Issue No 26.
Sepsis in the African American Population
By Afsha Rais
Sepsis is a whole body reaction to a severe infection. Experience says that there are individual and racial differences in severe sepsis, but why the differences exist is not quite clear. A higher infection rate? Higher risk for acute organ dysfunction? Genetics? Environment? Social status? The answers to those questions may help physicians decide about better management and treatment of this and similar serious condition. Let’s see how SJSM student collected and explained the data related to the presentation, management and treatment of the African American patients with septic conditions.
Sepsis in the African American Population
Saint James School of Medicine
December 23, 2015
According to Centers for Disease Control and Prevention, there are over 1 million cases of sepsis each year, and is becoming one of the leading causes of deaths in the United States. A general conceptual criterion for diagnosis of sepsis has been established but there are some atypical presentations of the illness that may present. The incidence of sepsis varies among ethnic groups and genders in the population and it appears to be the highest among the African American males.1, 2 The continuum of sepsis includes an increased risk for mortality. Therefore, it is vital to have a set of criteria for the diagnosis of sepsis in this population in an effort to decrease morbidity and mortality from severe sepsis and eventual multi-organ failure. Furthermore, it is imperative for clinicians to recognize the incidence of atypical presentations that may present in possible septic patients. This study was designed to focus on the presentation of this sepsis in the African American population at Jackson Park Hospital. In doing so, precedence for criteria in the early detection and care for sepsis will be established.
Retrospective study to analyze the presentation, management and treatment of the African American patients diagnosed with sepsis or similar diagnosis.
Of the 139 patients in the study, septicemia was secondary to multiple sites of infection. The systemic inflammatory response syndrome (SIRS) criterion was used to identify the presenting signs of the patient, but the most common factor was the elevated neutrophil percentage. A total of 76% presented with elevated percentage of neutrophils, indicating that this value plays an integral role in determining the risk for sepsis development in the African Americans population (10.3, 95% CI 68.03-82.83%, p <0.0001). After determining the diagnostic criteria, the patient should be managed appropriately to prevent progression to severe sepsis and septic shock. Early initiation of antibiotics in suspected sepsis should be within 1 hour of admission. Of the patients receiving antibiotics in the study, a majority were treated within 12 hours of admission, which played a vital role in delaying the progression of the disease.
Various factors should be evaluated when determining risk for sepsis in the African American population. The SIRS criteria are important, but it is important to look beyond the pre-determined criteria to delay the progression of the disease, specifically the neutrophil percentage.
Keywords: Sepsis, systemic inflammatory response syndrome (SIRS), criteria, African American, septicemia, neutrophil,
The terms systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock was initially defined in 1991 by The American College of Chest Physicians and Society of Critical Care Medicine. In 2001, these terms were further modified to include a broad range of clinical criteria that can assist in early bedside diagnosis of sepsis.
There are many diseases that present with similar physiologic changes in the human body. The phrase “systemic inflammatory response syndrome” was proposed to better understand the general inflammatory response to various insults versus inflammatory processes arising from infection.1,2 The cardinal signs of SIRS (Table 1) include change in body temperature, heart rate, respiratory rate and alternation of white blood count from baseline in the absence of known causes for such abnormalities including chemotherapy and induced leukopenia.1,2,3,4 When the etiology of an inflammatory insult is infectious, and two or more of the SIRS criteria is identified, the term used is sepsis.
|Table 1. Criteria for SIRS|
|Temperature||>38o C or <36o C|
|Heart Rate||>90 beats/minutes|
|Respiratory Rate||>20 breaths/minute or PaCO2 lower than 32mmHg|
|White Blood Cell Count||>12,000/uL or <4,000/uL or >10% bands|
An infection is classified as a microbial phenomenon. A microbe has the ability to penetrate a tissue when the epithelial barrier is interrupted causing the activation of an inflammatory response by the normally sterile host tissue. Severe sepsis becomes the diagnosis when there is involvement of an organ dysfunction, hypoperfusion abnormality or sepsis-induced hypotension.2 Severe sepsis is now considered to be the most common cause of death in non-coronary critical care units.4 Examples of organ dysfunction include – but are not limited to – decrease in urinary output, lactic acidosis, acute altered mental status, acute respiratory distress, and the presence of coagulapthy.3
Sepsis-induced hypotension is defined as blood pressure of less than 90 mmHg systolic or its reduction by 40 mmHg or more from baseline blood pressure, in the absence of other cause for hypotension.2 Septic shock refers to late stage sepsis which occurs when the cache or pro-inflammatory molecules existing within the body are provoked by an infectious etiology, thereby inducing hypotension secondary to systemic vasodilation, or decreased vascular resistance. This physiological disturbance often persists despite adequate volume resuscitation. Figure 1 illustrates a conceptual framework of the relationship between SIRS, sepsis, severe sepsis and septic shock.
