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An evidence-driven tool to guide the early recognition and treatment of sepsis and septic shock. Developed by the ACEP Expert Panel on Sepsis.

Detect
Identify Sepsis EARLY

Early identification is paramount – delays are lethal. Sepsis is an infection with an abnormal physiologic response, meaning organ duress or failure and immunologic dysregulation. The response is what separates sepsis from simple infection. Septic shock is the most severe form and exists when infection induces a failed hemodynamic response; often hypotension refractory to fluids and requiring vasopressor support to correct are present.

Failing to recognize sepsis and septic shock will cause delays in therapy – especially resuscitation and antibiotics – and worsen outcomes.1,2

Use screening at triage and during ED care by physicians, nurses, or electronic tools to increase early sepsis identification.3 It often takes more than one look to detect sepsis or septic shock.

Suspect sepsis/septic shock in clear cases such as those with fever, leukocytosis, and hypotension.

Sepsis also presents without classic findings – think of it when caring for someone with unexplained altered mental status, respiratory failure, or if clinical instinct suggests something is “not right” in a patient with a seemingly routine infection or suspected infection.

If you think sepsis may be present (e.g., any signs of infection and organ dysfunction) start therapy quickly, order cultures, and give antibiotics.

Reassess after initial evaluation. Some patients will develop sepsis after the initial assessment when it might not have been present at triage, and many need more or different therapy to reverse sepsis.

References
  1. Kumar A, Roberts D, Wood KE, 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;34:1589-1596.
  2. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235-2244. .
  3. Venkatesh AK, Slesinger T, Whittle J, et al. Preliminary performance on the new CMS sepsis-1 national quality measure: early insights from the Emergency Quality Network (E-QUAL). Ann Emerg Med. 2018;71:10-15.
Measure Lactate

Do not let a “normal blood pressure” dissuade you from considering sepsis. Patients with a suspected or diagnosed infection and a high lactate are at increased risk of adverse outcomes and often are septic.1-3

Get a venous or arterial blood lactate level early in patients with suspected infection and sepsis but normal or mildly abnormal vital signs.3-4 This measurement may help detect occult cases of sepsis earlier.

Elevated blood lactate is associated with higher risk for subsequent hypotension and mortality.

Lactate greater than 2 mmol/L is abnormal, and levels above 4 mmol/L should trigger resuscitation.5

Patients with a history of cirrhosis or renal failure may have a slightly elevated baseline blood lactate, but no matter what the reason, any elevated lactate is a poor prognostic finding.

References
  1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;15:801-810..
  2. Khosravani H, Shahpori R, Stelfox HT, Kirkpatrick AW, Laupland KB. Occurrence and adverse effect on outcome of hyperlactatemia in the critically ill. Crit Care. 2009;13:R90.
  3. Shapiro NI, Howell MD, Talmor D, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005;45:524-528.
  4. Gallagher EJ, Rodriguez K, Touger M. Agreement between peripheral venous and arterial lactate levels. Ann Emerg Med. 1997;29:479-483.
  5. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739-746.
Act
GIVE A CRYSTALLOID BOLUS TO START AND REASSESS

Give fluids in 500-mL to 1,000-mL increments based on clinical response.1-5

If any hypotension, signs of poor perfusion, or an elevated blood lactate, the recommended target volume of initial fluid is 30 mL/kg, given as quickly as can be done safely. But recognize all patients do not need this volume – assess during and after any bolus to ensure best care.

If severely hypotensive, intolerant of fluids from volume overload, or not responsive to fluids, start norepinephrine and target a mean pressure of 65 mmHg.6-7 Do not wait to add this therapy in those with ongoing shock.

A history of heart failure, liver failure, or renal failure is not a contraindication to fluid resuscitation. These patients are better managed with boluses and frequent reassessment of intravascular volume status, with the total volume of fluid resuscitation titrated based on response to therapy.

Using adequate, large peripheral intravenous access for early resuscitation is ideal for fluid therapy and can be used to start vasopressor therapy.8-9 Central venous catheters aid vasopressor and volume infusion but can be started later if secured, non-distal peripheral IV access exists.

