false
Catalog
SCCM Resource Library
Sepsis Definitions and Their Impact on Other Popul ...
Sepsis Definitions and Their Impact on Other Populations
Back to course
[Please upgrade your browser to play this video content]
Video Transcription
Hello and thank you for joining me today to discuss sepsis definitions and their impact on other populations, specifically in heart failure, COPD, and oncologic patients. My name is Anne Raine Brown and I'm a clinical pharmacy specialist in critical care at MD Anderson Cancer Center in Houston, Texas. For this presentation, we will discuss the impact of the sepsis definition on different patient populations care, specifically in heart failure, COPD, and oncology. Let's start off with a few patient cases. The first is a 67 year old male with severe ischemic cardiomyopathy with an ejection fraction of 20% who presents with several days of shortness of breath, orthotmia, lower extremity edema, a productive cough, and fever. Notable findings include an elevated heart rate, he's in a-fib, his systolic blood pressure is less than a hundred, he's tachypneic and hypoxic, he has a leukocytosis, elevated lactate, and acute kidney injury. Notably, his QSOFA score is a 2. The next patient is a 61 year old female who was hospitalized with recurrent acute myelogenous leukemia and she's receiving induction chemotherapy. One week after completing her chemotherapy, she's neutropenic and develops abrupt onset of fevers, raggers, and shortness of breath. She's altered, she has a fever, she's tachycardic, hypotensive, tachypneic, and hypoxic. Her QSOFA score is a 3. Finally, we have a 70 year old male with severe COPD who presents with three days of progressive shortness of breath, wheezing, a productive cough, purulent sputum, and the subjective fevers. He was recently hospitalized for a COPD exacerbation and just finished a prednisone taper. He's febrile, tachycardic, has borderline blood pressure, tachypneic, and hypoxic. His QSOFA score is a 1. Interestingly, in this particular patient, the SERS score would be a 3 based on temperature, heart rate, and respiratory rate. We'll talk about diagnosing sepsis or septic shock in these patients shortly, but first let's discuss the evolving definition of sepsis. The initial sepsis definition, which included SERS or systemic inflammatory response syndrome, was nearly ubiquitous in hospitalized patients and occurs in many benign conditions, both related and not related to infection, having a low specificity. The updated sepsis 3 definitions in 2016 was the first revision since 2001 and reflected considerable advances made in the pathophysiology, management, and epidemiology of sepsis. Still over five years later, clinicians are struggling to apply the criteria to a diverse patient population with multiple comorbidities. The third international consensus definitions for sepsis and septic shock, or the sepsis 3 definitions, define sepsis as life-threatening organ dysfunction due to a dysregulated host response to infection and septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities substantially increase mortality. The sepsis 3 definitions are supposed to offer more specificity in describing the life-threatening conditions and aimed at achieving greater clarity and consistency in how sepsis is diagnosed, reported, and treated. The practical definition of sepsis includes either a QSOFA score of greater than or equal to 2 outside of the ICU or a change of two points in the SOFA score within the ICU population. Septic shock differs from sepsis in that the complications are more severe and the risk of patient death is greater. The task force identified two new clinical criteria that clinicians should use in diagnosing patients with septic shock. These included persistent hypotension requiring vasopressors to maintain a mean arterial pressure greater than or equal to 65 and the serum lactate greater than 2 despite adequate volume resuscitation. To facilitate the diagnosis of sepsis, the task force also identified new clinical criteria that clinicians could use outside of the ICU to quickly evaluate and assess patients for sepsis. The revised definitions recommended discarding the term SERS due to the overly sensitive inclusion of patients at low risk of poor outcomes and a low specificity and the adoption of the sequential organ failure assessment or SOFA in place of SERS. The focus is also on organ dysfunction as a marker of sepsis severity with a total SOFA score of 2 or greater meeting the criteria for sepsis. The new diagnostic tool is named QuickSOFA and consists of three simple tests that clinicians can conduct at the bedside to identify patients at risk for sepsis. These include an alteration in mental status with a GCS less than 15, a decrease in systolic blood pressure of less than 100, and a respiratory rate greater than 22. Several studies have shown that QSOFA score is less sensitive but more specific than SERS to predict mortality of inpatients, especially for those not