The lethal duo of hypoxemia and ischemia: not only for the brain but also for the gut*.

November 2013 • Volume 41 • Number 11 In hemorrhagic shock, cardiac output and oxygen transport cannot support the oxidative metabolism and oxygen consumption eventually falls. Multiple organ failure and death are predictable consequences of the accumulated oxygen debt (1). When the reduction in oxygen transport is not enough to immediately lead to death, some pathophysiologic events could be triggered at tissue level. The gut could be the perfect scenario for the development of ischemic and inflammatory mechanisms responsible for delayed multiple organ failure (2). Contrary to the general belief, mesenteric blood flow is not selectively decreased in hypovolemic shock; yet, an intramural redistribution of microvascular flow might render the villi hypoperfused (3). Ischemia could thus alter the integrity and function of the mucosal barrier, and translocation of bacteria and their products from the intestinal lumen to systemic circulation might ensue, an alleged mechanism for the development of multiple organ failure (2). Although the effects of ischemic hypoxia on villi microcirculation and histology have been extensively studied (3, 4), the consequences of added hypoxic hypoxia on villi perfusion have not been previously addressed. This combination of insults might be also operative in other situations. For example, in traumatic brain injury (TBI), it is well known that hypotension and hypoxia play a relevant role as secondary insults in increasing mortality and poor neurologic outcomes (5). In experimental TBI, cerebral lactate-pyruvate ratios are higher during hypoxia and hypotension, compared with isolated insults—suggesting that their deleterious effects are synergistic (6). Hence, hypoxia and hypotension were characterized as the “lethal duo” in TBI (7). In this issue of Critical Care Medicine, Harrois et al (8) give substantial insights into the subject. They found that isolated hypoxemia or bleeding induces only slight alterations in villi microcirculation. In hypoxemia, there were minor decreases in the RBC velocity in villi capillaries and tips, but the RBC flow and the fraction of perfused villi were unaffected. Probably, a compensatory increase in cardiac output preserved most of the capillary perfusion. In hemorrhage, there were reductions in RBC velocities and flow and minimal decrease in the fraction of perfused capillaries. In contrast to the individual effects of hypoxemia or hemorrhage, the combined injury deeply disturbed the villi microcirculation: The reductions in RBC velocities were more pronounced, and the fraction of perfused capillaries was severely decreased. In the isolated insults, the alterations in microcirculation were almost exclusively restricted to convective capillary oxygen transport. The fall in RBC velocity in itself does not seem a significant factor to compromise tissue oxygenation. The diffusional transport was probably unaffected, as its main determinant, the perfused capillary density, was preserved. Hypoxia plus ischemia, however, altered both convective and diffusional oxygen transport. Such microvascular derangement might have severe consequences. The implications of microcirculatory variables to evaluate tissue oxygenation and to predict outcome are illustrated by a recent quantitative characterization of sublingual microcirculation in patients with septic shock (9). Survivors and nonsurvivors had similar RBC velocities, but perfused capillary density and the heterogeneity were more severely disrupted in nonsurvivors. Therefore, tissue oxygenation may be more jeopardized by alterations in perfused capillary density than by decreases in flow velocity. Besides, the presence of heterogeneous capillary flow is a key cause for impaired oxygen extraction (10). Regrettably, heterogeneity was not evaluated in the present study. The mechanism responsible for the synergistic detrimental effect of hypoxemia and ischemia was not explored in this study. There is, however, an obvious explanation for the dramatic fall in the fraction of perfused vessels. The increase in cardiac output, which acts as compensatory response to hypoxemia, might have been prevented by hemorrhage. Thus, the reduction in systemic and intestinal oxygen transport must have been larger than in the isolated insults. The resulting tissue hypoxia could trigger vasoconstrictor mechanisms overcoming the locally mediated vasodilation and produced more flow diversion from the gut mucosa, resulting in a profound alteration in villi perfusion. On the contrary, some experimental data suggest that increased arterial oxygenation might protect the gut from ischemic damage and improve the outcome of experimental hemorrhagic shock (11). Unfortunately, systemic and regional oxygen transport, and microvascular perfusion in other territories, was not measured. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3182982507 Arnaldo Dubin, MD, PhD Servicio de Terapia Intensiva Sanatorio Otamendi y Miroli Buenos Aires; and Cátedra de Farmacología Aplicada Facultad de Ciencias Médicas Universidad Nacional de La Plata La Plata, Argentina