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Sepsis: Introduction

  • It’s nothing new to healthcare workers that sepsis is a big deal, and often at the top of provider’s differential diagnosis when patients begin to decompensate and the cause is not yet clear. There is good reason, too. The incidence of sepsis from 1979 – 2000 increased by 8.7% from 82.7 to 240.4 per 100,000 population (1). The incidence of sepsis is increasing as a result of the aging population, progressive increase in antibiotic resistance, reliance on implanted devices, organ transplantation, and an increasing prevalence of patients with long-term immunosuppressive diseases who are at risk for severe infection and sepsis (1).
  • In order to understand the importance of the sepsis bundle and why there is an emphasis on treating sepsis as a medical emergency, similar to a STEMI or a CVA.
  • Sepsis is a life-threatening syndrome consisting of numerous signs, symptoms, hemodynamic, and laboratory findings caused by an excessive and dysfunctional host immune response to severe infection that leads to dysregulated organ dysfunction (2). Septic shock is a more severe subset of sepsis that commonly presents with circulatory and/or metabolic dysfunction. Septic shock carries a 30-40% mortality risk (2).
  • The current sepsis definitions were published by the Third International Sepsis Task Force in 2016 are based on the fact that it is the dysregulated immune response, and not the infectious agent itself, that is the cause of the pathophysiological process (2).

Diagnostic Approach to Sepsis

  • Early phases of sepsis can be subtle even in the carefully monitored patient, but if the subtle signs are missed and the clinical signs of septic shock become glaringly apparent, you and your clinical team are acting much too late.
  • Fever is a characteristic sign, but hypothermia can also be present (and has the connotation of a worse prognosis).
  • Below is a table depicting the most common hemodynamic changes seen in sepsis (1).



Finding in Sepsis


Heart Rate

>/= 100b/min

Major compensatory mechanism for low systemic vascular resistance

Mean arterial blood pressure

<65 mmHg

Hallmark of septic shock if it remains low after adequate fluid resuscitation

Cardiac index

>4 L/min/m2

Cardiac index usually elevated in early septic shock; may be depressed in late septic shock

Pulmonary arterial occlusion pressure (PAOP)

8-16 mmHg

Assure that hypovolemia is not the cause of hypotension; perform fluid resuscitation until PAOP returns to normal

Central venous pressure (CVP)


Indicator of volume status. If it is <6 the patient is likely volume depleted. A normal or high value can have many different causes

Systemic vascular resistance (SVR)

<800 dyne/s/cm-5

SVR often low in early septic shock; may become elevated in later phases of septic shock
Mixed venous O2 saturation (SvO2) or


central venous O2 saturation (ScvO2)

< 70%


Low mixed venous O2 saturation or central venous O2saturation (from superior vena cava) indicates poor oxygen delivery to tissues
Oxygen consumption (Vo2)


Typically increased in early septic shock


  • The updated guidelines use the Sequential (Sepsis Related) Organ Failure Assessment Score (SOFA) to define sepsis. The SOFA score assesses the degree of organ dysfunction across numerous domains. A score of 2+ reflects an overall mortality of about 10% in the setting of a suspected infection (1). The laboratory data included in the SOFA score focuses on coagulopathy, hepatic dysfunction, and/or renal dysfunction (1). Other laboratory data (such as WBC) can aid in the diagnosis of infection but are not used to define sepsis or septic shock.
  • A bedside tool called qSOFA (Quick SOFA) was developed to quickly identify adult patients with suspected infection who are likely to have poor outcomes (1). The presence of any 2 of the following is equal to a positive qSOFA: 1) respiratory rate >/= 22/min; 2) Glasgow Coma Score <15; and/or 3) SBP </= 100 mmHg (1). The qSOFA is best used to identify early organ dysfunction in adults on general medical/surgical floors, whereas the SOFA score is used more in the critical care setting (1).
  • The qSOFA tool can be used to quickly screen and identify patients who are at risk for deterioration. It is being used both on admission and as ongoing tool to track changes in patient condition.
  • The chart below illustrates common laboratory findings seen in sepsis (1).