admitted to the intensive care unit. Even with the added specificity of the QSOFA score and avoidance of SERS, the definition of shock should be approached cautiously in certain patient populations. Patients with infections and organ dysfunction are exceptionally heterogeneous in terms of demographic characteristics, underlying conditions, microbiology, and other clinically relevant factors. There have been several studies evaluating the sensitivity and specificity of both SOFA and SERS and predicting in-hospital mortality in the oncologic population. Like patients from the general population admitted to an ICU for suspicion of infection, SERS criteria has poor specificity in the oncologic population. The minimalism of its criteria are more pronounced in an oncologic population. For example, hematologic tumors and chemotherapy can both generate abnormal test results that impact the SERS score. Cancer can also be associated with fever that contributes to rapidly fulfilling the SERS criteria. To my knowledge, there have not been similar comparisons of the performance of these scores in patients with heart failure and COPD. Overall, the sepsis mortality rate ranges from about 12% to 17%. However, based on the severity of sepsis, mortality can be as low as 5% in sepsis without organ dysfunction or can increase to upwards of 35% for septic shock. In a cohort of patients with solid tumors and hematologic malignancies from 1994 to 2015, those with septic and septic shock had a 30-day mortality of 42.6%. Other studies have demonstrated a mortality rate of 39.9%, suggesting that mortality rates of cancer patients with sepsis are in line with those reported in patients with other severe comorbid conditions. Despite recent improvements and advances in patient management, mortality rate of sepsis in patients with malignancies remains higher than those in non-cancer patients. In this retrospective analysis by Nathan and colleagues looking at intra-hospital mortality in oncologic patients admitted to the ICU for suspected infection, they compared sepsis 2 and sepsis 3 definitions. They reported an overall intra-hospital mortality of 37%, similar between those with solid tumors and hematologic malignancies. When looking specifically at septic shock, patients fulfilling the new sepsis 3 definitions of septic shock had a higher mortality than those according to the 2001 definition at 68% versus 60%. The new definition seems to be appropriate to use in the oncologic population and an increase of two points of the SOFA score seems to be the most discriminant factor for intra-hospital mortality. Interestingly, the differences in mortality utilizing the sepsis 3 criteria for septic shock in hematologic malignancies alone demonstrate an even higher gap between mortality rates. In a recent study published by some of my colleagues at MD Anderson, they found that of those patients meeting sepsis 3 definitions, hospital and 28-day mortality rates were 73.9% and 67.7% respectively. This study again highlights the impact of the sepsis 3 definitions on mortality rates. Despite the decrease in the reported historical sepsis mortality rates over the past 20 years, the mortality rates in the oncologic population still remain unacceptably high. Studies have also demonstrated that sepsis in the setting of heart failure further worsens outcomes and mortality. Walker and colleagues tried to quantify the effect of sepsis on mortality in heart failure with reduced ejection fraction patients and found that sepsis accounts for up to 1 fourth of death in people with heart failure. You can see here that within the non-cardiovascular deaths on the left, 55.1% were due to sepsis, representing about 23% of all deaths. The remaining non-cardiovascular deaths were accounted for by cancer and 24.8%. Multivariate analysis also demonstrated that COPD was independently associated with increased risk of sepsis death with a hazard ratio of 2.43. These grim rates underline the need for early identification, workup, and management of heart failure patients and patients with other comorbidities with concomitant sepsis. Jones and colleagues published a very informative review of sepsis and pre-existing heart failure in the Journal of Intensive Care Medicine this past year. Underlying cardiac dysfunction of heart failure will worsen outcomes in a hemodynamically unstable state such as sepsis or septic shock, particularly in heart failure with reduced ejection fraction. In a study by Abu and colleagues, a retrospective review of 174 patients presenting with sepsis showed patients with a reduced ejection fraction conferred higher in hospital mortality, 57% versus 34.5%. Gabra and colleagues evaluated patients with sepsis and pre-existing heart failure and observed trends towards increased mortality, but it was not statistically significant. Elk-Haloff found that patients with severe sepsis or septic shock and comorbid heart failure had a 75% mortality rate one year after discharge, which is larger