Paul O’Donnell, PharmD, BCCCP, BCPS
Roshni Sreedharan, MD
Nadia Ferguson, PharmD, BCPS, BCCCP
The combined estimates of severe sepsis and sepsis amount to 50 million cases worldwide, accounting for 5.3 million deaths annually.1,2 Improvements in standards of care have decreased mortality rates since the initial publication of the Surviving Sepsis Campaign Guidelines in 2004.3 Subsequent updates to the guidelines have culminated in the 2018 creation of the hour-1 sepsis bundle.4 This latest initiative provides a more pragmatic approach for obtaining blood cultures and lactate measures, administering fluids and antimicrobials, and initiating vasopressors in a timely manner. As a result, hospital mortality from sepsis is now approximately 30%.
Nevertheless, disparities are found among different populations diagnosed with sepsis. Healthcare disparity is defined as a difference in the quality of care provided that is not due to access-related factors, clinical needs, preferences, or appropriateness of intervention. Racial and gender disparity in the recognition, treatment, and outcomes of sepsis has been well documented and is an area of ongoing research.
Large epidemiological studies have observed lower incidences of sepsis in women compared to men.5,6 This, in part, may be due to biological differences between the sexes. For example, hormones appear to influence the body’s response to infection, including the ability of estrogen to attenuate organ damage.7-9 Differences in mortality, however, have not been consistently observed. In fact, some studies have observed higher mortality rates in women.10-12 A large retrospective study of more than 18,000 patients reported an approximately 10% higher risk of hospital mortality in women with sepsis, despite accounting for confounders like age.10 In contrast, Xu et al observed a higher 1-year mortality rate in men with sepsis than in women.11 The recently published French and European Outcome Registry in Intensive Care Unit (FROG-ICU) study observed no sex-related differences in overall mortality at 1 year and in the subgroup of those with sepsis.12 Some of the inconsistencies observed in survival differences between men and women possibly can be explained by differences in study design, differing definitions of sepsis, or control for confounding variables.
Treatment effects were assessed to determine the impact on survival between the sexes. Pietropaoli and colleagues observed that women were less likely to receive venous thromboembolism prophylaxis, invasive mechanical ventilation, and hemodialysis catheters and more likely to have code status limitations.10 While the DISPARITY study observed no difference in Surviving Sepsis Campaign resuscitation bundle compliance between men and women,13 the same researchers found that the mean time to antibiotic delivery for women being treated for sepsis or septic shock was 1.18 times longer than the time observed in men.14
Disparities have also been noted in racial minorities, as some studies have observed higher adjusted rates of complications and deviations from standards of practice in the management of sepsis in these groups compared with white populations.15 Although several factors, including poverty and reduced access to healthcare, could contribute to the poorer outcomes in racial minorities, variability in care persists despite adjustments.
Quality improvement initiatives and protocol development play a crucial role in improving patient care. Subsequent to mandated protocol-based sepsis treatment in New York, a consistent reduction in mortality from sepsis was seen.16 As protocol completion rates increased from 60.1% to 72.1% during the initial implementation of these best practices, sepsis-related hospital mortality rates declined from 25.4% to 21.3%. Interestingly, protocol completion rates were better in white patients (14 percentage point increase) than in black patients (5.3 percentage-point increase). Hospitals that cared for a larger proportion of racial minorities lagged behind in keeping up with performance standards. Although the intention of this mandate was to improve patient care as a whole, the potential for widening disparities was not anticipated or addressed, and the vigilance needed to prevent such occurrences was unrecognized. These gaps in the provision of appropriate care for all patients must be identified and addressed in a timely manner.
