Recognizing Sepsis and Septic Shock in the First Minutes to Hours of Care
Principles of Sepsis Recognition
- (1)Sepsis is a confirmed or suspected infection with new or worsening organ dysfunction and dysregulated host response to infection; it is not defined by a single datum or finding.
- •Septic shock exists in a subset of sepsis patients with circulatory dysfunction, and it confers higher mortality.
- •Septic shock—like sepsis—has a spectrum of disease, ranging from hypotension alone to hypotension requiring vasopressor support with an elevated blood lactate level after initial sepsis resuscitation. All patients with impaired cardiovascular function from sepsis are best managed with early detection and prompt treatment, similar to those with more severe presentations of septic shock.
- (2)Any guideline or care pathway or bundle must accommodate the reality that sepsis detection can be difficult. The clinical findings of sepsis overlap with many other conditions and often require extended time and effort to detect. Therefore, guidance is most applicable when the diagnosis of sepsis is established rather than simply considered as one of multiple potential causes of illness.
- •The differential diagnosis of sepsis in patients is often broad, and accurate diagnosis of sepsis may require advanced or repeated testing and observation to distinguish it from other causes of acute illness.
|First Consensus Definitions (1991)|
|Second Consensus Definitions (2001)|
|Third Consensus Definitions (2016)|
|Infection||Pathology caused by invasion of normally sterile environment by pathogenic microorganisms||No change||Not defined|
|Sepsis||Inflammatory response from infection with the SIRS criteria proposed to define an inflammatory response||Suspected or confirmed infection with ≥2 SIRS criteria, as defined below:|
- Temperature of >38 °C or <36 °C
- Heart rate >90 beats/min
- Respiratory rate >20 breaths/min or PaO2 <32 mm Hg
- White blood cell count >12,000 or <4,000 cells/mm3 or >10% band neutrophils
|Organ dysfunction (defined by increase in SOFA score of ≥2) caused by dysregulated response to infection with a threat to survival|
|Severe sepsis||Sepsis associated with organ dysfunction||Sepsis with organ dysfunction, defined as any of the following:|
- Lactate 2 mmol/L or greater
- International normalized ratio > 1.5
- Creatinine > 2.1 mg/dL or urine output < 0.5 mL/kg per hour
- Platelet count < 110,000/L
- Oxygen saturation < 90%
|Eliminated (now redundant with “sepsis”)|
|Septic shock||Sepsis with concurrent hypotension despite adequate fluid resuscitation plus perfusion abnormalities, such as elevated lactate levels, low urine output, or altered mental status||Sepsis with concurrent hypotension despite adequate fluid resuscitation||Sepsis with vasopressors required to maintain MAP >65 mm Hg and lactate >2 mmol/L after fluid resuscitation|
Early Screening and Detection of Those With Sepsis
- (1)Standardized early sepsis screening tools may improve sepsis recognition and care. However, there is no validated evidence-based tool or strategy to reliably accomplish this goal in the ED or out-of-hospital setting.
Initial Care Steps in the Emergency Department and the Out-of-Hospital Environment
Principles of Early Sepsis Management
- (1)History and physical examination may help to detect infection and organ dysfunction.
- (2)Once sepsis is recognized, prompt action to treat infection and reverse or prevent hypotension and hypoperfusion is important. However, time thresholds for care must be based on distinguishing sepsis from other clinical diagnoses.
- •Accruing evidence of infection, organ dysfunction, and hypotension or hypoperfusion requires longitudinal observation, meaning thresholds based on searchable administrative times alone may not be feasible.
