Sepsis Care – What’s New? The CMS Guidelines for Severe Sepsis and Septic Shock have arrived

Author: Krystal Baciak, MD (EM Resident Physician, Jacobi/Montefiore EM) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF)

Every minute a patient presents to an emergency department with severe sepsis or septic shock; the mortality for this condition ranges from 25-50%.1,2 As of October 1, 2015 CMS has issued new benchmarks for the care of severe sepsis and septic shock that all hospitals in the U.S. must meet. The new CMS criteria are as follows:

Table 1 – Definitions
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Table 2 – Treatment Benchmarks

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The Definitions

The definition of severe sepsis is derived from the surviving sepsis guidelines published in 2012 and is based on the International Sepsis Definitions Conference in 2003.1 While the SIRS definition is one commonly used in practice, the definition of organ dysfunction may by unreliable in certain patients. Every end-stage renal or cirrhotic patient would meet the criteria of severe sepsis based on this definition and may be overtreated. We all can agree that a patient experiencing acute kidney or liver dysfunction secondary to sepsis should be treated much more aggressively than an end-stage renal patient who meets SIRS criteria for a viral URI or strep throat. This new criteria does not leave much room for clinician judgment or individualized patient care which is likely more appropriate than a shotgun approach. The definition of septic shock included in the CMS guidelines is currently a conglomerate of the previous definitions of severe sepsis and septic shock. The previous definition of septic shock did not include a lactate level of ≥4; this was part of the definition of severe sepsis. This definition is consistent with the inclusion criteria for the original EGDT, ProMISe, ProCESS, and ARISE trials; we should all be familiar and comfortable with these criteria.2-5 Whether the criteria should be used to define septic shock is debatable.

The Treatment Guidelines

Lactate

The lactate level > 2 is an unexpected criterion for definition of severe sepsis. The EGDT inclusion criteria for severe sepsis or septic shock is a patient who meets 2 or more SIRS criteria, a SBP <90 despite fluid challenge of 20-30 cc/kg, or a lactate ≥4.2 These criteria were used in the Rivers trial and again in the inclusion criteria for the ProMISe, ProCESS, and ARISE trials that have recently been published.2-5 The surviving sepsis campaign states there is no randomized trials using a lactate cutoff for severe sepsis below 4; however, they acknowledge that some institutions may be using a lower lactate cutoff1. Additionally, in the ProMISe, ProCESS, and ARISE trials, the repeat lactate was obtained only if the initial lactate levels were ≥4.3-5 The surviving sepsis campaign suggests targeting our resuscitations to normalize the lactate (level 2C recommendation)1. While there is literature to suggest a lactate between 2 and 4 is associated with an increased risk of death independent of organ dysfunction,6,7,9 there is currently no major study using a lactate cutoff between 2 and 4 as inclusion criteria for EGDT or their protocol-derived care. At this time, the new CMS lactate parameters are not based on any available evidence; nor are they consistent with the current surviving sepsis discussion surrounding serial lactate levels.

Blood cultures and Antibiotics

The surviving sepsis campaign suggests obtaining appropriate cultures prior to antibiotic administration if they do not cause significant delay in treatment which is defined as longer than 45 minutes (grade 1C recommendation).1 In contrast, the new CMS guidelines state you must have two blood culture sets drawn prior to antibiotic administration and do not mention an exception for a significant delay in treatment. The surviving sepsis guidelines state blood cultures are rapidly sterilized within hours of the initial dose of antibiotics, and therefore, they should be drawn prior to giving antibiotics.1 Weinheimer et al. demonstrates the utility of drawing 2 sets of blood cultures stating two separate cultures will pick up 99% of all bloodstream infections.10 They also noted that if the first culture grew a contaminant, the likelihood of the second culture growing the same contaminant was very low.10,11 This study supports the recommendation that two separate blood cultures be obtained prior to antibiotic administration. Positive cultures will aid in the de-escalation of therapy that is crucial to appropriate inpatient care, consistent with the surviving sepsis guidelines,1 and has shown a mortality benefit in severe sepsis and septic shock patients.15 That being said, the advantages of drawing appropriate cultures prior to antibiotic administration must be weighed against the evidence showing that delaying appropriate antibiotic therapy causes an increase in mortality. One study shows that for every hour delay in antibiotic administration for a hypotensive septic shock patient, the mortality rate increases by 7.6% per hour.13 Another study confirms that there is a significant mortality benefit in giving antibiotics within one hour of recognition of septic shock.12 While generally it is possible to draw the required cultures and start the appropriate antibiotics in a timely fashion, it is not difficult to imagine how antibiotics may be given prior to obtaining all of the cultures in a busy emergency department. The new CMS regulations leave little room for physician judgement in this regard, and the data clearly shows that timely dosing of antibiotics is very important for the sickest patients.

