instituted in ateam-focused, systems-based approach has beenshown to decrease patient morbidity and mortality

from sepsis.1 This article reviews sepsis, severe sepsis, andseptic shock, and discusses recommended diagnosis criteriaand management strategies of these conditions.

DEFINITION AND DIAGNOSTIC CRITERIA

The systemic inflammatory response system (SIRS) maybe initiated due to noninfectious causes, such as trauma,

pancreatitis, adrenal insufficiency, or burns. The definingcriteria of SIRS in adults requires two or more of the fol-lowing criteria:• temperature greater than 38.3° C (100.9° F) or less than36° C (96.8° F)• heart rate greater than 90 beats/minute• respiratory rate greater than 20 breaths/minute or PaCo

2

less than 32 mm Hg• white blood cell (WBC) count greater than 12,000 cells/ mm3, less than 4,000 cells/mm3, or consisting of more than10% bands.

Sepsis is an activation of the SIRS in response to an infec-tious cause, such as bacterial, viral, or fungal pathogens

(Figure 1). In a patient with evidence of SIRS activation,after initial resuscitation measures every effort should be

made to identify the infectious agent to differentiate SIRSfrom sepsis.2

Severe sepsis is sepsis associated with organ dysfunction,including renal dysfunction, hypotension, respiratory failure,

or altered mental status. Septic shock is severe sepsis withhypotension unresponsive to adequate IV fluid resuscita-tion. For the purposes of these definitions, hypotension isdescribed as a systolic blood pressure less than 90 mm Hg,a mean arterial pressure less than 70 mm Hg, or a reductionin systolic BP of more than 40 mm Hg from baseline.2

INCIDENCE

Before 2000, about 500,000 cases of sepsis were reportedin the United States each year.3 The number and rate ofhospitalizations for septicemia or sepsis more than doubledbetween 2000 and 2008. Hospitalization rates for sepsisor septicemia were similar for women and men, but sig-

nificantly increased for patients over 65 years and pediatricpatients under 1 year. Based on the National HospitalDischarge Summary from 2011, almost 17% of patientshospitalized for septicemia or sepsis died compared to2% of patients hospitalized for other causes.4 The CDC,using data from the National Vital Statistics Report,estimated more than 35,000 people died from sepsis inthe United States in 2011. Septicemia was the 11th mostcommon cause of death in the United States in 2011, aslight decrease of 0.9% from 2010.5

Current recommendations for diagnosis and

management of sepsis and septic shock Jami S. Smith, MPA, PA-C

Jami S. Smith works in the simulation division of the Department

of Emergency Medicine at Drexel University College of Medicine in

Philadelphia, Pennsylvania, and practices emergency medicine in

the Philadelphia area. The author has indicated no relationships to

disclose relating to the content of this article.

DOI: 10.1097/01.JAA.0000435007.55340.07

Copyright © 2013 American Academy of Physician Assistants

ABSTRACT

Early recognition of sepsis and early goal-directed therapyfollowing evidence-based bundles can reduce patient mortal-ity from sepsis and septic shock. This article reviews currentrecommendations for diagnosis and management.

Keywords: sepsis, early goal-directed therapy, systemicinflammatory response, organ failure, hemodynamic

management



Current recommendations for diagnosis and management of sepsis and septic shock

JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 43

RISK FACTORS

Risk factors associated with the development of sepsis andsevere sepsis are related to patient demographics, comor-bidities, and complications of medical care. Patients are atincreased risk if they are over 65 years old or under 1 yearold, or have conditions such as HIV, cancer, cirrhosis,alcohol abuse, or diabetes. An increased prevalence ofsepsis also is associated with complications from centralvenous catheter use, endotracheal intubation, surgery, andtransfusions.6

CLINICAL PRESENTATION

Once the patient is identified as at risk for sepsis, the his-tory and physical examination should focus on identifyingthe source of the infection and recognizing any comorbidconditions and all associated symptoms. These steps willhelp determine the extent of disease progression andappropriate treatment. Physical examination findingsconsistent with severe sepsis include the SIRS criteria aswell as decreased urine output, altered mental status,decreased capillary refill, and skin mottling.1

