Edited By: David Manthey, MD
Wake Forest University School of Medicine
- Describe the criteria for the sepsis syndromes: SIRS, sepsis, severe sepsis and septic shock.
- Explain the utility of lactate in the identification and management of severe sepsis in the Emergency Department
- List the steps of Early Goal Directed Therapy
- Describe the the benefits of early antimicrobial administration and factors influencing selection in patients with sepsis syndromes in the Emergency Department
Sepsis syndromes encompass a wide array of infectious processes ranging from upper respiratory illnesses to pneumonia to pyleonephritis to cholecystitis to cellulitis.
The key is not the specific site of infection, but rather the host's response to the infection. An exaggerated response may lead to derangements in inflammation, coagulation, and fibrinolysis. Progression may lead to the formation of microvascular thrombosis, tissue hypoperfusion, organ dysfunction, multiple organ dysfunction, and even death!
The classically taught presentation of severe sepsis and septic shock is the elderly patient with multiple comorbidities, who presents with fever, cough, and dyspnea. Exam may reveal findings consistent with pneumonia, along with evidence of end organ failure and/or shock. The patient may exhibit an altered mental status, severe hypoxia, and acute renal failure.
This presentation is rare, and more often, patients present with more obscure complaints and physical exam findings. Sometimes patients may present with complaints of weakness, malaise, altered mental status, or simply "not eating." The source of infection may be readily apparent (cellulitis), may require extensive testing (intra-abdominal abscess), or may be completely obscure (subacute endocarditis) in the ED.
A careful history and physical, combined with high clinical suspicion is the key to the identification and proper management of septic patients.
Patients with suspected sepsis syndromes should be risk stratified into one of four categories:
SIRS (systemic inflammatory response syndrome) requires the presence of two of the four factors:
- Temperature less than 36.0 C or greater than 38.0 C
- Heart rate greater than 90 BPM
- Respiratory rate > 24 breaths per minute or PaCO2 < 32
- WBC less than 4,000 or greater than 12,000; or Bandemia >10%
Sepsis is SIRS plus the presence of infection.
Severe Sepsis is sepsis plus evidence of organ failure or lactate > 4.0 mmol/dL. Organ failure may be exhibited by:
- CNS (Delirium)
- Pulmonary (ALI/ARDS)
- Liver (Hyperbilirubinemia)
- Acute renal failure
- Lactate more than 4.0 mmol/dL
Septic Shock is sepsis plus hypotension that is unresponsive to two fluid boluses of 20-30 cc/kg. Hypotension is defined as a systolic blood pressure less than 90mm Hg or 40mm Hg below baseline blood pressures. Electronic medical records have facilitated assessment of baseline blood pressures.
- ABG, platelets, liver function tests, BUN/creatinine
White Blood Count (WBC) is useful to determine the presence of SIRS, either less than 4,000 or greater than 12,000, or a bandemia greater than 10%.
Lactate Measurement. Patients with severe sepsis and septic shock will often exhibit elevations of lactate, as evidence of global hypoperfusion. Lactate levels are highly prognostic of mortality in this population. Arterial lactates do not add significant value over venous and may delay assessment. The key is to run the test as quickly as possible, preferably as point of care testing. Levels above 2.5 mmol/dL are prognostic for higher mortality; levels above 4.0 mmol/L indicate even higher mortality
Procalcitonin may assist in the risk stratification of sepsis syndromes. Literature suggests that levels are elevated with the presence of systemic bacterial and fungal infections, but not with viral infections. Localized infections and subacute bacterial endocarditis may yield false negatives. Values above 2.0 ng/dl are concerning for severe sepsis and 10.0 ng/dl for septic shock.
Cultures and radiographs may be useful to determine the source and etiology of infection. Blood and urine cultures should be obtained before antibiotic administration. Other cultures, such as cerebrospinal fluid, peritoneal fluid, synovial fluid, abscess material, etc. should be obtained as indicated.
Further diagnostic testing, as noted above, is necessary to elicit the presence of end organ failure and thus severe sepsis.
So how do you make the diagnosis?
With infectious diseases in the Emergency Department, there is no gold standard. There are no ideal tests. WBC, CRP, ESR, CXR, U/A, and blood cultures all have surprisingly low sensitivities and specificities.
Listen to the History
Elicit an infectious history on all patients, especially those with nonspecific complaints. Remember that patients who are not febrile in the ED may have been febrile at home. Measure rectal temperatures in elderly patients as they are more reliable than oral temperatures. Up to 15% of infected elderly patients will have an elevated rectal temperature when the oral appears normal.
Look at lactate
If a patient is ill appearing or hypotensive, obtain a point of care lactate stat. Think of this as both the Troponin and ECG of sepsis. Remember levels above 2.5 are prognostic for higher mortality; levels above 4.0 indicate even higher mortality and open the "cath lab."
