INDEX
• About : Septicaemia.
• UK Stats: Sepsis: Antibiotics 'not working'.
• - Media -: What is sepsis and how can I spot it?
• Report: Sepsis lives can be saved, says ombudsman.
• Research : Vital Signs: Epidemiology of Sepsis ....
• Reports : For the Public, and, Healthcare Professionals & Researchers.
• Recovery: Antibiotics for Treating Sepsis.
• Guidelines: Antibiotic Guidelines 2015-2016 ...
• Cost, USA: National Inpatient Hospital Costs ...

  Options: Pathophysiology.

  Options: Treatment considerations.

• -Focus-: Monographs on Toxins and Enhancers.

About : Septicaemia. INDEX
https://en.wikipedia.org/wiki/Sepsis

Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. Common signs and symptoms include

• fever,
• increased heart rate,
• increased breathing rate, and
• confusion.

There also may be symptoms related to a specific infection, such as

• a cough with pneumonia, or
• painful urination with a kidney infection.

In the very young, old, and people with a weakened immune system, there may be no symptoms of a specific infection and the body temperature may be low or normal, rather than high.

Severe sepsis is sepsis causing poor organ function or insufficient blood flow.
Insufficient blood flow may be evident by

• low blood pressure,
• high blood lactate, or
• low urine output.

Septic shock is low blood pressure due to sepsis that does not improve after reasonable amounts of intravenous fluids are given.

Sepsis is caused by an immune response triggered by an infection.
Most commonly, the infection is bacterial, but it may also be from fungi, viruses, or parasites.
Common locations for the primary infection include lungs, brain, urinary tract, skin, and abdominal organs.

Risk factors include
• young or old age,
• a weakened immune system from conditions such as
• cancer
• diabetes,
• major trauma,
• burns.

An older method of diagnosis was based on meeting at least two systemic inflammatory response syndrome (SIRS) criteria due to a presumed infection. In 2016, SIRS was replaced with qSOFA which is two of the following three:

1. increased breathing rate,
2. change in level of consciousness, and
3. low blood pressure.

Blood cultures are recommended preferably before antibiotics are started, however, infection of the blood is not required for the diagnosis. Medical imaging should be used to look for the possible location of infection.

Other potential causes of similar signs and symptoms include

• anaphylaxis,
• adrenal insufficiency,
• low blood volume,
• heart failure, and
• pulmonary embolism,
• others.

Sepsis usually is treated with intravenous fluids and antibiotics.
Typically, antibiotics are given as soon as possible.
Often, ongoing care is performed in an intensive care unit.
If fluid replacement is not enough to maintain blood pressure, medications that raise blood pressure may be used.

Mechanical ventilation and dialysis may be needed to support the function of the lungs and kidneys, respectively.
To guide treatment, a central venous catheter and an arterial catheter may be placed for access to the bloodstream.
Other measurements such as cardiac output and superior vena cava oxygen saturation may be used.

People with sepsis need preventive measures for deep vein thrombosis, stress ulcers and pressure ulcers, unless other conditions prevent such interventions. Some might benefit from tight control of blood sugar levels with insulin. The use of corticosteroids is controversial. Activated drotrecogin alfa, originally marketed for severe sepsis, has not been found to be helpful, and was withdrawn from sale in 2011.

Disease severity partly determines the outcome.
The risk of death from sepsis is as high as 30%, from severe sepsis as high as 50%, and from septic shock as high as 80%.

Rates of disease have been increasing. (or, are being diagnosed and reported more frequently.)
Sepsis is more common among males than females.
The medical condition has been described since the time of Hippocrates.
The two terms, "septicemia" and "blood poisoning", refer to the microorganisms or their toxins in the blood and are no longer commonly used.

UK Stats: Sepsis: Antibiotics 'not working'. INDEX
http://www.bbc.com/news/health-28870734
Hugh Pym, Health editor @bbcHughPym on Twitter
https://www.twitter.com/bbcHughPym
20 August 2014

Patients are dying from sepsis because of a lack of effective antibiotics, an expert is warning.

Mark Bellamy, president of the Intensive Care Society, told the BBC the problem of resistance would get worse unless new and effective antibiotics were developed.

Sepsis is triggered by infections and causes around 37,000 deaths a year in the UK.
NHS England says hospitals should work together to tackle the problem.

Sepsis usually develops from blood poisoning and involves a dramatic reaction by the body's immune system.
If not treated quickly it can lead to organ failure or death.
Early symptoms can include a high temperature and a fast heartbeat.

