Editor’s Perspective What We Already Know about This Topic Both saline and hydroxyethyl starch can be used for fluid resuscitation of hemorrhagic shock Hemodynamic coherence is the concordant performance of macro- and microcirculation It is not known whether saline or hydroxyethyl starch resuscitation achieves better hemodynamic coherence What This Article Tells Us That Is New In a sheep model of hemorrhagic shock, resuscitation with both saline and hydroxyethyl starch restored mean arterial pressure (macrocirculation) After fluid resuscitation with hydroxyethyl starch, microcirculatory perfused vessel density and microvascular flow index (microcirculation) both improved, whereas saline only marginally improved microvascular flow index and perfused vessel density decreased further Resuscitation with hydroxyethyl starch but not saline maintained hemodynamic coherence after hemorrhagic shock Background Fluid resuscitation in hemorrhagic shock aims to restore hemodynamics and repair altered microcirculation. Hemodynamic coherence is the concordant performance of macro- and microcirculation. The present study on fluid therapy in hemorrhagic shock hypothesized that the choice of fluid (0.9% sodium chloride [saline group] or balanced 6% hydroxyethyl starch 130/0.4 [hydroxyethyl starch group]) impacts on hemodynamic coherence. Methods After instrumentation, 10 sheep were bled up to 30 ml/kg body weight of blood stopping at a mean arterial pressure of 30 mmHg to establish hemorrhagic shock. To reestablish baseline mean arterial pressure, they received either saline or hydroxyethyl starch (each n = 5). Hemodynamic coherence was assessed by comparison of changes in mean arterial pressure and both perfused vessel density and microvascular flow index. Results Bleeding of 23 ml/kg blood [21; 30] (median [25th; 75th percentile]) in the saline group and 24 ml/kg [22; 25] ( P = 0.916) in the hydroxyethyl starch group led to hemorrhagic shock. Fluid resuscitation reestablished baseline mean arterial pressure in all sheep of the hydroxyethyl starch group and in one sheep of the saline group. In the saline group 4,980 ml [3,312; 5,700] and in the hydroxyethyl starch group 610 ml [489; 615] of fluid were needed ( P = 0.009). In hemorrhagic shock perfused vessel density (saline from 100% to 83% [49; 86]; hydroxyethyl starch from 100% to 74% [61; 80]) and microvascular flow index (saline from 3.1 [2.5; 3.3] to 2.0 [1.6; 2.3]; hydroxyethyl starch from 2.9 [2.9; 3.1] to 2.5 [2.3; 2.7]) decreased in both groups. After resuscitation both variables improved in the hydroxyethyl starch group (perfused vessel density: 125% [120; 147]; microvascular flow index: 3.4 [3.2; 3.5]), whereas in the saline group perfused vessel density further decreased (64% [62; 79]) and microvascular flow index increased less than in the hydroxyethyl starch group (2.7 [2.4; 2.8]; both P < 0.001 for saline vs. hydroxyethyl starch). Conclusions Resuscitation with hydroxyethyl starch maintained coherence in hemorrhagic shock. In contrast, saline only improved macro- but not microcirculation. Hemodynamic coherence might be influenced by the choice of resuscitation fluid.

