Sepsis 2db2f83a91154dc588f8473142c19d3c

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Sepsis 1
📒
Sepsis 
Dates
Type 📒 Lesson
Topic
Sepsis: dysregulated host response to infection that leads to acute organ dysfunction. 
This definition distinguishes sepsis from uncomplicated infection that does not lead to 
organ dysfunction, a poor course, or death
💡 Sepsis is commonly associated with coagulation disorders
Septic shock: subset of sepsis cases in which underlying circulatory and 
cellular/metabolic abnormalities are profound enough to substantially increase mortality 
risk.
Many patients develop acute organ dysfunction in response to infection but without a 
measurable inflammatory excess (i.e., without the systemic inflammatory response 
syndrome [SIRS]).
Sepsis-3 clinical criteria: (1) a suspected infection and (2) acute organ dysfunction, 
defined as an increase by two or more points from baseline (if known) on the sequential 
(or sepsisrelated) organ failure assessment (SOFA) score
@February 23, 2021
Sepsis 2
Can arise from both community-acquired and hospital-acquired infections
💡 Of these infections, pneumonia is the most common source, accounting for 
about half of cases; next most common are intraabdominal and genitourinary 
infections
Staphylococcus aureus and Streptococcus pneumoniae are the most common gram-
positive isolates, while Escherichia coli, Klebsiella species, and Pseudomonas 
aeruginosa are the most common gramnegative isolates.
The clinical features of sepsis were considered the result of an excessive inflammatory 
host response (SIRS)
Specific response of each patient depends on the pathogen (load and virulence) and 
the host (genetic composition and comorbidity), with different responses at local and 
systemic levels.
proinflammatory reactions (directed at eliminating pathogens) are responsible for 
“collateral” tissue damage in sepsis
antiinflammatory responses are implicated in the enhanced susceptibility to secondary 
infections
Select mechanisms implicated in the pathogenesis of sepsis-induced organ and 
cellular dysfunction
Sepsis 3
1. The inflammatory response is typically initiated by an interaction between 
pathogen-associated molecular patterns (PAMPs) expressed by pathogens and 
pattern recognition receptors expressed by innate immune cells on the cell 
surface (Toll-like receptors [TLRs] and C-type lectin receptors [CLRs]), in the 
endosome (TLRs), or in the cytoplasm (retinoic acid inducible gene 1–like 
receptors and nucleotide-binding oligomerization domain–like receptors [NLRs])
2. Tissue damage and necrotic cell death lead to release of damage-associated 
molecular patterns (DAMPs) such as uric acid, high-mobility group protein B1, 
S100 proteins, and extracellular RNA, DNA, and histones
3. These molecules promote the activation of leukocytes, leading to greater 
endothelial dysfunction, expression of intercellular adhesion molecule (ICAM) 
and vascular cell adhesion molecule 1 (VCAM-1) on the activated endothelium, 
coagulation activation, and complement activation.
4. This cascade is compounded by macrovascular changes such as vasodilation 
and hypotension, which are exacerbated by greater endothelial leak tissue 
edema, and relative intravascular hypovolemia. Subsequent alterations in 
cellular bioenergetics lead to greater glycolysis (e.g., lactate production), 
mitochondrial injury, release of reactive oxygen species, and greater organ 
dysfunction
Coagulation abnormalities 
Frequently leads to disseminated intravascular coagulation
Abnormalities in coagulation are thought to isolate invading microorganisms 
and/or to prevent the spread of infection and inflammation to other tissues and 
organs
Coagulation (and other) proteases further enhance inflammation via protease-
activated receptors. In infections with endothelial predominance (e.g., 
meningococcemia), these mechanisms can be common and deadly.
Organ Dysfunction
💡 mechanisms that underlie organ failure in sepsis are only partially known
Sepsis 4
Impaired tissue oxygenation plays a big role 
Hypotension, reduced red-cell deformability, and microvascular thrombosis
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
Uncontrolled release of NO that causes vasomotor collapse 
Mitochondrial damage due to oxidative stress and other mechanisms impairs 
cellular oxygen utilization
Anti-inflamatory mechanisms 
Phagocytes can switch to an anti-inflammatory phenotype that promotes tissue 
repair, while regulatory T cells and myeloid-derived suppressor cells further 
reduce inflammation
neuroinflammatory reflex may also contribute: sensory input is relayed through 
the afferent vagus nerve to the brainstem, from which the efferent vagus nerve 
activates the splenic nerve in the celiac plexus, with consequent norepinephrine 
release in the spleen and acetylcholine secretion by a subset of CD4+ T cells. 
