Sepsis/SIRS/MODS

Question 1

Antipyretic Therapy in Critically Ill Septic Patients:
A Systematic Review and Meta-Analysis
Drewry et al 2016 Critical Care medicine

Answer 1

Antipyretic treatment does not significantly improve
28-day/hospital mortality in adult patients with sepsis.
suspected benefits:
- decreased metabolic rate –> decreases oxygen consumption, cardioprotective?
- disadvantage –> higher temp inhibits microorganism growth, slows viral replication, and augments antibiotic efficacy

Question 2

what are the benefits of elevated temperature in sepsis? Drewry et al 2016 CCM

Answer 2

high temperature inhibits microorganism growth, slows viral replication and augments antibiotic efficacy

Question 3

what are the negative effects of elevated temperature in sepsis? Drewry et al 2016 CCM

Answer 3

raises the metabolic rate, increases oxygen consumption, and can adversely affect cardiac function

Question 4

A feasibility study investigating the utility of a point‐of‐care rapid immunoassay for detecting septic peritoneal effusion in dogs,
Human et al 2021, JVECC

Answer 4

• RIA testing was similarly sensitive in identifying septic peritonitis compared to cytology and bacterial culture but was not very specific or accurate. As a stand-alone test, RIA commonly had false-positive test results, making it unreliable in identifying septic peritonitis
• Cytology had the best overall predictive values and accuracy for diagnosing septic peritonitis (PPV 100%, NPV 97.9%, and accuracy 98%) compared to RIA and bacterial culture

Question 5

What is the most accurate diagnostic modality to identify septic peritonitis in dogs? Human et al 2021, JVECC

Answer 5

cytology of abdominal fluid (performed by clinical pathologist)

Question 6

what survival rate for septic peritonitis are reported in current literature? Human et al 2021, JVECC

Answer 6

Recent veterinary literature reports survival
rates that vary from 36.4% to 89%

Question 7

The ProCESS Investigators - 2014

Answer 7

protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.

Question 8

Biomarker Guided Diagnosis of Septic Peritonitis in Dogs, Martiny et al, 2019, Vet Front

Answer 8

the marker that best differentiated SP
from NSA was the effusion lactate concentration

Question 9

Which type of lactate do bacteria mostly produce and which type do lactate meters usually measure?
Martiny et al, 2019, Vet Front

Answer 9

bacteria produce predominantly D-lactate isomers, lactate meters usually only measure L-lactate isomers (so potentially effusion lactate in SP even higher, or measured lactate from leukocyte cell metabolism

Question 10

What is the “NO-generating loop”? Troia et al, 2020, Vet Front

Answer 10

methemoglobin activates endothelial cells by stimulation of inflammatory cytokines, leading to further iNOS expression, thus closing a “NO-generating loop”

Question 11

How are NO and methemoglobin produced during sepsis?, Troia et al, 2020, Vet Front

Answer 11

Inflammatory cytokines and bacterial lipopolysaccharides in sepsis activate endothelial cells
and stimulate the production of an inducible form of nitric oxide synthase (iNOS). As a result, nitric oxide
(NO) is produced, contributing to vasodilation and distributive shock. NO acts as a cytostatic and cytotoxic molecule against microorganisms and host cells, and interacts with hemoglobin forming methemoglobin and nitrates.

Question 12

How does NO in sepsis exacerbate signs of septic shock/ cause septic shock?, Troia et al, 2020, Vet Front

Answer 12

No is contributing to vasodilation and distributive shock. NO acts as a cytostatic and cytotoxic molecule against microorganisms and host cells

Question 13

What are the clinical signs of methemoglobinemia? Troia et al, 2020, Vet Front

Answer 13

Methemoglobin is unable to bind oxygen, and
its overproduction leads to impaired aerobic cellular metabolism, hypoxia, chocolate-brown colored blood and mucous membranes, cyanosis, and death

Question 14

How do you measure methemoglobin and what is its reference interval? Troia et al, 2020, Vet Front

Answer 14

with a co-oximeter
cited references: normal methemoglobin concentrations are usually kept <0.5–3% of total hemoglobin in humans and dogs
reference interval used for study: < 2.2%

Question 15

What toxins are known to cause methemoglobinemia in small animal patients? Troia et al, 2020, Vet Front

