Sepsis is a common and life-threatening condition that requires early recognition and swift initial management. Diagnosis and treatment of sepsis and septic shock are fundamental for emergency clinicians, and include knowledge of clinical and laboratory indicators of subtle and overt organ dysfunction, infection source control, and protocols for prompt identification of the early signs of septic shock. This issue is a structured review of the literature on the management of sepsis, focusing on the current evidence, guidelines, and protocols.
A 65-year-old man with COPD and diabetes presents from home with a productive cough (green sputum) for 1 week, dyspnea on exertion, and fever. Albuterol at home provided no relief. His vital signs are: heart rate, 102 beats/min; respiratory rate, 22 breaths/min; blood pressure, 130/89 mm Hg, and SpO2, 94% on room air. He is speaking in full sentences and does not appear to be in respiratory distress. He has rales at the right lung base, mild wheezes, and tachycardia. Chest radiograph confirms right lower lobe pneumonia. The patient has no recent hospitalizations. You believe that he looks clinically well and may be able to be discharged home with antibiotics, but you are also concerned for sepsis and wonder if this would be a wise decision...
A 45-year-old man with hypertension and prostate cancer in remission presents complaining of 3 days of burning with urination, fevers, and chills. His vital signs are: heart rate, 110 beats/min; respiratory rate, 20 breaths/min; blood pressure, 130/90 mm Hg; SpO2, 98% on room air; and temperature, 38.4°C (101.2°F). He is alert and fully oriented. His physical exam reveals mild suprapubic tenderness without rebound or guarding and bilateral costovertebral angle tenderness. Lab findings include a WBC count of 18,000 with 5% bands, a creatinine of 1.5 mg/dL, a platelet count of 130 x 103/mm3, 80 WBCs on urinalysis with positive nitrite and leukocyte esterase, and a serum lactate of 1.2 mmol/L. After receiving ibuprofen and a fluid bolus, the patient feels better and states, “I need to go get my dog!” The nurse asks you if she can remove the IV for the patient to be discharged, which sounds reasonable, but something worries you...
A 70-year-old woman with diabetes mellitus, hypertension, and colon cancer arrives via EMS from a local nursing home for right foot swelling and redness. Paramedics report 2 days of increasing confusion. Her initial blood pressure was 85/50 mm Hg, with a heart rate of 90 beats/min. Her initial glucose was 270 mg/dL. The patient is alert but unable to provide a history. During transfer into her bed, the patient screams in pain as her right leg bumps the bed rail. Your focused exam reveals tachycardia, clear breath sounds, and no acute distress. Her right foot and leg are extremely tender, warm, and erythematous. She has crepitus over the dorsum of the foot and right calf tenderness, but no pretibial edema. The nurse rechecks her vital signs, revealing a blood pressure of 70/40 mm Hg. You order and initiate a fluid bolus. You consider the best antibiotic(s) to start and whether you should initiate pressors before she has received a 30 mL/kg fluid challenge...
Sepsis is triggered by a systemic infection and is a life-threatening, dysregulated response to infection.1 Immune abnormalities induced by invading pathogens or tissue damage produce both the inflammatory and immunosuppressive features of the disease, which causes organ dysfunction and can lead to death. Sepsis may lead to cellular abnormalities and perfusion deficits, causing septic shock. Optimal management strategies for sepsis have been an issue of intense research since a landmark study by Rivers and colleagues published in 2001 identified a 16% mortality reduction with randomization to an early aggressive care bundle termed early goal-directed therapy (EGDT). EGDT involves the administration of fluids, inotropes, and blood, and the achievement of hemodynamic goals to improve tissue oxygenation, as indicated by a central venous oxygen saturation (ScvO2) > 70%.2 After 3 recent multicenter trials failed to validate the results of that study, however, EGDT is no longer recommended.3-5 Nonetheless, in general, early, aggressive management of sepsis is recommended and has been shown to improve outcomes.6-9
This issue of Emergency Medicine Practice reviews the recent changes in sepsis criteria, prognosticators, and quality metrics and offers recommendations on the recognition and treatment of sepsis, severe sepsis, and septic shock in the emergency department.