The acetylcholine release targets α7 cholinergic receptors on macrophages, 
reducing proinflammatory cytokine release
💡 Patients who survive early sepsis but remain dependent on intensive care 
occasionally demonstrate evidence of a suppressed immune system.
Clinical Manifestations 
Quite variable and depoend on the initial site of infection, the offending pathogen, 
pattern of acute organ dysfunction, the underlying health of the patient, and the delay 
before initiation of treatment.
Cardiorespiratory Failure
Classically manifests as acute respiratory distress syndrome (ARDS), defined 
as hypoxemia and bilateral infiltrates of noncardiac origin that arise within 7 
days of the suspected infection. ARDS can be classified by Berlin criteria as 
Sepsis 5
mild (PaO2/FiO2, 201–300 mmHg), moderate (101– 200 mmHg), or severe 
(≤100 mmHg)
Cardiovascular compromise typically presents as hypotension
The cause can be frank hypovolemia, maldistribution of blood flow and 
intravascular volume due to diffuse capillary leakage, reduced systemic 
vascular resistance, or depressed myocardial function. After adequate volume 
expansion, hypotension frequently persists, requiring the use of vasopressors. 
In early shock, when volume status is reduced, systemic vascular resistance 
may be quite high with low cardiac output; after volume repletion, however, this 
picture may rapidly change to low systemic vascular resistance and high 
cardiac output.
Kidney Injury
>50% of septic patients, increasing the risk of in-hospital death by six- to 
eightfold
AKI manifests as oliguria, azotemia, and rising serum creatinine levels and 
frequently requires dialysis.
AKI may occur in up to 25% of patients in the absence of overt hypotension. 
Current mechanistic work suggests that a combination of diffuse 
microcirculatory blood-flow abnormalities, inflammation, and cellular 
bioenergetic responses to injury contribute to sepsis-induced AKI beyond just 
organ ischemia
Neurologic Complications
Typically presents as coma or delirium
Sepsis-associated delirium is considered a diffuse cerebral dysfunction caused 
by the inflammatory response to infection without evidence of a primary central 
nervous system infection
Critical-illness polyneuropathy and myopathy are also common, especially in 
patients with a prolonged course.
For survivors of sepsis, neurologic complications can be severe, many of these 
limitations persist for up to 8 years
Additional 
Sepsis 6
Ileus, elevated aminotransferase levels, altered glycemic control, 
thrombocytopenia and disseminated intravascular coagulation, adrenal 
dysfunction, and sick euthyroid syndrome
Adrenal dysfunction in sepsis is widely studied and is thought to be related 
more to reversible dysfunction of the hypothalamic–pituitary axis or tissue 
glucocorticoid resistance than to direct damage to the adrenal gland
Diagnosis
Laboratory and Physiologic Findings
Only tachycardia (heart rate, >90 beats per min) was present in >50% of 
encounters; the most common accompanying abnormalities weretachypnea 
(respiratory rate, >20 breaths per min), hypotension (systolic blood pressure, 
≤100 mmHg), and hypoxia (SaO2, ≤90%). Leukocytosis (WBC count, >12,000/
μL) was present in fewer than one-third of patients and leukopenia (WBC count, 
<4000/μL) in fewer than 5%
If measured, metabolic acidosis with anion gap may be detected, as respiratory 
muscle fatigue occurs in sepsis-associated respiratory failure
Less common findings include serum hypoalbuminemia, troponin elevation, 
hypoglycemia, and hypofibrinogenemia.
Treatment
Prompt diagnosis
The initial management of infection requires several steps: forming a probable 
diagnosis, obtaining samples for culture, initiating empirical antimicrobial therapy, and 
achieving source control
More than 30% of patients with severe sepsis require source control, mainly for 
abdominal, urinary, and soft-tissue infections
Antibiotic delays may be deadly. For every 1-h delay among patients with sepsis, a 3–
7% increase in the odds of in-hospital death is reported
Empirical antifungal therapy should be administered only to septic patients at high risk 
for invasive candidiasis
2 bundles of care
Sepsis 7
a) Initial management: (1) early administration of appropriate broad spectrum 
antibiotics, (2) collection of blood for culture before antibiotic administration, and (3) 
measurement of serum lactate levels
b) Management bundle: (1) an intravenous fluid bolus, (2) treatment with 
vasopressors for persistent hypotension or shock, and (3) remeasurement of serum 
lactate levels. Implementation of these two bundles has been associated with 
improved outcome in large multinational studies.
