Association between initial norepinephrine dose and minute by minute mean arterial pressure.

backgroundNeither the magnitude nor the timing of mean arterial pressure (MAP) increase after norepinephrine (NE) initiation is well defined, leaving clinicians without clear criteria for adequate starting doses. This study aimed to characterize minute-by-minute MAP responses to different initial NE doses in intensive care unit (ICU) patients with shock.

methodsWe included patients admitted to seven ICUs in Japan between 2013 and 2024 who had hypotension (MAP ≤ 65 mmHg) and initiated NE infusion more than 30 min after ICU admission. Invasive MAP data were collected during the observational period, defined as 30 min before to 120 min after NE initiation. Time-dependent effects were estimated with a generalized additive model adjusting for potential confounders, to evaluate MAP changes with varying starting NE doses.

resultsAmong the 81,829 patients, 5,349 who received NE were analyzed, of whom 2,006 (37.5%) had sepsis. Both the maximum MAP rise and the 15-min rate of increase were higher at an NE infusion rate of 0.100 µg/kg/min, compared with 0.025 and 0.050 µg/kg/min (p < 0.01). Model outputs indicated that NE infusion rates of 0.025 and 0.050 µg/kg/min failed to achieve a MAP ≥ 65 mmHg within 60 min when baseline MAP was below 53.9 and 48.4 mmHg, respectively. Failure to achieve MAP ≥ 65 mmHg within 60 min was independently associated with increased ICU mortality (odds ratio: 1.49 [1.27-1.76], p < 0.01). In sepsis, the initial MAP slope at 0.025 µg/kg/min was significantly smaller than in non-sepsis (p < 0.01).

conclusionHigher initial NE doses were associated with both larger and faster MAP increases. Lower starting doses appeared insufficient to achieve a target MAP within 60 min in patients with severe hypotension.