Background Conflicting data exist on the renal effects of hydroxyethyl starch (HES) preparations. The current study evaluates the effects of saline-based 6% HES 130/0.4, 10% HES 200/0.5, and a balanced isotonic crystalloid on renal function and microscopic changes in ovine endotoxemic shock. Methods Thirty sheep were subjected to endotoxin infusion (Salmonella typhosa) at incremental doses until mean arterial pressure was less than 65 mmHg. Animals were randomized to receive fluid resuscitation with saline-based 6% HES 130/0.4, 10% HES 200/0.5, or a balanced isotonic crystalloid (n = 10 each). Animals surviving the 12-h intervention period were anesthetized and killed. Kidney samples were taken for microscopic analyses. Results Endotoxemia was associated with hemoconcentration, protein extravasation, and arterial hypotension. Fluid resuscitation established a hypotensive-hyperdynamic circulation with increased cardiac index and oxygen delivery and decreased afterload. Diuresis was lowest in animals treated with 10% HES 200/0.5. In addition, plasma creatinine and urea concentrations increased in sheep treated with 10% HES 200/0.5 (1.2 +/- 0.1 and 19 +/- 2 mg/dl) when compared with the other two groups (0.9 +/- 0.1 and 15 +/- 1 mg/dl, 6% HES 130/0.4; 0.9 +/- 0.1 and 15 +/- 1 mg/dl, crystalloids; each P < 0.05). Electron microscopic tubular injury score was highest in sheep treated with 10% HES 200/0.5 (P < 0.001 vs. 6% HES 130/0.4). Conclusions In ovine endotoxemic shock, saline-based 10% HES 200/0.5 was linked to impaired renal function and more pronounced tubular epithelial injury when compared with 6% HES 130/0.4 and balanced crystalloids.

Background Terlipressin has been suggested as the ideal drug to treat anesthesia-induced hypotension in patients under long-term renin-angiotensin system inhibitor treatment for arterial hypertension. The authors compared the effects of terlipressin and norepinephrine on systemic hemodynamic parameters and gastric mucosal perfusion using a laser Doppler flowmetry technique in patients treated with renin-angiotensin system inhibitors who experienced hypotension at induction of anesthesia. Methods Thirty-two patients scheduled for carotid endarterectomy under general anesthesia and treated with renin-angiotensin system inhibitors had hypotension after induction of general anesthesia. They were randomized to receive 1 mg of terlipressin (n = 16) or norepinephrine infusion (n = 16) to counteract anesthesia-induced hypotension. A laser Doppler probe was introduced into the gastric lumen. All measurements were performed just before surgery, during hypotension, at 30 min, and at 4 h. Results Terlipressin produced an increase in mean arterial pressure and a decrease in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05) over 30 min that were sustained for 4 h. During the infusion, norepinephrine produced an increase in mean arterial pressure and in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05). If compared to norepinephrine, terlipressin reduced oxygen delivery and oxygen consumption (P < 0.05) and increased arterial lactate concentrations (P < 0.05). Conclusion This study showed the efficacy of terlipressin in the treatment of hypotension episodes in anesthetized patients chronically treated with renin-angiotensin system inhibitors, angiotensin converting-enzyme inhibitors, and angiotensin II receptor antagonists. However, the negative effects on gastric mucosal perfusion and the risk of iatrogenic oxygen supply dependency of terlipressin need to be taken into account.

Background Inadequate splanchnic perfusion in septic shock is associated with increased morbidity and mortality. As result of splanchnic ischemia, mucosal permeability increases. Considering the implication of improved mucosal perfusion in terms of maintenance of mucosal barrier integrity, dopamine-1 receptor stimulation could be helpful in septic shock. The goal of the current study was to determine the effects of fenoldopam on systemic hemodynamic parameters and gastric mucosal perfusion in patients with septic shock. Furthermore, the authors tested the hypothesis that the addition of fenoldopam (0.1 microg x kg(-1) x min(-1)) to a combination of norepinephrine and dobutamine (5 microg x kg(-1) x min(-1)) may improve gastric mucosal perfusion in septic shock. Methods Patients with septic shock were randomized to a double-blind 2-h infusion of fenoldopam (n = 20) or placebo (n = 20). Each group received dobutamine (5 microg x kg(-1) x min(-1)), and the dosage of norepinephrine was adjusted to achieve a mean arterial pressure between 70 and 80 mmHg. A laser-Doppler probe and tonometer were introduced into the gastric lumen. Results A significant increase in gastric mucosal perfusion, detected by laser-Doppler flowmetry, was observed in the group treated with fenoldopam (P < 0.05). In addition, this increase in microcirculatory flow occurred despite the fact that systemic flow remained unchanged. Differences in gastroarterial partial pressure of carbon dioxide values were not statistically significant in the fenoldopam and placebo groups. Conclusions The study showed that, for the same mean arterial pressure, short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock.