Sepsis Flashcards
What is the veterinary definition of sepsis
Systemic inflammatory response to infection
SIRS+ Infection
Abnormal Temp, HR, tachypenia, or Abnormal WBCC
Dogs 2/4, Cats 3/4
What is the veterinary definition of severe sepsis
Sepsis with 1 or more organ dysfunction
No consensus statment
What is the veterinary definition of septic shock
Hypotension despite normal intravascular volume (pressor dependent)
What is the veterinary definition of MODS
2 or more organ dysfunction with SIRS or SEPSIS
Renal, CV, Resp, Hepatic (Tbili), coagulation, GI, Endothelial (Vasculatitis/edema), laminitis
What is the SEPSIS 3 Definition of Spesis
life threatening organ dysfunction caused by a dysregulated host response to infection
Acute increase of SOFA points and infection
What is the SEPSIS 3 definition of septic shock
underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality
What is not included in SEPSIS 3
Severe sepsis (redundant) SIRS (deemed not useful)
What are the 4 key components of innate immunity
Physical barriers
chemical barriers
Phagocytic cells
blood protiens (cytokines, chemokines)
What are the 5 key features of the innate immunity
Constitutive ( always present) rapid response Limited diversity of receptors No memory Not specific for individual microbial antigens
What are pathogen associated molecular patterns
PAMPs small molecular motifs that recognize non-self
Highly conserved across bacteria/virus as have to be present for survival
What is the gram – and gram + PAMP
Lipopolysacchride – Gram -
Liptoechnoic acid and Peptidoglycan —Gram +
What are the phagocytic cells of the body and how does it work
Macrophages, Neutrophils, NK cells
PAMP binding to pattern recognition receptor causes reshaping of membrane around.
In the cell respiratory burst occurs to have ROS and NO attack organism
What does TLR 4 bind
Gram Neg LPS
What does TLR 2 bind
Gram +
What does TLR 5 bind
Flagelan
What is the major TLR 4 pathway that is important in cell signalling for the PAMP
MYD88 —-> i kappa B kinase —-> NFkappa B
Ultimately Increase in IL6, TNF alpha, and IL1
What are 4 key components of how cytokines function
Pleiotropism – one mediator had multiple functions
Redundancy - Multiple molecules have same outcome
Synergy – Two different on same cell increases effect
Antagonism — IL 10 most important anti-inflammatory
What are three common early pro-inflammatory cytokines
TNF alpha
IL1 Beta
IL-6
Recruit luekocytes to site of infection and activate them to kill
What are the fever inducing cytokines
IL-6 and TNF alpha stimulat hypothalmus to induce fever
What does HMGB-1 do in sepsis
Late pro-inflammatory to amplify inflammatory response
What is the major Anti-inflammatory cytokines
IL 10, TGF beta
How does the innate immunity contribute to sepsis coagulopathy
Increase procoagulatory pathways- trigger expression of TF on epithelial and wBCS
Decrease Reg of anticoagulant by decrease of Protien C and incrase of PAI 1
Activation of arachadonic cascade– phopholiase A2
Endothelial dysfunction- tight junctions become less tight
How does NO induce vasodilation in sepsis
inducible nitric oxide synthase by PAMPs and TNF alpha and IL-1
Leads to vasodilation
What are the most inflammatory compliment cascade
C5a and C3a
How does non infectious SIRS occur
Tissue damage results in damage associated molecular patterns
Heat shock protiens, ATP and DNA
What is the veterinary definition of SIRS
Inflammatory response to an insult that has systemic effects rather than localized at insult.
How does a positive fluid balance at day 3 affect outcome in Sepsis (CCM 2017, 2018)
Decreased survival
Does not mater why negative fluid balance it leads to increased survival
How does balanced fluids versus saline compare in pediatric patients with sepsis
improved survival, decreased AKI, shorter duration of vasoactive medications.