Resuscitation

The surviving sepsis guidelines suggest the use of an initial crystalloid bolus of 30cc/kg for resuscitation of severe sepsis and septic shock (grade 1B recommendation).1 They also recommend maintaining a MAP >65 with vasopressors, if appropriate (grade 1C recommendation).1 There is a body of research suggesting that a MAP lower than 65 is associated with an increase in mortality among septic shock patients, which is consistent with the CMS benchmark and surviving sepsis guidelines.20 In a 70 kg patient, 30 cc/kg amounts to roughly 2L of fluid prior to reassessment, which seems reasonable in most patients. This number is similar to a study showing that the optimal amount of fluid is approximately a 3L positive fluid balance at 4 hours after the initiation of resuscitation.17 However, there is literature showing that fluid overload is detrimental to septic shock patients and can cause an increase in mortality independent of other risk factors such as their APACHE II scores.16-18 Another study demonstrated up to 64% of patients at their institution with septic shock have significant LV dysfunction.19 As we all know with our CHF patients, fluid overloading patients with myocardial dysfunction can lead to increased intubation, ICU days, morbidity and mortality. I’m not suggesting we withhold fluids from patients who desperately need them, but a one-sized fits all resuscitation of 30 cc/kg may not be the best option for every patient. Unfortunately, the CMS guidelines are firm on the 30 cc/kg fluid resuscitation.

Reassessment

The CMS guidelines now require documentation of volume status reassessment via physical exam and any two of the four additional studies shown in Table 2. First, of course you are going to reassess your patient in septic shock; I have yet to meet a provider who ignores one of these patients. The specific requirement to reassess one’s patient seems completely unnecessary. As for the required additional testing, both the RUSH exam and passive leg raise or fluid challenge exam seem appropriate in this setting. The RUSH exam can be a critical part of the evaluation of undifferentiated shock and allows one to evaluate “the pump, the tank, and the pipes.” Bedside ultrasound is gaining ground in many clinical settings and allows a non-invasive way to evaluate the fluid status of a patient. For more information regarding the RUSH exam, see http://www.emdocs.net/rush-protocol/. Additionally, passive leg raise or fluid challenge can be a useful way to evaluate the fluid responsiveness of a shock patient. The passive leg raise has a 95% accuracy rate to determine if a patient remains fluid responsive.16 It is easy to perform, costs no money, and garners results within 3 minutes. As for the CVP and SvO2 measurements, both require central venous access. Not every patient with an initial lactate of 4 requires central venous access, and central lines are not without their own complications. A study by Jones et al. shows that lactate clearance was equivalent to SvO2 measurements in determining the mortality of septic shock patients.21 Lastly, CVP will likely be elevated in patients with underlying right heart failure or pulmonary hypertension;22 thus, using it as a marker for fluid resuscitation may not be accurate for these patients. It is not in the best interest of the patient to insert unnecessary central lines when equivalent information can be gathered via non-invasive methods. At the end of the day, we are already reassessing our septic shock patients; CMS has now dictated how we document our reassessments.

The new CMS guidelines have caused some controversies within the emergency medicine community.  Many providers have voiced their concerns that we will be harming patients with antibiotics and fluids they do not need.23,24 Furthermore, there is little to no evidence to suggest any clinical improvement based on these new guidelines, and an abundance of research to suggest the new guidelines will be harmful for certain patients. As for the guidelines, for the time being they are here to stay. Hopefully as more research is published the guidelines will be aligned more appropriately to be in the best interest of our patients.

