This document discusses sepsis, including its definition, causes, pathophysiology, clinical features, treatment, and research. The key points are:
- Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It is divided into sepsis and septic shock.
- Common causes are pneumonia, abdominal/urinary infections. Risk factors include chronic diseases and older/younger age.
- Pathophysiology involves a complex host response involving both pro- and anti-inflammatory mechanisms that can lead to organ dysfunction.
- Treatment focuses on early management bundles within 6 hours including antibiotics, fluids, vasopressors, and source control, as well as organ
An illustration about what happens from the beginning to the end of a septic shock & what are the factors that cause it.
*There are notes provided in some slides.
An illustration about what happens from the beginning to the end of a septic shock & what are the factors that cause it.
*There are notes provided in some slides.
The definition of sepsis continues to change for both patients and healthcare providers. Medicine does not currently share a consensus understanding of sepsis which may place patients at greater risk.
This presentation goes beyond the controversy of Sepsis-3 and provides a Data Science solution to the 3,000-year-old problem known as sepsis.
Etiopathogenesis and pharmacotherapy of Asthma
the pathophysiology of selected disease states and the rationale for drug therapy;
b. the therapeutic approach to management of these diseases;
c. the controversies in drug therapy;
d. the importance of preparation of individualised therapeutic plans based on diagnosis;
e. needs to identify the patient-specific parameters relevant in initiating drug therapy,
and monitoring therapy (including alternatives, time-course of clinical and laboratory
indices of therapeutic response and adverse effects);
f. describe the pathophysiology of selected disease states and explain the rationale for
drug therapy;
g. summarise the therapeutic approach to management of these diseases including
reference to the latest available evidence;
h. discuss the controversies in drug therapy;
i. discuss the preparation of individualised therapeutic plans based on diagnosis; and
j. identify the patient-specific parameters relevant in initiating drug therapy, and
monitoring therapy (including alternatives, time-course of clinical and laboratory indices of therapeutic response and adverse effects).
Latest definition of sepsis, application of qSOFA, latest evidence on treatment of septic shock,role of fluids, role of steroids, isobalance salt solution
The definition of sepsis continues to change for both patients and healthcare providers. Medicine does not currently share a consensus understanding of sepsis which may place patients at greater risk.
This presentation goes beyond the controversy of Sepsis-3 and provides a Data Science solution to the 3,000-year-old problem known as sepsis.
Etiopathogenesis and pharmacotherapy of Asthma
the pathophysiology of selected disease states and the rationale for drug therapy;
b. the therapeutic approach to management of these diseases;
c. the controversies in drug therapy;
d. the importance of preparation of individualised therapeutic plans based on diagnosis;
e. needs to identify the patient-specific parameters relevant in initiating drug therapy,
and monitoring therapy (including alternatives, time-course of clinical and laboratory
indices of therapeutic response and adverse effects);
f. describe the pathophysiology of selected disease states and explain the rationale for
drug therapy;
g. summarise the therapeutic approach to management of these diseases including
reference to the latest available evidence;
h. discuss the controversies in drug therapy;
i. discuss the preparation of individualised therapeutic plans based on diagnosis; and
j. identify the patient-specific parameters relevant in initiating drug therapy, and
monitoring therapy (including alternatives, time-course of clinical and laboratory indices of therapeutic response and adverse effects).