Answer 15

toxicants or chemicals able to induce hemoglobin oxidation (e.g., aniline, sulfonamides, nitrates, acetaminophen, hydroxicarbamide, tetracaine)

Question 16

what three subgroups of septic shock are characterized in humans and small animals? Troia et al, 2021, Front Vet

Answer 16

• vasoplegic shock
• cryptic shock
• dysoxic shock
  *

Question 17

Classification of Septic Shock Phenotypes Based on the Presence of Hypotension and Hyperlactatemia in Cats, Troia et al, 2021, Front Vet

Answer 17

• Cats with dysoxic shock had significantly higher APPLEfast and APPLEfull scores compared to vasoplegic and cryptic shock.
• Mortality rates were not significantly different among cryptic (57%), dysoxic (65%) and vasoplegic shock (91%)
• MODS occurrence was significantly lower in cats with cryptic shock (57%) compared to patients affected by dysoxic (94%) and vasoplegic (100%) shock.
• Septic shock in cats defines a subset of patients with greater disease severity, organ dysfunction and mortality compared to uncomplicated sepsis

Question 18

What is dysoxic shock (subgroup septic shock)? Troia et al, 2021, Front Vet

Answer 18

patients with hyperlactatemia and hypotension requiring vasopressors

Question 19

What is cryptic shock (subgroup septic shock)?

Answer 19

patients with occult hypotension, characterized by hyperlactatemia without hypotension

Question 20

What is vasoplegic shock (subgroup septic shock)?

Answer 20

patients with hypotension requiring prolonged vasopressor therapy but without developing hyperlactatemia

Question 21

Sepsi-3 definition of “Septic Shock” Troia et al, 2021, Front Vet

Answer 21

According to the Third International Consensus Definition Sepsis-3:

septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone.

Question 22

What is the definition of septic shock in small animals? Troia et al, 2021, Front Vet

Answer 22

in small animals, septic shock is defined as a state of fluid-refractory hypotension requiring vasopressor support

Question 23

How did mortality rates and length of hospitalization differ between cats in cryptic, dysoxic, or vasoplegic septic shock? Troia et al, 2021, Front Vet Sci

Answer 23

they were not significantly different, but mortality trended upwards from cryptic (57%), to dysoxic (65%), and to vasoplegic (91%) shock

Question 24

How did the occurence of MODS differ between cats with either cryptic, dysoxic, or vasoplegic septic shock?

Troia et al, 2021, Front Vet Sci

Answer 24

patients with cryptic (57%) shock were significantly less likely to develop MODS than dysoxic and vasoplegic shock patients

Question 25

How did risk of mortality and occurence of MODS differ between cats in septic shock vs uncomplicated sepsis and 2/4 SIRS criteria vs 0/4 SIRS criteria?

Troia et al, 2021, Front Vet Sci

Answer 25

• Cats with septic shock had a significantly higher frequency of MODS (91% vs. 28%, P < 0.0001) and a significantly higher mortality rate (73% vs. 43%, P = 0.0085) than cats with uncomplicated sepsis.
• patients presenting with at least 2/4 SIRS criteria had significantly higher frequency of MODS (76% vs. 24%, P = 0.022) and mortality (67% vs. 36%, P = 0.01) compared to those not fulfilling the feline SIRS criteria

Question 26

What parameters were associated with nonsurvival in septic shock in Troia et al, 2021, Front Vet Sci?

Answer 26

Non-survivors had significantly lower

• body temperature
• BCS
• hematocrit
• lymphocyte count
• serum albumin compared to survivors.

Non-survivors had significantly higher:

• circulating methemoglobin
• serum bilirubin
• serum urea
• activated partial thromboplastin time
• APPLEfast score

Question 27

What is the prognostic utility of lactate concentration in cats according to the current literature? Troia et al, 2021 Front Vet Sci

Answer 27

The prognostic utility of lactate concentrations in cats appears unclear according to the available literature

Question 28

What is SAA marker? Troia et al, 2021, Front Vet Sci

Answer 28

Serum amyloid A (SAA), a major feline acute phase protein, shown to be an excellent marker for systemic inflammation in cats

Question 29

What are the 4 cateogories for SIRS identification and what is the cutoff to identify SIRS? Kleinbart et al, 2017, JAVMA

Answer 29

It is generally accepted that a diagnosis of SIRS can be made on the basis of manifestation of ≥ 2 of the following 4 conditions:

• body temperature outside of the RI;
• heart rate outside of the RI;
• tachypnea or hyperventilation, indicated by decreased Paco2;
• and leukocytosis, leukopenia, or band neutrophil fraction > 5%

Question 30

what hemostatis parameters were signifcantly altered in spetic cats in Kleibart et al, 2017, JAVMA?