The 2001 Consensus Conference resulted in modified criteria to increase the accuracy and clinical diagnosis of sepsis. The expanded definition of sepsis enhanced the SIRS criteria to a list of six principles: Sepsis, general parameters, inflammatory parameters, hemodynamic parameters, organ dysfunction parameters and tissue perfusion parameters (Table 2).3, 4
Figure 1. Relationship between SIRS, Sepsis, Severe sepsis and septic shock
|Table 2: Modified criteria for sepsis based on the 2001 Consensus Conference 3,4|
|Sepsis||Documented or suspected infection|
|General parameters||Fever, hypothermia, tachycardia, tachypnea, altered mental status, significant peripheral edema or positive fluid balance, hyperglycemia in absence of diabetes|
|Inflammatory parameters||Leukocytosis (>12,000/uL), leukopenia (<4,000/uL), >10% bands with normal white blood count, increased C-reactive protein, increased procalcitonin|
|Hemodynamic parameters||Hypotension, elevated cardiac index|
|Organ dysfunction parameters||Hypoxemia, acute oliguria, increased creatinine level, coagulation abnormalities (increased INR), thrombocytopenia, hyperbilirubinemia, ileus|
|Tissue perfusion parameters||Lactic acidosis, decreased capillary refill, skin mottling|
Bacterial infection leading to systemic illness has become a progressively common condition among hospitalized patients. These patients are also considered severely ill when compared to patients admitted with comparable diagnoses. In the recent years, there has been an increase in the incidence of sepsis, severe sepsis and sepsis related deaths in the United States. It affects more than 750,000 people annually, with an estimated annual mortality between 25% to 30% for severe sepsis and nearly 50% for septic shock.5, 6 A fourth of the hospitalized patients with severe sepsis will expire during the course of their treatment. A plethora of hypotheses exist in an effort to explain mortality from sepsis, some of which include: increased life expectancy, increasing prevalence and incidence of chronic diseases, immunosuppression, invasive procedures and multidrug-resistant infections.2 It is the lethality of sepsis that indicates the need for early recognition and treatment with appropriate antimicrobial agents.
Many factors predispose a patient in the risk for developing sepsis. For example, advanced age greater than sixty-five, obesity, male gender, black race and increased chronic diseases are important risk factors for the development and continuum of sepsis.2 More than half of patients who have progression of sepsis to severe sepsis have at least one chronic health condition, including diabetes mellitus, cancer, chronic pulmonary, renal and liver disease. Cancer is one of the most common co-morbidities in which patients experience severe sepsis, with the source of infection being related to the type of cancer.2 For example, individuals with lung cancer are at 10-fold risk of developing pneumonia. The proposed explanation is due to the depression of host defense system, signifying that any disease process that suppresses the host immune system is at increased risk for developing sepsis. Environmental risk factors must also be taken into account, especially with regards to the seasons. It has been found that respiratory infections peak in the winter months while genitourinary infections peak in the summer. 2
Studies consistently report a higher incidence of severe sepsis among black patients when compared to white patients. It is somewhat unclear, however, whether these statistics are due to higher infection rate among the black population, differences in susceptibility to infections, or an increased risk of developing acute organ dysfunction.2,7 It is imperative to understand why this population is at risk in an effort to decrease mortality from sepsis, severe sepsis and septic shock during hospitalization. Many African Americans have a condition known as “benign ethnic neutropenia”, however, it remains in question whether this condition puts the population at an increased risk of infection. On the other hand, it has been established that a higher prevalence of chronic diseases among the black population leads to an increased incidence of organ dysfunction. In this case, primary prevention should be the goal with close follow up and management of chronic diseases. Furthermore, efforts at implementing primary prevention at the community level – such as increasing availability of vaccinations – would help abolish any increase in incidence of sepsis is due to differences in susceptibility to infections. 7
Hematopoiesis is the production of new blood cells in the body. The major cell line responsible for inflammation and immune response is known as granulocytes, also known as polymorphonuclear leukocytes (PML). There are different types of granulocytes, including neutrophils, eosinophils, basophils and mast cells. The blood cell lineage is portrayed in Figure 2. The most abundant of these cells are neutrophils. The main function of neutrophils is to destroy bacteria, but they also play an important role in defense against other infections, including those of viral etiologies. The normal functioning of neutrophils depends on their ability to leave the bone marrow and anchor to the endothelium. During the inflammatory process, they must then demarginate from this endothelium and migrate between neighboring cells in response to chemotactic gradients to ingest and kill the microbial invader.14 A defect in any of these functionalities can increase the risk of developing an infection.
