Why the study?
Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established.
Does continuous intravenous norepinephrine infusion improve systemic hemodynamics and survival in a mouse model of sepsis?
Does continuous intravenous norepinephrine infusion improve systemic hemodynamics and survival in a mouse model of sepsis?
Continuous intravenous norepinephrine infusion in a mouse sepsis model improved hemodynamics but not survival, with early heart rate response serving as a strong predictor of mortality.
Norepinephrine augments MAP/HR without survival benefit in septic mice; leaves open optimal vasopressor translation to clinical sepsis.
Sepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of continuous intravenous norepinephrine infusion in a septic cecal ligation and puncture (CLP) mouse model, evaluating systemic hemodynamics and body temperature post-hoc. CLP surgery significantly decreased mean arterial blood pressure (MAP), heart rate, and body temperature within six hours. Continuous norepinephrine infusion (NE+, n = 12) started at the time of CLP surgery significantly increased MAP at 24 and 30 hours and heart rate at 6, 18, 24, and 30 hours after CLP vs CLP alone (NE-, n = 12). However, addition of norepinephrine did not improve survival rate (NE+ n = 34, NE- n = 31). Early (6 hours or earlier, when the animal became visibly sick) MAP did not predict 7-day mortality. However, heart rates at 3 and at 6 hours after CLP/norepinephrine (NE+) were highly predictive of mortality, as also been found in one clinical study. We conclude that limited hemodynamic support can be provided in a mouse sepsis model. We propose that heart rate can be used to stratify severity of illness in rodent preclinical studies of sepsis therapeutics.
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Yamashita et al. (2022) studied this question.
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