Knowing Sepsis

Submitted by Marina E. Bitanga BSN, RN, CCRN

Introduction

Sepsis is a serious medical condition caused by overwhelming immune response to infection (1). The body releases immune chemicals into the blood to combat the infection (1). Those chemicals trigger widespread inflammation, which leads to blood clots and leaky blood vessels resulting to impaired blood flow, and that deprive organs of nutrients and oxygen and leads to organ damage (1).

Sepsis is a major challenge in hospitals, where it is one of the leading causes of death (1). It occurs unpredictably and can progress rapidly (1).

In general, a person with sepsis can be contagious depending on the aggressiveness of the infecting organism, so precautions such as hand washing, sterile gloves, masks, and clothing coverage should be considered depending on the patient’s infection source (2). Most researchers suggest sepsis itself is not contagious but a condition that can develop after one or many types of infectious agents invade the bloodstream (2). An incubation period or contagious period vary depending on the organism that may lead to the development of sepsis (2).

In the United States, sepsis affects 2 percent of all patients admitted to hospitals and has an associated 25 percent mortality (10). Sepsis is the most expensive condition facing the United States health care system with costs exceeding $23 million in 2013 (10), In Europe and Central Asia, the impact of sepsis is comparable to that in the United States, but East Asia and the Pacific battle against an even higher incidence rate (10). Current efforts remain focused on early recognition and treatment, but preventive strategies have not been aggressively deployed (10).

The number of sepsis cases per year has been on the rise in the United States likely due to several factors (1):

Increased awareness and tracking of sepsis (1)
People with chronic diseases are living longer and the average age in the United States is increasing (1). Sepsis is more common and more dangerous in the elderly and on those with chronic diseases (1).
Some infections can no longer be cured in antibiotic drugs (1). Such antibiotic-resistant infections can lead to sepsis (1).
Medical advances have made organ transplant operations more common (1). People are at higher risk for sepsis if they had an organ transplant or have undergone any other procedure that requires the use of medications to suppress the immune system (1).

This article will explore the epidemiology of sepsis, causes, how sepsis is being diagnose, signs and symptoms, risks factors, how sepsis is prevented, as well as the management and treatment.

Causes

Bacterial infections (2)

The common bacterial causes of sepsis are gram negative bacilli like E. Coli, P. aeruginosa, E, corrodens, and Haemophilus influenza in neonates (2). The bacteria begin infecting almost penetration or ruptured intestine from trauma, surgical site, intravenous catheter, etc, (2). The infecting agents or toxins spread directly or indirectly into the bloodstream allowing them to spread to almost any other organ system (2). Other bacteria include S. aureus, Streptococcus species, Enterococcus species, Neisseria, and Candida species (2).
Fungal infections (2)
Infection or agents that may cause system inflammatory response syndrome (2)

Risk Factors

Very young, younger than 1 and elderly (2)
People who are very ill due to an infectious agent (2)
People in Intensive Care Unit (2)
Approximately 50 percent of ICU patients have a nosocomial infection and are intrinsically at high risk for sepsis (6).
People with weakened immune system (2)(5)
People with pre-existing medical condition (2) such as diabetes (5), lung diseases (5), cancer and kidney disease (5)
People with devices such as catheters, breathing tubes, or other devices (2)
People with extensive burns (2)
65 years old and older (5)
The incidence of sepsis is disproportionately increased in older adult patients and age is an independent prediction of mortality due to sepsis (6). Older adult non survivor tend to die earlier during hospitalization and older adult survivor more frequently required skilled nursing or rehabilitative after hospitalization (6).
Bacteremia – patients often develop systemic consequences of infection (6). A study of 270 blood cultures, 95% of positive blood culture were associated with sepsis or septic shock (6).
Immunosuppression (6)
Comorbidities that depress host defense (eg. Neoplasms, renal failure, hepatic failure, AIDS, asplenism) and immunosuppressant medications (6).
Cancer (6) for infection – related conditions
Most common comorbidities. Analysis of subgroup of patients with cancer in the 1979 – 2001 National Hospital Discharge Survey found cancer of all types increased the risk of developing sepsis almost 10 – fold (6).
Community Acquired Pneumonia (6)
Severe sepsis and septic shock develop in approximately 48 and 5% of patients hospitalized with community acquired pneumonia (6),
Previous Hospitalization (6)
Hospitalization is thought to induce an altered human microbiome, particularly in patients treated with antibiotics (6). Patients with hospitalization for infection – related conditions especially Clostridium difficile infection are at great risk (6).
Genetic Factors (6)
Genetic defects have been identified that impair recognition of pathogens by the innate immune system, increasing susceptibility to specific classes of microorganisms (6).