Deadly
The Intensive Care Society recently launched a campaign to raise awareness of sepsis to avoid what it says are thousands of preventable deaths. There are 37,000 deaths a year in the UK because of sepsis, compared with just more than 35,000 from lung cancer and 16,000 from bowel cancer. The society, along with the UK Sepsis Trust, argues that there is inadequate recording of sepsis cases by hospitals and insufficient knowledge of the steps required to recognise and treat it early.

Case study

Julie Bignone nearly died because of sepsis and spent 7 weeks in hospital - some of them in a critical condition.

Feeling feverish, she assumed she had a bad dose of flu.
After a weekend in bed, she went to her GP and was told to come back if her condition worsened and antibiotics would be prescribed. But later that day, with her family growing more anxious she was taken to hospital by ambulance.

Julie was found to have pneumonia in both lungs and sepsis and doctors feared she might not survive.
She only pulled through after several weeks in intensive care and heavy doses of antibiotics.
She feels now that she should have acted on her instinct early on that she was suffering from something a lot worse than flu.

Julie says:
"There's a lot of scope for getting it wrong with sepsis because the symptoms are not specific enough - we need to get a system where doctors listen to patients more and allow them to have more of an opinion".

Failing antibiotics

Prof Bellamy, who is based at the Leeds Institute of Biomedical and Clinical Sciences, said:

"For the first time this year I have had a couple patients for whom we had no effective antibiotic treatment, it's rare - but two years ago it would still have been regarded as a theoretical problem."

He says it is crucial to raise the profile of sepsis, and to ensure it is tackled early to give the patient the best chance of survival. The diminishing impact of antibiotics, in his view, underlines the urgency of the task. He said there was a "spectre emerging of moving into a post-antibiotic era".

NHS England has acknowledged the scale of the problem.
Bruce Warner, its deputy director of patient safety, said:

"We know there are many preventable deaths due to sepsis each year and our top priority has to be saving those lives we can save and having as big an impact as we can."

NHS England wants to encourage greater co-ordination within hospitals to ensure sepsis is diagnosed and treated quickly.

It cited Nottingham University Hospitals Trust, which has been praised for use of laptops by staff to record patient data and symptoms and ensure they are analysed quickly by clinicians.

Media: What is sepsis and how can I spot it? INDEX
http://www.bbc.co.uk/programmes/articles/.../what-is-sepsis-and-how-can-i-spot-it
2018 ?

The six most common signs

1. Slurred Speech or confusion
2. Extreme shivering or muscle pain
3. Passing no urine (in a day)
4. Severe Breathlessness
5. “I feel like I might die”
6. Skin mottled or discoloured

Sepsis causes 8 million deaths worldwide every year.
It can strike any of us, young or old, and there are numerous triggers.
Yet most people have never heard of it and even fewer understand it.

Sepsis, sometimes called septicaemia or blood poisoning, happens when the body’s immune system goes into overdrive in response to an infection.

The initial problem could be anything from a chest infection to a cut finger, but if the immune system overreacts it can trigger a catastrophic attack on that infection that threatens the body’s own tissues and organs leading to shock, organ failure and death.

What’s more, those lucky enough to survive may have to live with amputations or lasting health problems due to extreme organ and tissue damage.

The key to beating sepsis is spotting it quickly and treating it early.

A recent report by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD), launched in November 2015, identified a number of ways in which treatment of the condition can be improved and emphasised that early recognition is vital in saving lives.

But it isn’t just doctors who need to be on the lookout for sepsis – it’s something that we should all be more aware of.

The problem is that sepsis can be very tricky to spot.

There are lots of different symptoms associated with the condition and many of them can be easily mistaken for something less dangerous. In fact the first signs are often similar to flu, a chest infection or a stomach bug.

Then, as the condition develops, these symptoms worsen and some more distinctive red flags emerge.

These can vary from patient to patient, but after discussions with sepsis survivors the UK Sepsis Trust has compiled a list of the six most common signs.

Red flags like these are signs that the body’s organs, such as the lungs, brain and kidneys, are beginning to fail.
In the case of babies and young children some of these symptoms can present differently.
The child may become lethargic and stop feeding, they might feel cold to the touch and their breathing could become rapid. Another sign is if they haven’t had a wee or wet their nappy for 12 hours.

If you recognise these symptoms either in yourself or someone else you should seek urgent medical treatment.
Although sepsis is dangerous, a quick response can make a huge difference. Sepsis CAN be beaten – if we all become more aware of the condition and learn to recognise the symptoms, we could save thousands of lives.