than the severe sepsis one-year mortality rate of about 40 to 44%. In contrast, Ouellette and Shaw observed no association between ejection fraction and clinical outcomes in patients with sepsis. Many of these studies were restricted to patients with sepsis with a reduced ejection fraction, where the impact of septic myocardial depression was not differentiated from pre-existing cardiac dysfunction, which makes the examination and also true impact of pre-existing heart failure on patients with sepsis difficult. The impact of heart failure directly on sepsis outcomes is further confounded as nearly half of heart failure patients are plagued by frailty. The combination of aging and multiple complex disease states produces an additive deterioration, causing greater morbidity and mortality. Patients with COPD have been reported to be at a higher risk of developing sepsis due to the use of corticosteroids, underlying comorbidities, and possibly impaired barrier function. In a study by Chen and colleagues, they found that patients with COPD and sepsis had poor outcomes due to higher risk of severe exacerbations, mortality, pneumonia, and serious pneumonia, even after propensity score matching. In addition to mortality rates remaining higher than those without severe comorbid conditions, there's also significant variability in the application of sepsis definitions in patients with complex comorbidities. There's wide variation in diagnostic accuracy of these tools, with most having poor predictive values. Variability in how clinicians diagnose sepsis has important implications for clinical care, epidemiologic and clinical studies, public health surveillance, and pay for performance initiatives, in addition to quality improvement programs. Let's go back to our patients presented earlier to discuss this variability. The first patient was our severe ischemic cardiomyopathy patient and was treated with one liter of normal saline, received IV Levaquin, and five milligrams of diltiazem for AFib with RVR. Their blood pressure dropped to 80 over 60, they were noted to have cool extremities, and a repeat lactate was 4.1. The patient developed worsening hypoxemia and altered mental status and was therefore intubated. A central line was placed and the patient was started on norepinephrine and dobutamine. An initial CVP was 16 and a central venous oxygen saturation of 48%. The patient was transferred to the ICU and continued on norepinephrine, dobutamine, as well as amiodarone for rate control. They were also gently diuresed with a furosemide drip. Antibiotics were broadened to include vancomycin and cefepime and both cultures remained negative throughout the hospital course with sputum cultures showing mixed respiratory flora. The lactate and white blood cell count normalized, urine and output and creatinine improved, and the patient was extubated on ICU day 3 and transitioned off of all vasopressors on day 4. The patient completed a seven-day course of antibiotics and was discharged from hospital day 10. Our next patient with AML and neutropenia and hypotension had blood cultures drawn, was started on IV vancomycin and cefepime, given 4 liters of normal saline and IV acetaminophen. Her blood pressure remained low. She had a repeat lactate level of 5. She was transferred to the medical ICU where she was intubated due to worsening hypoxia and she was started on norepinephrine drip for persistent hypotension. Her tunneled CVC was removed and blood cultures grew gram-negative rods and 4 out of 4 bottles and was eventually speciated as Pseudomonas. By ICU day 3, she was on 4 vasopressors, max ventilator settings, and developed anorak renal failure. She expired on ICU day 4. Finally, our COPD patient who returned after a recent exacerbation was given IV solumedrol, albuterol, and Atraventinibs. Also started on IV antibiotics with vancomycin and cefepime and started on non-invasive positive pressure ventilation. The patient's respiratory distress worsened and he was urgently intubated. A CT angiogram showed no evidence of pulmonary embolism and no consolidation. The patient was intubated for 3 days, continued on steroids, bronchodilators, and IV antibiotics. His fever resolved, his blood pressure remained stable, blood cultures were negative, and the sputum culture grew H-influenza. A chest X-ray remained clear. The patient was extubated on ICU day 4, completed a 7-day course of levofloxacin, and was discharged to rehab on hospital day 10. These patient case studies I just presented in yellow, amongst a couple others, were sent out in a survey to critical care clinicians to quantify inter-observer variability in diagnosing sepsis. These focus on the patient populations we are interested in today. Respondents were given both the initial presentation and the subsequent hospital course in all the cases, as the primary interest was in whether variability in diagnosing sepsis would exist even after patient's clinical courses were clear. Subjectivity in diagnosing sepsis