Suspect Cl load as a factor
What are the negative acute phase proteins
Alpha 1 proteinase inhibitor
Albumin
Transferin
CCM 2017 How did fever alter outcome in sepsis
Shorter hospitalization stay and decreased mortality in multivariate analsysis despite them getting better care
What are the benefits of fever
negative feed back on pyrogenic cytokiens, increase immune function, antibiotic activity during fever
CCM 2018, LOV-ED Data How did PaCO2 alter survival in mechanically ventilated septic patients
Increase of 1 mmHg was assocated with a 3% increase in survival
PaCO2 Survivors 44 mmHg
Non survivors 39 mmHg
JVECC 2017 How do platelet indices related to survival in dogs with sepsis
Larger= Increase MPV, more readily activiated
Increase in MPV 3 fold increase in non survivor
JVECC 2019 Which sepsis inflammatory biomarker was increased in dogs with sepsis compared to controls.
HGMB-1
JVECC 2019 Which sepsis inflammatory biomarker was a predictor of mortality
CCL2
JVECC 2018 in evaluating patients with sepsis was was found to increase survival if euthanized patients were excluded
Higher plasma cholesterol
Was not outside of reference range
JVECC 2019 In a review of cats with septic peritonitis what was the improvement with appropriate abx choice
4.4 x more likely to survive
JVECC 2019 In a review of cats with septic peritonitis what was found to decrease survivial
Hypocalcemia
Higher glucose in non survivors (stats not given)
Vet Journal 2017 What is the delta neutrophil index and how is it useful in sepsis
fraction of circulating immature granulocytes in peripheral blood. Machine calculates
Some overlap but was good for identifying sepsis
CCM 2018 How does SAP (glycoprotein) and TPA (serine protease) alter as a predictor of 14 day mortality
decrease SAP lead to death
Increased TPA led to death
CCM 2017 What is Procalcintonin useful for in sepsis
Discontinuation of antibiotic therapy as it it decrases
CCM 2017 MOSES Study: How did a change in procalcitonin alter mortality in sepsis patients
Increased mortality rate if <80% decrease of PCT on day 4
What were the initiation of EGDT in the Rivers study and what was the outcome difference?
SIRS 2/4; BP < 90 after fluid or Lactate > 4 mmlol/L
What was EGDT In the Rivers study
Central catheter CVP 8-12 (500 ml q 30 minutes to reach) MAP < 65 mmHg receives pressors Vasodilators until MAP < 90 mmHg CvO2 < 70% received RBC transfusion til HCT 30%. If still less then dobutamine 28 day mortality 49% standard, 33% EGDT
What was the outcome of the ARISE 2014 trial (location)
Australia, New Zealand
EGDT did not reduce all cause mortality at 90 days
What was the outcome of PROCESS 2014 trial (location)
US
Third group was protocolized standard care
No difference in mortality at 60 days
21% EGDT, 18% PSC, 18% usual
What was the outcome in PROMIS 2015 trial (location)
England
No difference in 90 day mortality
EDGT 29.5%, Usual 29%
What was PRISM and what was the outcome
Meta analysis of promise, arrise, and process
EGDT 24% and Usual 25%
No difference, did not include PSC group
NEJM 2017 in time bundled care what changed the mortality outcome in septic pateints
Each hour to complete 3 hr bundle increased mortality (even in first three hours)
Same increase with antibiotics
CCM 2017 How did time to second dose of antibiotics alter outcome in septic patients
association with the increase length of time for second dose of abx: Increased mortality, length of stay and MV days
CCM 2018 In a time bundled care what was noted despite care being delivered within the time frame set by bundle
Delay of 50 mins for blood cultures led to stat significant mortality increased
3 hr ‘safe’ window not likely true
CCM 2017 What was noted about antibiotic administration in the ED compared to pre ED
Delay in abx treatment in the ED but not pre ED increased in hospital mortality
CCM 2017 In a comparision of previous cohorts of septic patients how many patients were no longer included in the septic shock 3 criteria (~%) and what was the change in mortality in the two groups.