Latest definition of sepsis, application of qSOFA, latest evidence on treatment of septic shock,role of fluids, role of steroids, isobalance salt solution
surviving sepsis guidelines - Notes are made from surviving sepsis guidelines 2016 article to assist medical students and residents to grasp subject in a easy to read format in a step wise manner. Resources: surviving sepsis guidelines 2016 (free access article)
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
2. INTRODUCTION
• Sepsis-3 definition(2016) is life-threatening organ dysfunction caused
by a dysregulated host response to infection
(SEPSIS-1(1991) ; “sepsis”, when SIRS results from a infection)
• Severe Sepsis to describe instances in which sepsis is complicated by
acute organ dysfunction, hypoperfusion, or hypotension
• Septic shock is a subset of sepsis with circulatory and
cellular/metabolic dysfunction associated with a higher risk of
mortality (sepsis induced hypotension persists after adequate fluid
resuscitation)
3. • The new definition abandoned use of host inflammatory response
syndrome criteria (SIRS) in identification of sepsis and eliminated the
term severe sepsis
• Divides sepsis into two distinct categories: sepsis and septic shock
• Definition of “septic shock” was altered to “a subset of sepsis in
which underlying circulatory and cellular metabolism abnormalities
are profound enough to substantially increase mortality.”
4. • An earlier sepsis definition, Sepsis-1, was developed at a 1991
consensus conference in which SIRS criteria were established.
• Four SIRS criteria were defined, namely tachycardia (heart rate >90
beats/min), tachypnea (respiratory rate >20 breaths/min), fever or
hypothermia (temperature >38 or <36 °C), and leukocytosis,
leukopenia, or bandemia (white blood cells >1,200/mm3,
<4,000/mm3 or bandemia ≥10%).
5. • This is clinically identified by “vasopressor requirement to maintain a
mean arterial pressure of > 65 mmHg and serum lactate level >
2mmol/L in the absence of hypovolemia” and identifies a subset of
patients with a hospital mortality rate of > 40%
6. • As part of the 2016 SCCM/ESICM evaluation of criteria for identifying
septic patients, the task force compared traditional SIRS criteria to
other methods, including the Logistic Organ Dysfunction System
(LODS) and Sequential Organ Failure Assessment (SOFA) scoring
• Based on this analysis, the authors recommended use of SOFA scoring
to assess the severity of organ dysfunction in a potentially septic
patient
7.
8. • Recognizing these practical limitations, the 2016 SCCM/ESICM task
force described a simplified method termed “quick SOFA” to facilitate
easier identification of patients potentially at risk of dying from sepsis
9. • Prognostic accuracy for in-hospital mortality between SIRS criteria
and qSOFA score is area of debate
• qSOFA score provided inadequate sensitivity for early risk assessment
• This clearly shows that use of qSOFA score risks missing early
identification of sepsis when treatment is most effective
• The introduction of the Sepsis-3 definition is still relatively new to the
critical care literature, but given the ease of SOFA calculation and high
specificity of SOFA/qSOFA scores, it is likely to be adopted as a
consensus definition for future clinical research
10.
11. Incidence and Causes
• Depends on how acute organ dysfunction is defined and on whether
that dysfunction is attributed to an underlying infection
• Organ dysfunction is often defined by the provision of supportive
therapy (e.g., mechanical ventilation)
• Severe sepsis occurs as a result of both community-acquired and
health care–associated infections
• Pneumonia is the most common cause, accounting for about half of
all cases, followed by intraabdominal and urinary tract infections
12. • Staphylococcus aureus and Streptococcus pneumoniae are the most
common gram-positive isolates, whereas Escherichia coli, klebsiella
species, and Pseudomonas aeruginosa predominate among gram-
negative isolates
13. • Risk factors for severe sepsis are related both to a patient’s
predisposition for infection and to the likelihood of acute organ
dysfunction if infection develops
• Chronic diseases (e.g., the acquired immunodeficiency syndrome,
chronic obstructive pulmonary disease, and many cancers) and the
use of immunosuppressive agents
• Higher in infants and elderly persons than in other age groups, higher
in males than in females, and higher in blacks than in whites
14. Clinical Features
• Highly variable
• Depends on
the initial site of infection,
the causative organism,
the pattern of acute organ dysfunction,
the underlying health status of the patient
the interval before initiation of treatment
15. • Acute organ dysfunction most commonly affects the respiratory and
cardiovascular systems
• Respiratory compromise is classically manifested as the acute
respiratory distress syndrome (ARDS)
• Defined as hypoxemia with bilateral infiltrates of noncardiac origin
• Cardiovascular compromise is manifested primarily as hypotension or
an elevated serum lactate level
• After adequate volume expansion, hypotension frequently persists,
requiring the use of vasopressors, and myocardial dysfunction may
occur
16. • Central nervous system dysfunction, critical illness polyneuropathy
and myopathy, acute kidney injury, paralytic ileus, elevated
aminotransferase levels, altered glycemic control, thrombocytopenia
and disseminated intravascular coagulation, adrenal dysfunction, and
the euthyroid sick syndrome are all common
17.
