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Septic Shock & Hypotension: Comparing Vasopressor Agents

Sepsis is characterized by a dysfunctional immune response to infection—norepinephrine can contribute to this immune dysregulation.

Administration of vasopressor agents like norepinephrine can be useful in treating hypotensive septic shock patients. But with any treatment, there are risks associated which must be weighed into individual clinical cases. Sepsis is characterized by a dysfunctional immune response to infection—norepinephrine can contribute to this immune dysregulation.

In order to explore the immune response impact of norepinephrine, a team from the Radboud Centre for Infectious Diseases in Nijmegen, the Netherlands, looked at immunomodulation associated with the agent alongside that caused by the alternate vasopressor vasopressin.

Results were published in the American Journal of Respiratory and Critical Care Medicine.

Leukocytes from donors were stimulated in the presence or absence of vasopressin and norepinephrine. Experiments were conducted in both human and animal models.

There were 30 healthy volunteers and 190 C57BL/6J Mice examined in the study. The mice were administered a continuous infusion of norepinephrine or vasopressin via micro-osmotic pumps and were challenged with lipopolysaccharide or underwent cecal ligation and puncture.

The 30 healthy volunteers were randomized to a 5-hour infusion of norepinephrine, vasopressin or saline, and intravenously challenged with lipopolysaccharide.

Among a cohort of septic shock patients, the relation between norepinephrine infusion rate and the use of β-blockers, and plasma cytokines was also assessed.

The study team found that norepinephrine “attenuated pro-inflammatory mediators and reactive oxygen species, while augmenting anti-inflammatory interleukin-10 production both in vitro and in lipopolysaccharide-challenged mice.”

Norepinephrine infusion during cecal litigation and puncture resulted in increased bacterial spread to spleen, liver and blood.

In volunteers challenged with lipopolysaccharide, norepinephrine increased plasma interleukin-10 concentrations and attenuated release of pro-inflammatory cytokine interferon gamma-induced protein-10.

On the other hand, vasopressin exerted no immunomodulatory effects across the various experimental setups. In patients, β-blocker use was associated with a more pro-inflammatory cytokine balance. Conversely, higher norepinephrine infusion rates were correlated with a more anti-inflammatory cytokine balance.

“Norepinephrine dysregulates the immune response in mice and humans, and compromises host defense. Therefore, it may significantly contribute to sepsis-induced immunoparalysis, whereas vasopressin does not have untoward immunologic effects,” the study authors concluded.