Further Reading/References

  1. Dellinger et al (2013). Surviving sepsis campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Critical Care Medicine 41(2): 580-637.
  2. Rivers et al (2001). Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. New England Journal of Medicine 345(19): 1368-1377.
  3. Mouncey et al (2015). Trial of Early, Goal-Directed Resuscitation for Septic Shock. New England Journal of Medicine 372(14): 1301-1311.
  4. Peake et al (2014). Goal-Directed Resuscitation for Patients with Early Septic Shock. New England Journal of Medicine 371(16): 1496-1506.
  5. Yealy et al (2014). A Randomized Trial of Protocol-Based Care for Early Septic Shock. New England Journal of Medicine 370 (18): 1683-1693.
  6. Trzeciak et al (2007). Serum lactate as a predictor of mortality in patients with infection. Intensive Care Medicine 33:970-977.
  7. Puskarich et al (2012). Prognostic Value of Incremental Lactate Elevations in Emergency Department Patients with Suspected Infection. Academic Emergency Medicine 19(8): 983-985.
  8. Reddy et al (2015). Lactic Acidosis: Clinical implications and management strategies. Cleveland Clinic Journal of Medicine 82(9): 615-624.
  9. Mikkelsen et al (2009). Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Critical Care Medicine 37(5): 1670-1677.
  10. Weinstein et al (1983). The Clinical Significance of Positive Blood Cultures: A Comprehensive Analysis of 500 episodes of Bacteremia and Fungemia in Adults. Laboratory and Epidemiologic Observations. Reviews of Infectious Diseases 5(1): 35-53.
  11. Weinstein et al (1997). The Clinical Significance of Positive Blood Cultures in the 1990s: A Prospective Comprehensive Evaluation of the Microbiology, Epidemiology, and Outcome of Bacteremia and Fungemia in Adults. Clinical Infectious Diseases 24: 584-602.
  12. Gaieski et al (2010). Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Critical Care Medicine 38(4): 1045-1053.
  13. Kumar et al (2006). Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine 34 (6): 1589-1595.
  14. Garnacho-Montero et al (2015). Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality. Critical Care 19(1): 302.
  15. Garnacho-Montero et al (2014). De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Medicine 40: 32-40.
  16. Podcast 111 by Dr. Paul Marik. Fluids in Sepsis, A New Paradigm. http://emcrit.org/podcasts/paul-marik-fluids-sepsis/.
  17. Boyd et al (2011). Fluid resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality. Critical Care Medicine 39(2): 259-265.
  18. Kelm et al (2015). Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock 43(1): 68-73.
  19. Pulido et al (2012). Clinical spectrum, frequency, and significance of myocardial dysfunction in severe sepsis and septic shock. Mayo Clinic Proceedings 87(7): 620-628.
  20. Leone et al (2015). Optimizing mean arterial pressure in septic shock: a critical reappraisal of the literature. Critical Care 19: 101.
  21. Jones et al (2010). Lactate Clearance vs Central Venous Oxygenation Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial. Journal of the American Medical Association 303(8): 739-746.
  22. Doepp et al (2008). Internal jugular vein valve incompetence in COPD and primary pulmonary hypertension. Journal of Clinical Ultrasound 36(8): 480-484.
  23. http://emcrit.org/blogpost/current-state-of-severe-sepsis-quality-measures/. We are Complicit – A glimpse into the current state of Severe Sepsis/Septic Shock Quality Measures. Posted June 11, 2015.
  24. Weingart and Faust (2015). News: Future of ED Sepsis Care May be Out of Our Hands – Unless We Agitate. Emergency Medicine News 37(9): 31-32.

20 thoughts on “Sepsis Care – What’s New? The CMS Guidelines for Severe Sepsis and Septic Shock have arrived”

  1. So why is it that I still have discussions about “knowing the source” vs the required suspected source with residents?

    1. Good point Jeffrey. I tend to have similar talks with my residents and it always goes back to educating & reviewing sepsis / severe sepsis / septic shock definitions with them no matter how mundane it may be and their prior knowledge about it (right or wrong). As long as you have a suspected source, you should not delay initiating your institution protocol until further confirmation is made

    1. Thanks for reading and the clarification! The criteria for septic shock is based on lactate > 4, not 2. Studies have demonstrated that lactate levels greater than 2 are associated with worse prognosis, though CMS measures include levels > 4 for septic shock.

  2. Britt,
    Awesome Job. However, the measures require the 30 cc/kg fluid bolus to be initiated with in 3 hours of presentation of septic shock patients, not 6 as your table describes. Your table is otherwise very clear and helpful.
    Thank You for this post.

  3. Britt,
    Awesome Job. However, the measures require the 30 cc/kg fluid bolus to be initiated with in 3 hours of presentation of septic shock patients, not 6 as your table describes. Your table is otherwise very clear and helpful.
    Thank You for this post.

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