Signs and Symptoms

Altered mental status (altered consciousness, mental confusion, or delirium) (2)
Fast respiratory rate > 22 breaths/ minute (2)
Low blood pressure with systolic BP equal or less 100 (2). Cool and pale extremities, lightheadedness or absent urine output in case of septic shock
Elevated heart rate (2)
Fever (2) Temperature >38
Low body temperature (hypothermia)
Reduced carbon dioxide (PaCO2) level in the blood (2)
Chills (2)
Dizziness (2)
Fatigue 92)
Shivering (2)
Facial flushing (2)
Shortness of breath (2)
Dysfunction of one or more organs (2)
Shock
Sleepiness (2)
Clammy or sweaty skin (5)

Sign of end-organ perfusion (6)

Warm, flushed skin in early phase (6) then cool due to redirect of blood flow to core organs (6). Decreased capillary refill, cyanosis or mottling may indicate shock (6).
Ileus or absent bowel sounds are often an end-stage sign of hypoperfusion (6).

Laboratory Signs:

Leukocytosis (WBC) >12000 or leukopenia WBC count < 4000 (6)
Normal WBC count with greater than 10% immature forms (6)
Hyperglycemia (plasma glucose >140 mg/ dl) in the absence of diabetes (6)
Plasma C-reactive protein more than 2 standard deviations above the normal value (6)
Arterial hypoxemia (arterial oxygen tension 9PaO2)/ fraction of inspired oxygen (FIO2) <300)(6)
Acute oliguria (urine output <0.5 ml/kg/hr) for at least 2 hours despite adequate fluid resuscitation) (6)
Creatinine increase >0.5 mg/d or 44.2 micromol/L (6)
Coagulation abnormalities (international normalized ratio (INR) >1.5 or activated partial thromboplastin time (Aptt) >60 secs (6)
Thrombocytopenia platelet count <100,000 (6)
Hyperbilirubinemia (plasma total bilirubin >4 mg/dl or >0 micromol/ L (6)
Adrenal insufficiency (eg. Hyponatremia, hyperkalemia), and the euthyroid sick syndrome can also be found in sepsis (6)
Elevated serum lactate level (eg. >2 mmol/ L) can be manifestation of organ hypoperfusion (6)
Pneumonia on chest xray or fluid collections on CT of abdomen (6)
Positive blood cultures (6)

Epidemiology

Incidence:

It was estimated that 164,000 cases of sepsis occurred in the United States in the late 1970’s (7).
One national database analysis of discharge records from hospitals in the United States estimated an annual rate of more than 1,665,000 cases of sepsis between 1979 and 2000 (7).
Another retrospective population- based analysis reported increased rates of sepsis and septic shock from 13 to 78 cases per 100,000 between 1998 and 2009 (7).
A retrospective analysis of an international database reported a global incidence of 437 per 100,000 person – years for sepsis between the years 1995 and 2015 (7).
In an analysis of 27 hospitals, between 2005 and 2014 rates of septic shock determined by clinical criteria increased from 12.8 to 18.6 per 1000 hospital admissions and mortality decreased from 55 to 51 percent (7).
The incidence of sepsis varies among the different races ana ethnic groups. But appears to be highest among African - American males (7).
The incidence is also greatest during the winter, probably due to the increased prevalence of respiratory infections (7).
Older patients greater than 65 years of age account for the majority (60 to 85 percent) of all episodes of sepsis (7).

Pathogens

Gram positive bacteria are most frequently identified in patients with sepsis in the United States. The incidence of fungal sepsis has increased over the past decade but remains lower than bacterial sepsis (7).

Disease severity

The proportion of patients with sepsis who also had at least one dysfunctional organ increased from 26 to 44 between 1993 to 2003 (7).

Prevalence of infection in Intensive Care Unit (9):

In an international study of 1265 ICUs, 60 percent of ICU patients at the time of survey were considered infected, with infection being a strong independent prediction for mortality (9).

