Alexander Malloy, DO, Paul Wetstein, MD, Patrick Golden, DO, Catherine Uyehara, PhD. Department of Clinical Investigation, Tripler Army Medical Center
OBJECTIVES: In severe hemorrhagic shock, early vasopressor support helps to prevent administration of excessive fluids to restore arterial pressure. While the goal of early resuscitation is to stabilize perfusion pressure to preserve blood flow to vital organs, the effect of vasoconstrictors on tissue oxygenation is not well understood. Of particular concern in reducing morbidity after trauma, is the ability to prevent brain injury resulting from prolonged hypoxemia. In this study, we tested the hypothesis that brain oxygen utilization may be adversely affected by hypoperfusion resulting from the use of vasopressor therapy to restore blood pressure after hemorrhage.
METHODS: Hemorrhagic shock was induced in fifteen Yorkshire 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. Brain oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction in relation to systemic oxygen debt, mean arterial pressure (MAP) and cardiac output (CO) were assessed. Also, in order to develop methods to obtain continuous clinical assessment of tissue oxygen utilization, oxygen sensor measurements were compared against direct measurements of arterial and venous blood oxygenation at baseline, one hour after hemorrhage, and after one hour of acute resuscitation with crystalloid fluid alone (NS; normal saline equal to no more than 2 times the blood shed volume) or crystalloid in combination with vasopressor therapy: phenylephrine (PE; 5 mcg/kg/min), norepinephrine (NE; 0.075 mcg/kg/min), or vasopressin (VP; 30 mg/kg/min).
RESULTS: With the hemorrhage-induced decrease in MAP and CO, whole body DO2 was significantly decreased by 40%, but VO2 remained constant at 2.7 + 0.2 ml/kg/min. With resuscitation, hypotension and oxygen debt accumulation were reversed and whole body DO2 was increased to similar levels in all treatment groups despite different degrees of MAP restoration. Brain DO2 decreased with hemorrhage but brain VO2 was maintained with improved oxygen extraction. Brain VO2 was similar with all resuscitation treatments and vasopressor therapy did not interfere with maintenance of brain VO2.
CONCLUSION: Avoidance of hypoxemia resulting in brain injury remains a primary preventative goal during hemorrhagic shock. Preservation of cerebral function is paramount. This study demonstrates that despite severe oxygen debt accumulation during hemorrhage and decreased DO2, the use of vasopressors in resuscitation did not adversely affect brain VO2 for the acute period of vasopressor use. The physiological compensatory response to hemorrhage of maintaining intracranial blood flow and oxygen consumption was unaffected by the short term use of vasopressors during resuscitation. Brain injury from hypoxemia can be avoided despite extreme decreases in MAP and CO with resuscitative measures that maintain cerebral blood flow during severe hemorrhagic shock.