Common infections that can progress to sepsis and severesepsis originate from the lungs, bloodstream, skin and softtissue, urinary tract, abdomen, and central nervous system(Table 1). The Acute Physiology and Chronic HealthEvaluation (APACHE) II tool has been developed andvalidated to predict mortality and stratify acutely ill patientsby likely prognosis. APACHE II uses these variables to

calculate the risk of increased mortality: temperature, meanarterial pressure (MAP), heart rate, respiratory rate, oxy-genation, arterial pH, serum sodium, serum potassium,serum creatinine, hematocrit, white blood cell count,Glasgow Coma Scale score, age, and chronic health condi-tions.1,7 Scoring systems in the ED help clinicians identifypatients at risk for sepsis and those who would benefitfrom implementation of EGDT. Patients over age 65 withan elevated lactate level and elevated APACHE II have agreater risk of death during hospitalization.8,9

DIAGNOSTIC TESTING

In addition to the specific SIRS criteria, other diagnosticindicators of organ dysfunction and hypoperfusion includelow central venous pressure, oliguria, anuria, increasedserum creatinine, thrombocytopenia, elevated liver functiontests, increased prothrombin time, and increased serumlactate levels.1

Before administering antibiotics to a patient suspectedof having sepsis, obtain two sets of blood cultures. If avascular access device has been in place more than 48hours, also obtain one culture from that site.10 Obtain

cultures from other sites that are likely sources of the infec-tion, such as wounds or urine. Although results from thesecultures will ultimately direct therapy, empiric treatmentwith broad-spectrum antibiotic therapy is appropriatepending results from cultures.

Tests for inflammatory markers such as plasma C-reactiveprotein and plasma procalcitonin may trend the manage-ment of severe sepsis or septic shock.10 Prompt use ofdiagnostic imaging studies, including radiography, ultra-sound, CT scan, and MRI can assist in identifying the

Key points

Early recognition of the systemic inflammatory response

system (SIRS) criteria and identification of an infectious

process should prompt initiation of early goal-directed

therapy (EGDT). EGDT should focus on hemodynamic resuscitation,

restoring tissue oxygenation, identifying infection, and

infection control within 6 hours of recognition of sepsis or

severe sepsis.

Hospital-specific guidelines should be created by an

interprofessional, interdisciplinary team with resources for

education and implementation.

EGDT and systematic hospital guidelines have been shown

to improve patient outcomes.

Table 1.

Infectious sources of sepsis and severe sepsis6

Source of infection Clinical syndrome

Lungs

• Pneumonia • Lung abscess

Bloodstream • Bacteremia

• Fungemia

Skin and soft tissue • Cellulitis

• Fasciitis

• Osteomyelitis

Genitourinary tract • Cystitis

• Pyelonephritis

Central nervous system • Meningitis

• Encephalitis • Intracranial abscess

Abdomen • Cholecystitis

• Cholangitis

• Pancreatitis

• Appendicitis

• Diverticulitis

• Perforated viscus with

secondary peritonitis

• Spontaneous bacterial

peritonitis

Other • Febrile neutropenia

• Asplenia



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REVIEW ARTICLE

source of severe sepsis and septic shock. These studiesshould be used to identify possible hidden sources of infec-tion, such as bowel ischemia, pancreatitis, cholangitis,pneumonia, and abscess.10

TREATMENT

The initial focus of EGDT should be hemodynamic resus-citation, restoring tissue oxygenation, identifying infection,and controlling infection.1 Initial resuscitative efforts shouldoccur within the first 6 hours regardless of the location ofthe patient within the hospital. Goals of initial resuscitationinclude maintaining central venous pressure between 8and 12 mm Hg, MAP at or above 65 mm Hg, urine outputat or above 0.5 mL/kg/hour, and central venous oxygensaturation at or above 70% (or mixed venous oxygensaturation at or above 65%). Patients should be givenhigh-flow oxygen and airway support as necessary. Otherinterventions include administering IV fluids, transfusingpacked red blood cells as required to maintain the patient’shematocrit at or above 30%, and administering norepi-nephrine if the patient has persistent hypotension.10 Anti-biotic therapy should be started as soon as possible andwithin 1 hour of recognition in patients with severe sepsisor septic shock.10