Related Links

LINK: UK Sepsis Trust (sepsistrust.org)
http://sepsistrust.org/public/what-is-sepsis/

LINK: NCEPOD ‘Just Say Sepsis’ Report (www.ncepod.org.uk)
http://www.ncepod.org.uk/2015sepsis.htm

LINK: NHS Sepsis (www.nhs.uk)
http://www.nhs.uk/conditions/Blood-poisoning/Pages/Introduction.aspx

Report: Sepsis lives can be saved, says ombudsman. INDEX
http://www.bbc.com/news/health-24063623

More must be done to save the lives of patients with sepsis, says a report from the Health Service Ombudsman.

It found significant failings in treatment of the condition, which is caused when the body's immune system overreacts to infection.

It focused on 10 patients who were not treated urgently enough and died.

The National Institute for Health and Care Excellence will produce guidance for GPs and clinicians to help them recognise sepsis at an early stage.

Around 37,000 people are estimated to die of sepsis each year, accounting for 100,000 hospital admissions.

The Ombudsman, who investigates complaints from people who have received poor service from the NHS in England, said diagnosing and treatment presented some real problems because the condition was hard to spot and treat.

Sepsis can lead to swelling and blood clotting - and cause internal organs to stop working.

The most common causes of severe sepsis are pneumonia, bowel perforation, urinary infection, and severe skin infections.

Julie Mellor, the Health Service Ombudsman, said it was time for the NHS to act.

"In the cases in our report, sadly, all patients died. In some of these cases, with better care and treatment, they may have survived.

"We have worked closely with NHS England, NICE, UK Sepsis Trust and Royal Colleges to find solutions to the issues identified in our report. NICE and NHS England have already agreed to take forward the recommendations of our report.

We know it is not easy to spot the early signs of sepsis, but if we learn from these complaints ... then lives can be saved
Julie Mellor, Health Service Ombudsman

The report recommended improving the recognition and treatment of sepsis by providing medical staff with clear clinical guidance.

She also recommended that NHS England launch a public awareness campaign which targets vulnerable groups of patients, such as those who are weak or in hospital.

Clinical staff should attach more importance to listening to the relatives of patients since they can be the first to recognise the patient's deterioration, she said, and more senior doctors should be involved in patient care.

Simple life-savers
Dr Ron Daniels, chairman of the UK Sepsis Trust, said there was a straightforward solution.

"The best hospitals have achieved better outcomes from sepsis by adopting a simple set of life-saving measures, collectively known as the Sepsis 6, and ensuring that a culture of awareness around sepsis has been created.

"We now need to spread this awareness to other health professionals and to the public, and to underpin this with guidance from NHS England and the National Institute for Health and Care Excellence."

He said the recommendations would potentially save 12,500 more lives every year.

Dr Mike Durkin, NHS England's director of patient safety, said the NHS would use the findings to work with GPs and hospitals to reduce deaths from sepsis.

"This report and guidance will help us to build on the work that is already in place to emphasise the importance of education, early detection and prompt treatment.

"We all need in every setting to understand the importance of identifying deterioration in both adults and children, in reducing the admission of full-term babies to neonatal care and identifying problems in vulnerable older people in the first 48 hours of acute illness."

Dr Peter Carter, chief executive of the Royal College of Nursing, said the report showed the tragic consequences of sepsis.

"It is vital that all staff are provided with training and support to enable them to recognise the signs and symptoms of sepsis, and crucially to know how to act quickly when sepsis is diagnosed."

Research : Vital Signs: Epidemiology of Sepsis .... INDEX
https://www.cdc.gov/mmwr/volumes/65/wr/mm6533e1.htm...
On August 23, 2016, this report was posted online as an MMWR Early Release.

Shannon A. Novosad, MD; Mathew R.P. Sapiano, PhD; Cheri Grigg, DVM; Jason Lake, MD; Misha Robyn, DVM; Ghinwa Dumyati, MD; Christina Felsen, MPH; Debra Blog, MD; Elizabeth Dufort, MD; Shelley Zansky, PhD; Kathryn Wiedeman, MPH; Lacey Avery, MA; Raymund B. Dantes, MD; John A. Jernigan, MD; Shelley S. Magill, MD; Anthony Fiore, MD; Lauren Epstein, MD

Abstract
... Results: Medical records of 246 adults and 79 children (aged birth to 17 years) were reviewed.
Overall, 72% of patients had a health care factor during the 30 days before sepsis admission or a selected chronic condition likely to require frequent medical care.