The diagnosis of sepsis has undergone a metamorphosis since the inception of standardized definitions in 1991.10 Shifting away from the systemic inflammatory response syndrome (SIRS) criteria previously utilized,11 in 2014 the Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force and, by an expert consensus process, agreed in 2016 on updated definitions and criteria to be tested clinically. The Third International Consensus Definitions for Sepsis and Septic Shock (“Sepsis-3”) redefined sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection.”1
Sepsis-3 also redefined septic shock as “hypotension not responsive to fluid resuscitation,” with the added requirement for vasopressors to maintain a mean arterial pressure (MAP) ≥ 65 mm Hg and a lactate > 2 mmol/L. These new definitions were adopted by the 2016 Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock.9
Sepsis-3 cited new insights into sepsis pathobiology, the lack of sensitivity and specificity of SIRS criteria, and the excessive focus on inflammation as some of the reasons for the changes. The updated definitions in Sepsis-3 emphasize organ dysfunction in the setting of infection, which can be quantified using the sequential (sepsis-related) organ failure assessment (SOFA) score. For expansion of the criteria for scoring SOFA, see Table 1.
Sepsis-3 also derived a bedside assessment tool for sepsis screening in patients with infection who are not in intensive care units (ICUs). Called the quick SOFA (qSOFA) score, it includes 1 point for each of 3 criteria: (1) respiratory rate ≥ 22 breaths/min, (2) altered mental status, or (3) systolic blood pressure (SBP) ≤ 100 mm Hg. A qSOFA score ≥ 2 is suggestive of sepsis.12 Sepsis-3 recommends that, for a qSOFA score < 2, the full SOFA score, including laboratory results, should be used.12
Though the Sepsis-3 tool is more specific for sepsis, using SOFA may be problematic for the emergency clinician. SOFA components can be unfamiliar, with complex ICU-focused scoring on criteria not typically obtained routinely in potentially septic ED patients. These include arterial blood gases for respiratory evaluation and total bilirubin for hepatic dysfunction. In addition, qSOFA has been criticized as insensitive for sepsis screening,13-21 though it may have increased specificity for mortality22,23 and predicting organ dysfunction.24
Emergency clinicians should note that the current Centers for Medicare and Medicaid Services (CMS) SEP-1 quality measure, which is used to evaluate institutional sepsis bundle compliance, has not adopted Sepsis-3. The controversial CMS SEP-1 mandate is based on the presence of SIRS criteria, categorizes any infection with organ dysfunction as severe sepsis, and defines septic shock as “hypotension not responsive to fluids or serum lactate ≥ 4 mmol/L regardless of hypotension.”25,26 Therefore, hospital quality measures assess CMS quality metrics based on the 2001 International Sepsis Definitions Conference11 and not Sepsis-3. There is no indication that this will change, so it is important to know the differing metrics and definitions. A comparison of Sepsis-3 to the 2001 Sepsis definitions as well as CMS SEP-1 criteria are presented in Table 2.
To evaluate clinically relevant articles regarding the diagnosis and early management of sepsis, severe sepsis, and septic shock, a search of the National Library of Medicine PubMed database was performed using the following search terms: sepsis management, septic shock management, and clinical sepsis treatment guidelines, with a date range of 2000 to 2018. Acknowledging the breadth of the sepsis literature, additional specific searches were performed including intravenous fluids, antibiotics, vasopressors, corticosteroids, lactate, lactate clearance, and sepsis. References relevant to prehospital and emergency department (ED) care of septic patients were included. Only adult, human studies were considered, and publications in English (with the exception of 3 Chinese studies on lactate clearance). Current consensus guidelines were also reviewed.
Guidelines have recently been augmented with high-powered randomized clinical trials of sepsis and septic shock that evaluated management strategies, adding to specific recommendations for treatment and resuscitative endpoints. Several studies have recently examined invasive (EGDT) versus less-invasive early resuscitation strategies, and these results have led to recommendations against routine use of invasive strategies that do not confer a mortality benefit. Recommendations for volume of intravenous (IV) fluids, early antibiotics, and infection source control are based on national metrics and observational studies and not randomized clinical trials of early sepsis patients. Randomized trials using serum lactate for both screening and as a resuscitative endpoint support a strong recommendation for its use. Norepinephrine is the current vasopressor of choice, given both randomized trial data and several observational studies. A recent large randomized trial of hydrocortisone for septic shock did not show mortality benefits, but did show improved secondary outcomes.
