Sophie Dunberry-Poissant1, Kim Gilbert2, Caroline Bouchard2, Frédérique Baril3, Anne-Marie Cardinal3, Sydnée L'Ecuyer3, Mathieu Hylands4, François Lamontagne5,6, Guy Rousseau2,7, Emmanuel Charbonney8,9. 1. Département de Médecine, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, QC, H3C 3J7, Canada. 2. Centre de Recherche Hôpital du Sacré-Cœur de Montréal (HSCM), 5400 boul. Gouin Ouest, Montréal, QC, H4J 1C5, Canada. 3. Université de Montréal, 2900 Edouard Montpetit Blvd, Montréal, QC, H3T 1J4, Canada. 4. Département de chirurgie, Université de Sherbrooke, 3001- 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada. 5. Centre de recherche du CHU de Sherbrooke, 3001- 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada. 6. Department of Medicine, Université de Sherbrooke, 3001- 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada. 7. Département de pharmacologie et physiologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, QC, H3C 3J7, Canada. 8. Département de Médecine, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, QC, H3C 3J7, Canada. emmanuel.charbonney@umontreal.ca. 9. Centre de Recherche Hôpital du Sacré-Cœur de Montréal (HSCM), 5400 boul. Gouin Ouest, Montréal, QC, H4J 1C5, Canada. emmanuel.charbonney@umontreal.ca.
Abstract
BACKGROUND: 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. METHODS: Following 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). RESULTS: No 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). CONCLUSION: Organ 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.
BACKGROUND: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. METHODS: Following 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). RESULTS: No 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). CONCLUSION: Organ 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.
Authors: Wolfgang G Voelckel; Claus Raedler; Volker Wenzel; Karl H Lindner; Anette C Krismer; Christian A Schmittinger; Holger Herff; Klaus Rheinberger; Alfred Königsrainer Journal: Crit Care Med Date: 2003-04 Impact factor: 7.598
Authors: Karl H Stadlbauer; Horst G Wagner-Berger; Claus Raedler; Wolfgang G Voelckel; Volker Wenzel; Anette C Krismer; Guenter Klima; Klaus Rheinberger; Walter Nussbaumer; Daniel Pressmar; Karl H Lindner; Alfred Königsrainer Journal: Anesthesiology Date: 2003-03 Impact factor: 7.892
Authors: Samuel W Ross; A Britton Christmas; Peter E Fischer; Haley Holway; Amanda L Walters; Rachel Seymour; Michael A Gibbs; B Todd Heniford; Ronald F Sing Journal: J Trauma Acute Care Surg Date: 2015-11 Impact factor: 3.313