Abstract
BackgroundHaemostasis and correction of hypovolemia are the pillars of early haemorrhage shock (HS) management. Vasopressors, which are not recommended as first-line therapy, are an alternative to aggressive fluid resuscitation, but data informing the risks and benefits of vasopressor therapy as fluid-sparing strategy is lacking. We aimed to study its impact on end organs, in the setting of a haemodynamic response to the initial volume resuscitation.MethodsFollowing controlled HS (60 min) induced by blood withdrawal, under anaesthesia and ventilation, male Wistar rats (N = 10 per group) were randomly assigned to (1) sham, (2) HS with fluid resuscitation only [FR] and (3) HS with fluid resuscitation to restore haemodynamic (MAP: mean arterial pressure) then norepinephrine [FR+NE]. After a reperfusion time (60 min) during which MAP was maintained with fluid or norepinephrine, equipment was removed and animals were observed for 24 h (N = 5) or 72 h (N = 5) before euthanasia. Besides haemodynamic parameters, physiological markers (creatinine, lactate, pH, PaO2) and one potential contributor to vasoplegia (xanthine oxidase activity) were measured. Apoptosis induction (caspase 3), tissue neutrophil infiltration (MPO: myeloperoxidase) and illustrative protein markers were measured in the lung (Claudin-4), kidney (KIM-1) and brain amygdala (Iba1).ResultsNo difference was present in MAP levels during HS or reperfusion between the two resuscitation strategies. FR required significantly more fluid than FR+NE (183% vs 106% of bleed-out volume; p = 0.003), when plasma lactate increased similarly. Xanthine oxidase was equally activated in both HS groups. After FR+NE, creatinine peaked higher but was similar in all groups at later time points. FR+NE enhanced MPO in the lung, when Claudin-4 increased significantly after FR. In the brain amygdala, FR provoked more caspase 3 activity, MPO and microglial activation (Iba1 expression).ConclusionOrgan resuscitation after controlled HS can be assured with lesser fluid administration followed by vasopressors administration, without signs of dysoxia or worse evolution. Limiting fluid administration could benefit the brain and seems not to have a negative impact on the lung or kidney.
Highlights
Haemostasis and correction of hypovolemia are the pillars of early haemorrhage shock (HS) management
During HS, the lowest mean arterial pressure (MAP) reached was the same (27 ± 1 vs 26.5 ± 0.5 mmHg; p = 0.66), as well as the time spent under MAP of 30 mmHg (11.1 ± 1.6 vs 10.5 ± 1.1 min; p = 0.73)
The Fluid resuscitation and norepinephrine (FR+NE) group was resuscitated with the pre-established limited volume (11 ± 1 ml), with a MAP ≥ 55 mmHg in all animals
Summary
Haemostasis and correction of hypovolemia are the pillars of early haemorrhage shock (HS) management. Vasopressors, which are not recommended as first-line therapy, are an alternative to aggressive fluid resuscitation, but data informing the risks and benefits of vasopressor therapy as fluid-sparing strategy is lacking. We aimed to study its impact on end organs, in the setting of a haemodynamic response to the initial volume resuscitation. Fluid resuscitation restores circulating volume in order to compensate for decreased end-organ perfusion. Vasopressors, which are not currently recommended for HS, constitute a potential fluid-sparing strategy [7]. They are commonly used when polytrauma is associated with traumatic brain injury, presumably to avoid low cerebral perfusion pressures [8, 9]. Existing clinical data remains inconclusive and their net effects remain uncertain [10]
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