Progressive hemorrhage: administer oxygen or early resuscitation?

Abstract

Hemorrhage is one of the main causes responsible for the impairment of blood flow, with subsequent tissue hypoperfusion and hypoxia. As the circulating blood volume decreases, oxygen consumption (VO 2 ) remains constant for a considerable amount of blood loss. When the oxygen delivery (DO 2 ) drops below a critical level, i.e. 10 mL O 2 / min per kg, VO 2 falls abruptly. This signifies a blood volume loss of approximately 50%, associated with substantial reduction in cardiac output and mixed venous oxygen saturation [1]. At this stage of ischemia, deep tissue hypoxia leads the severely O 2 -deprived cell to prime for generation of ROS, upon O 2 re-entry during reperfusion [2]. Cellular priming consists of ATP depletion, since ATP degrades, reaching the level of hypoxanthine with concurrent xanthine oxidase accumulation. This situation is associated with either absolute O 2 restriction (no-flow state) or prolonged O 2 debt (low flow state) [3]. The profuse and sudden oxygen re-entry at resuscitation acts as a cofactor, allowing xanthine oxidase to convert hypoxanthine to uric acid. The resulting by-products are superoxide anions (O 2 -) and hydrogen peroxide (H 2 O 2 ), representing the main molecules of the initial oxidative burst [2]. The aforementioned reactive oxygen species, along with the free radicals generated by NADPH oxidase within the neutrophils, attack peroxidating cell membranes. Consequently, ischemia/ reperfusion injury occurs, the global equivalent of which is hemorrhagic shock and resuscitation.Recently, the importance of limited resuscitation [4-7] has been widely acknowledged. Patients with penetrating truncal trauma, in which resuscitation was delayed, had a higher survival rate to discharge (70%) compared with promptly resuscitated patients (62%, P = 0.04) [4]. Likewise, a systemic review of animal studies [5] has also shown a lower risk of death in animals resuscitated to hypotensive levels than in animals resuscitated to normotensive levels (P \ 0.00001). The small volume resuscitation with fluids such as hypertonic saline [6] or albumin 25% [7] has similarly shown a higher survival rate compared with infusion of isotonic fluids.The approach of attempting to lessen reperfusion injury by adjusting the inspired O 2 may apply either before [8] or during [9-12] resuscitation. As far as the first case is concerned, the impact of inspired oxygen concentration on tissue oxygenation (tPO 2 ) in the absence of resuscitation was the subject of a study from Dyson et al. [8], published in this issue of the journal. The latter case is represented by hypoxemic resuscitation [9][10][11][12]; a process in which hypoxemia is applied during the first few minutes of resuscitation and, as shock reverses, it gradually turns to normoxemia.In the aforementioned study [8], tissue oxygenation improves at mild (less than 20%) blood volume losses similarly to normovolemia, in response to higher inspired oxygen admixtures. Adversely, at significant (more than 50%) blood volume losses, higher inspired oxygen admixture...

Year in review in Intensive Care Medicine 2009: II. Neurology, cardiovascular, experimental, pharmacology and sedation, communication and teaching

“…This study indicates that hypoxemia and hyperoxemia both altered organ perfusion during severe and progressive hemorrhage. In an editorial, Dr. Douzinas [65] stated that we should keep in mind that CO and mixed venous oxygen tension are higher in isovolemic anemia than hypovolemia or hypoxemia. Therefore, it would be interesting to resuscitate the animals at different levels of blood volume loss and, by varying FiO 2 and measuring oxidative parameters, to determine if the management should mainly lie with O 2 therapy or with resuscitation efforts.…”

Pathways to Reduce Late Mortality of Hemorrhagic Shock

“…Excess of O 2 therapy during significant hemorrhage intensifies the physiological compensatory responses of vasoconstriction and blood flow redistribution [145]. Therefore, compared with room-air breathing, high flow or high concentration O 2 therapy deteriorates both hemodynamics and tissue/cellular hypoxia, in spite of the significantly higher arterial blood oxygenation.…”