1. “I didn’t reassess the patient’s lactate.”
Lactate clearance can aid in assessing a patient’s response to treatment. Persistently elevated lactate may indicate inadequate resuscitation or alternative diagnoses. Particular attention should be given to patients with limited lactate clearance, as persistent elevation is associated with poor outcomes.
5. “I wasn’t sure of the patient’s source of infection, so I waited to give antibiotics.”
Patients with presumed sepsis and hypotension have an increased mortality when antibiotics are delayed. In such cases, administering broad-spectrum antibiotics prior to source confirmation is recommended. For stable patients in whom sepsis is being considered, source-directed antibiotics should be administered as soon as practical and, ideally, within 1 hour of sepsis recognition.
9. “I used dopamine as the first-line vasopressor for septic shock.”
Recent literature and guidelines support norepinephrine as the first-line vasopressor for septic shock. Dopamine is associated with increased risk of arrhythmias and mortality compared with norepinephrine.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.
Points and Pearls Excerpt
Most Important References
|Table of Contents|
The SOFA score predicts mortality risk for patients in the intensive care unit based on lab results and clinical data.
Why to Use
The SOFA score can be used to determine the level of organ dysfunction and mortality risk in ICU patients.
When to Use
Calculate the SOFA score using the worst value for each variable in the preceding 24-hour period.
Even though it is calculated sequentially based on the worst value for each variable in the past 24 hours, the SOFA score is not meant to indicate the success or failure of interventions or to influence medical management.
Abbreviations: ICU, intensive care unit; SOFA, sequential organ failure assessment.
Kamal Medlej, MD
Clinical prediction scores such as the SOFA and the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE II) can be measured on all patients who are admitted to the ICU, to determine the level of acuity and mortality risk. This information can then be used in various ways, such as to provide the family with a prognosis, for clinical trials, and/or for quality assessment.
The SOFA score is not designed to influence medical management. It should not be used dynamically or to determine the success or failure of an intervention in the ICU.
The SOFA variables were selected by a working group of the European Society of Intensive Care Medicine (Vincent 1996). In the initial validation study, 1449 patients were enrolled over a period of 1 month from 40 ICUs in 16 countries (Vincent 1998). The study found that the SOFA score had a good correlation to organ dysfunction/failure in critically ill patients.
The SOFA score was also prospectively validated in an observational cohort study conducted by Ferreira et al (2001) at the ICU of a university hospital in Belgium. The study included 352 patients and found that the SOFA score was a good indicator of prognosis.
Jean-Louis Vincent, MD, PhD
The qSOFA score identifies patients with suspected infection who are at high risk for in-hospital mortality outside of the intensive care unit.
Why to Use
The qSOFA score identifies patients with suspected infection who are at high risk for in-hospital mortality outside of the ICU. It may help increase suspicion or awareness of a severe infectious process and prompt further testing and/or closer monitoring of the patient.
When to Use
Use the qSOFA for patients aged ≥18 years who have a confirmed or suspected infection and are in a non-ICU setting (ie, prehospital, ward, emergency department, or step-down unit).
The qSOFA score should be used to predict mortality, not to diagnose sepsis, per the 2016 Surviving Sepsis Campaign guidelines.
A “positive" qSOFA score (≥ 2) suggests high risk of poor outcomes in patients with suspected infection. These patients should be more thoroughly assessed for evidence of organ dysfunction. A positive qSOFA score by itself should not trigger sepsis-directed interventions such as the initiation of broad-spectrum antibiotics; rather, it should prompt clinicians to further investigate for the presence of organ dysfunction or increase the frequency of patient monitoring.
Abbreviations: ICU, intensive care unit; qSOFA, quick sequential organ failure assessment.
Kamal Medlej, MD
The Sepsis-3 task force recommended that a positive qSOFA score should prompt the calculation of a SOFA score to confirm the diagnosis of sepsis. This recommendation remains controversial, as the qSOFA has been shown to be more predictive than the SOFA outside of the ICU setting. Even if the patient’s qSOFA score is initially "negative" (< 2), it can be repeated if there is a change in the patient’s clinical status.