We recommend balanced crystalloid solutions (Plasma-Lyte or Ringer’s) over 0.9% saline for most to avoid acidosis and renal dysfunction.10-12

Consider red cell transfusion for those with Hgb 7 g/dL or less or concomitant active bleeding.13

DO NOT DELAY FLUID THERAPY

Do not delay fluid and vasopressor therapy, esp. if hypotension exists. Prompt resuscitation of ED septic shock patients is associated with more rapid resolution and improved survival rates.1,7

References
  1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45:486-552.
  2. Sakr Y, Rubatto Birri PN, Kotfis K, et al. Higher fluid balance increases the risk of death from sepsis: results from a large international audit. Crit Care Med. 2017;45:386-394.
  3. The ProCESS Investigators: Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-1693.
  4. ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-1506.
  5. Mouncey PR, Osborn TM, Powers GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301-1311.
  6. Asfar P, Meziani F, Hamel J-F, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370:1583-1593.
  7. Seymour CW, Rosengart MR. Septic shock. Advances in diagnosis and treatment. JAMA. 2015;314:708-717.
  8. Lewis T, Merchan C, Altshuler D, Papadopoulos J. Safety of the peripheral administration of vasopressor agents. J Intensive Care Med. 2019;34:26-33.
  9. Delaney A, Finnis M, Bellomo R, et al. Initiation of vasopressor infusions via peripheral versus central access in patients with early septic shock: A retrospective cohort study. Emerg Med Australas. 2020;32:210-219.
  10. Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med. 2018;378:819-828.
  11. Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829-839.
  12. Brown RM, Wang L, Coston TD, et al. Balanced crystalloids versus saline in sepsis: A secondary analysis of the SMART clinical trial. Am J Respir Crit Care Med. 2019;200:1487-1497.
  13. Holst L, Haase N, Wetterslev J, et. al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-1391.
START ANTIBIOTICS EARLY AND GET SOURCE CULTURES QUICKLY

Obtain appropriate cultures before antibiotics are initiated, but do not delay antibiotic administration solely to get cultures. Urine and blood cultures are commonly and easily obtained. Microbiologic samples allow for later tailoring of antibiotics; cultures obtained in the ED before antibiotics are important.

While giving the right antibiotics as soon as possible is best, trying to treat anyone within one hour of arrival with antibiotics who may later be found to have sepsis exposes some to unneeded therapies. We recommended broad coverage IV antibiotics as quickly as possible from recognition of sepsis or septic shock.

To optimize the identification of pathogens, obtain at least two blood cultures before antibiotics.

Culture other sites, tissues, or fluids (cerebrospinal fluid, wounds, respiratory secretions) that might be the source of infection; these do not sterilize quickly and can be sampled as antibiotics are given.

Adequate soft tissue and respiratory samples can be hard to obtain in the ED and rarely impact management.

Surrogate tests for bacterial infection (C-reactive protein and procalcitonin) cannot currently effectively guide ED care in adult patients with sepsis or septic shock.3

Choose antibiotics based on suspected site of infection and local antimicrobial resistance patterns.6

Antifungal therapy is best used in those patients at risk for fungal sepsis rather than routinely.

GET SOURCE CONTROL7

Consider removing an intravascular device if suspected as the source of infection.

Obtain appropriate consults (surgical or interventional radiology) when needed for source control.

References
  1. Weinstein MP, Reller LB, Murphy JR, et al. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis. 1983;5:35-53.
  2. Blot F, Schmidt E, Nitenberg G, et al. Earlier positivity of central venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis. J Clin Microbiol. 1998;36:105-109.
  3. Simon L, Gauvin F, Amre DK, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39:206-217.
  4. Kumar A, Roberts D, Wood KE, 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;34:1589-1596.
  5. Sterling SA, Miller WR, Pryor J, et al. The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med. 2015;43(9):1907-1915.
  6. Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136:1237-1248.
  7. Jimenez MF, Marshall JC; International Sepsis Forum. Source control in the management of sepsis. Intensive Care Med. 2001;27 Suppl 1:S49-S62.
Reassess
REPEAT LACTATE MEASUREMENT

Re-measure lactate at least 2 hours after starting resuscitation in patients with an initial abnormal lactate to help gauge progress.

Persistence of elevated lactate, even in the absence of hypotension, is associated with poor outcomes.1 If lactate was elevated initially, try to resuscitate to a relative lactate decline (called clearance) of at least 10%.2

References
  1. Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;32:1637-1642.
  2. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739-746.
REASSESS THE PATIENT AFTER FLUID BOLUSES

Look for signs of adequate fluid resuscitation or any complications from volume therapy.1,2

There is no singular ideal total fluid target. Commonly, 4 to 6 L of total IV crystalloid solution is given for those with sepsis and hypotension during the first 6 hours.3-6

Early titrated but aggressive resuscitation, with fluid and/or vasopressors, is more important than any specific prescribed method of delivering or reassessing therapy.

