Sepsis (Key points only)

Question 1

Criteria for SIRS in horses/foals

Answer 1

2 or more of the following (plus an etiology of SIRS)

• Fever or hypothermia (>102.6 or <99°F)
• Tachycardia (>60 bpm)
• Tachypnea (>20 bpm)
• Neutrophilia or neutropenia (>12,000 or <4,000)
• Venous blood lactate >2.5
• Blood glucose <50 (suspicious still if <180)

Question 2

Toxic moiety in endotoxemia

Answer 2

• Lipid A (the pi-shaped molecule on the end)

Question 3

Early clinical signs (30 min to 2 hours) of sepsis

Answer 3

• Vasoconstriction primarily
• Leads to blanched mucous membranes and hypertension systemically
• In terms of pulmonary system leads to tachypnea

Question 4

Later clinical signs of sepsis (>1.5-2 hrs)

Answer 4

• Vasodilation
• Hypotension and decreased cardiac output
• Also obtundation
• Fever
• Also: colic, laminitis, diarrhea

Question 5

Consequences of vasodilation

Answer 5

• Cool extremities
• Prolonged CRT
• Congested mm/toxic lines

Question 6

Consequences of decreased cardiac output

Answer 6

• Tachycardia

- Poor peripheral perfusion (tissue/organ hypoxia) –> hyperlactatemia

Question 7

What usually keeps gram negative bacteria in the GI tract?

Answer 7

• Inact mucosal barrier

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Question 8

Gram negative infections that can lead to endotoxemia

Answer 8

• Gram-negative bacteria in cecum (GI infection or ischemia/inflammation), pleuropneumonia, placentitis/metritis, wounds, septicemia)
• Contaminated IV

Question 9

Five stages of endotoxemia

Answer 9

1. Physical barriers are breached (damage –> overwhelming Kupffer cells –> increased portal endotoxemia and bacterial translocation combined lead to SIRS)
2. Inflammatory mediator production

Stage 3: Neutrophil activation and margination

Stage 4: compromised perfusion

Stage 5: Recovery or not

Question 10

Key inflammatory mediators

Answer 10

• IL1, IL6, and TNFalpha

Question 11

True/false: Horses are not sensitive to endotoxin

Answer 11

• FALSE

- Horses are EXQUISITELY sensitive to endotoxin

Question 12

Typical acid base disorder in endotoxemia

Answer 12

• Mixed acid-base

- Metabolic acidosis and compensatory respiratory alkalosis common

Question 13

Treatment principles of Endotoxemia

Answer 13

1. Circulatory support
2. Minimize inflammation
3. Neutralize circulating endotoxin
4. Treat the underlying cause

Question 14

What electrolytes would you want to supplement if a horse isn’t eating?

Answer 14

• K+, Mg2+, Ca2+
• Mg and K+ are intracellular
• Mg and Ca2+ are helpful for GI function

Question 15

Which NSAID and dose do you commonly use for reduction of inflammation in endotoxemia?

Answer 15

• Flunixin meglumine at an anti-endotoxic dose
• She can use the normal dose
• Likely better than Firoxocib (chronic pain, phenylbutazone, ketoprofen)

Question 16

Pentoxyfylline role in inhibiting inflammation

Answer 16

• Reduces TNF-alpha

- Increases perfusion

Question 17

Medications to neutralize endotoxin

Answer 17

• Polymixin B (careful as it is nephrotoxic and neurotoxic; NOT USED AT AN ANTIMICROBIAL DOSE; NOT USED IF ELEVATED CREATININE)
• Smectite
• Biosponge

Question 18

Treating the cause of endotoxemia

Answer 18

• ID underlying etiology
• Antimicrobials can exacerbate
• Wait until extremely neutropenic to give antibiotics

Question 19

If you have to use antibiotics to treat endotoxemia, which ones would you choose?

Answer 19

• Aminoglycosides

- Rapid kill, gram-negative spectrum

Question 20

Promising treatment for endotoxemia

Answer 20

• Ethyl pyruvate that likely works via antioxidant effects

Question 21

Basic pathophysiology of SIRS

Answer 21

• Macrophage activation
• Production of inflammatory mediators (e.g. cytokines)
• Stimulation of neutrophils
• Increased vascular permeability due to production of vasoactive mediators
• Coagulation disorder