18. Pathophysiology
HOST RESPONSE
• Infection triggers a much more complex, variable, and prolonged host
response
• Both proinflammatory and antiinflammatory mechanisms can
contribute to clearance of infection and tissue recovery on the one
hand and organ injury and secondary infections on the other
• Specific response in any patient depends on the causative pathogen
(load and virulence) and the host (genetic characteristics and
coexisting illnesses)
19. • Proinflammatory reactions (directed at eliminating invading
pathogens) are thought to be responsible for collateral tissue damage
in severe sepsis
• Antiinflammatory responses (important for limiting local and systemic
tissue injury) are implicated in the enhanced susceptibility to
secondary infections
20.
21. Innate Immunity
• Pathogens activate immune cells through an interaction with pattern-
recognition receptors
• Four main classes — toll-like receptors, C-type lectin receptors,
retinoic acid inducible gene 1–like receptors, and nucleotide-binding
oligomerization domain–like receptors
• Receptors recognize structures that are conserved among microbial
species, so-called pathogen-associated molecular patterns, resulting
in the up-regulation of inflammatory gene transcription and initiation
of innate immunity
22. Coagulation Abnormalities
• Invariably associated with altered coagulation, frequently leading to
disseminated intravascular coagulation
• Excess fibrin deposition is driven by
coagulation through the action of tissue factor, a transmembrane
glycoprotein expressed by various cell types
impaired anticoagulant mechanisms, including the protein C
system and antithrombin;
compromised fibrin removal owing to depression of the
fibrinolytic system
23. • Protease-activated receptors (PARs) form the molecular link between
coagulation and inflammation
• PAR1 in particular is implicated in sepsis.
• Exerts cytoprotective effects when stimulated by activated protein C
or low-dose thrombin but exerts disruptive effects on endothelial-cell
barrier function when activated by high-dose thrombin
24. Antiinflammatory Mechanisms and
Immunosuppression
• Immune system harbors humoral, cellular, and neural mechanisms
that attenuate the potentially harmful effects of the proinflammatory
response
• Phagocytes can switch to an antiinflammatory phenotype that
promotes tissue repair
• Regulatory T cells and myeloid derived suppressor cells further reduce
inflammation
25. • Neural mechanisms can inhibit inflammation
• Neuroinflammatory reflex, sensory input is relayed through the
afferent vagus nerve to the brain stem, from which the efferent vagus
nerve activates the splenic nerve in the celiac plexus
• Results in norepinephrine release in the spleen and acetylcholine
secretion by a subset of CD4+ T cells
• Acetylcholine release targets α7 cholinergic receptors on
macrophages, suppressing the release of proinflammatory cytokines
26. • Spleen, the lungs also showed evidence of immunosuppression; both
organs had enhanced expression of ligands for T-cell inhibitory
receptors on parenchymal cells
• Enhanced apoptosis, especially of B cells, CD4+ T cells, and follicular
dendritic cells, has been implicated in sepsis-associated
immunosuppression and death
27. Organ Dysfunction
• Impaired tissue oxygenation plays a key role
• Several factors — including hypotension, reduced red-cell
deformability, and microvascular thrombosis — contribute to
diminished oxygen delivery in septic shock
• Inflammation can cause dysfunction of the vascular endothelium,
accompanied by cell death and loss of barrier integrity, giving rise to
subcutaneous and body-cavity edema
• Mitochondrial damage caused by oxidative stress and other
mechanisms impairs cellular oxygen use
28. • Injured mitochondria release alarmins into the extracellular
environment, including mitochondrial DNA and formyl peptides,
which can activate neutrophils and cause further tissue injury
29.