Pneumonia was the most common infection leading to sepsis.
The most common pathogens isolated from blood cultures were Escherichia coli in adults aged =18 years, Klebsiella spp. in children aged =1 year, and Enterococcus spp. in infants aged <1 year; for 106 (33%) patients, no pathogen was isolated.

Eighty-two (25%) patients with sepsis died, including 65 (26%) adults and 17 (22%) infants and children. ...

Introduction
Many different infections can lead to sepsis, a serious and often fatal clinical syndrome that is characterized by organ dysfunction and can be difficult to diagnose. Sepsis is associated with high morbidity and mortality and accounted for $23.7 billion in health care expenditures in 2013. Identifying specific sepsis prevention strategies is a public health priority.

Evaluations of sepsis epidemiology have typically used death certificate or health services utilization data; these methods have well-described limitations. ...

Results Adult patients with sepsis. Charts of 290 adult patients with sepsis were selected, and reviews were completed for 246 (85%); 44 (15%) records were excluded, most commonly because encounter information was missing. The median age of adult patients with sepsis was 69 years; 127 (52%) were male (Table 1). The median length of hospital stay was 9 days.

Most patients

238 [97%]) had at least one comorbidity;
87 (35%) had diabetes mellitus,
79 (32%) had cardiovascular disease (...),
56 (23%) had chronic kidney disease, and
50 (20%) had chronic obstructive pulmonary disease.

The most common illnesses leading to sepsis were pneumonia (85 [35%]), urinary tract infections (62 [25%]), gastrointestinal infections (28 [11%]), and skin/soft tissue infections (26 [11%]) (Table 2).

Pathogens were isolated from blood cultures of 75 (30%) patients and from urine cultures of 70 (28%); these groups were not mutually exclusive. The most common pathogens identified from blood were Staphylococcus spp. (including both S. aureus and coagulase negative Staphylococcus), Escherichia coli, and Streptococcus spp. (Table 3). For 76 (31%) patients with sepsis, no pathogen was identified in any culture or nonculture based tests.

... Pneumococcal vaccination before the sepsis hospitalization was documented for 108 (44%) patients, and influenza vaccination in the year before admission was documented for 87 (35%) patients.

Among the 155 patients admitted from a private residence, 23 (15%) were discharged to a long-term care facility.
65 (26%) patients died during their sepsis hospitalization, including 47 (representing 72% of deaths) who were aged =65 years,
and 7 (representing 11% of deaths) who had no health care factors in the 30 days preceding admission.

Pediatric patients with sepsis.
Records of 88 pediatric patients with sepsis were selected for review, and reviews were completed for 79 (90%), including 31 infants aged <1 year (39%), and 48 children, aged 1–17 years (61%) (Table 1).

... Among infections leading to sepsis, respiratory infections were most common, and preceded sepsis in 29% of all pediatric patients, followed by gastrointestinal infections (24%) (Table 2). Among 41 (52%) patients for whom a pathogen was identified in a blood culture, Enterococcus spp. and Klebsiella spp. were most commonly identified in infants (14%) and children (9%), respectively (Table 3). In 30 (38%) pediatric patients, sepsis was diagnosed but no pathogen was isolated. Seventeen (22%) pediatric cases died during their sepsis hospitalization, including 12 (39%) infants and five (10%) children.

Conclusions and Comments.

... Patients with sepsis experience severe illness and serious adverse outcomes, including long hospital stays (median = 10 days), discharge to long-term care settings (20%), and death (25%). Similar to other studies, sepsis most commonly occurred among patients with one or more comorbidities, and a majority of patients developed infections leading to sepsis outside a hospital.

Among all patients with sepsis, 72% had either a health care factor in the month preceding admission or a chronic condition likely to require frequent contact with the health care system, suggesting that opportunities exist for prevention or earlier recognition of infections leading to sepsis. Although multiple infections and organisms among patients with sepsis were identified in this study and in others, in many cases a specific pathogen is not determined.

Because different types of infections can lead to sepsis, many interventions that are currently viewed as pathogen-specific or disease-specific should also be considered opportunities to prevent sepsis and included in efforts to improve sepsis education. ...

Among those patients for whom sepsis onset was determined, 79.4% were classified as having sepsis onset outside of the hospital (i.e., first medical record documentation of sepsis at admission or in the first 3 hospital days). The majority of patients in this analysis had recent interactions with the health care system before admission. While this likely reflects the vulnerability of chronically ill patients to infection, it also suggests that health care facilities and providers could play a central role in sepsis prevention by providing age-appropriate and condition-appropriate vaccination to all patients and optimizing the health status of patients with chronic conditions. ...