|Evaluation for source of infection||Obtain historical elements of when the patient became ill and time course of symptoms.||Focused history and physical examination. Recommended testing includes bacterial and viral specimens for culture or analysis, urinalysis, chest x-ray, and selective cross-sectional imaging as directed by presenting signs, symptoms, and the results of other diagnostic tests.|
|Severity assessment||Obtain vital signs. Administer supplemental oxygen to maintain SpO2 ≥92%.||Assess for organ dysfunction by physical examination and laboratory assessment. Recommended evaluation for most patients includes blood lactate, complete blood count with differential, chemistry panel, liver function tests, mental status assessment, cardiovascular assessment (heart rate, blood pressure), and respiratory assessment (rate, work of breathing, SpO2). Administer supplemental oxygen to maintain ≥92%.|
|Treatment and prevention of hypotension||Establish whether hypotension (typically defined as a MAP <65 mm Hg or SBP <90–100) is present.||Use intravenous fluids and/or vasopressors to resolve hypotension/hypoperfusion.|
|Intravenous fluid||We recommend using a bolus of isotonic crystalloid (a balanced crystalloid solution is preferred) in patients with systolic blood pressure <100 mm Hg and without signs of fluid overload. An initial administration of 500–1,000 mL of isotonic crystalloid is an acceptable, common approach.||Current data do not identify a specific fluid volume that optimizes patient outcomes. In patients with SBP <100 mm Hg, MAP <65 mm Hg, or other signs of hypoperfusion and without signs of fluid overload, initial administration of 500–2,000 mL (or up to approximately 30 mL/kg) of isotonic crystalloid is an acceptable, common approach. Frequent assessments of fluid status and assessment of the hemodynamic response to fluid administration should guide whether additional fluid is given. Balanced crystalloid solutions are the preferred type of fluid.|
|Vasopressors||Insufficient data are available to make a recommendation about administration of out-of-hospital vasopressors.||The timing of vasopressor use—after how much volume and based on what response—is not evidence-based. Many initiate a vasopressor infusion (norepinephrine recommended as first-line therapy) for profound shock or persistent hypotension after initial intravenous fluid delivery. Earlier vasopressor use before completing a set volume of fluid administration may be an acceptable alternative. Vasopressors may be administered by peripheral intravenous line or intraosseous line without central venous access. Titrate vasopressors to maintain MAP ≥65 mm Hg.|
|Antibiotics||Insufficient data are available to make a recommendation about administration of out-of-hospital antibiotics.||We recommend prompt administration of antibiotics in the ED, but we reserve very short time thresholds for those with infection and shock and note there are insufficient data to recommend a specific time threshold for administration of antibiotics. In a patient without a confirmed source of infection, broad-spectrum antibiotics with activity against gram-negative and gram-positive bacteria according to local antibiotic susceptibility should be administered. Patients with identified sources of infection (eg, pneumonia, UTI) may have therapy targeted according to source-specific guidelines.|
|Infection source control||No specific action.||Remove accessible temporary devices that appear infected (eg, temporary urinary and vascular catheters). Consult surgical or procedural specialists for evaluation of patients with infectious sources potentially amenable to procedural source control (eg, abscess, necrotizing soft tissue infection, toxic megacolon).|
- (1)EMS providers can expedite sepsis care through a focused history and by obtaining corroborating data prior to transport.
- (2)Selecting and rapidly transporting sepsis patients to an ED capable of providing necessary early sepsis care are important factors in out-of-hospital sepsis care.
- (3)Out-of-hospital antibiotic therapy has the potential to improve outcomes, but it is not currently supported by data and cannot yet be recommended for routine use.
Evaluation for Source of Infection
- (1)We support obtaining blood cultures in the ED without delaying care in those with suspected sepsis.
- (2)In those without an identified source of infection, we support obtaining a chest x-ray and urinalysis (with urine culture if urinalysis is suggestive of infection) in the ED.
- (3)We support sampling possible infection sources based on medical history, symptoms, and physical examination findings (eg, cerebrospinal fluid, peritoneal fluid, wounds).
- (4)Targeted computed tomography (CT) based on clinical suspicion is preferred to routine whole-body imaging.
- (1)Clinicians should use multiple clinical and laboratory findings to detect sepsis and guide care.
- (2)We support initially measuring blood lactate levels in the ED (venous or arterial) and repeating lactate measurement after initial resuscitation only if elevated above 4 mmol/L or if there is suspicion of clinical deterioration.
