Effects of balanced hydroxyethyl starch solutions on gut mucosal microcirculation and exhaled nitric oxide in septic rats: A randomised, animal study.

CONTEXT: Balanced hydroxyethyl starch (HES) solutions with a molecular weight of 130 kDa (tetrastarches) are frequently used in clinical practice. These solutions are derived either from waxy maize or potato starch and they are not bioequivalent. OBJECTIVES: Investigation of the effects of waxy maize-derived and potato-derived starches on intestinal microcirculation and pulmonary inflammation in experimental sepsis. DESIGN: A randomised (three groups), blinded animal study. SETTING: Animal experimental facility in a university hospital. ANIMALS: Twenty-one male Sprague-Dawley rats weighing 275 to 300 g. INTERVENTION: Sepsis was induced by caecal ligation and puncture. Animals received balanced crystalloid infusion (6 ml kg h) for 23 h followed by randomised 1 h bolus infusion (30 ml kg h) of crystalloid: balanced crystalloid solution or waxy maize starch: 6% wt/vol HES 130/0.4 or potato starch: 6% wt/vol HES 130/0.42. Results are presented as median (interquartiles). MAIN OUTCOME MEASURES: Using intravital microscopy, mucosal perfusion was assessed by intercapillary area (ICA) between all perfused capillaries (ICAtotal) and continuously perfused capillaries only (ICAcont). Mucosal blood flow was calculated from arteriolar diameter and red blood cell velocity. Intestinal wall 3-nitrotyrosine (3-NTint) content and exhaled nitric oxide (exNO), to indicate pulmonary inflammation, were measured. RESULTS: Both tetrastarches improved capillary perfusion compared to the crystalloid group, as indicated by reduced ICAtotal [crystalloid 1054 (905 to 1211) µm; waxy maize starch 789 (744 to 940) µm, P <0.05; potato starch 674 (536 to 693) µm, P < 0.05] and reduced ICAcont [crystalloid 1060 (996 to 1340) µm; waxy maize starch 860 (793 to 975) µm, P <0.05; potato starch 701 (558 to 728) µm, P <0.05]. Mucosal blood flow and systemic blood pressure did not differ significantly between groups. 3-NTint was comparable among all groups. exNO was significantly reduced from 11.1 (5.0 to 16.5) ppb to 4.2 (4.0 to 4.8) ppb in the waxy maize group, whereas no significant difference was detected in the potato starch group 6.2 (4.8 to 10.5). CONCLUSION: Bolus infusion of balanced 6% wt/vol tetrastarches augments mucosal capillary perfusion. Pulmonary inflammation in sepsis is differentially influenced by tetrastarches produced from different raw materials.

Effects of titrated arginine vasopressin on hemodynamic variables and oxygen transport in healthy and endotoxemic sheep.

OBJECTIVE: To determine the effects of titrated arginine vasopressin (AVP) alone or in combination with norepinephrine (NE) on hemodynamics and oxygen transport in healthy and endotoxemic sheep. DESIGN: Prospective controlled trial. SETTING: University research laboratory. SUBJECTS: Six adult ewes. INTERVENTIONS: Healthy sheep received AVP as a titrated infusion, initiated with 0.6 units/hr and increased by 0.6 units/hr every 15 mins, either until mean arterial pressure was increased by 20 mm Hg vs. baseline or a maximum of 3.6 units/hr was administered. After 90 mins, AVP infusion was continued with the investigated dosage, and NE (0.2 microg x kg(-1) x min(-1)) was also infused for 90 mins. After a 24-hr period of recovery, endotoxemia was induced and maintained (Salmonella typhosa endotoxin, 10 ng x kg(-1) x min(-1)) in the same sheep for the next 19 hrs. After 16 hrs of endotoxemia, AVP and NE were administered as described previously. MEASUREMENTS AND MAIN RESULTS: Hemodynamics were obtained at baseline, every 15 mins during the titration period, and 60 and 90 mins after additional NE infusion. Variables of oxygen transport were calculated before and after the titration period. In healthy and endotoxemic sheep, AVP reduced heart rate and cardiac index (p <.001) and compromised oxygen delivery (p <.001) and oxygen consumption (healthy sheep, p =.003; endotoxemic sheep, p <.001). Vasopressin infusion did not alter mean pulmonary arterial pressure but increased pulmonary vascular resistance index in both groups (p <.001). Additional infusion of NE further augmented mean arterial pressure and increased cardiac index during endotoxemia (p <.001). This was accompanied by an increase in oxygen delivery and consumption (p <.05 each). CONCLUSIONS: During ovine endotoxemia, AVP decreased cardiac index, compromised oxygen delivery, and increased pulmonary vascular resistance index. These side effects may limit its use as a sole vasopressor during sepsis. Potentially, a simultaneous infusion of AVP and NE could represent a useful therapeutic option.