Compared with patients in the general hospital population, patients in ICUs have more chronic comorbid illnesses and more severe acute physiologic derangement and are relatively immunosuppressed (9).
High frequency of indwelling catheters among ICU patients provides portal of entry of organisms into vital body organs and sites (9). Equipments associated with proper maintenance of these devices might serve as reservoirs and vectors for pathogens and be related to horizontal patient-to-patient transmission of pathogens (9).
Multidrug-resistant pathogens such as methicillin-resistant staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Acinetobacter baumannii, Enterobacteriaceae that produce extended-spectrum beta-lactamases and / or carbapenemases (eg. ESBLs and CREs), and carbapenem-resistant pseudomonas aeruginosa (9). Infections caused by these resistant pathogens are difficult to treat and are associated with increased morbidity, mortality, and costs (9).
ICU patients are subjected to increased selective pressure and increased colonization pressure (9).

An overall rate of 14.7 percent (or 22.5 infections per 1000 ICU day) was observed in multicenter prospective cohort surveillance study of 46 hospitals in Central and South America, India, Morocco, and Turkey (9).

Ventilator associated pneumonia (VAP); 24.1 cases per 1000 ventilator days (range 10.0 to 52.7 cases) (9). VAP is the infection of lung tissue that develops 48 hours or more after intubation in mechanically ventilated patients (9). Nosocomial pneumonia is the second most common hospital-acquired infection and occurs frequently in the setting of endotracheal intubation and mechanical ventilation (9).
Catheter-related bloodstream infection (CRBSI); 12.5 cases per 1000 catheter days (range 7.8 to 18.5 cases) (9). Arterial and central venous catheters are frequently used in critical care patients because of the need for hemodynamic monitoring and intravenous therapeutics (9). These are more common in ICU and are associated with significant morbidity and mortality (9).
Catheter-associated urinary tract infections (CAUTI); 8.9 cases per 1000 catheter days (1.7 to 12.8 cases) (9). Most common nosocomial infection, accounting for more than 40 percent of all nosocomial infections (9). In the United States, CAUTIs are responsible for 900,000 additionall cause of nosocomial bloodstream infection (ie urosepsis), which have an attributable mortality of approximately 15 to 25 percent (9). Medicare and Medicaid Services (CMS) does not reimburse hospitals for CAUTIs, which further increases the cost burden of these infections on hospital in the United States (9).

Prevention

Antibiotic utilization controls (9)
Antibiotic stewardship programs in the ICU setting have been impactful and associated with decreases in drug-resistant bacteria in some study setting (9). There maybe concerns that antibiotic stewardship may result in a delay in the initiation of appropriate antimicrobial therapy, which has been associated with poor outcomes with infections caused by multi – and extensively drug-resistant infections (9).
Infection control measures (9)
Adhere to hand hygiene, daily bathing with chlorhexidine, and implementation of device- specific strategies to decrease infection should be performed on a routine basis for all patients in ICU (9). Contact precautions for infected patients or colonized with resistant organisms, patients with wound drainage that cannot be contained by dressings, and for patients with diarrhea (9). Surveillance for drug-resistant organisms is also important for identification and control of epidemic and endemic rates of resistance (9).
Contact precautions, cohorting, and dedicated staff (9)
Wearing gown and gloves when entering a patient room and removing them prior to or shortly after existing (9). These precautions should be routinely implemented when caring for ICU patients who have a history of or are found to have infection or colonization with resistant Organisms (9).
Decolonization / patient bathing (9)
Daily chlorhexidine bathing for all ICU patients. Chlorhexidine gluconate (CHG), an antiseptic agent with broad-spectrum activity against many organisms, is an effective method of decreasing both hospital-acquired infections (ie bloodstream infections, urinary tract infections, surgical-site infections, and ventilator-associated pneumonia) and colonization with drug resistant organisms among patients in ICU (9).
Digestive and oropharyngeal decontamination (9)
Proposed as a method to reduce infection in critically ill patients by reducing microorganism Colonization at these sites (9). Modest mortality benefits have been demonstrated among ICU patients treated with selective oropharyngeal decontamination (SOD) an VRE, d selective digestive decontamination (SDD) in Netherlands (9).
Surveillance (9)
This is critical for early identification and control of epidemic outbreaks and endemic increases of resistant bacteria (9). The incidence and prevalence of isolation of multidrug-resistant bacteria (eg. MRSA, VRE, and carbapenem-resistant Enterobacteriaceae) should be monitored and these data should be disseminated to nurses and clinicians who work in the ICU through a form that is easy to interpret (9).
Environmental Cleaning (9)
Environmental cleaning, disinfection, and sterilization are basic and important measures used to prevent or reduce infections in the ICU, as in the rest of the hospital environment (9).