Risk stratify sepsis
Risk stratify patients by sepsis syndrome, Mortality in the Emergency Department Sepsis (MEDS) Score, lactate, and procalcitonin. Pneumonias may be risk stratified with the pneumonia severity index and CURB-65.
Many patients with infectious diseases may not present classically, just like acute coronary syndromes. Testing may be negative. This may be due to immunosuppression, age related changes in physiology, or the natural course of the disease. Remember that fevers fluctuate and may be suppressed by antipyretics. Delirium will fluctuate (a hallmark feature). Most importantly, do not ignore abnormal vital signs!
You can download the PDF file (Sepsis Flow Chart) and follow along.
What is a "bundle?" A bundle is a group of "best evidence-based practices" that should be implemented together to achieve an improved outcome (mortality).
Early Goal Directed Therapy (EGDT). This was the landmark study that revolutionized the care of the septic patient. Patients with severe sepsis and septic shock were randomized to receive either standard therapy or early goal directed therapy (standard therapy plus optimization of central venous oxygen saturation (ScvO2 > 70mm Hg)). The treatment group showed an absolute risk reduction (ARR) of 16%, which is one life save per 6 patients treated! (Number needed to treat, NNT)
- Rapid identification of the patient.
- Lactate within 10 minutes of arrival.
- Rapid central venous access (within 2 hours).
- Preload: rapid, early fluid boluses to achieve a Central Venous Pressure (CVP) between 8-12 mm Hg.
- Afterload: titrate vasopressors to achieve Mean Arterial Pressure (MAP) between 65 to 90 mm Hg. (Norepinephrine is preferred, but conclusive evidence is lacking to guide this decision.)
- Maintain urine output of 0.5 cc/kg/hour in adults
- Central Venous Oxygen Saturation (ScvO2) Conceptually, think of this as either significant oxygen debt or poor oxygen delivery. If ScvO2 is less than 70%, then:
- If hematocrit is < 30%, transfuse packed red blood cells to increase oxygen delivery
- If hematocrit is > 30%, then initiate dobutamine to increase cardiac index
- Reassess goals. CVP, MAP, ScvO2, and lactate should show improvement.
The key to EGDT is the EARLY. In one study, patients with early resuscitation (less than 24 hours) had an odds ratio of 0.5 for mortality, when compared to those with late resuscitation (more than 24 hours). Time is tissue and shock must be reversed!
Steroids: There is currently conflicting evidence regarding the efficacy of stress dose steroids in patients with severe sepsis and septic shock. They may be beneficial in patients with vasopressor refractory shock or patients with known adrenal insufficiency.
Antibiotics: According to the Surviving Sepsis Guidelines, antimicrobials should be administered within three hours of arrival to the Emergency Department. In the largest study of antimicrobials in septic shock, patients who received "effective" antibiotics within one hour of the development of hypotension had a survival of 79.9%. This dropped by 7.6% with every hour in delay of administration.
Choosing "effective" antibiotics without the benefit of culture results and sensitivities can be difficult. Therefore, it is imperative that the practitioner consider the source of infection, setting where infection occurred (community versus health care associated pneumonias), local resistance patterns, prior culture results and therapies (avoid recently used antimicrobials), and comorbid factors. Combination therapy is generally recommended for neutropenia and pseudomonas, though evidence is lacking.
There are no cut and dry rules to determine disposition. This is generally determined by severity of infection, immune status, host response, response to therapy, comorbidities, patient?s access to care, physician risk tolerance, local practice patterns, and hospital crowding issues.
Patients with SIRS and sepsis, who are young and do not have immunosuppression or significant comorbidities may often be discharged home. Those who do may require admission. Those with severe sepsis and septic shock will require admission to an intensive care unit, unless there has been significant improvement in EGDT variables.
Pearls and Pitfalls
- Be suspicious in patients with nonspecific presentations
- Risk stratify patients by sepsis syndromes and rapid lactate assessment
- Administer appropriate antibiotics early and initiate EGDT where indicated.
- Reassess the patient frequently to ensure response to therapy and lack of deterioration.
- Surviving Sepsis Campaign. http://www.survivingsepsis.org/
- Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-77. (RCT 263 patients)
- Jones AE. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis. Crit Care Med 2008;36:2734-2739.
- Annane D, Sebille V, Charpentier C, et al. Effect of Treatment with Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients with Septic Shock. JAMA 2002; 288(7):862-871 (RCT 300 patients)
- Sprung CL. Hydrocortisone therapy for patients with septic shock. NEJM 2008;358: 111-124 (RCT 499 patients).
- Kumar, et al. Duration of Hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006 Vol 34, No 6. (Retrospective 2,154 patients from 14 ICU registries).
- Dellinger RP, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock 2008. Crit Care Med 2008;
- DeBacker D, Comparison of Dopamine and Norepinephrine in the Treatment of Shock. NEJM. 2010;362:779-789