Hemodynamic management Fluid resuscitation is amainstay of hemodynamic management for patients withsepsis. Patients with hypovolemia should receive 30 mL/ kg of crystalloid fluid or colloid equivalent, with a targetcentral venous pressure (CVP) of 8 to 12 mm Hg in patientswho are not intubated, and 12 to 15 mm Hg in those onmechanical ventilation.10 Continue fluids as long as thepatient shows hemodynamic improvement. Decrease fluidadministration if the patient’s CVP increases without evi-dence of improving hemodynamic status.

If the patient’s hypotension is life-threatening, administervasopressors to maintain a target MAP of 65 mm Hg orgreater. Norepinephrine and epinephrine are the recom-mended vasopressors for patients with severe sepsis orseptic shock. Vasopressin may be added to norepinephrineto increase MAP or reduce the amount of norepinephrineneeded.10 Follow the patient’s BP, tissue perfusion, lactatelevels, and urine output to direct hemodynamic manage-ment. For patients with elevated cardiac pressure anddecreased cardiac output, inotropic therapy with dobuta-mine is indicated.10

Source control The methods used to control an infectionsite and moderate the mechanisms responsible for antimi-crobial growth and impaired host defenses are known assource control. Source control should be initiated within12 hours of the patient being diagnosed with sepsis.10 Surgical methods of source control include drainage of alocal source of infection, debridement of infected necrotictissue, definitive correction of the underlying cause of thesepsis, and removal of invasive devices such as cathetersand orthopedic hardware.10,11

Patients with pancreatitis with peripancreatic necrosisare an exception to the 12-hour timeline for source con-trol. In these patients, interventions should be delayed

until viable and nonviable tissue has been adequatelydemarcated.10

PHARMACOTHERAPY

Broad-spectrum antibiotics should be started within 1 hourof recognition of sepsis or severe sepsis and then de-escalatedonce culture results are obtained and antibiotic therapycan be targeted. Consider empiric combination antibiotictherapy for gram-negative coverage in patients who areneutropenic, have a history of multiple drug-resistant

FIGURE 1. Early biomechanical events in sepsis



Current recommendations for diagnosis and management of sepsis and septic shock

JAAPA

Journal of the American Academy of Physician Assistants www.JAAPA.com 45

infections, or are in refractory septic shock. Reassess thechoice of therapy daily for effectiveness, to prevent toxicityand resistance, and to minimize cost. Discontinue antibiot-ics if the cause of the patient’s sepsis is found to benoninfectious.10

Corticosteroids are only recommended for septic patientswho have hypotension unresponsive to fluid resuscitationand vasopressor therapy.10

SUPPORTIVE THERAPY

Follow the ARDSNet protocol and maintain low tidalvolume ventilation in patients who need mechanical ven-tilation for sepsis-induced acute lung injury or acute respi-ratory distress syndrome.12

In stabilized patients, keep the blood glucose level under180 mg/dL. Use hemodialysis as indicated in hemodynami-cally unstable patients with acute renal failure. Prophylaxisfor stress ulcers and deep vein thrombosis also should beprescribed if indicated.10

TAKING A TEAM-BASED APPROACH

A number of clinical guidelines describe the identificationand management of sepsis and severe sepsis. These guide-lines cannot direct patient outcomes and improvement

unless they are consistently implemented in clinical prac-tice. A dynamic interdisciplinary, interprofessional teamcan bring its collective experience into the developmentof hospital-specific guidelines based on available resourcesand the Surviving Sepsis Campaign (SSC) recommenda-tions. Interdisciplinary teams from the emergency, criticalcare, and nursing departments should be formed to addressthe implementation of early sepsis recognition and man-agement guidelines. These teams might include physicians,PAs, advanced practice nurses, nurses, pharmacists, labo-

ratory scientists, and admissions clerks.13 An interdisciplinary clinical implementation team is key

because patients with sepsis are typically transferred to theICU from the ED or other units within the hospital. TheSSC notes that the potential for outcome improvement in

settings other than the ICU is substantial. SeeTable 2

forexamples of sepsis resuscitation and management bundles.A systematic plan of resource allocation and educationthroughout the hospital, with the goal of early recognitionand aggressive initial treatment of sepsis and severe sepsis,can improve patient outcomes.