- (3)After noting whether hypotension is present, no scoring system accurately stratifies individual sepsis patient risk at the earliest stages of care. We recommend assessment of sepsis severity through identifying acute organ dysfunction; collecting data needed to calculate the Sequential Organ Failure Assessment (SOFA) score is one reasonable systematic approach.
|System (Measurement)||Score||Recommended Action in ED|
|Respiratory||Assess SpO2 without supplemental oxygen if feasible. Apply oxygen to maintain SpO2 ≥92%. Note SpO2 and oxygen delivery once SpO2 has stabilized at ≥92%.|
|PaO2/FiO2 ratio||≥400||300–399||200–299 or <200 without invasive or noninvasive ventilation||100–199 with invasive or noninvasive ventilation||<100 with invasive or noninvasive ventilation|
|Approximate SpO2 and oxygen delivery|
|Without invasive or noninvasive ventilation||SpO2 ≥97% on room air||SpO2 92%–96% on room air||Supplemental O2 to maintain SpO2 ≥92%||NA||NA|
|With invasive or noninvasive ventilation||SpO2 97%–100%||SpO2 92%–96% on FiO2=0.3||FiO2 0.31–0.69 to maintain SpO2 ≥92%||FiO2 ≥0.7 to maintain SpO2 ≥92%|
|Coagulation||Obtain CBC with platelet count.|
|Liver||Obtain liver function tests with total bilirubin concentration.|
|Total bilirubin (mg/dL)||<1.2||1.2–1.9||2.0–5.9||6.0–11.9||>12.0|
|Cardiovascular||Assess initial MAP. Initiate fluid resuscitation. Administer vasopressors as needed to maintain MAP ≥65 mm HG.|
|MAP and vasopressor use||MAP ≥70 without vasopressors||MAP <70 without vasopressors||Dopamine <5 or dobutamine any dose||Dopamine 5.1–15, epinephrine ≤0.1, or norepinephrine ≤0.1||Dopamine >15, epinephrine >0.1, or norepinephrine >0.1|
|Central nervous system||Note highest Glasgow Coma Scale in ED (after resuscitation).|
|Glasgow Coma Scale||15||13–14||10–12||6–9||<6|
|Renal||Obtain chemistry panel with creatinine concentration.|
|Serum creatinine (mg/dL)||<1.2||1.2–1.9||2.0–3.4||3.5–4.9||≥5.0|
Intravenous Fluid and Timing of Vasopressors
- (1)We agree with delivering an intravenous (IV) fluid bolus during initial management of patients who have hypotension or findings of hypoperfusion absent signs of fluid overload.
- •We do not support a prespecified volume or body mass‒adjusted volume of fluid for all patients, though we recognize many patients benefit from 30 mL/kg of crystalloid. Patient response may serve as the best indicator of the appropriateness of fluid resuscitation volume, rather than the delivery of a prespecified volume.
- •We do not recognize a specific minimum fluid amount before starting vasopressor support.
- i.Vasopressor support may be coupled with plasma volume expansion to prevent cardiovascular collapse in those with severe hypotension or life-threatening hypoperfusion without requiring that a fluid administration threshold be reached prior to vasopressor initiation.
- •We think serial examinations (using more than one bedside tool to assess the adequacy of resuscitation) are best, with no one approach demonstrated as superior to alternative approaches.
- (2)We support using balanced crystalloid solutions (Ringer’s solution or Plasmalyte) as the primary resuscitation fluid in patients with sepsis, especially if volumes of more than 1 L are used.
- •Infusions of saline solution can cause hyperchloremic metabolic acidosis and may impair renal performance in commonly prescribed resuscitative doses.
Fluid Volume and Concurrent Titration of Vasopressors
|Clinical Signs of Hypoperfusion||Clinical Signs of Fluid Overload|
|SBP <100 mm Hg (or less than baseline SBP for patients with baseline SBP <100 mm Hg)||Development of pulmonary crackles with fluid administration|
|MAP <65 mm Hg (or less than baseline MAP for patients with baseline MAP <65 mm Hg)||Increased jugular venous distention with fluid administration|
|Heart pulse rate >110 beats/min||Increased work of breathing with fluid administration|
|Shock index (pulse rate/SBP) >1.0||Increased hypoxemia with fluid administration|
|Elevated serum lactate levels||Chest x-ray signs of pulmonary edema|
|Peripheral capillary refill time >3 seconds|
|Ultrasound signs consistent with pulmonary edema (eg, B-lines)|
|Depressed mental status|
|Decreased urine output (<0.5 mL/kg per hour)|
- (1)Norepinephrine is an excellent first-line vasopressor for patients with septic shock.