It is best to use more than one method at more than one point in time to assess resuscitation adequacy. Methods to measure adequacy, intravascular volume or fluid responsiveness include the following1

  • Bedside vital sign assessment (including shock index – heart rate / systolic blood pressure, <0.8); and
  • Clinical examination to assess perfusion and volume status; or ANY TWO of the following:
    • Passive leg raises, pulse pressure variation >/= 13% (if arterial line placed) or heart rate variability to assess volume responsiveness2; or
    • Ultrasound assessment of vascular filling; or
    • Stroke volume variation3; or
    • Central venous pressure measurement (target 8-12 mm Hg while recognizing a trend is more important than one absolute value) or central venous oximetry (targeting 70%); or
    • Repeat serum lactate level if elevated above 4 mmol/L initially (should drop by 10% or more in 1 to 2 hours if resuscitation is adequate)7,8

DO NOT DELAY more fluid and vasopressor therapy. Prompt resuscitation of ED septic shock patients enhances resolution and improves survival rates.1,7,9

Repeat vital signs. Check blood pressure, heart rate, shock index – look for changes.

References
  1. Seymour CW, Rosengart MR. Septic shock. Advances in diagnosis and treatment. JAMA. 2015;314:708-717.
  2. Mackenzie DC, Noble VE. Assessing volume status and fluid responsiveness in the emergency department. Clin Exp Emerg Med. 2014;1:67-77.
  3. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580-637.
  4. ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-1506.
  5. The ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-1693.
  6. Mouncey PR, Osborn TM, Powers GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301-1311
  7. Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;32:1637-1642.
  8. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739-746.
  9. Rochwerg B, Alhazzani W, Sindi A, et al. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014;161:347-355.
Titrate
Monitor Patient Response

Titrate further fluids/vasopressors to patient response to therapy.

Vasopressors are often needed.

ADDRESS ONGOING HYPOTENSION

In patients with profound or ongoing hypotension after fluid resuscitation or those who have signs of volume overload and signs of shock, use continuous IV norepinephrine, targeting a mean arterial pressure of 65 mm Hg.1,2

A well-secured non-distal larger-bore peripheral IV catheter may be used to initiate therapy. Monitor any peripheral IVs used for vasopressor therapy frequently for extravasation.

Epinephrine is a second-line therapy for patients not responding adequately to norepinephrine, and dopamine is rarely needed. If starting epinephrine, consider corticosteroids (e.g, hydrocortisone 50-100 mg IV x 1 dose) while drawing a cortisol level.

Target a mean arterial pressure (MAP, measured by an arterial line or calculated by diastolic BP plus 1/3 of the pulse pressure) of 65 mm Hg. Higher blood pressure targets do not confer a better outcome.

References
  1. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362:779-789.
  2. Asfar P, Mezaiani F, Hamel JF, et al. High versus low blood pressure target in patients with septic shock. N Engl J Med. 2014;370:1583-1593.
ACEP Expert Panel on Sepsis

ACEP Expert Panel on Sepsis

Donald M. Yealy, MD, FACEP, Chair

David T. Huang, MD, MPH, FACEP

Alan E. Jones, MD, FACEP

Nicholas M. Mohr, MD, MS, FACEP

H. Bryant Nguyen, MD

Tiffany M. Osborn, MD, FACEP

Wesley H. Self, MD, MPH

Nathan I. Shapiro, MD

Todd L. Slesinger, MD, FACEP

Thomas E. Terndrup, MD, FACEP

Arjun K. Venkatesh, MD, MBA, FACEP

Scott D. Weingart, MD, FACEP

ACEP Staff

Sandra M. Schneider, MD, FACEP, Staff Liaison • Marta Foster • Stacie Jones • Margaret Montgomery • Travis Schulz

Publisher’s Notice

The American College of Emergency Physicians (ACEP) makes every effort to ensure that contributors to its resources are knowledgeable subject matter experts. Readers are nevertheless advised that the statements and opinions expressed in this resource are provided as the contributors’ recommendations at the time of publication and should not be construed as official College policy. ACEP recognizes the complexity of emergency medicine and makes no representation that this resource serves as an authoritative resource for the prevention, diagnosis, treatment, or intervention for any medical condition, nor should it be the basis for the definition of or standard of care that should be practiced by all health care providers at any particular time or place. If drugs are mentioned, they generally are referred to by generic names; brand names might be added for easier recognition. Device manufacturer information, if provided, is listed according to style conventions of the American Medical Association. To the fullest extent permitted by law, and without limitation, ACEP expressly disclaims all liability for errors or omissions contained within this publication, and for damages of any kind or nature, arising out of use, reference to, reliance on, or performance of such information.

© Copyright 2018, American College of Emergency Physicians, Dallas, Texas. All rights reserved. Except as permitted under the US Copyright Act of 1976, no part of this resource may be reproduced, stored, or transmitted in any form or by any means, electronic or mechanical, including storage and retrieval systems, without permission in writing from the publisher. Produced in the USA.

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