Neutropenia is defined as a reduction in circulating PML and increase in band formation (immature neutrophils) with an absolute neutrophil count below 1.5 x 109/L in children and adults over the age of 1.13 Because neutropenia is the single most important risk factor for an infection, the ranges have been classified as mild (1.0 to 1.5 x 109/L), moderate (0.5 to 1.0 x 109/L) and severe (<0.5 x 109/L).13 The relationship between neutropenia and infection has been a main focus for researchers for many years. It was originally recognized in 1902 by Brown and Ophuls who found the occurrence of severe leukopenia in a patient with fatal infectious pharyngitis. Further research in 1930 by Roberts and Kracke showed that neutropenia came prior to the infection.13 Years later, Doan was able to differentiate between acute and chronic neutropenia, highlighting bone marrow insufficiency as a very possible and relevant etiology of chronic neutropenia. This eventually became known as “maturation arrest”, which is a decrease in the production of mature cells from the cell line itself.13
Normal blood leukocyte counts are generally between 4 – 10 x 109/L, with neutrophils representing 45–74% of the cells, bands 0–4%, lymphocytes 16–45%, monocytes 4–10%, eosinophils 0–7%, and basophils 0–2%.14 These values differ among individuals of different ethnic groups, with lower leukocyte numbers for African-American ethnic groups.14 As previously mentioned, each of these cells have specific functions and can be informative in diagnosing a disease process. Because an alteration in the number and type of leukocytes can be associated with specific disease processes, total white blood cell (WBC) count (cells per μL) and differential counts should be obtained.14
Figure 2: Hematopoiesis – the blood cell lineage. 
Benign Ethnic Neutropenia
The African American population is at an increased risk for sepsis for reasons that remain unclear. A study conducted by Broun reported significant granlucytopenia in 25% of black patients admitted for elective surgery.13 Another study conducted by Karayalcin found that 30% to 40% of 231 black hospital employees had low WBC values attributed to a significant decrease in granulocytes.13 The second National Health and Nutrition Examination Survey in 1978 to 1980 demonstrated that 42.6% of black females ages 3 to 74 years had leukopenia with neutropenia, whereas only 27.1% of white females in that age group had WBC levels below 5.0 x109/L. Among black males between the ages of 3 to 74 years, 48.1% had WBC levels below 5.0 x109/L compared to 25.2% of white males.13 Benign ethnic neutropenia (BEN) is commonly noted in African American adults as a diagnosis of exclusion.7 This condition is classified as neutrophil counts less than 1.5 x 109 cells/L.12 There have been many discussions on the etiology of BEN, whether it is inherited or acquired due to environmental factors, including poor nutrition.13
It is important to differentiate BEN from other causes of neutropenia including congenital neutropenia, cyclic neutropenia and chronic idiopathic neutropenia. These conditions are common in the white population, associated with severe neutrophil count less than 0.5 x 109 cells/L, and lead to oral, cutaneous or systemic infections.12 History and physical examinations are imperative in diagnosing BEN. It is important to ask questions about frequency and duration of infections, severity of infections, exposures to toxins, and symptoms of malabsorption.13 Physical exam should include comprehensive evaluation for infection with attention particularly to the ears, lungs, soft tissues, oral mucosa, gingiva and perianal mucosa. These findings are important in excluding other causes for neutropenia, which should be eliminated prior to diagnosis of BEN. These include but are not limited to pharmacologically induced suppression, comorbid infections, neoplastic disease, autoimmune disease, hematologic/oncologic disorders, and metabolic disturbances.12
The prevalence of BEN is low in the United States when compared to the African population outside of the United States. Most recent data showed that BEN is described in up to 25% to 40% of those of African descent outside of the United States, while 4% of adult African American men and 2% to 3% of African American women in the United States.12 Many studies have been concluded to determine the mechanism of BEN. Mason confirmed that bone marrow aspirates from normal healthy neutropenic black adults had normal cellularity and normal maturation of all cell lines.13 This indicates that the defect in these patients was in the release of mature granulocytes from bone marrow storage to the circulating blood.13