- (2)Titrating vasopressors to maintain a MAP of at least 65 mm Hg in most patients is a common target.
- (3)Early vasopressors can be administered through a well-secured nondistal peripheral IV catheter.
- (1)We support early antibiotics once sepsis is diagnosed or deemed likely. The strongest support for initial intravenous antibiotics is in those with suspected diagnosis of septic shock—that is, patients with infection and any hypotension or hypoperfusion.
- •Shorter time to antibiotics is preferred, but the precise time frame to optimally support outcomes remains to be defined.
- •Emerging data will help address the impact of the timing of subsequent doses, especially for patients who remain in the ED due to the lack of an appropriate inpatient bed.
- •Antivirals are less clearly time sensitive in the earliest phases of disease.
- (2)For sepsis patients without an identified pathogen, we recommend initiation of broad-spectrum antibiotics with activity against gram-negative and gram-positive bacteria according to local susceptibility patterns.
Antimicrobials: General Principles
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Timing of Antibiotics
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Infection Source Control
- (1)We support early identification of infections requiring source control, and we recommend early consultation and procedural intervention to control infection sources.
- (2)No specific timing threshold for achieving source control currently exists.
Titration of Care
Ongoing Fluid Administration
- (1)Fluid administration after an initial bolus should be based on serial assessments of the patient and response to therapy.
- (2)No singular assessment approach is superior, and we recommend using multiple assessments, including basic vital signs and physical examination methods (a clinical evaluation) or more advanced physiologic measurements (quantitative evaluation) at multiple time intervals.
- (3)If using a quantitative resuscitation approach, we recommend dynamic measures over static measures.
Vascular Access and Invasive Monitoring
- (1)Vasopressor administration through peripheral intravenous or intraosseous catheters that are monitored for signs of good functioning is acceptable for short-term use.
- (2)Invasive hemodynamic devices, including central venous and arterial catheters, may aid but are not routinely needed in early sepsis care.
Subsequent Doses of Antibiotics
- (1)Patients who remain in the ED for prolonged periods should have subsequent doses of antibiotics administered according to the optimal dosing schedule for each medication.
Adjunctive Early Sepsis Therapies
- (1)Routine corticosteroid therapy does not benefit sepsis patients unless there is concomitant adrenal insufficiency or the patient is on high-dose corticosteroid therapy for comorbid disease management prior to the onset of sepsis.
- (2)Other adjuncts, including angiotensin II (or analogs), vitamin C, vitamin D, and thiamine—alone or in combination—lack strong evidence supporting benefit and are not recommended.
Role of Interhospital Transfer, Inpatient Boarding, and Care Transitions in Sepsis Management
- (1)ED boarding (defined as prolonged care awaiting inpatient transfer) presents additional risk for sepsis patients. If local facilities do not have the capabilities to promptly care for critically ill patients, we recommend transfer of sepsis patients from the initial ED to an accepting facility with capabilities for managing these patients.
- (2)Each institution should develop a plan that defines explicit accountability for sepsis patients receiving prolonged ED care.
- (1)We support recommendations and quality assessment tools required by government or regulatory bodies as important ways to improve the outcomes of those with sepsis, and we believe these should be based on the best available evidence and should undergo regular reevaluation.
- (2)The creation of recommendations, guidelines, and quality assessment tools must include input from all relevant stakeholders engaged at each phase of care and must incorporate assessment of impact on both targeted patients and others receiving care.
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This report has been organized by the American College of Emergency Physicians and has been endorsed by the American Academy of Emergency Medicine, the American College of Osteopathic Emergency Physicians, the American Osteopathic Board of Emergency Medicine, the Association of Academic Chairs of Emergency Medicine, the Council of Emergency Medicine Residency Directors, the Emergency Medicine Residents’ Association, the Emergency Nurses Association, the Infectious Diseases Society of America, the National Association of EMS Physicians, the Society for Academic Emergency Medicine, the Society of Critical Care Medicine, and the Society of Hospital Medicine
Continuing Medical Education exam for this article is available at http://www.acep.org/ACEPeCME/.