Patient Safety Tip of the Week

April 1, 2014

Expensive Aspects of

Sepsis Protocol Debunked



In the past decade we’ve had considerable focus on identifying and managing sepsis. Because of the high mortality and morbidity rates associated with sepsis it’s logical that we should apply the same efforts to sepsis that we apply to conditions such as MI, stroke, and other conditions. Over the past few years the Surviving Sepsis Campaign has focused on improving morbidity and mortality from sepsis, stressing early recognition, timely antibiotics and goal-directed therapy, with adequate fluid resuscitation.


We all pretty much agree on the importance of early recognition, timely antibiotics, and early fluid resuscitation. As we noted in our March 15, 2011 Patient Safety Tip of the Week “Early Warnings for Sepsis” the Surviving Sepsis Campaign protocols focus on delivery of antibiotics within 3 hours of an emergency department admission and one hour of a non-emergency department admission. One study confirmed the impact on mortality of antibiotic administration in the emergency department within the first hour (Gaieski 2010). The use of serum lactate levels as a measure of possible tissue hypoperfusion has also helped in recognizing sepsis earlier.


But some of the more invasive aspects of existing guidelines and protocols, specifically interventions such as use of central venous catheters for measurement of central venous pressure and central venous oxygen saturation, have often been subject to criticism. These also stress the capabilities of some of our smaller hospitals. Similar criticisms have also been made about the role of vasopressors and inotropes in protocols.


In New York State our Department of Health has mandated that all hospitals have in place protocols for managing sepsis (NYSDOH 2013). The regulations require the hospitals to include in their protocols reference to specific physiologic thresholds or clinical conditions that would trigger use of centeral venous catheters.


It’s thus very timely that the results of the ProCESS trial have just been published in the New England Journal of Medicine (The ProCESS Investigators 2014). The ProCESS trial involved 31 medical centers and over 1300 patients with sepsis. The patients were randomized to one of 3 treatment arms. One arm received the full early goal-directed therapy (EGDT) protocol, which included the invasive monitoring plus guidelines for vasopressors and blood transfusions. The second arm also received management by a protocol but it did not require the invasive monitoring, vasopressors/inotropes, or blood transfusions. The third arm was the “usual care” group where the clinicians basically decided how to manage the patient.


The primary end-point of the trial, mortality at 60 days, did not differ across the 3 trial arms. There were also no differences in secondary outcomes such as 90-day mortality, one-year mortality, and need for organ support.


In the accompanying editorial (Lilly 2014) Craig Lilly, MD notes that guidelines such as those included in state legislation and those endorsed by the National Quality Forum (NQF) need to be updated now to remove the requirement for central hemodynamic monitoring. It’s pretty clear now that the expense and potential unintended consequences of such monitoring are no longer necessary.



And now a moment on our “soapbox”: It’s also interesting that sepsis mortality rates for even “usual care” now are on the order of 18-21% compared to over 40% a couple decades ago. While we like to think that’s because we have gotten so much better at identifying and managing sepsis, might there be other reasons contributing to that “decline”? Some authors (Lynn 2014) have questioned how we can rely on a simple definition for sepsis which requires the breach of only a few static thresholds. We like to point out that 2 significant drivers may have changed the landscape and created a population of “sepsis” that has a lesser mortality rate. CMS data clearly show that a few years back there was a significant change in the number of pneumonia cases and sepsis cases (Lindenauer 2012). The number of pneumonias decreased and sepsis cases increased. Why? Hospitals (often with the help of the third party "clinical documentation programs" that help billing) began using the definition of sepsis that required two of the SIRS criteria in a patient suspected of having infection in order to have a DRG for sepsis. You could have a patient with pneumonia happily pushing his IV pole up and down the hallway who meets those threshold criteria and now gets a label of "sepsis", which of course gets a significantly higher reimbursement than pneumonia. The same research group just recently showed how such coding changes have affected reported mortality rates for both pneumonia and sepsis (Rothberg 2014). They note that such shifts in coding reduce the pneumonia mortality rate lower (because sicker patients are shifted to the sepsis or respiratory failure diagnosis codes) and also reduce the mortality rate for sepsis (because the newly added patients are less sick than the average sepsis patient).


Also, CMS readmission penalties apply to pneumonia but not to sepsis. So there was additional pressure on hospitals to see if patients met the sepsis "criteria". And, as pointed out in the recent coding impact article (Rothberg 2014) the Surviving Sepsis Campaign may have increased awareness of sepsis, resulting in more patients with pneumonia being coded as sepsis since they met the SIRS criteria requirement.


Another recent retrospective analysis from Australia and New Zealand (Kaukonen 2014) showed that the mortality rates for ICU patients admitted with severe sepsis declined from 35% to 18.4% over the period 2000-2012. The trend was steady and amounted to a 1.3% annual decline in mortality for severe sepsis. There was a similar decline in mortality for patients with non-sepsis diagnoses. There was also a trend toward greater discharge to home in patients with severe sepsis compared to other diagnoses.


The accompanying editorial (Angus 2014) cites reasons why they think changes in coding are not the culprit. However, they do note that these data once again strongly demonstrate that false conclusions may easily arise from studies with before-and-after designs. They also note that this trend of declining mortality in patients with severe sepsis means we need to be looking at outcome measures other than death when designing studies of interventions in sepsis (and other conditions).

Soapbox aside, we still need to focus on early recognition, timely antibiotics and adequate fluid rescuscitation to reduce morbidity and mortality from sepsis. But let’s do away with the recommendations for invasive interventions of questionable value.







Surviving Sepsis Campaign. Website.



Gaieski DF, Mikkelsen ME, Band RA, et al. 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. Crit Care Med 2010; 38(4): 1045-53



NYSDOH. Sepsis Regulations: Guidance Document 405.4 (a)(4). 2013



The ProCESS Investigators. A Randomized Trial of Protocol-Based Care

for Early Septic Shock. N Engl J Med 2014; published online March 18, 2014



Lilly CM. The ProCESS Trial - A New Era of Sepsis Management. N Engl J Med 2014; published online March 18, 2014



Lynn LA. The diagnosis of sepsis revisited - a challenge for young medical scientists in the 21st century. Patient Safety in Surgery 2014; 8:1 (2 January 2014)



Lindenauer PK, Lagu T, Shieh M-S, et al. Association of Diagnostic Coding With Trends in Hospitalizations and Mortality of Patients With Pneumonia, 2003-2009. JAMA 2012; 307(13): 1405-1413



Rothberg MB, Pekow PS, Priya A, Lindenauer PK. Variation in Diagnostic Coding of Patients With Pneumonia and Its Association With Hospital Risk-Standardized Mortality Rates: A Cross-sectional Analysis. Ann Intern Med 2014; 160(6): 380-388



Kaukonen K-M, Bailey M, Suzuki S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA 2014; Published online March 18, 2014



Angus DC, Iwashyna TJ. Declining case fatality rates for severe sepsis good data bring good news with ambiguous implications. JAMA 2014; Published online March 18, 2014










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