Early Norepinephrine Administration may Reduce Pulmonary Edema risk in Septic Shock Patients: Study

Norepinephrine remains, to this day, a vasopressor of paramount importance in the management of septic shock, though the best timing of initiation is still debatable. Some higher and recent studies showed conflicting effects with respect to early or late NE administration about the outcome. This meta-analysis was intended to clarify these controversies compared to mortality and other outcomes between early versus late NE administration in patients with septic shock.

An extended search was done in studies on PubMed, EMBASE, the Cochrane Library, and KMBASE. They randomized adults with sepsis, divided into an early NE group and a late NE group according to specific time points or by differences in the protocols for NE use. Primary outcome measurements included overall mortality, secondary outcome measurements were ICU length of stay, ventilator-free days, renal replacement therapy-free days, vasopressor-free days, adverse events, and total fluid volume.

The study findings were as follows:

• A total of 12 studies (4 randomized controlled trials [RCTs] and 8 observational studies) comprising 7,281 patients were analyzed.

• No significant difference was found between the early NE group and the late NE group in RCTs (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41–1.19) or observational studies (OR, 0.83; 95% CI, 0.54–1.29).

• In the two RCTs that did not employ a restrictive fluid strategy and prioritized vasopressors over intravenous fluids, the early NE group showed significantly lower mortality than the late NE group (OR 0.49; 95% CI, 0.25–0.96).

• The early NE group had more ventilator-free days in observational studies (mean difference [MD], 4.06; 95% CI, 2.82–5.30).

• Three of the RCTs contributing data for this outcome measured the incidence of pulmonary edema, which was lower with early NE: OR 0.43; 95% CI, 0.25–0.74.

• There were no differences in ICU length of stay, days free from renal replacement therapy, days free from vasopressor use, adverse events, or fluid volume between the two groups.

There was no significant difference in overall mortality for septic shock based on the timing of NE administration. On the other hand, early NE significantly reduced the incidence of pulmonary edema and dramatically reduced the mortality rate in those studies that used the intervention without fluid restriction, compared to late NE administration in the same studies.These results suggest that timing itself may not be as important to overall mortality regarding NE administration; there are other important clinical benefits to be derived.

Reference:

Ahn, C., Yu, G., Shin, T. G., Cho, Y., Park, S., & Suh, G. Y. (2024). Comparison of early and late norepinephrine administration in patients with septic shock: a systematic review and meta-analysis. Chest. https://doi.org/10.1016/j.chest.2024.05.042