Laboratory Study

Typical Findings


White Blood Cell count

Leukocytosis or leukopenia

Stress response, increased margination of neutrophils in sepsis can cause transient neutropenia; toxic granulation

Platelet count


Look for evidence of fragmentation hemolysis; thrombocytopenia may be accompanied by DIC

Coagulation studies

Elevated prothrombin time (INR), aPTT, low fibrinogen levels, elevated D-dimer; evidence of fibrinolysis

Coagulopathy very common, but overt DIC is not common (< 15% of patients)

Liver enzymes

Elevated alkaline phosphatase, bilirubin, and transaminases; low albumin

Generally a late finding in sepsis, indicates hepatic ischemia and transaminases typically >10 times upper limit.

Plasma lactate

>2.2 mmol/L caused by hypermetabolism, anaerobic metabolism, inhibition of pyruvate dehydrogenase

Poor prognostic feature if not improved rapidly by fluid resuscitation; diagnostic criterion for septic shock (with suspected infection).

Can have other causes of elevation- high sensitivity with low specificity.

C-reactive protein

Elevated as an acute phase reactant from hepatic synthesis

Acute-phase reactant, sensitive, but not specific for sepsis


Hyperglycemia or hypoglycemia

Acute stress response can lead to hyperglycemia, inhibition of gluconeogenesis can lead to hypoglycemia

Arterial blood gas (ABG)

Respiratory alkalosis (early); metabolic acidosis (late)

Reduced arterial O2 content and mixed venous O2 saturation

Learner exercise

Think about your clinical experiences. Have you seen patients with sepsis who presented with atypical signs (hypothermia, respiratory alkalosis, etc.).

Do you think this delayed their diagnosis and care? How will you use this information to better detect patients who may have sepsis? 

Over the years many tools have been identified in hopes of detecting sepsis early. How does the sensitivity and specificity of each of these tools affect their usability? 

A Word on Sepsis Shock

  • Septic shock occurs in up to 15% of patients with sepsis (1).
  • It is defined as hypotension requiring intravenous vasopressors to maintain a MAP >/= 65mmHg and a serum lactate of >2mmol/L (1).
  • In a patient with early septic shock, the hemodynamics will reflect a high cardiac output and a low systemic vascular resistance indicative of profound vasodilation and a compensatory increase in cardiac output in an attempt to preserve peripheral vascular perfusion. As shock progresses, myocardial performance diminishes and circulating blood volume is continually lost to the interstitial space, which perpetuates the profound hypotensive state. Sepsis-induced myocardial dysfunction may ensue. This results in a potentially reversible heart failure state due to myocardial depression.
  • The management of the patient in septic shock hinges on prompt recognition of the patients deteriorating condition and expeditious administration of antibiotic therapy coupled with infectious source control. Simultaneously, the failing organ systems must be supported through measures such as, fluid resuscitation, vasopressors, blood transfusions, respiratory support, and inotropic agents. You can find more details regarding the initial management of sepsis in the Surviving Sepsis Campaign guidelines.

What Is a “Bundle,” and Why Are They Used?

  • The Surviving Sepsis Campaign developed the internationally endorsed “sepsis bundle” separately from their guidelines as a way to guide sepsis quality improvement (3). The bundles consist of various components of sepsis care including, fluid resuscitation, timely and appropriate antibiotic administration, blood cultures, and the use of serum lactate levels (4).
  • The bundle elements were designed in such a way so as to be updated as new evidence emerged (3).
  • In response to the most recent guidelines published in 2016, there has been a revised “hour-1 bundle” as opposed to the previous 3 hour and 6 hour bundles (3) (5).
  • There has been evidence that shows an association between compliance with bundles and improved survival in patients with sepsis and septic shock. In a multi-center, retrospective, observational study of adult patients with a hospital discharge diagnosis of severe sepsis or septic shock, overall mortality was lower in those who received bundle-adherent care (17.9%) when compared to those who did not (20.4%) (4). Interestingly, when the patients in the study were divided into subgroups by suspected source of infection, there was only a statistically significant mortality benefit to bundle-adherent sepsis care in patients diagnosed with pneumonia (4).

Learner exercise

How do you think the shift from a 3/6 hour bundle to a 1 hour bundle with affect patient care?

How can hospitals adapt to this measure?

Is the allocation of additional resources justified? 

1-Hour Bundle Components and Strategies to Expedite Care

  • The most critical change in the Surviving Sepsis Campaign bundles is that the previous 3-hour and 6-hour bundles are now combined into a single “hour-1 bundle” with the intention of beginning resuscitation and management immediately upon presentation (3) (5). While more than one hour may be needed for patient resuscitation to be completed, the initiation should begin immediately upon suspicion that the patient may be presenting with sepsis.