Answer 30

• increased aPTT time
• decreased protein C activity
• increased D-dimer concentration

Question 31

nonregenerative anemia was relatively common (29%) in septic cats in Kleibart et al, 2017, JAVMA. What possible underlying causes are suggested?

Answer 31

mostly likely due to inflammation, possibly including

• low-grade hemolysis,
• oxidative damage,
• inflammation-associated disruption of iron metabolism,
• decreased RBC life span,
• inadequate erythropoietin production,
• and insufficient bone marrow response to erythropoietin

Question 32

metarubricytosis was relatively common (35%) in septic cats in Kleibart et al, 2017, JAVMA. What is the proposed underlying cause for metarubricytosis in sepsis?

Answer 32

metarubricytosis (= nucleated RBCs) might have been pathological and possibly attributable to blood-bone marrow barrier disruption, which can be associated with:

• inflammation
• infection
• necrosis
• hypoxia
• thrombosis
• infarction
• hyperthermia

Question 33

what electrolyte derangements were common in septic cats in Kleinbart et al, 2017, JAVMA?

Answer 33

• hyponatremia, accompanied by hypochloremia
• hypocalcemia

Question 34

hypalbuminemia (47%) and hypoproteinemia (73%) was common in septic cats in Kleinbart et al, 2017, JAVMA. What underlying causes does the author propose?

Answer 34

Hypoalbuminemia was attributed to:

• increased loss,
• malnutrition,
• increased capillary permeability and leakage,
• hepatic dysfunction,
• decreased production caused by the acute phase response,
• loss into effusions,
• antidiuretic hormone activation-related dilutional effects

Question 35

hyperbilirubinemia was shown in 55% of septic cats in Kleibart et al, 2017, JAVMA. What is the proposed underlying cause and how does this differ from studies on humans and dogs?

Answer 35

• low-grade hemolysis might be the cause for the hyperbilirubinemia in these septic cats
• sepsis-induced cholestasis has been described in dogs and humans –> low ALP and GGT in this population of cats was not indicative of cholestasis
• hepatpcellular damage also less likely because ALT was typically within RI in this population

Question 36

high serum CK and AST was common in cats in Kleinbart et al, 2017, JAVMA. What is the proposed underlying cause?

Answer 36

muscle damage

• possibly due to muscle ischemia, hypotension, shock, and hypoxia leading to rhabdomyolysis-like states in some cats,
• whereas in cats with bite wounds and cellulitis, direct muscle damage, trauma, and infection were likely more important cause

Question 37

Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis, Kleinbart et al, 2017, JAVMA

Answer 37

• novel findings included metarubricytosis, hypertriglyceridemia, high circulating muscle enzyme activity
• confirmed: hemostasis derangements, hypoalbuminemia/hypoproteinemia, hyponatremia, hypochloremia, hypocalcemia, hyperbilirubinemia
• no clinicopathologic findings were significantly associated with deat

Question 38

Comparison of continuous arterial pressure waveform analysis with the lithium dilution technique to monitor cardiac output in conscious dogs with systemic inflammatory response syndrome, Duffy et al, 2009, AJVR

Answer 38

there is poor agreement between CO measurements via pulseCO and LiDCO methods, indicating that PulseCO method does not accurately track changes in CO in conscious critically ill dogs over time

Question 39

What is the Cardiac Index, and how is it superior to CO? Duffy et al, 2009, AJVR

Answer 39

Cardiac index is the CO indexed to BSA (body surface area) and is a more accurate value for comparing CO in animals of varying sizes.

