“This modeling thing, it’s pretty easy, but actually it’s also really tough.” Cara Delevingne
The necessity
The action
The proposed outcome
Study Design
(WG-1) | 1. Survival follow-up should reasonably reflect the clinical time course of the sepsis model |
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2. Therapeutic interventions should be initiated after the septic insult replicating clinical care | ||
3. We recommend that the treatment be randomized and blinded when feasible | ||
4. Provide as much information as possible (e.g. ARRIVE guidelines) on the model and methodology, to enable replication. | ||
a. Consider replication of the findings in models that include co-morbidity and/or other biological variables (i.e., age, gender, diabetes, cancer, immuno-suppression, genetic background and others).
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b. In addition to rodents (mice and rats), consider modeling sepsis also in other (mammal) species.
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c. Consider need for source control
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Humane Modeling
(WG-2) | 5. The development and validation of standardized criteria to monitor the well-being of septic animals is recommended |
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6. The development and validation of standardized criteria for euthanasia of septic animals is recommended (exceptions possible) | ||
7. Analgesics recommended for surgical sepsis consistent with ethical considerations | ||
d. Consider analgesics for nonsurgical sepsis
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Infection Types
(WG-3) | 8. We recommend that challenge with LPS is not an appropriate model for replicating human sepsis |
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9. We recommend that microorganisms used in animal models preferentially replicate those commonly found in human sepsis | ||
e. Consider modeling sepsis syndromes that are initiated at sites other than the peritoneal cavity (e.g. lung, urinary tract, brain)
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Organ Failure/ Dysfunction
(WG-4) | 10. Organ/system dysfunction is defined as life threatening deviation from normal for that organ/system based on objective evidence |
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11. Not all activities in an individual organ/system need to be abnormal for organ dysfunction to be present | ||
12. To define objective evidence of the severity of organ/system dysfunction, a scoring system should be developed, validated and used, or use an existing scoring system. | ||
13. Not all experiments must measure all parameters of organ dysfunction but animal models should be fully exploited | ||
f. Avoid hypoglycemia
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Fluid Resuscitation
(WG-5) | 14. Fluid resuscitation is essential unless part of the study |
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15. Administer fluid resuscitation based on the specific requirements of the model | ||
16. Consider the specific sepsis model for the timing of the start and continuation for fluid resuscitation | ||
17. Resuscitation is recommended by the application of iso-osmolar crystalloid solutions | ||
g. Consider using pre-defined endpoints for fluid resuscitation as deemed necessary
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h. Avoid fluid overload
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Anti-microbial Therapy
(WG-6) | 18. Antimicrobials are recommended for pre-clinical studies assessing potential human therapeutics |
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19. Antimicrobials should be chosen based on the model and likely/known pathogen | ||
20. Administration of antimicrobials should mimic clinical practice | ||
i. Antimicrobials should be initiated after sepsis is established
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