How Sepsis Is Diagnosed

Blood test A blood sample drawn from two distinct site is tested for (4):

Evidence of infection
Clotting problems
Abnormal liver or kidney function
Impaired oxygen availability
Electrolyte imbalances

Other laboratory tests (4):

Check urine for signs of bacteria for urinary tract infection
Wound secretions sample if it looks infected to show what type of antibiotic might work best
Respiratory secretions maybe tested to determine what type of germ is causing the infection

Imaging tests (4):

X-rays to visualize problems in your lungs
Computerized tomography to see if there is infection in your appendix or pancreas
Ultrasound which uses sound waves to produce real-time image on a video monitor. It is useful to check for infections in gallbladder or ovaries
Magnetic resonance imaging (MRI) is useful in identifying soft tissue infections. Uses radio waves and strong magnet to produce cross-sectioned images of the internal structures of your body.

The blood test, Accelerate Pheno Test BC Kit was approved by FDA in 2017 to allow a more rapid and specific diagnosis and provide information about treatment options to treat the causative agent(s) of sepsis early and more effectively. It can identify the genus and species of common gram- negative and gram- positive bacterial infections that can lead to sepsis, show their sensitivity or resistance to several antibiotics and can identify sepsis caused by candida fungal species (2).

Management and Treatment

Tissue perfusion
This is achieved by the aggressive administration of intravenous fluids, usually crystalloids (balanced crystalloids or normal saline) given at 30 ml/ kg (actual body weight), started by one hour and completed within the first 3 hours following presentation (8).
Empiric antibiotic therapy
Targeted at the suspected organism(s) and site(s) of infection and preferably administered within the first hour (8). Total duration aimed at 7-10 days (8). Efforts are to identify and control the source(s) of infection (ideally within 6-12 hours) in all patients with sepsis (8). Also consider removal of devices suspected to be infected, adequacy of the antimicrobial regimen, or nosocomial super infection for those who fail therapy or those who fail having initially responded to therapy (8).

Vasopressors
This is useful in patients who remain hypotensive despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema (8). Most experts prefer to avoid dopamine and favor norepinephrine as the first-choice agent (8). Vasopressin (up to 0.03 units/ minute) is used to reduce dose of norepinephrine or epinephrine (for refractory hypotension) (8).

Glucocorticoids
Corticosteroid therapy is appropriate in patients with septic shock that is refractory to adequate fluid resuscitation and vasopressin administration (8).

Inotropic therapy
This therapy is for patients who fail to respond to adequate fluids and vasopressors, particularly those with diminished cardiac output (8). Dobutamine is a suitable first choice agent, epinephrine is a suitable alternative (8). Inotropic therapy should not be used to increase the cardiac index to supra normal levels (8).

Red blood cell transfusions
These are for patients with a hemoglobin 7g or less per deciliter with exceptions of suspicion of concurrent hemorrhagic shock or active myocardiac ischemia (8).

Procalcitonin
This is used in guiding antibiotic discontinuation in patients with known community-acquired pneumonia and acute bronchitis (8).

Supportive therapies (8)

Nutrition
Stress ulcer prophylaxis
Venous thromboembolism prophylaxis
Intensive insulin therapy
External cooling or antipyretics
Mechanical ventilation, sedation, weaning
Investigational therapies for sepsis and acute respiratory distress syndrome (e.g. intravenous immune globulin, antithrombin, thrombomodulin, heparin, cytokine and toxin inactivators, as well as hemofiltration, statins, beta-2 agonists, beta blockade, and vitamin C/ thiamine/ hydrocortisone combination) (8).

Patients with sepsis who have demonstrated a response to therapy, rate of fluid management should be reduced or stopped, vasopressor support weaned, and if necessary diuretics administered (8). Once pathogen identification and susceptibility data return, antimicrobial therapy should be narrowed (8).