A more detailed study on BEN was published in the Journal of Clinical Oncology by Hsieh, Tisdale and Rodgers to determine when to initiate or resume chemotherapy in cancer patients with BEN. Analysis of direct bone marrow examination in 12 individuals with BEN showed normal cellularity and leukocyte maturation. A retrospective analysis showed bone marrow from 240 African American donor contained lower nucleated cell and CD34+ cell number per recipient weight.12,13 Many studies continued to show that African Americans had lower total nucleated cells. The summary concluded from the retrospective and meta-analysis was such that African Americans have normal stem-cell number, normal myeloid maturation, and a minor reduction in hematopoietic myeloid progenitors at steady-state.12 The minor reduction may account for the lower number of demargination of neutrophils from the vascular endothelium and bone marrow stores during stress, such as infections. However, the exact etiology still remains unclear.
Pathogenesis of Sepsis
The normal physiologic response to an infection is a complex process that recognizes the microorganism invasion and initiates repair of the injury caused by the invasion. There are many mediators that come into play to fight the infection in an immunocompetent host. However, a microorganism that does not ordinarily cause systemic disease in an immunocompetent host can still occur and lead to sepsis. The human immune system works in a very sophisticated way to ensure that infections are defeated prior to injury to tissue. Nevertheless, certain microbes often exploit acquired deficiencies in host defenses, indwelling catheters or foreign matter, or obstruct fluid drains to survive within the human body.16 This explains the variation in the source of infection from respiratory, genitourinary, gastrointestinal, skin and soft tissue.9 The most common site of infection in patients with sepsis is the respiratory tract, with pneumonia being the leading presentation. Furthermore, gram-positive microorganisms have increased in frequency over gram-negative infections, with a small number of patients manifesting with fungal, viral or parasitic infections.2,9
The process for regulating infection invasion is quite intricate. It is regulated by a mixture of pro-inflammatory and anti-inflammatory mediators. These are secreted by the body’s immune host defenses, such as macrophages, that become activated and invade tissues to engulf the microbe. The main pro-inflammatory mediators include tumor necrosis factor-alpha (TNFα) and interleukin-1 (IL-1).15 TNFα stimulates leukocytes to release other mediators to express cell-surface antigens that will allow neutrophil adhesion at the site of infection. The other mediators released are the interleukins responsible for B-cell and T-cell release to destroy microbes causing infections. It is TNFα, along with IL-1, that is in large part responsible for fever, tachycardia, hypotension and other nonspecific symptoms of illness that occur during a course of an infection. Anti-inflammatory mediators, such as IL-10, are cytokines that inhibit the production of excess TNFα and IL-1. TNFα at high levels can lead to shock and death, which explains why anti-inflammatory mediators are necessary.15 Other important mediators include coagulation factors. Intravascular thrombosis, an inflammatory response, is important to wall off the microbe causing the infection. This helps prevent the spread of inflammation and infection to surrounding tissues.16
The balance between pro-inflammatory and anti-inflammatory mediators explains the normal response to infection invasion – adherence, chemotaxis, phagocytosis of microbe, killing of microbe and cleaning of debris from injured tissue.11 Sepsis is the release of pro-inflammatory mediators beyond the limited boundaries of the infection to cause a more generalized response.15 Pinsky and Matuschak conceptualized sepsis as malignant intravascular inflammation – uncontrolled, unregulated and self-sustaining.17 It was thought to be intravascular because the blood spreads mediators that are confined to cell-to-cell interactions within the interstitial space and inflammation because the characteristics visualized during sepsis are augmentations of normal inflammatory response.11,16,17 Occasionally during sepsis, the circulating bacteria causing the infection can elicit multi-organ dysfunction and hypotension directly by overstimulating inflammatory responses within the vasculature.16 This process explains the transition from sepsis to severe sepsis and septic shock.