Implementation and adherence to hospital-establishedprotocols has been shown to improve patient outcomes.1 Because sepsis is one of the top 10 most expensive diseasesmanaged by hospitals, early and aggressive treatmentshould decrease the economic burden, although this hasnot yet been proven in the research. Sepsis and septic shockimpose a significant burden on patient morbidity and thefinancial health of the US healthcare system. As the inci-dence of sepsis continues to rise with our aging population,early recognition and EGDT remains the best chance tomake a significant effect on this devastating inflammatoryprocess. JAAPA

REFERENCES 1. Rivers EP, Ahrens T. Improving outcomes for severe sepsis and

septic shock: tools for early identification of at-risk patients andtreatment protocol implementation. Crit Care Clin. 2008;24:1-47.

2. Bone RC, Balk R, Cerra F, et al. Definitions for sepsis and organfailure and guidelines for the use of innovative therapies insepsis. The ACCP/SCCM Consensus Conference Committee,American College of Chest Physicians/Society of Critical CareMedicine. Chest. 1992;101(6):1644-1655.

3. Martin GS, Mannino D, Eaton S, Moss M. The epidemiology of

sepsis in the United States from 1979 through 2000. N Engl JMed . 2003;348:1546-1554.

4. Hall M, Williams S, DeFrances C, Golosinskiy A. Inpatient carefor septicemia or sepsis: a challenge for patients and hospitals,NCHS Data Brief 62, June 2011. http://www.cdc.gov/nchs/data/ databriefs/db62.pdf.

5. Hoyert D, Xu J. Deaths: preliminary data for 2011. NationalVital Statistics Reports. 2012;61(6):1-51.

6. O’Brien JM, Ali N, Aberegg S, Abraham E. Sepsis. Am J Med .2007;120:1012-1022.

7. Knaus WA, Draper E, Wagner D, Zimmerman J. APACHEII: a severity of disease classification system. Crit Care Med. 1985;13:818-829.

8. Juneja D, Singh O, Dang R. Admission hyperlactatemia: Causes,incidence, and impact outcome of patients admitted in a generalmedical intensive care unit. J Crit Care. 2011;26:316-320.

9. Seymour CW, Band R, Cooke C, et al. Out-of-hospital charac-teristics and care of patients with severe sepsis: A cohort study. JCrit Care. 2010;25:553-562.

10. Dellinger RP, Levy M, Carlet J, et al. Surviving Sepsis Campaign:International Guidelines for management of severe sepsis andseptic shock: 2012. Crit Care Med. 2013;41:580-637.

11. Marshall JC, Maier R, Jiminez M, Dellinger E. Source control inthe management of severe sepsis and septic shock: An evidence-based review. Crit Care Med . 2004;32:S513-S526.

12. Fan E, Needham D, Stewart T. Ventilatory management of acutelung injury and acute respiratory distress syndrome. JAMA. 2005;294(22):2889-2896.

13. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapyin the treatment of severe sepsis and septic shock. N Engl J Med .2001;345:1368-1377.

Table 2. Surviving Sepsis Campaign bundles10

Resuscitation (to be completed within 3 hours)

• Obtain serum lactate level

• Obtain blood cultures before administering broad-

spectrum antibiotics• Administer broad-spectrum antibiotics

• Administer 30 mL/kg crystalloid for hypotension or lactate

≥ 4 mmol/L

Management (to be completed within 8 hours)

• Administer vasopressors for hypotension that does not

respond to initial fluid resuscitation; maintain a MAP ≥ 65

mm Hg

• In the event of persistent arterial hypotension despite

adequate fluid resuscitation or initial lactate ≥ 4 mmol/L

(36 mg/dL), measure CVP and central venous oxygen

saturation

• Remeasure the patient’s lactate if the initial level was

elevated

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Current RecGOROommendations for Diagnosis and Management of Sepsis and Septic Shock