The findings in this report are subject to at least five limitations.

First, the assessment examined medical records from a small sample of patients and hospitals; characteristics of patients with sepsis could be different elsewhere, although these results are consistent with previous studies.

Second, a sample of adult and pediatric records were reviewed, and the numbers of records are not proportional to the actual number of adult and pediatric patients with sepsis in these facilities.

Third, to identify patients with sepsis and septic shock, administrative codes were used along with confirmation that at least one provider had documented sepsis in the medical record, rather than application of an objective definition based on physiological or laboratory criteria. Therefore, although this approach has obvious limitations, it reflects the clinical impression of treating providers.

Fourth, because this analysis relied on medical records for all information, data might be incomplete.
Information on outpatient clinic visits was not collected; therefore, the proportion of patients with sepsis who have health care factors before their sepsis hospitalizations might have been underestimated.

Finally, in many patients more than one infectious process was present, and it is possible that not all of the infections and organisms described actually caused sepsis in an individual patient. ...

Reports: For the Public, and, Healthcare Professionals & Researchers. INDEX
https://www.cdc.gov/sepsis/datareports/index.html
LINK 2: https://www.cdc.gov/vitalsigns/sepsis/
LINK 3: https://www.cdc.gov/vitalsigns/pdf/2016-08-vitalsigns.pdf
August 23, 2016

1-800-CDC-INFO (232-4636)
Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30329

A CDC evaluation found 7 in 10 patients with sepsis had recently used healthcare services or had chronic diseases requiring frequent medical care.

In adults, these common infections can lead to sepsis.
• Lung infection such as pneumonia (35%)
• Kidney or urinary tract infection (25%)
• Gut, stomach, or intestine infection (11%)
• Skin infection (11%)

Sepsis Statistics

More than 1.5 million people get sepsis each year in the U.S
About 250,000 Americans die from sepsis each year
One in three patients who die in a hospital have sepsis

Sepsis is deadly when it’s not quickly recognized and treated.

Certain people with an infection are more likely to get sepsis.

CDC evaluation found more than 90% of adults and 70% of children who developed sepsis had a health condition that may have put them at risk.

Sepsis occurs most often in people 65 years or older or younger than 1 year, with weakened immune systems, or with chronic medical conditions (e.g., diabetes).

While less common, even healthy infants, children, and adults can develop sepsis from an infection, especially when not treated properly.

Certain infections and germs lead to sepsis most often.*

Four types of infections are often associated with sepsis: lung, urinary tract, skin, and gut.
Common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus.

Recovery: Antibiotics for Treating Sepsis. INDEX
https://academic.oup.com/cid/article/3966709/Sepsis-National-Hospital-Inpatient-Quality-Measure...
“Sepsis National Hospital Inpatient Quality Measure (SEP-1):
Multi-stakeholder Work Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis,”
the material was published in Clinical Infectious Diseases.
Edward J Septimus, Craig M Coopersmith, Jessica Whittle, Caleb P Hale, Neil O Fishman, Thomas J Kim
Clinical Infectious Diseases, Volume 65, Issue 9, 16 October 2017,
Pages 1565–1569, https://doi.org/10.1093/cid/cix603
Published: 14 July 2017
(Restricted Access -- Cost for temporary access)

Abstract
The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis.

The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis.

Guidelines: Antibiotic Guidelines 2015-2016
Treatment Recommendations for Adult Inpatients. INDEX
https://www.hopkinsmedicine.org/amp/guidelines/antibiotic_guidelines.pdf
LINK 2: insidehopkinsmedicine.0rg/amp
The Johns Hopkins Hospital
Antimicrobial Stewardship Program
Osler 425
(443) 287-4570 (7-4570)
Many contributors, 163 pages, 2015

6.15 -- Sepsis with no clear source, p 99

EMPIRIC TREATMENT Cultures MUST be sent to help guide therapy.

Vancomycin (see dosing section, p. 150) (if at risk for MRSA) ± Gentamicin (see dosing section, p. 146) OR PLUS Gentamicin (see dosing section, p. 146) PLUS Vancomycin (see dosing section, p. 150)

*NOTE:
If patient has history of ESBL-producing organism or has suspected intra abdominal sepsis and recent prolonged exposure ( 7 days) to Piperacillin/tazobactam or Cefepime, substitute with Meropenem 1 g IV Q8H.

TREATMENT NOTES
For patients with renal insufficiency or aminoglycoside intolerance, a beta-lactam may be combined with a fluoroquinolone IF 2 agents are needed.