DiMeglio and colleagues looked at the various factors that result in racial disparities in sepsis management and put forth useful suggestions that could potentially narrow this gap.15 Several patient-, community-and environment-based factors seemed to propagate race-based disparities. A higher prevalence of several chronic comorbidities, including diabetes, obesity, and HIV, in black versus white populations predisposes to a higher likelihoods of developing sepsis and having worse outcomes from it. The disparity between white and black populations is improving, but still exists, in the expected years of life that are free of activity limitations caused by chronic conditions. Low socioeconomic status, decreased access to preventative medical services, and lack of insurance in minority groups are factors associated with worse disease outcomes. The lack of insurance coverage could result in a delay in presentation to the hospital, which is clearly related to increased sepsis mortality and morbidity rates. Similarly, the lack of access to healthcare and preventative health services also plays an important role in sepsis-related healthcare outcomes for minorities. Interestingly, even when adjusted for socioeconomic status, blacks had a higher incidence of severe sepsis compared with their white counterparts. Factors other than socioeconomic status and access to healthcare clearly play a role in the racial disparities observed.
The role of unconscious bias in disparities in sepsis management cannot be overlooked. Schrader and Lewis investigated racial disparities in the emergency room triage process and reported that black patients had longer wait times and lower acuity ratings than white patients.17 These delays could have a huge impact on patient outcomes when treating sepsis, in which every minute in identification and treatment counts. Given the possibility of disparities in how women and racial minorities with sepsis are treated, practitioners should identify and address potential sources of biases. Further research is needed to adequately assess the cause of disparities in sepsis mortality.
As a community of critical care providers and members of the healthcare system, we must seek to eliminate both gender-based and racial disparities in the care we provide for our patients. The first step in this process is acknowledgment of the problem. Targeted efforts at improving the access to, and quality of, healthcare provided to minority populations would be a step toward eliminating these barriers.
- Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259-272.
- Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med. 2001;29:S109-S116.
- Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.
- Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign bundle: 2018 update. Crit Care Med. 2018;46:997-1000.
- Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546-1554.
- Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med. 2007;35:1244-1250.
- Nicol T, Bilbey DL, Charles LM, Cordingley JL, Vernon-Roberts B. Oestrogen: The natural stimulant of body defence. J Endocrinol. 1964;30:277-291.
- Kuebler JF, Jarrar D, Toth B, et al. Estradiol administration improves splanchnic perfusion following trauma-hemorrhage and sepsis. Arch Surg. 2002;137:74-79.
- Bosch F, Angele MK, Chaudry IH. Gender differences in trauma, shock and sepsis. Mil Med Res. 2018;5:35.
- Pietropaoli AP, Glance LG, Oakes D, Fisher SG. Gender differences in mortality in patients with severe sepsis or septic shock. Gend Med. 2010;7:422-437.
- Xu J, Tong L, Yao J, et al. Association of sex with clinical outcome in critically ill sepsis patients: a retrospective analysis of the large clinical database MIMIC-III. Shock. 2019;52:146-151.
- Hollinger A, Gayat E, Feliot E, et al. Gender and survival of critically ill patients: results from the FROG-ICU study. Ann Intensive Care. 2019;9:43.
- Madsen TE, Simmons J, Choo EK, Portelli D, McGregor AJ, Napoli AM. The DISPARITY Study: do gender differences exist in Surviving Sepsis Campaign resuscitation bundle completion, completion of individual bundle elements, or sepsis mortality? J Crit Care. 2014;29:473 e7-11.
- Madsen TE, Napoli AM. The DISPARITY-II study: delays to antibiotic administration in women with severe sepsis or septic shock. Acad Emerg Med. 2014;21:1499-1502.
- DiMeglio M, Dubensky J, Schadt S, Potdar R, Laudanski K. Factors underlying racial disparities in sepsis management. Healthcare (Basel) 2018;6(4):133.
- Corl K, Levy M, Phillips G, Terry K, Friedrich M, Trivedi AN. Racial and ethnic disparities in care following the New York State Sepsis Initiative. Health Aff (Millwood). 2019;38:1119-1126.
- Schrader CD, Lewis LM. Racial disparity in emergency department triage. J Emerg Med. 2013;44:511-518.