Complications

Impaired blood flow to vital organs such as brain, heart, and kidneys (4).
Blood clots to form in organs, arms, legs, fingers, and toes leading to varying degree of organ failure and tissue death (4).
Higher for future infections if you have episode of severe sepsis (4).
Excessive activity of neutrophils (10).
Excessive factors of infection in blood called tumour necrosis factor (10).
Injury to the blood vessel walls or endothelial injury (10).
Post-sepsis syndrome (PSS) maybe due to myopathy and neuropathy resulting from the inflammation, tissue ischemia, and ischemic-reperfusion injury to various organs (11).

Post-sepsis syndrome can involve:

Muscle weakness (11)
Excessive fatigue (11)
Chest pain (11)
Anxiety (11)
Impaired memory (11)
Cognitive impairment (11)
Post-traumatic stress disorder (PTSD) (11)
Hallucinations (12)
Loss of self-esteem (12)
Panic attacks (12)
Difficulty sleeping, either difficulty getting to sleep or staying asleep (12)
Nightmares (12)

Prognosis

The Mortality in Emergency Department Sepsis (MEDS) score is used to determine the patient’s prognosis in cases of sepsis (11). Mortality in severe sepsis and in septic shock is between 20% to 35%, and 40% to 60% (11). More patients die within few months due to inadequately controlled infection, underlying illness, or complication (11).

Conclusion

Sepsis happens when an infection you already have in your skin, lungs, urinary tract, or somewhere else trigger a chain reaction throughout your body (5).

Even with the extensive worldwide efforts to decrease sepsis, the incidence and mortality of sepsis are continuing to increase (13). Current efforts remain focused on early recognition and treatment, but preventive strategies have not been as aggressively deployed (13). Although the US Centers for Disease Control and Prevention recognizes the fundamental benefits of prevention-oriented strategies, prevention of sepsis through prevention of infection, particularly hospital-acquired infection, remains a clinical challenge (13).

References

National Institute of General Medical Sciences. Sepsis. Content updated January 2018. Https://www.nigms.nih.gov/education/pages/factsheet_sepsis.aspx
Davis CP. Sepsis (septicemia) diagnosis, causes, treatment, and symptoms. Https://www.medicinenet.com/sepsis/article.htm
Roberts C. The signs, symptoms, and causes of sepsis. January 12, 2015. Https://www.activebeat.com/your-health/the-signs-symptoms-and-causes-of-sepsis/?utm_...
Mayo Clinic Staff. Sepsis-symptoms and causes. Https://www.mayoclinic.org/diseases-conditions/sepsis/...
Centers for Disease Control and Prevention. What cause sepsis? Reviewed last August 27, 2019. Https://www.cdc.gov/sepsis/education/index.html/
Neviere R. Sepsis syndromes in adults: epidemiology, definitions, clinical presentation, diagnosis, an…. Last updated July 24, 2019. Https://www.uptodate.com/contents/sepsis-syndromes-in-adults-epidemiology-definitions-...
Neviere R. Sepsis syndromes in adults: epidemiology, definitions, clinical presentation, diagnosis, an…. Last updated September 9, 2019. Https://www.uptodate.com/contents/sepsis-syndromes-in-adults-epidemiology-definitions-...
Schmidt GA, Mandel A. Evaluation and management of suspected sepsis and septic shock in adults-uptodate. Last updated July 12, 2019. Https://www.uptodate.com/contents/evaluation-and-management-of-suspected-sepsis-and-s...
Marchaim D, Kaye K. Infections and antimicrobial resistance in the intensive care; epidemiology and preve….Last updated May 15, 2019. Https://www.uptodate.com/contents/infections-and-antimicrobial-resistance-in-the-intensiv...
What is sepsis? www.news.medical.net/health/What-is-Sepsis.aspx
Thomas L. Everything you need to know about sepsis. Https://www.news-medical.net/health/Everything-You-Need-To-Know-About-Se
Post-Sepsis Syndrome/ Sepsis Alliance. What is post-sepsis syndrome? Https://www.sepsis.org/sepsis-basics/post-sepsis-syndrome
Giuliano KK, Baker D. Sepsis in the context of nonventilator hospital-acquired pneumonia. American Journal of Critical Care. January 2020, Volume 29, No1, P10. Doi:https://doi.org/10.4037/ajcc2020402