57% of patients did not meet the Sepsis 3 criteria
Sepsis 3 mortalitiy 28.5%
Pts excluded from sepsis 3 14%
CCM 2017 IN a study of time in German with training of staff what led to improved outcomes in septic patients
medical ICU, blood cultures before abx, adequate dose of abx, 1-2 L crystalloid bolus within 6 hrs, > 6 L in first 24 hrs, Less HES
CCM 2017 In a Bayesian approach review of the River’s EGDT and the following larger trials what was noted to improve outcome and what was noted about EGDT effect for the most severe (apache score) patients
Faster ABX, survival reduced 10% for every 1 hr delay
EGDT may harm the most sick as mortality increased for incrased APACHE score
What are 4 factors that synthetic glucocorticoids have versus endogenous
Less MC activity
Less tightly bound to cortisol binding protien in plasma
Undergoes less hepatic metabolism
Higher affinity for GC receptor
JVECC 2017 List 5 effects GCs have on the body
Bronchodilation - increase B2 receptor expression
CNS- cerebral blood flow and lytes concentrations
Enhances vascular response to vascular substances
supppress production of vasodilators
NEJM 2018 What was the outcome of hydrocortisone and fludrocortisone in septic shock administered for 7 days with no taper
Decrease mortality
Decrease vasopressor time, decreased MV, increased hyperglycemia
Define CIRCI
Endocrinological dysfunction in critically ill patients resulting in inadequate cortisol activity for existing severity of illness leading to fluid and vasopressor refractory shock
NEJM 2018 ADRENAL: How did hydrocortisone as a CRI alter outcome in septic patients
No difference in mortality
Faster resolution of shock, and no difference in ventilator days
Which articles showed improvement with steroids, and which did not for septic shock patients
NEJM 2018 Hydrocortisone+ fludrocortisone and French 2002 showed benifit
Adrenal and Corticus no change in mortality
CCM 2017 How did patients receiving oral prednisone prior to developing sepsis/ARDS have increased and decreased risks of
Decreased risk of ARDS
Possible increase in mortality
CCM 2017 How did relative bradycardia alter outcome with septic shock
HR < 80; improved outcome
21% vs. 34 %
NEJM 2017 ATHOS-3 How did the addition of angiotensin II to norepi in vasodilatory shock improvements
Increased BP with reduction of catecholamine dose
Best response in those with doses belwo 0.5 mcg/kg/min
CCM 2017 Which patients should not receive Angiotensin II in a safety review
Worsens asthma and heart disease
CCM 2017 In a review of VASST with the SEPSIS 3 outcomes what was the difference between norepi and vasopression
Vasopressin mortality was less than Norepi in patients with lactate of < 2 mmol/L
The less sick
VASST- What was the out come between Norepi and vasopressin
Norepi and vasopression were equal
Monett CCM 2011 How does Norepi alter the hearts ability to respond
increase right and left ventricular preload
Increase in cardiac index
Lacelet 2007 What is the differences of Norepi + dobutamine versusus Epi
No difference in mortality or ICU stay
VANISH How did Norepi or Vasopression + steroid alter AKI
Neither altered AKI
CCM 2015 In pediatrics what was the outcome of dopamine versus epinephrine on mortality
Dopamine increased mortality and health associated infections
Dopamine was started about 1 hr later than EPI which may have altered outcomes
JVECC 2019 How does the timing/route of nutrition in dogs with septic peritonitis alter outcome
parental nutrition decreased survival
If ate on own decreased LOH
JVECC 2019 In 2 cases out did Esmolol used for
for tachycardia without hypovelmia
Human 2013 study that improved heart rate improved mortality significantly
JVECC 2019 In a study of gastrotomy tubes in sepsis how did they alter outcome
~4 days to eat on own, 2/24 had major complications
~50% complication rate
JVECC 2019 How did peritoneal lavage alter bacterial isolates