Potential sources (e.g.: pneumonia, peritonitis, etc.) should be considered when selecting therapy.

Empiric Therapy is only appropriate when cultures are pending (72 hours max).

Vancomycin should almost always be stopped if no resistant gram positive organisms are recovered in cultures.

...

Cost, USA: National Inpatient Hospital Costs:
The Most Expensive Conditions by Payer, 2013 INDEX
https://www.hcup-us.ahrq.gov/reports/
statbriefs/sb204-Most-Expensive-Hospital-Conditions.pdf
Agency for Healthcare Research and Quality (AHRQ)
H-CUP, HEALTHCARE COST AND UTILIZATION PROJECT
Celeste M. Torio, Ph.D., M.P.H., and Brian J. Moore, Ph.D.
2013 -- 15 pages -- STATISTICAL BRIEF #204

Health care expenditures have maintained a relatively stable share of the Gross Domestic Product since 2009, reaching 17.5 percent in 2014. ... Although only 7.2 percent of the U.S. population had a hospital inpatient stay in 2012, the mean expense per stay associated with those hospitalizations was over $18,000, making hospitalization one of the most expensive types of health care treatment. ...

The five most expensive conditions — septicemia; osteoarthritis; liveborn (newborn) infants; complication of device, implant or graft; and acute myocardial infarction — accounted for approximately one-fifth of the total aggregate costs for hospitalizations.

Septicemia ranked among the four most costly conditions in he hospital for all four payer groups.

Table 1: The 20 most expensive conditions treated in U.S. hospitals, all payers, 2013 Rank 1 -- Septicemia
-- Aggregate hospital costs, $ millions: 23,663 -- National costs, % 6.2 -- Number of hospital stays, thousands, 1,297
(Highest ranking in each of these categories !!)
[It was also the most expensive condition billed to the USA Medicare.]
{It was 2nd of 20 as the most expensive condition billed to USA Medicaid}.
It was also 1st in a list of The 20 most expensive conditions for uninsured individuals.
There is no record of how many deaths resulted from a lack of diagnosis and treatment of scepticemia.

hcup@ahrq.gov
David Knutson, Director
Center for Delivery, Organization, and Markets
Agency for Healthcare Research and Quality 
5600 Fishers Lane
Rockville, MD 2085

Options: Pathophysiology. INDEX
https://en.wikipedia.org/wiki/Sepsis

Sepsis is caused by a combination of factors related to the particular invading pathogen(s) and to the status of the immune system of the host. The early phase of sepsis characterized by excessive inflammation (sometimes resulting in a cytokine storm) may be followed by a prolonged period of decreased functioning of the immune system. Either of these phases may prove fatal. On the other hand, systemic inflammatory response syndrome (SIRS) occurs in people without the presence of infection, for example, in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis. ...

Microbial factors
Bacterial virulence factors, such as glycocalyx and various adhesins, allow colonization, immune evasion, and establishment of disease in the host. Sepsis caused by gram-negative bacteria is thought to be largely due to a response by the host to the lipid A component of lipopolysaccharide, also called endotoxin. Sepsis caused by gram-positive bacteria may result from an immunological response to cell wall lipoteichoic acid. Bacterial exotoxins that act as superantigens also may cause sepsis. Superantigens simultaneously bind major histocompatibility complex and T-cell receptors in the absence of antigen presentation. This forced receptor interaction induces the production of pro-inflammatory chemical signals (cytokines) by T-cells.

There are a number of microbial factors that may cause the typical septic inflammatory cascade.
An invading pathogen is recognized by its pathogen-associated molecular patterns (PAMPs). ... These PAMPs are recognized by the pattern recognition receptors (PRRs) of the innate immune system, which may be membrane-bound or cytosolic. ... Invariably, the association of a PAMP and a PRR will ... up-regulate the expression of pro-inflammatory and anti-inflammatory cytokines.

Host factors
Upon detection of microbial antigens, the host systemic immune system is activated.
Immune cells not only recognize PAMP, but also Damage-associated molecular pattern (DAMP) from damaged tissues. Uncontrolled immune response was then activated because leukocytes are not recruited to the specific site of infection, but instead they are recruited all over the body. Then, immunosuppression state ensues ... (and) The apoptosis (cell death) of lymphocytes further worsens the immunosuppression. Subsequently, multiple organ failure ensues because tissues are unable to use oxygen efficiently ....

Inflammatory responses cause multiple organ dysfunction syndrome ....

Increased permeability of the lung vessels causes leaking of fluids into alveoli, which results in pulmonary edema and acute respiratory distress syndrome (ARDS).