The risk of developing sepsis depends on the type of microorganism invading the host. The bacterial cell wall components, such as endotoxin, peptidoglycan, and lipoteichoic acid and the bacterial toxins contribute to the development of sepsis. In a study conducted on a large series of patients with positive blood cultures, the risk for developing severe sepsis was related to the site of the primary infection.16 Results showed the bacteremia arising from pulmonary or abdominal source was eightfold more likely to be associated with severe sepsis than urosepsis.16 Bacterial proteins and toxins lead to cellular injury and tissue damage, which is the precursor to organ dysfunction. This process is accompanied by excess release of pro-inflammatory and anti-inflammatory mediators, worsening organ dysfunction and ultimately leading to organ and multi-organ failure – the hallmark of severe sepsis. The pathogenesis of severe sepsis thus may differ according to the microorganism, the ability of the host’s innate defense mechanisms to sense and respond to it, the site of the primary infection, the presence or absence of immune defects, and the prior physiologic status of the host.11,15,16,17
The study was a retrospective, population-based analysis of hospitalized patients from April 2013 to September 2014 with the diagnosis of sepsis and septicemia at the Jackson Park Hospital, Chicago, IL. The study was limited to African American patients because of the rise in incidence rates of sepsis seen in this population. There were set exclusion and inclusion criteria prior to data collection to ensure accurate determination of presentation of sepsis in African American population. The exclusion criterion was immunocompromised patients including those with cancer either receiving or not receiving chemotherapy. The inclusion criteria were as follows: 1) must meet some of the criteria for SIRS; 2) show evidence of bacteremia; 3) probable multi-organ failure; 4) must have normal white blood count and/or be afebrile. The evidence of bacteremia was determined by cultures obtained: blood, urine, sputum, wound. (Table 3)
Table 3: Initial inclusion criteria
|Pt ID (#)||Date and time of Admission||Diagnosis||Bacteremia (Y/N)|
The data was classified into SIRS criteria on arrival and on day 4 of admission (Table 4 and 5). This helped recognize the initial presentation of patients with sepsis or pre-sepsis, in order to determine management and treatment plan. While eradicating the microbe is essential in treatment of infection, we analyzed when the first antibiotic was given to the patient and how that altered the SIRS criteria. Lastly, we evaluated risk of organ dysfunction on day 4 of admission and the disposition of the patient during their hospital visit (Table 6). Database management and calculation of statistics were performed using Microsoft Excel.
Table 4: SIRS values on arrival
|SIRS CRITERIA – initial values
|Temp on arrival||Respiratory rate (RR) on arrival||Heart rate (HR) on arrival||Blood pressure (BP) on arrival||Initial White blood count (WBC)||Differential for Left shift|
Table 5: SIRS values on day 4 of admission
|SIRS CRITERIA – Day 4 values|
Table 6: Antibiotics, organ dysfunction and disposition in patients with sepsis diagnosis
|Time antibiotics was initiated and which one||Results on day 4 of admission – renal failure, liver failure, etc.||Urinalysis (UTI?)||Chest X-ray (Pna?)||Disposition (with date)|
A total of 139 patients with the diagnosis of sepsis or severe sepsis were studied. While more patients had the diagnosis of sepsis, they did not meet our inclusion criteria and many were excluded due to their immunosuppressed state. The average age of the patients in the study was 66.6 years old with the range between 22 years to 98 years old. The presence of infection was determined by cultures obtained on admission. Among those that were in the study, the most common infection was site unspecified, indicating that there was bacteremia but the exact site is unknown and/or multiple. Of the multiple sites, patients had concurrent bacteremia and urinary infection. Additionally, of the patients with positive cultures, 15 were MRSA positive. (Table 7) Other common areas of infections were respiratory, genitourinary, and wound. There were 4 patients who had suspected sepsis but continued to have negative cultures during their hospitalization.
