Sepsis is on the rise: it’s an undeniable reality for those of us in critical care. We’re seeing an unmistakable increase among all age groups, but particularly among the elderly. There are many factors contributing to this trend. Three of the most dynamic are the aging population, underlying conditions that lead to immunosuppression, and the increase in antibiotic resistance. In the United States, compared with most other industrialized nations, sepsis is associated with higher morbidity, mortality, and health care costs. To reverse this trend, however, U.S. hospitals need only to adopt proven protocols to reduce sepsis mortality and utilize new tools to help quickly identify patients likely to fall victim to sepsis.
What lies ahead…
Data presented at the 2011 CHEST conference demonstrate the impact sepsis is having on patients who are over 65 years of age and who have an underlying medical condition that leads to immunosuppression. Fernandez et al. conducted a retrospective study of hospital patients 65 or older who were discharged from the hospital after being treated for sepsis.1 Sepsis was defined by infection and at least one sepsis-induced organ failure. Immunosuppression was defined as a comprehensive variable that could include malignancy, immunosuppressive therapies, HIV/AIDS, neutropenia, and others.
Fernandez concluded that elderly patients with severe sepsis and immunosuppression, lung metastases, neutropenia, and cisplatin therapy have an associated much higher 30-day mortality rate than sepsis patients in this age group who do not have these conditions or therapies. Discharge records showed that of the 9,139 sepsis patients studied who were 65 or older, the most common immunosuppressive conditions included cancer (25%), solid organ tumor (27%), and corticosteroid therapy (22%).
As many are aware, age in itself is a risk factor for sepsis, even without underlying medical conditions. Currently, those 65 and older account for one-eighth of the U.S. population, but this demographic accounts for two-thirds of all sepsis cases.2
Unfortunately, we are on the front end of an enormous bulge in the population of Americans who will be 65 and older. “The first U.S. Baby Boomers [turned] 65 in 2011, inaugurating a rapid increase in the older population during the 2010 to 2030 period. The older population in 2030 is projected to be double that of 2000, growing from 35 million to 72 million,” according to a study published by the U.S. Dept. of Census in 2005 titled “65+ in the United States: Current Population Reports Special Study.”
In fact, this study shows that the trend of the older population growing at a faster pace than the total population will accelerate dramatically from 2010 to 2040. Whereas the total population of the U.S. is expected to increase by nearly 20% in the two decades between 2010 and 2030, the population of U.S. residents 65 years of age and older will increase at nearly four times that rate (78%) in the same time period. “This differential growth will result in nearly 1 in 5 Americans being aged 65 and older in 2030, compared with about 1 in 8 in 2010,” according to the study.
Knowing that the population is about to become much older and that age is associated with an increased risk of sepsis, and assuming that this patient population will still suffer from cancer or other immunosuppressive conditions, the Baby Boom is about to become the Sepsis Boom.
…and what can be done
Two steps could be taken immediately to prevent this looming crisis. The first would be to require hospitals to make sepsis one of the core measures that would push for standardizing protocols and reporting of mortality rates. Until that happens, sepsis will be one of hundreds of problems competing for scarce resources and priority status. The second step toward improvement would be to adopt screening tests for sepsis such as lactate and procalcitonin as standard blood tests for all elderly patients who are admitted to the hospital. As noted earlier, this population is at increased risk, and they also may not always display the classic SIRS (systemic inflammatory response syndrome) criteria because of comorbid conditions and concomitant medications.
Lactate levels correlate with depth of shock, are prognostic for patient outcome, and are a good screening tool for occult shock. In fact, lactate testing is required by the Early Goal Directed Therapy (EGDT) protocol3 that has been studied in septic patients. Lactate is a marker to bring patients into EGDT, and it is also an endpoint goal (improvement in lactate level) at the six-hour mark. Each hospital can individualize the protocol to fit its needs. At my hospital, we require procalcitonin testing at the same time as lactate, strive for a one-hour mark for antibiotics, expect central line placed within 90 minutes, and utilize “dynamic” measures of preload in addition to CVP for fluid management.
Procalcitonin (PCT) is one of the more useful biomarkers for sepsis. It spikes in the bloodstream in response to major bacterial infections. Procalcitonin will rise well before lactate levels, allowing early therapy prior to the development of shock for septic patients. PCT could become another marker to bring patients into EGDT, along with blood pressure and lactate levels. Another area for PCT use is in making an earlier diagnosis of infection in patients already in the hospital for other reasons. Early appropriate antibiotics may be the most important effector of mortality in sepsis, and procalcitonin will often rise prior to the clinical diagnosis of infection being made, allowing for earlier initiation of antimicrobials. PCT will also help distinguish sepsis from non-sepsis SIRS. Finally, PCT can assist in defining the cause of shock or lactic acidosis in unstable patients that present for whom diagnosis is still unclear. PCT rises with bacterial sepsis, but usually does not in hypovolemic, cardiogenic, or obstructive shock.
If the truth be told, we physicians are not as good at diagnosing sepsis as we think we are. Without additional biomarkers such as lactate and procalcitonin, doctors clinically attempting to make the diagnosis of sepsis at the bedside are usually only about 70 to 80% accurate.4 For such a deadly (but treatable) condition, this isn’t good enough. However, with the widespread use of procalcitonin, 95% accuracy is very attainable.
Coincidentally, we are finding that procalcitonin is helping us treat another booming patient population: people with diabetes. In addition to sepsis patients, the ICU is seeing more and more patients with diabetic ketoacidosis (DKA), which is a life-threatening complication that occurs when insufficient insulin production forces the body to metabolize body fat. Like sepsis, this often causes an increase in lactate. Almost all of these patients will have two or more of the SIRS criteria, and infection is the most common “initiator” of DKA. PCT can be a good screen for sepsis and the initiation of antimicrobials. Many of these patients will even get brought in to EGDT because of elevated lactate levels or hypotension. However, if PCT is low even when lactates are high, we anecdotally have not seen positive cultures. We are soon to begin a larger study to determine the safety of withholding EGDT in DKA patients who have low PCT levels.
Mark H. Oltermann, MD, is director of the Medical ICU at John Peter Smith Hospital in Fort Worth, Texas. He is also vice chairman of the Department of Internal Medicine. Dr. Oltermann’s interests include sepsis, nutrition and ventilator management. He has published several studies on these topics as well as a chapter on nutritional considerations for septic patients in Nutrition Support for the Critically Ill Patient: A Guide to Practice.
References
- Fernandez J, Shorr A, Mortensen E, Anzueto A, Restrepo M. Mortality of elderly patients with immunosuppression and severe sepsis. CHEST. 2011, abstract.
- The effect of age on the development and outcome of adult sepsis: discussion, Crit. Care Med. 2006;34(1)15-21. 2006; Lippincott Williams & Wilkins.
- Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.
- Harbarth S, et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164:396-402.