30.
31. Treatment
• The Surviving Sepsis Campaign, an international consortium of
professional societies involved in critical care, treatment of infectious
diseases, and emergency medicine, recently issued the third iteration
of clinical guidelines for the management of severe sepsis and septic
shock
• The most important elements of the guidelines are organized into two
“bundles” of care
• An initial management bundle to be accomplished within 6 hours
after the patient’s presentation and a management bundle to be
accomplished in the ICU
32. • Implementation of the bundles is associated with an improved
outcome
• Principles of the initial management bundle are to provide
cardiorespiratory resuscitation and mitigate the immediate threats of
uncontrolled infection
• Resuscitation requires the use of intravenous fluids and vasopressors,
with oxygen therapy and mechanical ventilation provided as
necessary
33. • a standardized approach has been advocated to ensure prompt,
effective management
• Initial management of infection requires forming a probable
diagnosis, obtaining cultures, and initiating appropriate and timely
empirical antimicrobial therapy and source control (i.e., draining pus,
if appropriate)
• The choice of empirical therapy depends on the suspected site of
infection, the setting in which the infection developed (i.e., home,
nursing home, or hospital), medical history, and local microbial-
susceptibility patterns
34. • Inappropriate or delayed antibiotic treatment is associated with
increased mortality.
• Current guidelines recommend combination antimicrobial therapy
only for neutropenic sepsis and sepsis caused by pseudomonas
species
• Empirical antifungal therapy should be used only in patients at high
risk for invasive candidiasis
35. • After the first 6 hours, attention focuses on monitoring and support
of organ function, avoidance of complications, and de-escalation of
care when possible
• De-escalation of initial broad spectrum therapy may prevent the
emergence of resistant organisms, minimize the risk of drug toxicity,
and reduce costs
• Only immunomodulatory therapy that is currently advocated is a
short course of hydrocortisone (200 to 300 mg per day for up to 7
days or until vasopressor support is no longer required)
36. Search for new therapies
RECENT FAILURES
• One of the great disappointments during the past 30 years has been
the failure to convert advances in our understanding of the
underlying biologic features of sepsis into effective new therapies
• The specific agents can be divided into those designed to interrupt
the initial cytokine cascade (e.g., antilipopolysaccharide or anti–
proinflammatory cytokine strategies) and those designed to interfere
with dysregulated coagulation (e.g., antithrombin or activated protein
C
37. • The only new agent that gained regulatory approval was activated
protein C
• All other strategies thus far have not shown efficacy
• with broader immunomodulatory effects, glucocorticoids have
received the most attention
• Intravenous immune globulin is also associated with a potential
benefit
• studies suggesting that the use of statins reduces the incidence or
improves the outcome of sepsis and severe infection,64 such findings
have not been confirmed
38.
39.
40. Conclusions
• Severe sepsis and septic shock represent one of the oldest and most
pressing problems in medicine
• With advances in intensive care, increased awareness, and
dissemination of evidence-based guidelines, clinicians have taken
large strides in reducing the risk of imminent death associated with
sepsis
• Strategies are also needed to reach the many millions of patients with
sepsis who are far from modern intensive care
• To further improve the outcome of patients with sepsis through the
development of new therapeutic agents, newer, smarter approaches
to clinical trial design and execution are essentia
41. • These updated definitions and clinical criteria should replace previous
definitions, offer greater consistency for epidemiologic studies and
clinical trials, and facilitate earlier recognition and more timely
management of patients with sepsis or at risk of developing sepsis
Editor's Notes
atients who met two or more of these criteria fulfilled the definition of SIRS, and Sepsis-1 was defined as infection or suspected infection leading to the onset of SIRS