Table 7: Number of patients and their sites of infection
|Characteristic||Number of patients|
|Site of infection|
|Bacteremia, exact site unspecified||50|
|Error in obtaining culture||32|
|Negative culture in suspected sepsis||4|
|Multiple sites of infection||23|
The data was further analyzed to define the presentation of patient on admission. It was essential to determine the SIRS criteria on admission to determine if the African American population presents with signs differ from innate SIRS criteria. Table 8 depicts how many patients presented with SIRS criteria. A commonality determined during the study was the increased percentage of neutrophils and absolute neutrophil counts in patients with the diagnosis of sepsis/severe sepsis. Of the 139 patients, 54% had elevated white blood count and 50% presented with tachycardia. However, 76% presented with elevated percentage of neutrophils, indicating that this value should be considered when evaluating African Americans for risk of sepsis (10.3, 95% CI 68.03-82.83%, p <0.0001).
According to the original guidelines of diagnosis of SIRS, only 67 patients (48.2%) met two or more of the criteria. Additionally, 31 patients (22%) presented with elevated neutrophils, positive culture, and diagnosis of sepsis but had less than one of the SIRS criteria. While a significantly low percentage, it is important to acknowledge all the factors in diagnosis sepsis to decrease mortality in the African American population.
Table 8: SIRS criteria on admission
|SIRS criteria – on admission|
|Elevated percentage of neutrophils||105|
Suspicion for sepsis or developing severe sepsis should prompt appropriate management with initiation of antibiotics, as bacteria is the most common microbe for infection. Table 9 shows the time within admission the antibiotics were given, and the total number of patients that expired during hospitalization versus the number of patients that were discharged from the hospital.
Table 9: The number of patients and the time of initial antibiotics; Disposition from hospitalization.
|Initiation of antibiotics|
|Within 1 hour of admission||16|
|Within 4 hours of admission||34|
|Within 12 hours of admission||67|
|Within 24 hours of admission||18|
|Within 48 hours of admission||0|
|Within 72 hours of admission||1|
|Within 96 hours of admission||3|
|Deceased during hospitalization||45|
|Discharged (home/nursing home/rehab/etc.)||94|
Early initiation of antibiotics in suspected sepsis improves the outcome for the patient. Of the patients receiving antibiotics, 48.2% were given antibiotics within 12 hours of admission. Furthermore, 67.6% of the patients with sepsis and/or severe sepsis were discharged from the hospitalization, whereas 32.3% deceased during treatment (difference of 35.2%, 95% CI 23.24 to 46.07%, p<0.001). The most common cause of death was multi-organ failure from infection, despite initiation of antibiotics during hospitalization. Of the 45 patients who deceased during hospitalization, 5 patients deceased within a day of admission, 1 patient within two days of admission, 4 patients within three days of admission and the remaining 35 after four or more days of admission.
Lastly, it was determined that the percentages of PMNs were elevated in 76% of the patients in the study. Using this measurement, the SIRS criteria plus the percentage of neutrophils were evaluated on day four of admission, where applicable. Forty-seven patients continued to have elevated percentage of neutrophils after antibiotics were initiated, even without leukocytosis. This data could be used to determine the rate of infection eradication. Additional data was collected, but was not adequate for analysis or to yield accurate results. The utilization of this data will be discussed under recommendation for continuation of research.
Prompt diagnosis and treatment for sepsis is essential to decrease mortality and increase outcome. Delay in the management of sepsis can lead to severe sepsis and shock, which yields poor outcome. A meta-analysis of randomized trials in 2008 concluded that applying early quantitative resuscitation on patients with sepsis significantly reduces mortality.6,16,18 The early resuscitation included administration of fluids within six hours of admission, in part to avoid persistent hypoperfusion.8,15,16,18 Next, it is imperative to determine the site of infection to properly eradicate the infection using appropriate antimicrobial therapy. In a retrospective study conducted between July 1989 and June 2004 in fourteen intensive care units, it was concluded that effective antimicrobial administration within the first hour of documented hypotension increased survival and discharge from hospitalization in adult patients with septic shock.6,18,19 Therefore, the time and duration for diagnosing sepsis and initiating appropriate antimicrobial therapy is the strongest predictor of mortality in patients.6,8,15,18,19
The purpose of this study was to determine if presentation of sepsis differs in the African American population, in which mortality from sepsis appears to be high. During the study, 67% of the patients met the SIRS criteria, and while tachycardia and leukocytosis were evident in approximately 50% or more of the patients, it was still not enough to diagnose the patient with sepsis and initiate early treatment. As seen in the results, only 16 patients were treated with antibiotics within the first hour of admission, with majority receiving therapy within 12 hours of admission. However, only 20 patients spiked a fever during their admission, even with positive cultures showing evidence of sepsis. Analysis showed 76% of the patients had elevated percentage of neutrophils on admission. Therefore, it is important to understand if this finding can be useful in identifying risk of sepsis in the African American population, where leukocytosis and fever may not always elevate to suggest a sign of infection.
