Norepinephrine Decreases Fluid Requirements and Blood Loss While Preserving Intestinal Villi Microcirculation during Fluid Resuscitation of Uncontrolled Hemorrhagic Shock in Mice

AbstractAbstract The administration of both norepinephrine with crystalloid (normal saline [NS]) led to less fluid requirements than when animals only received NS to reach a target blood pressure. There was also no significant difference in the intestinal villi microcirculatory perfusion in the animals resuscitated with NS alone compared to animals given NS and norepinephrine. Background: Norepinephrine administration is controversial during hemorrhagic shock resuscitation to stabilize mean arterial pressure (MAP) level because it could have deleterious effects on local circulations. The authors investigated the effect of norepinephrine on intestinal microcirculation during fluid resuscitation in uncontrolled hemorrhagic shock. Methods: Mice (n = 6 per group) submitted to an uncontrolled hemorrhagic shock by tail section were randomly assigned to a resuscitation with fluid but without norepinephrine to target a MAP level of 50 mmHg (FR 50 ) or 60 mmHg (FR 60 ) or a resuscitation with fluid and norepinephrine to target a MAP level of 50 mmHg (FRNE 50 ) or 60 mmHg (FRNE 60 ). Intestinal microcirculation was observed by intravital microscopy. Results: Fluid requirements were lower in groups resuscitated with fluid and norepinephrine than in groups resuscitated with fluid without norepinephrine (74.6 ± 45.1 in FR 50 vs. 28.1 ± 10.0 µl/g in FRNE 50 ; P = 0.004 and 161.9 ± 90.4 in FR 60 vs. 44.5 ± 24.0 µl/g in FRNE 60 ; P = 0.041). Blood loss was not statistically different between FR 50 and FRNE 50 (14.8 ± 8.3 vs. 8.5 ± 2.9 µl/g; P = 0.180) but was significantly lower in FRNE 60 than in FR 60 (10.1 ± 4.2 vs. 22.6 ± 9.6 µl/g; P = 0.015). This beneficial effect was associated with the restoration of intestinal microcirculation to the same extent in fluid resuscitated groups without norepinephrine (FR 50 and FR 60 ) and fluid resuscitated groups with norepinephrine (FRNE 50 and FRNE 60 ). Conclusions: During MAP-directed resuscitation of uncontrolled hemorrhagic shock, the administration of norepinephrine decreased blood loss and fluid requirements while preserving intestinal villi microcirculation.