is to be expected early in a patient's clinical course, when symptoms are undifferentiated and diagnostic test results are still pending. However, in this study, case vignette format was used in which the patient's entire clinical course was presented, just as I have just presented to you. While sepsis 2 definitions were utilized, after surveying almost 100 critical care specialists, they found that despite the definitions, diagnosing sepsis was extremely subjective and variable. Overall, inter-rater agreement with respect to the five classifications, SERS, sepsis, severe sepsis, septic shock, or none of the above, in all five cases was poor, aside from the control case, which was the AML patient I presented earlier. There was wide range in the diagnoses assigned to the cases, and this was particularly noticeable for case A, which was the suspected pneumonia heart failure patient, as 34% of respondents diagnosed septic shock, 15% diagnosed severe sepsis, yet 30% diagnosed none of the above. When analyzing only cases A through D, agreement among respondents was nearly random. This study demonstrates a substantial amount of subjectivity in diagnosing sepsis. The survey was conducted before the release of the sepsis 3 definitions, which may have performance characteristics in terms of inter-observer variability that are different from those of the prior sepsis definitions. However, the new definitions use the same framework of seeking patients with acute organ dysfunction attributable to infection, and hence subjectivity in assigning sepsis diagnosis will likely persist. We need objective criteria and standardized methodology to enhance consistency and comparability in sepsis research, surveillance, and quality reporting. This is important even when considering the updated sepsis 3 definitions. Definitions of sepsis and shock should also be approached cautiously in heart failure, COPD, and oncologic patient populations due to the pathophysiology of these disease states and the overlapping and competing hemodynamics and treatment facts with sepsis syndrome. Clinicians should evaluate for acute versus chronic processes and assess whether organ dysfunction has an explanation other than infection or attribute dysfunction specifically to a dysregulated host response. Tachypnea is common in all forms of COPD and is frequently present during COPD exacerbations regardless of the presence of infection. Patients with heart failure with reduced EF have an average decreased baseline MAP. Consequently, a MAP less than 65 is usually not sufficient to diagnose shock in these patients. An elevated serum lactate level is also not specific for cellular dysfunction in sepsis, though it's included in the initial assessment of patients with sepsis. Cancer patients develop lactic acidosis for a variety of reasons and are underrepresented in most studies. Therefore, an elevated lactate level may lead to over diagnosis of sepsis and excessive antibiotic use. Heart failure patients may also have elevated lactates outside of septic shock. One study found that 25% of hospitalized advanced heart failure patients not in a state of shock had elevated plasma lactates of greater than 2.1. We know that lactate alone is neither sensitive nor specific enough to rule in or rule out the diagnosis of sepsis on its own, but other diagnostic overlap further confounds this issue. For this reason, we may need secondary indices to incorporate into the assessment of shock. Finally, a fundamental component of the new definitions of sepsis and septic shock remains the presence of infection, yet negative cultures are frequent in patients clinically identified as septic. This is particularly important in this subgroup population where the management may change substantially and affect outcomes, particularly with respect to fluid resuscitation, antibiotic exposure, and also the application of corticosteroids. Taking heart failure patients as an example, there are clear similarities but also differences in the management of patients with either sole heart failure and or cardiogenic shock versus solely sepsis and or septic shock. Despite significant overlap in the therapeutic approach of both conditions, there are interventions that are beneficial in heart failure that may be hazardous in septic patients and vice versa. Sepsis management is characterized by aggressive volume resuscitation with crystalloid fluid and hemodynamic support with vasopressors, which may appear antithetical to the conventional heart failure management that promotes preload and afterload reduction. With everything I've presented thus far, now we have to ask where we go from here. Recently, the updated surviving sepsis guidelines were published, recommending we move away from the QSOFA score, which is incorporated into the sepsis III definition. I think most would agree that the QSOFA score should not have ever been regarded as a diagnostic criterion for defining sepsis, but rather it should be regarded as a warning for