  • Measure lactate level: Serum lactate level serves as a surrogate for direct tissue perfusion measurement (3). In the absence of oxygen anaerobic metabolism ensues and lactate levels rise. It often represents the degree of tissue hypoxia present, and increased levels are associated with worse outcomes. If the initial lactate is >2mmol/L, it should be re-measured within 2-4 hours and used to guide resuscitation with the goal of achieving a lactic acid <2mmol/L (3).

Tips for expedited care:

Hospitals should have a threshold of >/= 2mmol/L for a critical lactic acid value, which will prompt any abnormal value to be communicated to the provider. Consider having non-nursing personnel collect the lactate level so that the nursing staff is free to focus on other tasks. The re-collection of lactates >2 can be automated by many electronic order entry systems and will help reduce fallouts due to re-collection. Point of care lactate is now readily available which can be very valuable.

All critical lactate values should be communicated to both the nurse and the provider. Traditionally this has been done by a call to the nurse who then notifies the provider. We suggest that lab calls both the provider and the nurse directly, to reduce the potential for error.


  • Obtain blood cultures prior to antibiotics. Blood cultures can become sterile within minutes of the first dose of appropriate antibiotic (3). By obtaining cultures before administering antibiotics, there is a better opportunity to identify pathogens, and therefore improve patient outcomes. Appropriate cultures include at least two sets of both aerobic and anaerobic cultures from two separate venipuncture sites. However, administration of antibiotic therapy should not be delayed past 1 hour in an effort to obtain cultures (3).

Tips for expedited care:

This is another task that can be delegated to non-nursing personnel, and the focus should be on sterile technique as contamination can completely change the treatment course for the patient. It may be helpful to have dedicated personnel and checklists for collecting blood cultures to ensure standardized care. Some evidence suggests that newer cleaning agents may reduce contamination.


  • Administration of broad-spectrum antibiotics. Empiric broad-spectrum antibiotic therapy with one or more intravenous antimicrobials to cover all likely pathogens should be started immediately (3). Once a pathogen is identified and sensitivities are established, the empiric antibiotics should be narrowed or discontinued if the patient is found to not to have an active infection (3).

Tips for expedited care:

Since time is of the essence when treating a patient presenting with sepsis, the empiric antibiotics should be kept in the on-unit medication storage for ease of access. Nurses should have immediate access to these medications.

All orders for sepsis antibiotics should be ordered as STAT (for the first dose). The providers should be trained to enter antibiotics orders directly after examining patients, if possible. Delays in ordering obviously lead to a delay in medication delivery. The goal should be to have a culture that recognizes and treats sepsis as a medical emergency, just as a code stroke or myocardial infarction.


  • Administer IV Fluid. Early effective fluid resuscitation is critical for the stabilization of sepsis-induced tissue hypoperfusion and septic shock (3). Initial fluid resuscitation should be begin immediately upon recognizing that a patient is presenting with sepsis and/or hypotension and elevated lactate (3). Fluid resuscitation should be completed within 3 hours of recognition. Current guidelines recommend that intravenous fluid resuscitation consist of 30 mL/kg bodyweight of crystalloid fluid (3).

Tips for expedited care:

Providers should communicate the need for intravenous fluids verbally to the nursing staff and place orders into the order entry system directly after examining patients. The patient should have 2-3 large bore IVs placed to facilitate the administration of IV fluids and IV antibiotics without sacrificing the timing of one or the other. Often times, placing a central line takes anywhere from 15-30 minutes, and will delay overall patient care during the first minutes. If additional venous access is needed, it is advisable to wait until the patient is stabilized so long as adequate reliable IV access is obtained.


  • Apply vasopressors. A critical part of sepsis resuscitation is restoring perfusion to the vital organs. If a patients blood pressure does not return to normal after the initial fluid resuscitation, then vasopressors should be initiated to maintain a mean arterial pressure (MAP) of >/= 65 mmHg (3). If a patient has profound hypotension and the decision is made by the medical team to initiate vasopressor therapy, there is no need to wait to initiate until central access is obtained (3). Vasopressors can be infused through a large bore peripheral IV safely for a short amount of time (3).

Tips for expedited care:

Within the ER and ICUs, there should be easy access to vasopressors, specifically norepinephrine, vasopressin, and epinephrine, in the event that a patient needs a vasopressor started. Additionally, institutions should have standing protocols for nurses to initiate a vasopressor in the event that a patient is consistently hypotensive despite adequate fluid resuscitation. This will save vital time by allowing the nurse to use their clinical judgment and restore vital organ perfusion quickly and efficiently while awaiting provider guidance.