Impaired utilization of oxygen in the liver impairs bile salt transport, causing jaundice (yellowish discoloration of skin).

In kidneys, inadequate oxygenation results in tubular epithelial cell injury (of the cells lining the kidney tubules), and thus causes acute kidney injury (AKI).

... in a human heart, impaired calcium transport, and low production of adenosine triphosphate (ATP), can cause myocardial depression, reducing cardiac contractility and causing heart failure.

In the gastrointestinal tract, increased permeability of the mucosa alters the microflora, causing mucosal bleeding and paralytic ileus.

In the central nervous system, direct damage of the brain cells and disturbances of neurotransmissions causes altered mental status.

Cytokines ... may activate procoagulation factors in the cells lining blood vessels, leading to endothelial damage. The damaged endothelial surface inhibits anticoagulant properties as well as increases antifibrinolysis, which may lead to intravascular clotting, the formation of blood clots in small blood vessels, and multiple organ failure.

The low blood pressure seen in those with sepsis is the result of various processes, including
• excessive production of chemicals that dilate blood vessels such as nitric oxide,
• a deficiency of chemicals that constrict blood vessels such as vasopressin, and
• activation of ATP-sensitive potassium channels. ...

Options: Treatment considerations. INDEX
https://en.wikipedia.org/wiki/Sepsis

Early recognition and focused management may improve the outcomes in sepsis.
Current professional recommendations include a number of actions ("bundles") to be followed as soon as possible after diagnosis. Within the first 3 hours someone with sepsis should have received antibiotics and, intravenous fluids if there is evidence of either low blood pressure or other evidence for inadequate blood supply to organs (as evidenced by a raised level of lactate); blood cultures also should be obtained within this time period. After 6 hours the blood pressure should be adequate, close monitoring of blood pressure and blood supply to organs should be in place, and the lactate should be measured again if initially, it was raised. A related bundle, the "Sepsis Six", is in widespread use in the United Kingdom; this requires the administration of antibiotics within an hour of recognition, blood cultures, lactate and hemoglobin determination, urine output monitoring, high-flow oxygen, and intravenous fluids.

.. the management of sepsis ... involves
• administration of fluids and antibiotics ..
• surgical drainage of infected fluid ...
• hemodialysis in kidney failure,
• mechanical ventilation in lung dysfunction,
• transfusion of blood products, and
• drug and fluid therapy for circulatory failure ...
• adequate nutrition ...
• Medication ....

Antibiotics
Two sets of blood cultures (aerobic and anaerobic) should be taken without delaying the initiation of antibiotics. ...
In severe sepsis and septic shock, broad-spectrum antibiotics (usually two, a ß-lactam antibiotic with broad coverage, or broad-spectrum carbapenem combined with fluoroquinolones, macrolides, or aminoglycosides) are recommended. However, combination of antibiotics is not recommended for the treatment of sepsis .... The choice of antibiotics is important in determining the survival of the person. Some recommend they be given within one hour of making the diagnosis, stating that for every hour of delay in the administration of antibiotics, there is an associated 6% rise in mortality. Others did not find a benefit with early administration.

Several factors determine the most appropriate choice for the initial antibiotic regimen.
These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a hospital or community-acquired infection, and which organ systems are thought to be infected. Antibiotic regimens should be reassessed daily and narrowed if appropriate. Treatment duration is typically 7–10 days with the type of antibiotic used directed by the results of cultures.

If the culture result is negative, antibiotics should be de-escalated according to person's clinical response or stopped altogether if infection is not present to decrease the chances that the person is infected with multiple drug resistance organisms. In case of people having high risk of being infected with multiple drug resistance organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, addition of antibiotic specific to gram-negative organism is recommended.

For Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin or teicoplanin is recommended.
For Legionella infection, addition of macrolide or fluoroquinolone is chosen.
If fungal infection is suspected, an echinocandin, such as caspofungin or micafungin, ... followed by triazole (fluconazole and itraconazole) for less ill people.

Prolonged antibiotic prophylaxis is not recommended in people who has SIRS without any infectious origin such as acute pancreatitis and burns unless sepsis is suspected.

Once daily dosing of aminoglycoside is sufficient to achieve peak plasma concentration for clinical response without kidney toxicity. Meanwhile, for antibiotics with low volume distribution (vancomycin, teicoplanin, colistin), loading dose is required to achieve adequate therapeutic level to fight infections. Frequent infusions of beta-lactam antibiotics without exceeding total daily dose would help to keep the antibiotics level above minimum inhibitory concentration (MIC), thus providing better clinical response. Giving beta-lactam antibiotics continuously may be better than giving them intermittently. Access to therapeutic drug monitoring is important to ensure adequate drug therapeutic level while at the same time preventing the drug from reaching toxic level.