patients with suspected infection who are likely to have poor outcomes. However, now there's need for further validation of the new recommendations in these complex subpopulations. Objective criteria and standardized methodology are needed to enhance consistency and comparability in sepsis research, surveillance, and quality reporting. Most of the data reported today was based on sepsis definitions predating even the 2016 update, so we will once again have to see our data lagging behind these recommendations. One of the studies the surviving sepsis campaign recommendation was based on was this cohort study of five commonly used point-based risk scores for 1.5 million hospitalizations across two U.S. states. The national early warning score had the highest discrimination for identifying inpatients at risk for death or ICU transfer. Compared with other tools calculating risk scores, the news was also more efficient at all sensitivity thresholds. There are several benefits associated with early warning score systems, and despite the widespread utility of these tools, there are several limitations, including challenges with implementation, potential for increased use of health care resources, and the validity of the measures used. These tools would benefit from further validation studies along with implementation to determine optimal intervention thresholds in different cancer, heart failure, and COPD populations to inform best implementation practices. So in summary, patients with comorbidities including heart failure, COPD, and cancer remain at increased risk for sepsis and sepsis-related mortality. We know that early identification and appropriate management in the initial hours after the development of sepsis improve outcomes, but the pathophysiologic and diagnostic overlap of these comorbidities makes identification and treatment challenging. When diagnosing sepsis, there's a substantial amount of subjectivity in deciding whether infection is present, whether acute organ dysfunction is present, and whether acute organ dysfunction is attributable to infection. Objective criteria and standardized methodology are needed to enhance consistency and comparability in sepsis research, surveillance, and quality reporting. Already with the new surviving sepsis campaign guidelines published this last year, recommendations are made to move away from utilizing the QSOFA for screening of sepsis or septic shop, paving the way for more variability in sepsis research and outcomes. Thank you for joining me virtually, and I'd be happy to address any questions.
Video Summary
In this video, Anne Raine Brown, a clinical pharmacy specialist in critical care, discusses the impact of the sepsis definition on different patient populations such as heart failure, COPD, and oncology. The sepsis definition has evolved over time, with the latest sepsis 3 definitions focusing on life-threatening organ dysfunction due to a dysregulated host response to infection. Brown emphasizes the need for objective criteria and standardized methodology to enhance consistency and comparability in sepsis research, surveillance, and quality reporting. She also points out the subjectivity in diagnosing sepsis, which can lead to variability in patient outcomes. The video highlights patient case studies and the challenges in diagnosing sepsis for patients with complex comorbidities. Brown concludes by discussing the recommendations and limitations of using early warning score systems to identify patients at risk for sepsis-related mortality.
Asset Subtitle
Sepsis, Research, 2022
Asset Caption
This session will explore the changes in sepsis definitions and their impact not only on the sepsis population but on other patient groups as well. Speakers will explore whether new methods of data analysis could help us get closer to the ultimate goal of better recognition and treatment of sepsis.
Meta Tag
Content Type
Presentation
Knowledge Area
Sepsis
Knowledge Area
Research
Knowledge Level
Foundational
Knowledge Level
Intermediate
Knowledge Level
Advanced
Learning Pathway
Sepsis Resources
Membership Level
Select
Tag
Sepsis
Tag
Clinical Research Design
Year
2022
Keywords
sepsis definition
patient populations
impact
objective criteria
diagnosing sepsis
early warning score systems
Sepsis
Research
Sepsis
Clinical Research Design
Presentation
Select
2022
Foundational
Intermediate
Advanced
Sepsis Resources
Society of Critical Care Medicine
500 Midway Drive
Mount Prospect,
IL 60056 USA
Phone: +1 847 827-6888
Fax: +1 847 439-7226
Email:
support@sccm.org
Contact Us
About SCCM
Newsroom
Advertising & Sponsorship
DONATE
MySCCM
LearnICU
Patients & Families
Surviving Sepsis Campaign
Critical Care Societies Collaborative
GET OUR NEWSLETTER
© Society of Critical Care Medicine. All rights reserved. |
Privacy Statement
|
Terms & Conditions
The Society of Critical Care Medicine, SCCM, and Critical Care Congress are registered trademarks of the Society of Critical Care Medicine.
×
Please select your language
1
English