HEMORRHAGE remains a major cause of early death after trauma. A recent review of all consecutive deaths in a level 1 trauma center revealed that irreversible shock with or without central nervous system injury accounted for 37% of all causes of death.1Resuscitation of hypotensive victims is based on the rationale that adequate perfusion of vital organs should be restored as soon as possible. However, one of the side effects of most methods of increasing organ perfusion is an elevated blood pressure, which, in the face of uncontrolled hemorrhage, may increase bleeding and have adverse consequences that could outweigh the potential benefits of improved perfusion. Resuscitation of patients in hemorrhagic shock concentrates essentially on fluid administration, with ongoing debates on the time, the volume, and the nature of solution to be used. The use of vasopressor agents, although not recommended as first-line treatment of patients with hemorrhagic shock, might help to restore rapidly blood pressure to the desired level, while limiting the volume of fluid infused. In this issue of Anesthesiology, Poloujadoff et al. 2examined the effects of norepinephrine in combination with saline infusion on short-term survival in ketamine-anesthetized rats undergoing uncontrolled hemorrhagic shock. Using a well-recognized experimental model, the authors nicely showed that the administration of an intermediate dose of norepinephrine in combination with fluids in either a hypotensive or a normotensive resuscitation strategy resulted in improved short-term survival. Interestingly, all animals receiving the higher norepinephrine dose died, as did the animals undergoing the normotensive resuscitation strategy with the use of fluids only.
The main objective of fluid resuscitation from uncontrolled hemorrhagic shock is to increase oxygen delivery to vital organs to maintain viability yet not to increase bleeding before hemostasis. The optimal fluid for this limited fluid resuscitation still needs to be determined. Among near isotonic crystalloids, there is increasing experimental evidence that lactated Ringer’s solution is superior to normal saline for resuscitation of uncontrolled hemorrhagic shock and could be associated with improved survival.3,4Although the type of fluid may be of importance, it seems even more crucial to adapt the amount of fluid to be given according to predefined clinical endpoints (“controlled” resuscitation).5
In patients with hemorrhagic shock, current international resuscitation guidelines recommend the use of vasopressors if pulseless electrical activity or bradyasystolic rhythm is imminent. In a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs mimicking these conditions, vasopressin but not epinephrine or fluid resuscitation enhances short-term survival.6,7In a similar model, resuscitation with small-volume hypertonic hyperoncotic hydroxyethyl starch combined with either norepinephrine or vasopressin resulted in similar survival rate, hemodynamic profile, and restoration of brain energy metabolism.8However, the use of vasopressor agents could also have potential advantages in the resuscitation from early stages of hemorrhagic shock. They increase venous return to the heart through their effect on venous vascular tone. They could be efficacious in treating the vasodilatory component of hypotension. Their use could also help to restore rapidly blood pressure to the desired level, while limiting the volume of fluid infused, which might be of particular interest when hemorrhage is associated with traumatic brain injury. In these conditions, there is experimental evidence that resuscitation strategy combining fluids and vasopressors improved outcome compared with fluids or vasopressors alone.9,10The results of the study of Poloujadoff et al. 2are in line with these observations.
In these different models of hemorrhagic shock, with or without associated traumatic brain injury, vasopressin did not demonstrate a clear superiority over catecholamines characterized by prominent α-adrenergic properties, such as phenylephrine or noradrenaline. Vasopressin restores vascular tone in vasoplegic shock states by at least four known mechanisms: activation of V1 vascular receptors, modulation of adenosine triphosphate–sensitive K+channels, modulation of nitric oxide, and potentiation of adrenergic and other vasoconstrictor (such as angiotensin II) agents. Because of its possible effects on myocardial contractility and coronary vasculature, its use in the context of hemorrhagic shock should be reserved to situations unresponsive to volume replacement and catecholamines vasopressors.11
As emphasized by Poloujadoff et al. ,2anesthetic agents may interfere with the cardiovascular response to hemorrhage of the experimental animals. Most of the anesthetic agents block the sympathetic response to stress in a dose-dependent manner. However, the sympathetic system plays an important role in the redistribution of blood flow from organs with relatively low oxygen demand, such as the splanchnic area and the skin, to tissues with high metabolic demand, such as the brain and the heart. This redistribution of blood flow allows the organism to adjust oxygen extraction when oxygen delivery to the tissues is reduced. By blocking the sympathetic response to stress, anesthetic agents could alter this compensatory mechanism, thereby reducing the tolerance of experimental animals to hemorrhage.12Ketamine, which possess indirect sympathomimetic properties, had the lesser effect on tissue oxygen extraction capabilities.12These observations could explain the favorable effects of ketamine in different models of hemorrhagic shock in comparison with other anesthetic agents.
Although it requires clinical validation, the approach proposed by Poloujadoff et al. 2seems quite attractive. Indeed, the combined use of fluids and vasoconstrictors to restore and to maintain a predefined target perfusion pressure according to the patient’s condition might be the more efficient approach, while reducing the risks of side effects associated with the use of each treatment alone.
Department of Anesthesiology, Centre Hospitalier Universitaire Brugmann-HUDERF, Brussels, Belgium. philippe.vanderlinden@chu-brugmann.be
