Sepsis Guidelines

Educational Objectives

The goal of this program is to improve management of sepsis. After hearing and assimilating this program, the clinician will be better able to:

1. Implement protocols for resuscitation of patients with sepsis.
2. Use steroids in combination to improve outcomes in patients with sepsis.
3. Select medications for stabilization of blood pressure in patients with sepsis.

Summary

Sepsis care protocols: a bundled approach to sepsis management was formerly used; studies found a mortality benefit to guideline-based care; the Severe Sepsis and Septic Shock Management Bundle (SEP-1) or the Centers for Medicare and Medicaid Services (CMS) core measure was implemented in 2016 and is used as a quality metric; initial lactate and blood cultures should be obtained and broad spectrum antibiotics given in ≤3 hr to meet SEP-1; in ≤6 hr, lactate should be repeated and a fluid bolus of 30 mL/kg should be given in cases of hypotension or shock; vasopressors should be given and volume assessment repeated in patients who remain hypotensive; later trials found that end-goal directed therapy was not better than usual care, because it does not account for individual patient characteristics; SEP-1 is falling out of favor

Fluid management: approaches include liberal and restrictive use of fluids; fluids increase perfusion, but may cause fluid overload, pathogenic edema, and dilutional coagulopathy; vasopressors augment perfusion by constricting arterioles and improving cardiac contractility but may cause tissue ischemia, increased cardiac strain, and arrhythmias; the 2021 Surviving Sepsis Campaign recommends a 30 ml/kg fluid bolus for patients in septic shock, given in ≤3hr (weak recommendation); Conservative vs Liberal Fluid Therapy in Septic Shock (CLASSIC) trial — found no difference in mortality between restrictive and standard study arms, and no statistically significant benefit toward either group; the trial was based on patients in the intensive care unit; Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial — based on patients with sepsis in the ED who were refractory to initial fluid therapy; the restrictive arm focused on use of vasopressors; the study found no statistically significant difference in outcomes

Saline vs balanced crystalloids for resuscitation: normal saline has more chloride than plasma; based on the amount of chloride given, changes in chloride levels and acidosis may cause acute kidney injury in patients with sepsis; 2 trials found similar outcomes with saline or balanced crystalloids in terms of major adverse kidney events, eg, mortality, new dialysis, and kidney injury; the composite outcome was significant in favoring crystalloids, but the study found no mortality benefit; a recent trial found no difference using plasma-Lyte A; currently available evidence slightly favors balanced crystalloids over saline for sepsis; evidence to support different amounts of fluid is not available; 20 mL/kg is recommended in the Surviving Sepsis Guidelines and the CMS core measure; the amount of fluid should be individualized

Management of sepsis: norepinephrine is the first-line therapy for blood pressure support in sepsis; vasopressin is second-line; levosimendan is not available in the United States and does not appear to significantly impact mortality; angiotensin II for refractory shock resulted in improvement in mean arterial pressure and Sequential Organ Failure Assessment score, but had no mortality difference

Steroids: in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock trial (Venkatesh et al, 2018) of hydrocortisone vs placebo, a statistically significant improvement was found in the resolution of shock with hydrocortisone, but no difference in mortality; in the Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial (Annane et al, 2018), a statistically significant difference in survival was seen in the hydrocortisone and fludrocortisone group compared with the placebo group; steroids may speed reversal of shock and refractory shock; the literature on mortality benefit is mixed; trials suggest minimal short term downsides and no increase in infections; neuromuscular weakness may increase if steroids are sustained; steroids may be considered in refractory septic shock, especially in patients who are vasopressor-resistant and in patients with prolonged vasopressor dependence

Vitamin C: the VITAMINS (Fujii et al, 2020) and VICTAS trials (Sevransky et al, 2021) found no difference in survival in the vitamin C groups vs control groups

Surviving Sepsis Guideline updates: vitamin C is not recommended; steroids should be given to patients on vasopressors, but which type or dose is not specified; a new recommendation was added for starting vasopressors peripherally before central access is established; the CLOVERS trial (Bartoli et al, 2023) determined that extravasation is not a significant concern

Challenges with core measures: several studies found no difference in mortality after SEP-1 was adopted as a quality metric; the guidelines may be causing an increase in use of broad-spectrum antibiotics; sepsis encompasses too many entities to have a discrete, specific, bundled approach; diagnosis of sepsis remains challenging; patients who were not designated to be treated according to bundle guidelines were often sicker and more challenging to diagnose

Changes to core measures: not giving a 30 ml/kg fluid bolus initially meant not meeting the core measure; exceptions were later made for patients with advanced heart failure and chronic kidney disease; the latest version of CMS does not penalize physicians as long as they document the reason for not giving a fluid bolus; an option to document why a fluid bolus was not given should be added to documentation templates; clinicians may document a reason other than sepsis for elevated lactate levels; the reason for not performing any element in the bundle also may be documented

Future directions: new measures may be developed which examine true clinical outcomes; emerging technologies include rapid microbiological assays, which eliminate the long wait times for culture results; changes to both pre- and post- ED care are expected

Readings

Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378(9):809-818. Doi:10.1056/NEJMoa1705716; Bartoli A, D'Angelo A, Ippolito D, Delgado F, Colombo G. The Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) randomized clinical trial. Intern Emerg Med. 2023;10.1007/s11739-023-03419-0. doi:10.1007/s11739-023-03419-0; Fujii T, Luethi N, Young PJ, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: The VITAMINS randomized clinical trial. JAMA. 2020;323(5):423-431. doi:10.1001/jama.2019.22176; Hjortrup PB, Haase N, Bundgaard H, et al. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med. 2016;42(11):1695-1705. doi:10.1007/s00134-016-4500-7; National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network, Shapiro NI, Douglas IS, et al. Early restrictive or liberal fluid management for sepsis-induced hypotension. N Engl J Med. 2023;388(6):499-510. Doi:10.1056/NEJMoa2212663; Ospina-Tascón GA, Hernandez G, Alvarez I, et al. Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis. Crit Care. 2020;24(1):52. Published 2020 Feb 14. Doi:10.1186/s13054-020-2756-3; Prescott HC, Ostermann M. What is new and different in the 2021 Surviving Sepsis Campaign guidelines [published online ahead of print, 2023 Jun 7]. Med Klin Intensivmed Notfmed. 2023;1-5. Doi:10.1007/s00063-023-01028-5; Ramsdell TH, Smith AN, Kerkhove E. Compliance with updated sepsis bundles to meet new sepsis core measure in a tertiary care hospital. Hosp Pharm. 2017;52(3):177-186. Doi:10.1310/hpj5203-177; Sevransky JE, Rothman RE, Hager DN, et al. Effect of vitamin C, thiamine, and hydrocortisone on ventilator- and vasopressor-free days in patients with sepsis: The VICTAS randomized clinical trial. JAMA. 2021;325(8):742-750. doi:10.1001/jama.2020.24505; Shi R, Hamzaoui O, De Vita N, Monnet X, Teboul JL. Vasopressors in septic shock: which, when, and how much? Ann Transl Med. 2020;8(12):794. doi:10.21037/atm.2020.04.24; Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378(9):797-808. doi:10.1056/NEJMoa1705835.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Scott was recorded at Rocky Mountain Winter Conference on Emergency Medicine, held February 26 to March 1, 2023, in Breckenridge, CO, and presented by Well Assembled Meetings, LLC. For information about upcoming CME activities from this presenter, please visit https: wellassembled.com/events. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

EM402302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.