Differential effects of catecholamines and vasopressin on regional blood flow distribution during resuscitation in a porcine model of severe hemorrhagic shock

Paul Wetstein, MD, Alexander Malloy, DO, Catherine Uyehara, PhD. Tripler Army Medical Center

Objectives: Vasopressor therapy is used to restore adequate tissue perfusion pressure and hemodynamic stability after severe hemorrhagic shock.  There remains concern with the use of exogenous vasopressors in severe shock due to the fear that excessive vasoconstriction will lead to tissue hypoperfusion and further hypoxemia.  The duration and type of vasopressor use that is acceptable for maintaining optimal blood pressure for perfusion of microcapillary beds during hemorrhagic shock remains to be defined.  The purpose of this study was to examine the effects of acute vasopressor therapy on regional microcirculatory blood flow distribution.  We hypothesized that different vasoactive agents will have unique regional blood flow distribution profiles when compared to distribution of blood flow with normal saline resuscitation.

Methods: Hemorrhagic shock was induced in 29 anesthetized Yorkshire cross pigs to achieve a shed blood loss of 30 ml/kg, a 50% decrease in mean arterial pressure, and an oxygen debt over 60 ml/kg.  Colored microspheres were used to determine regional microcirculatory flow of different vascular beds at baseline, one hour after the start of hemorrhage, after resuscitation with crystalloid and one hour after initiation of adjunctive blood pressure support.  The tissues harvested at necropsy at the conclusion of the experiments included the heart, kidney, cerebrum, cerebellum, midbrain, brainstem, skin, muscle, stomach, small intestine, large intestine, spleen, liver, pancreas and adrenal gland.  The modalities for resuscitation were crystalloid (NS; normal saline at 2 x shed blood volume, n=9), phenylephrine (PE; 5 mcg/kg/min; n=6), norepinephrine (NE; 0.1 mcg/kg/min, n=7) or vasopressin (VP; 30 ng/kg/min, n=7).  The relative ratio of the tissue specific regional flow in relation to the change in cardiac output (CO) was compared between baseline, at the end of hemorrhage, and one hour after the initiation of adjunctive pressure support.  Data were analyzed by ANOVA.

Results: Hemorrhage resulted in a 40% decrease in CO.  Despite this CO decrease, blood flow was maintained to the brain, heart, skin, and adrenal gland, versus decreased flow to the kidney, liver, pancreas, stomach, and large intestine.  This redistribution of regional flow tended to normalize with crystalloid resuscitation returning CO towards normal.  PE did not cause notable differences in regional blood shifts and relative regional blood flow with PE was proportional to CO changes during resuscitation.  NE appeared to increase flow to the heart and small intestine.  VP demonstrated the most striking changes in regional blood flow patterns compared to other pressors.  VP returned the renal blood flow proportion of CO to baseline levels, increased flow to the liver and adrenal glands, and decreased flow to the pancreas.

Conclusion: In our porcine model of severe hemorrhagic shock, where acute vasopressor administration is limited to one hour, phenylephrine, norepinephrine and vasopressin do not appear to have any detrimental effect on regional blood flow to vital organs.  After further investigation, further understanding of regional blood flow shifts during hemorrhage and resuscitation could guide pre-hospital choice of vasopressor support in hemorrhagic shock patients.