Intravenous fluids
The Surviving Sepsis Campaign has recommended 30 ml/kg of fluid to be given in adults in the first 3 hours followed by fluid titration according to blood pressure, urine output, respiratory rate, and oxygen saturation with a target mean arterial pressure (MAP) of 65 mmHg. ...

Crystalloid is recommended as the fluid of choice for resuscitation.
Albumin can be used if large amount of crystalloid is required for resuscitaition.
Crystalloid solutions and albumin are better than other fluids (such as hydroxyethyl starch) in terms of risk of death.
Starches also carry an increased risk of acute kidney injury, and need for blood transfusion.
Various colloid solutions (such as modified gelatin) carry no advantage over crystalloid.
Albumin also appears to be of no benefit over crystalloids.

Blood products
... Erythropoietin is not recommended in the treatment of anemia with septic shock because it may precipitate blood clotting events. Fresh frozen plasma transfusion usually does not correct the underlying clotting abnormalities before a planned surgical procedure. However, platelet transfusion is suggested for platelet counts below (10 × 109/L) without any risk of bleeding, or (20 × 109/L) with high risk of bleeding, or (50 × 109/L) with active bleeding, before a planned surgery or an invasive procedure. ...

Vasopressors
If the person has been sufficiently fluid resuscitated but the mean arterial pressure is not greater than 65 mmHg, vasopressors are recommended. Norepinephrine (noradrenaline) is recommended as the initial choice.

Norepinephrine raises blood pressure through a vasoconstriction effect, with little effect on stroke volume and heart rate.
If a single vasopressor is not enough to raise the blood pressure, epinephrine (adrenaline) or vasopressin may be added. However, one of the adrenaline side effects is that it reduces blood flow to abdominal organs and may cause increased lactate levels.

Vasopressin can be used in septic shock ... there is a relative deficiency of vasopressin when shock continues for 24 to 48 hours. However, vasopressin reduces blood flow to the heart, finger/toes, and abdominal organs, resulting in a lack of oxygen supply to these tissues.

Dopamine is typically not recommended.
Although dopamine is useful to increase the stroke volume of the heart, it causes more abnormal heart rhythms than norepinephrine and also has an immunosuppressive effect. ...Dobutamine may be used if heart function is poor or blood flow is insufficient despite sufficient fluid volumes and blood pressure.

Steroids
... During critical illness, a state of adrenal insufficiency and tissue resistance to corticosteroids may occur. ...

Anesthesia
A target tidal volume of 6 mL/kg of predicted body weight (PBW) and a plateau pressure less than 30 cm H2O is recommended for those who require ventilation due to sepsis-induced severe ARDS. High positive end expiratory pressure (PEEP) is recommended for moderate to severe ARDS in sepsis as it opens more lung units for oxygen exchange. ... It is recommended that the head of the bed be raised if possible to improve ventilation. ... Minimizing intermittent or continuous sedation is helpful in reducing the duration of mechanical ventilation.

General anesthesia is recommended for people with sepsis who require surgical procedures to remove the infective source. Usually inhalational and intravenous anesthetics are used. Requirements for anesthetics may be reduced in sepsis. Inhalational anesthetics can reduce the level of proinflammatory cytokines, altering leukocyte adhesion and proliferation, inducing apoptosis (cell death) of the lymphocytes, possibly with a toxic effect on mitochondrial function. Although etomidate has a minimal effect on the cardiovascular system, it is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death. ...

Paralytic agents should be avoided unless ARDS is suspected.

Newborns
Neonatal sepsis can be difficult to diagnose as newborns may be asymptomatic.
If a newborn shows signs and symptoms suggestive of sepsis, antibiotics are immediately started and are either changed to target a specific organism identified by diagnostic testing or discontinued after an infectious cause for the symptoms has been ruled out.

Other
Treating fever in people with sepsis does not affect outcomes.

A 2012 Cochrane review concluded that N-acetylcysteine (NAC) does not reduce mortality in those with SIRS or sepsis and may even be harmful. ...

... omega-3 fatty acids are not recommended as immune supplements for a person with sepsis or septic shock.
The usage of prokinetic agents such as metoclopramide, domperidone, and erythromycin are recommended for those who are septic and unable to tolerate enteral feeding. ... The usage of prokinetic agents should be reassessed daily and stopped if no longer indicated.