The qSOFA is a mortality predictor, not a diagnostic test for sepsis. It is still not clear how it will be used in the sequence of events from screening to diagnosis of sepsis to the triggering of sepsis-related interventions. The management of sepsis is continuously evolving and is detailed in the 2016 Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock (Rhodes 2017).
The qSOFA was introduced in February 2016 by the Sepsis-3 task force as a rapid, bedside clinical score to identify patients with suspected infection who are at greater risk for poor outcomes. The primary outcome was in-hospital mortality, and the secondary outcome was an ICU length of stay of ≥ 3 days. The qSOFA was meant to replace the systemic inflammatory response syndrome (SIRS) criteria, which were believed to be less sensitive and specific, although this remains controversial.
Seymour et al retrospectively derived and internally validated the qSOFA in a 2016 study that included 148,907 patients with suspected infection, either inside or outside of the ICU setting. For patients outside of the ICU with a qSOFA score ≥ 2, there was a 3- to 14-fold increase in the rate of in-hospital mortality. Among ICU patients, however, the predictive validity of the SOFA for in-hospital mortality was statistically greater than the qSOFA.
The qSOFA was prospectively validated in an emergency department population in a study by Freund et al published in 2017. The study, which included 879 patients across 30 emergency departments in 4 countries, found that use of the qSOFA resulted in greater prognostic accuracy for in-hospital mortality than either SIRS or severe sepsis.
Raith et al (2017) externally validated the SOFA and the qSOFA in a retrospective cohort analysis of 184,875 patients who had an infection-related admission diagnosis. The study found that, in an ICU population, an increase in the SOFA score of ≥ 2 points had greater prognostic accuracy for in-hospital mortality than the SIRS criteria or the qSOFA.
Christopher W. Seymour, MD, MSc
The Glasgow coma scale (GCS) estimates coma severity based on eye, verbal, and motor criteria.
Points to keep in mind:
Why to Use
The GCS is an adopted standard for mental status assessment in the acutely ill trauma and nontrauma patient and assists with predictions of neurological outcomes (complications, impaired recovery) and mortality.
When to Use
Abbreviation: GCS, Glasgow Coma Scale.
Daniel Runde, MD
Although it has been adopted widely and in a variety of settings, the GCS score is not intended for quantitative use. Clinical management decisions should not be based solely on the GCS score in the acute setting.
The modified Glasgow coma scale (modified GCS) is a 15-point scale that has been widely adopted, including by the original unit in Glasgow, as opposed to the 14-point scale. The modified GCS was developed to be used in a repeated manner in the inpatient setting to assess and communicate changes in a patient's mental status and to measure the duration of coma (Teasdale 1974).
In the acute care setting, the GCS has been shown to have highly variable reproducibility and interrater reliability (ie, 56% among neurosurgeons in 1 study, 38% among emergency department physicians in another study). In its most common usage, the 3 sections of the GCS are often combined to provide a summary of severity. The authors themselves have explicitly objected to the score being used in this way, and analysis has shown that patients with the same total score can have huge variations in outcomes, specifically mortality. A GCS score of 4 predicts a mortality rate of 48% if calculated 1 (eye) + 1 (verbal) + 2 (motor), and a mortality rate of 27% if calculated 1 (eye) + 2 (verbal) + 1 (motor), but a mortality rate of only 19% if calculated 2 (eye) + 1 (verbal) + 1 (motor) (Healey 2014).
In summary, the modified GCS provides an almost universally accepted method of assessing patients who have acute brain damage. The summation of the GCS components into a single overall score results in information loss and provides only a rough guide to severity. In some circumstances, such as early triage of severe injuries, an assessment of only a contracted version of the motor component of the scale (such as the SMS), can perform as well as the GCS and is significantly less complicated. However, the SMS may be less
Sir Graham Teasdale, MBBS, FRCP
Copyright © MDCalc • Reprinted with permission.
Faheem Guirgis, MD, FACEP; Lauren Page Black, MD, MPH; Elizabeth L. DeVos, MD, MPH, FACEP
Michael Allison, MD; Jeremy Rose, MD, MPH; Eric M. Steinberg, DO, FACEP
October 1, 2018
September 30, 2021
4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits. Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 2 Pharmacology CME credits
Date of Original Release: October 1, 2018. Date of most recent review: September 10, 2018. Termination date: October 1, 2021.
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