Neutrophilia, or an increase in the number of neutrophils circulating in the body, can be associated with many conditions, including inflammation or any active infection, pregnancy, chronic disease of the bone marrow such as leukemia, shock, trauma, family history, recent vaccination, and many more.8,10,14,16,20 In a study conducted on 292 patients, the neutrophil left-shift parameter was evaluated as a marker for inflammatory and/or infectious disease process.20 The focus of the study was to determine if presence of bands can be an indication for infectious process. It was concluded that while band count may have high specificity for inflammation, it is not useful as a screening test due to low sensitivity.20 The study also concluded that neutrophilia can be embarked secondary to stress, and not necessarily as part of an infectious process. However, it could be argued that an infection and stressful occurrence in the body can be congruent.
There is an increase in the incidence of sepsis in the African American population, secondary to delay in diagnosis. The study portrayed some inconclusive data that requires further investigation. While this may be evident, there were promising results to better evaluate the presence of infection leading to sepsis in the African American population. Clinicians must evaluate the patient thoroughly and maintain a high index of suspicion whilst evaluating the laboratory results to determine the early signs of infection in this population. Applying the SIRS criteria is effective and should be considered, but sepsis must not be preemptively ruled out in African American patients who do not fit established criteria.
Many African American patients present with chronically low level of leukocytes, which may cause hindrance when applying SIRS criteria. Furthermore, many infectious processes are noted by leukocytosis – leading to missed diagnoses within the studied population, increasing risk for severe sepsis and possibly septic shock. Therefore, it would be advised to obtain differentials when ordering a complete blood count to see if there is an elevation in the percentage of neutrophils. Early treatment in patients with suspected sepsis can be achieved by obtaining these results proactively when evaluating for leukocytosis or leukopenia. The results that may be obtained in future studies as suggested by this analysis may be promising in the attempt to decrease morbidity and mortality in septic patients both in the African American population as well as the general population.
RECOMMENDATION FOR FURTHER RESEARCH
The study conducted in this thesis led to some useful results and conclusions on sepsis in the African American population. However, it also uncovered many areas that require further study. These areas include the following:
- In the current study of 139 patients, antibiotics were initiated during the course of the admission. First, determine the exact hour within which the antibiotics were initiated, as studies show that appropriate treatment within one hour has many benefits in sepsis. Next, compare the progression of the disease and analyze how delay in appropriate treatment can increase mortality from sepsis.
- During the study, the antibiotics given to the patients to treat their source of infection. Further analysis is required to determine the types of antibiotics for the infection, and if early initiation of the proper antibiotic improved prognosis. This can be evaluated by looking at the SIRS criteria on arrival, with focus on neutrophil percentage, and the days following antibiotic treatment. This will demonstrate the relationship between progression of sepsis and neutrophil percentage, to understand if this should be an added criterion for determining the presence of sepsis in the African American population. Furthermore, it will conclude if this percentage is increased from the infection or other stressors in the patient.
- Determine if IV fluids were initiated within 6 hours of arrival and analyze if this intervention decreases risk of developing shock in the African American population.
It would not have been possible to write this thesis without the help and support of the people around me. I would like to dedicate this thesis to all of those who have helped me come this far in my studies.
First and foremost, I would like to thank my advisor, Dr. Mohammad Hussain, for his guidance, patience and enthusiasm towards my research. He was always available to give me feedback on my research and continued to motivate me to think outside the box. I would like to thank Dr. Usman Khan, PGY-III for his continued support and time towards my research. He always believed in me and my ability to accomplish whatever I set my mind on, providing encouragement, guidance and great ideas. I would also like to thank Dr. R. Nazneen for her guidance and valuable feedback throughout the course of my research. Extended thanks are due to Dr. Anuj Jain, staff from medical records at Jackson Park Hospital, Avis Self, LPN, Khandi Dotson, and all my colleagues and peers that supported me during my time at Jackson Park Hospital and Medical Center.