Pre 92.5 % positive
Post 87.5% positive
Isolation of MDR decreased by 1/3 post lavage
JAVMA 2017 In cats with sepsis (all causes) what coagulation abnormalities were noted
increase PTT, D-dimers, decreased protien C and antithrombin
JAVMA 2017 What was clinicopathological differences between dogs with sepsis and anaphylaxis
Anaphylaxis: younger, increse in eosinophils, Na Cl, ALT, decrease pH fibrinogen
Sepsis: Increased band neutrophils, glob, alp and decrease gluc
VET Journal 2018 How does calcitril in vitro work for WBC inflammation
shift from pro-inflammatory leukocyte to anti-inflammatory leukocyte
CCM 2018 What is the mortatilty difference when culture – versus culture + septic shock is compared
Survival the same
CCM 2018 How may thiamine administration alter lactate clearance in sepsis
May improve lactate clearance
Alcoholics and females likely to respond
CCM 2018 in pediatric kids in India how did probiotics alter cytokine levels
Decrease in IL-6 and TNF alpha; increase in IL10 and TGF beta
No mortality change
CCM 2017 How does calcium channel blockers alter mortality in Sepsis
decreases if receiving before
NO change for ACe inhibitors, ARBS, or beta blockers
JVECC 2019 Evaluation of host cytokine response what differences were present between Sepsis and SIRS
Not able to discern
JVIM 2019 How are angiopoietin-2 and Vascular endothelial growth factor (VEGF) altered in SIRS or Sepsis
ANG-2 increase in sepsis/SIRS and non survivors
VEGF- higher in sepsis only
JVECC 2017: What leads to an increase in CF DNA in dogs
sepsis and trauma with an ATT> 5
Not sarcomas
JVIM 2011 Is NT-pCNP an indicator of Septic peritonitis and where is it expressed from
No
expressed by vascular endotheilum and macrophages
CCM 2011 How does intestinal decontamination alter gram – bacteria
Oropharynx past of colistin, tobramycin, amphotericin B/NG tube
Decreased Gram - bacteria in gut
NEJM 2011 How did plasminogen activator and DNAse in plerural infections change outcomes
Together reduced surgical needs and had increased drainage,
DNAse as monotherpy had 3x surgical referal
CCM 2009 What is the PIRO models for staging severe sepsis
P- predisposition
I- Insult/infection
R- response
O- organ disfuction
How does lactate increase due to sepsis
Sepsis impares local tissue O2 extraction
How does prolonged decreased BP alter response
may lead to depletion of vasopressor stores, V1 receptors in smooth muscle inhibits NO production
CCM 2011 How does source and infection type location alter mortaltity and how does matter in PIRO
Does not change hospital mortality it is more important to receive the right antibiotics
The I in PIRO is irrelevant
What receptors and effects does dobutamine have
B1 ++; B2 +; Alpha +
Increases contractility, HR, CO
Decreases vasomotor tone
Variable BP
What receptors and effects does Dopamine have
B1 ++; B2 +; Alpha ++
Increase contractility, HR, Vasomotor tone, and BP
Variable effect of CO
What receptors and effect does epinephrine have
B1 +++; B2 +++; Alpha +++
Increases contractility, HR, CO, vasomotor tone, and BP
What receptors and effect does Norepi have
B1 +; B2 - ; Alpha +++
Increases contractility, vasomotor tone, and BP
Variable effects on HR and CO
What is the MOA of phylephrine
Sympathomemtic
What receptors and effect does Phylephrine have
B1 - ; B2 - ; Alpha +++
Increase in vasomotor tone and BP
Decrease in CO and HR
No effect on contractility
What is the MOA of vasopressin in BP
V1 receptors on vascular smooth muscle to cause vasoconstriction through the IP3 signal transduction pathway
What receptors and effect does vasopressin have
B1 – ; B2 - ; Alpha -
Increase vasomotor tone and BP
Decrease in HR and CO
No effect on contractility
What does IL-8 do
Rolling of WBC before diapodesis
What do Alpha adergnic agonists alter BP/Heart
Increase vasculomotor tone, but may decrease regional blood flow (splanchnic, renal)