Learner Exercise

How can you incorporate these tips and techniques for expedited care into your practice? 

What are some barriers you anticipate facing if you attempted to adopt these strategies? 

Do you think it is feasible for hospitals to adapt a 1 hour bundle?

Code Sepsis?

  • Despite bundle care and the diligent work of healthcare providers and beside nurses alike, many hospitals have identified an opportunity to save lives and reduce suffering through early sepsis detection, compliance with current standards of care and determining the appropriate level of care.
  • The Emergency Department Code Sepsis Project focuses on timely implementation of the SSC care bundle to reduce mortality and costs and to ensure appropriate level of care placement. By activating a ‘code sepsis’ it allows not only doctors and nurses to be aware of the urgency at hand, but also pharmacists, respiratory therapists, lab technicians, nursing support staff, and unit secretaries.
  • In some facilities, a ‘code sepsis’ is worked into the framework of the rapid response team. For example, if a nurse screens a patient for SIRS criteria and the patient meets the criteria, a page can be sent out from the patients current floor and this will mobilize the appropriate resources in order to facilitate swift and effective resuscitation.
  • In a retrospective observational quasi-experimental study conducted at the Hospital Clinico Universitario de Valladolid, researchers found that the in-hospital, intra-ICU, and 28-day mortality rates were all higher in the “pre code-sepsis” group (6). In –hospital mortality was 56% in the pre-code sepsis group, compared to 31% in the code sepsis group, p=0.035 (6). 28-day mortality also exhibited a statistical significant change (p= 0.035) with 44% and 23%, respectively (6). Intra-ICU stay was also longer in the pre-code sepsis group with an average stay of 10.5 days compared to 5 days in the code sepsis group, p = 0.05 (6).
  • The multidisciplinary nature of the code sepsis project creates a strong sense of teamwork centered around applying best evidence-based practice, mobilizing resources, avoiding procedure variability, and improving patient care and safety (6).
  • Hospitals that are struggling to meet sepsis measures should consider the addition of a “code sepsis” or “sepsis response team”.

Sepsis as a Medical Emergency

  • Each organization should strive for a culture that treats sepsis with the same urgency as any other medical emergency. Much of the delay in treatment with sepsis is due to a lack of standardized processes. Hospitals should work to develop sepsis protocols and sepsis response teams in order to increase compliance with bundles and decrease mortality.

Learner Exercise

How could a code sepsis benefit your sepsis patients?

Do you think that a code sepsis would expedite care in your facility?


  • Ultimately the one hour bundle is a call by the Surviving Sepsis Campaign and does not affect hospital reporting to Medicare/Medicaid. These measures (at the time of this writing) are still collecting data and reporting based on the 3/6 hour bundles previously set forth by the Surviving Sepsis Campaign. Expediting care may reduce mortality and morbidity associated with sepsis.

Course References and Disclaimer

References (Bibliography)

1) McCulloh, R. J., & Opal, S. M. (2017). Sepsis, Septic Shock, and Multiple Organ Failure. In Lange Critical Care. Retrieved March 8, 2019, from

2) Marini, J. J., & Dries, D. J. (2019). Sepsis and Septic Shock. In Critical Care Medicine: The essentials and more(pp. 576-594). Philadelphia, PA: Lippincott Williams & Wilkins. Retrieved March 8, 2019, from

3) Levy, M. M., Evans, L. E., & Rhodes, A. (2018). The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Medicine,44(6), 925-928. doi:10.1007/s00134-018-5085-0

4) Milano, P., Desai, S., Eiting, E., Hofmann, E., Lam, C., & Menchine, M. (2018). Sepsis Bundle Adherence Is Associated with Improved Survival in Severe Sepsis or Septic Shock. Western Journal of Emergency Medicine,19(5), 774-781. doi:10.5811/westjem.2018.7.37651

5) Hour-1 Bundle. (n.d.). Retrieved March 11, 2019, from

6) García-López, L., Grau-Cerrato, S., Frutos-Soto, A. D., Lamo, F. B., Cítores-Gónzalez, R., Diez-Gutierrez, F., . . . Andaluz-Ojeda, D. (2017). Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit. Medicina Intensiva (English Edition),41(1), 12-20. doi:10.1016/j.medine.2017.02.001

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