I would also like to thank my closest friends, family and Vera Masutti for always encouraging me with their best wishes.
Lastly, I would like to thank my parents, my brother and my sister. They have been the biggest supporters in my life, always cheering me from the sidelines with all my dreams and aspirations. They never gave up during rough times and always acknowledged the good times. My research and most importantly my studies would not have been possible without their support and enthusiasm.
- Martin GS, Mannino DM, Eaton S, Moss M. The Epidemiology of Sepsis in the United States from 1979 through 2000. New England Journal of Medicine N Engl J Med 2003; 348:1546-554.
- Mayr FB, Yende S, Angus DC. Epidemiology of Severe Sepsis. 2013;5(1):4-11.
- Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. CHEST Journal CHEST. 1992;101(6):1644-55.
- Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med Intensive Care Medicine. 2003;29:530-38.
- Lever A, Mackenzie I. Sepsis: Definition, Epidemiology, and Diagnosis. BMJ. 2007;335(7625):879-83.
- Gauer RL. Early Recognition and Management of Sepsis in Adults: The First Six Hours. American Fam Physician. 2013;88(1):44-53.
- Mayr FB, Yende S, Linde-Zwirbie WT, Peck-Palmer OM, Barnato A, Weissfield LA, et al. Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis. 2010;303(24):2495-503.
- Godara H, Hirbe A, Nassif M, Otepke H, Rosenstock A. Critical care. The Washington Manual of Medical Therapeutics. 34th ed. St. Louis: Wolters Kluwer and Lippincott Williams & Wilkins; 2014:284-289.
- Reich D, Nalls MA, Kao WHL, Akylbekova EL, Tandon A, Patterson N, et al. Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene. PLoS Genetics PLoS Genet. 2009;5(1)
- Abramson N, Melton B. Leukocytosis: Basics of Clinical Assessment. American Fam Physician. 2000;62(9):2053-060.
- Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Med Intensive Care Medicine. 2013;41(2):580-637.
- Hsieh MM, Tisdale JF, Rodgers GP, Young NS, Trimble EL, Little RF. Neutrophil Count in African Americans: Lowering the Target Cutoff to Initiate or Resume Chemotherapy? Journal of Clinical Oncology. 2010;28(10):1633-637.
- Haddy TB, Rana SR, Castro O. Benign Ethnic Neutropenia: What Is a Normal Absolute Neutrophil Count? Journal of Laboratory and Clinical Medicine. 1998:15-22.
- Dale DC. Chapter 65. Neutropenia and Neutrophilia. In: Lichtman AL, ed. Williams Hematology. 8th New York, NY: McGraw-Hill, 2010.
- Cinel I, Dellinger RP. Advances in Pathogenesis and Management of Sepsis. Current Opinion in Infectious Diseases. 2007;20(4):345-52.
- Munford RS. Severe Sepsis and Septic Shock. In: Kasper D, ed. Harrison’s Principles of Internal Medicine. 19th New York, NY: McGraw-Hill, 2015.
- Pinsky MR, Matuschak GM. A Unifying Hypothesis of Multiple Systems Organ Failure: Failure of Host Defense Homeostasis. Journal of Critical Care. 1990;5(2):108-14.
- Jones A, Brown M, Trzeciak S, Shapiro N, Garrett J, Heffner A, et al. 207: The Effect of a Quantitative Resuscitation Strategy on Mortality in Patients With Sepsis: A Meta-Analysis. Annals of Emergency Medicine. 2008;52(4):n. pag.
- Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of Hypotension before Initiation of Effective Antimicrobial Therapy Is the Critical Determinant of Survival in Human Septic Shock*. Critical Care Medicine. 2006;34(6):1589-596.
- Seebach JD, Morant R, Ruegg R, Seifert B, Fehr J. The Diagnostic Value of the Neutrophil Left Shift in Predicting Inflammatory and Infectious Disease. American Journal of Clinical Pathology. 1997;107(5):582-91.