Question 40

methematically the relationship between blood flow and arterial pressure requires reference to … ? Duffy et al, 2009, AJVR

Answer 40

… vascular resistance

Question 41

How does LiDCO work for cardiac output measurements?Duffy et al, 2009, AJVR

Answer 41

uses indicator-dilution technique to define CO, with lithium chloride used as the indicator

Question 42

How does pulseCO work for cardiac output measurements? Duffy et al, 2009, AJVR

Answer 42

The PulseCOb is a beat-to-beat CO monitor that calculates SV from the arterial pressure waveform by use of an autocorrelation algorithm

Question 43

List at least 3 possible methods of measuring CO in small animals

Duffy et al, 2009, AJVR

Answer 43

• thermodilution
• LiDCO
• pulseCO
• magnetic flowmetry
• indocyanine dilution
• partial carbon dioxide rebreathing
• transesophageal or transthoracic continuous wave Doppler ultrasonography
• thoracic bioimpedance

Question 44

Where are the alpha-adrenergic receptors located?

Silverstein & Beer, 2015, JVECC

Answer 44

• pre- and postsynaptic regions of sympathetic nerve endings on smooth muscles
• myocardium (but less than smooth muscles)

Question 45

what is the effect of stimulation of alpha-adrenergic receptors?

Silverstein and Beer, 2015, JVECC

Answer 45

stimulation vascular muscles –> vasoconstriction and increased blood pressure

stimulation myocardium –> slower onset, prolonged increased inotropy

Question 46

Where are the beta-adrenergic receptors located?

Silverstein and Beer, 2015, JVECC

Answer 46

• myocardium
• peripheral vascular and bronchial smooth muscles

Question 47

What effects does stimulation of the beta-adrenergic receptors have?

Silverstein and Beer, 2015, JVECC

Answer 47

• stimulation myocardium –> positive inotropic and chronotropic effects
• stimulation of vascular and bronchial smooth muscles –> relaxation
• stimulation –> increased splanchnic and microcirculatory perfusion

Question 48

Where are the dopamine receptors located?

Silverstein and Beer, 2015, JVECC

Answer 48

located in smooth muscles of renal, coronary, splanchnic and cerebrovascular beds

Question 49

What effect does stimulation of the dopamine receptors have? Silverstein and Beer, 2015, JVECC

Answer 49

vasolidation (dilates the renal, mesenteric, coronary, and intracerebral vascular beds)

Question 50

What are the adverse effects of beta-adrenergic receptor stimulation?

Silverstein and Beer, 2015, JVECC

Answer 50

• arrhythmias
• cellular modification increasing energy requirements
• lactate production
• immunosuppression (T cell and monocyte inhibition, reduced cytokine production)

Question 51

Why could it be detrimental to only stimulate alpha-adrenergic recptors and name an example of a pure alpha-agonist?

Silverstein and Beer, 2015, JVECC

Answer 51

sole alpha-adrenergic receptor stimulation would lead to vasoconstriction with not enough increase in heart rate and contractility to work against the increased afterload –> cardiac output would subsequently decrease

Question 52

How does current literature compare norepinephrine and dopamine?

Silverstein and Beer, 2015, JVECC

Answer 52

• some human trials found that dopamine improved myocardial contractility more than norepinephrine, others didn’t show that controversal
• incidence of tachyarrhythmias higher in people receiving dopamine
• several studies showed worse outcome in people receiving dopamine over norepinephrine, but differences often slight and not certain it can be extrapolated from human to veterinary medicine
• prospective research is currently conducted to assess difference in dogs and cats

Question 53

How does current literature compare norepinephrine to epinephrine?

Silverstein and Beer, 2015, JVECC

Answer 53

• higher doses of epi needed to achieve higher cardiac index and heart rate compared with norepi
• epi associated with elevated HR and serum lactate, decreased splanchnic perfusion for up to 48 hours in people
• epi more likely to cause tachyarrhythmias
• no difference in adverse events or outcome in 2 human studies
• no conclusive evidence as to which one is better –> still controversial

Question 54

How does vasopressin cause vasoconstriction?

Silverstein and Beer, 2015, JVECC

Answer 54

activates V1 receptor –> increased IC Ca via phosphatidylinositol-bisphosphonate cascade –> constriction of vascular smooth muscles

Question 55

How does vasopressin not lead to decreased CO despite causing vasoconstriction?

Silverstein and Beer, 2015, JVECC

Answer 55

increased systemic vascular resistance –> increased afterload –> BUT no decreased cardiac output observed, possibly due to increased coronary blood flow

Question 56

What is a proposed effect that prolonged hypotension has on vasopressin?

Silverstein and Beer, 2015, JVECC

Answer 56

prolonged hypotension –> may lead to depletion of endogenous vasopressin