💡 El concepto del síndrome de respuesta inflamatoria sistémica (SRIS), 
definido por ciertas anormalidades de los signos vitales y resultados de 
laboratorio, durante mucho tiempo ha sido utilizado para identificar la sepsis 
temprana. Sin embargo, se ha demostrado que los criterios de SIRS carecen 
de sensibilidad y especificidad para el mayor riesgo de mortalidad, que es la 
principal consideración para el uso de este modelo conceptual. La falta de 
especificidad puede deberse a que la respuesta delSRIS es a menudo 
adaptativa más que patológica
Lo visto en clase 
SIRS
Síndrome de respuesta inflamatoria sistémica 
Proceso de inflamación disregulada con origen a determinar y es potencialmente mortal 
(10% de mortalidad con un dx de SIRS) 
SIRS no es sepsis, sin embargo toda sepsis es un SIRS 
Mínimo 2 - 4 signos de SIRS
Fiebre o hipotermia
Taquicardia
Taquipnea
Hipocapnia 
Leucocitosis o leucopenia 
Sepsis 8
💡 IL-II y IL-10 
Sepsis grave: sepsis + disfunción orgánica originada por hipotensioón o hipoperfusión 
dependiente de la sepsis que responde a líquidos 
1. SIRS
2. Sepsis 
3. Sepsis grave (ya no sirve, salu2)
4. Choque séptico (40% - 70% de mortalidad) 
Choque séptico: sin respuesta a líquidos ni aminas, debido a que el endotelio no sirve 
del todo bien con uniones separadas, por lo tanto el líquido se extravasa y solo lo estás 
extravasando 
Bacteremia: Agente infeccioso identificado sin cuadro clínico de sepsis, una bacteria o 
agente infeccioso pasa a torrente sanguíneo 
qSOFA: Escala normalmente usada en urgencias y es totalmente visual, 2 o más 
puntos + un foco de infección obliga a pedir laboratoriales porque el paciente entra a 
sepsis 
1. Alteración del nivel de consciencia, glasgow menor o igual a 13
2. Tensión arterial sistólica menor o igual a 100 mmHg 
3. Frecuencia respiratoria mayor o igual a 22 rpm 
Sepsis 9
Laboratoriales:
VSG
PCR
Gasometría 
Lactato (mayor a 2 mmol es mal pronóstico) 
QS creatinina 
PFH
Sepsis 10
3= me voy, corteza cerebral dañada 
2= me fui
Escala SOFA
Disfunción orgánica causada por una respuesta anómala del huésped a la infección 
que supone una amenaza para la supervivencia 
Sepsis 11
Sequential Organ Failure Assesment 
Variación mayor o igual a 2 puntos 
Índice de Kirby: La división entre presión arterial de oxígeno entre fracción inhalada de 
oxígeno (21% es la de aire ambiente)
Presión Arterial Media: (P. Sistólica - P. Diastólica)/3 + P. Diastólica 
2 puntos o más nos hacen alusión a una falla orgánica múltiple 
Criterios de SIRS
A partir del 2 el paciente ya necesita vasopresores, principalmente se usa noradrenalina, después 
dopamina 
Sepsis 12
Factores de riesgo
ICU - 50% de riesgo
>65 años 
Neumonía
Diabetes Mellitus, obesidad
Bacteremia 
Inmunocompromiso 
Cáncer
Hospitalizaciones 
💡 VIH, Ancianos y Neonatos son los 3 grupos especiales a considerar debido a 
sus manejos 
Fisiopatología 
Sepsis 13
Manifestaciones clinicas
SIRS
Síndromes específicos de la fuente 
Distermia 
Cianosis/rubicundez
Estado mental 
Sepsis 14
Disminución de motilidad intestinal 
Más leucos 
Hiperglicemia 
PCR
Hipoxemia 
Oliguria 
Tiempos alargados de coagulación
Cr, BT, Plq 
Lactato
PCT
Sepsis
Hematocrito representa 3 veces la hemoglobina 
Hiponatremia secundaria a hiperglucemia, por cada 100 de glucosa se disminuye 2 de 
Na 
Si un paciente está deshidratado suelen aumentar los electrolitos 
Infección: invasión y multiplicación de agentes patógenos en tejidos o cavidades 
normalmente sanos 
Sepsis: disfunción orgánica que amenaza la vida causada por una respuesta 
desregulada del cuerpo a una infección
Sepsis 15
Cáncer hematógeno aumenta la probabilidad de sepsis 
SIRS es menos específico que qSOFA
Sensibilidad: capacidad de una prueba dx para demostrar a los verdaderos enfermos 
Especificidad: capacidad de una prueba dx para demsotrar a los verdaderos sanos 
Todo lo que tenga sensibilidad menor a 50% no sirve de mucho porque es echarse un 
volado 
Sepsis 16
Sepsis 17
Sepsis 18
Sepsis 19