The purpose of the study was to compare the effects of high and low dose of 6% hydroxyethyl starch solution (HES) on resuscitation for shock induced by intestinal ischemia/reperfusion (I/R) injury in rabbits. Thirty-two anesthetized rabbits were randomized into four groups of eight animals each, which was either treated with no fluid resuscitation as control, lactated Ringer's solution (LRS, 20ml/kg/h), LRS+HES (LRS 18ml/kg/h + HES 2ml/kg/h, low dose of HES) or only treated with HES (high dose of HES, 20ml/kg/h). These rabbits underwent the intestinal I/R injury developed by occluding superior mesenteric artery (SMA) with a noncrushing vascular clamp for 60min and then loosing the clamp for 240min. The fluid resuscitation began at the same time of reperfusion. Hemodynamic parameters including MAP, HR, aortic velocity (Qaorta, as CO) and SMA blood flow (Osma) were measured. Tissue oxygenation was assessed indirectly by measuring the tonometric parameters of gut, including difference between intestinal intramucosal PtCO2 and arterial PaCO2 (PCO2-gap), intestinal intramucosal pH (pHi), arterial lactate acid concentration and oxygen delivery (DO2). Mortality of the rabbits was calculated at the end. The results showed that hemodynamic parameters were significantly higher in group LRS+HES and HES than in group LRS and control (P<0.05). Low dose of HES was better than high dose of HES in restoring hemodynamic parameters (P<0.05). Low dose of HES could greatly decrease lactate and PCO2-gap, significantly improve pHi than other three groups (P<0.05), but high dose of HES did not do so, rather, which induced oral and nasal bleeding, even death of some animals. Low dose and high dose of HES significantly improved DO2 while LRS did not (P<0.05). Therefore low dose of HSE together with LRS was more effective than only high dose of HES or LRS in the resuscitation for shock induced by intestinal I/R injury in rabbits, because hemodynamic parameters increased suitably and tissue oxygenation was greatly improved.
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Introduction: Distributive shock is associated with a hyperdynamic hypotensive state in response to acute inflammation, and most commonly occurs in patients with sepsis. Nitric oxide is a key mediator in the development of distributive shock. Hypothesis: That the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene, would reduce mortality compared to placebo in patients with catecholamine-resistant distributive shock. Methods: In this phase 3, multicenter, randomized, placebo-controlled study, all patients with distributive shock, as assessed by the presence of at least two systemic inflammatory response syndrome (SIRS) criteria, and persistent catecholamine dependence despite adequate fluid resuscitation, who were admitted to one of 61 participating intensive care units were included. Patients were randomized to receive 0.25 mL/kg/h (20 mg/kg/h) pyridoxalated hemoglobin polyoxyethylene or an equal volume of placebo, infused for up to 150 h, in addition to conventional vasopressor therapy. Because treatment could not be blinded, vasopressors and ventilatory support were weaned by protocol. Results: Three-hundred and seventy-seven patients were randomized to pyridoxalated hemoglobin polyoxyethylene (n=183) or placebo (n=194). Age, gender, type of patient (medical or surgical), and APACHE II scores were similar in pyridoxalated hemoglobin polyoxyethylene and placebo patients. Baseline plasma nitrite and nitrate levels were elevated in both groups. Pyridoxalated hemoglobin polyoxyethylene infusion was associated with a rapid increase in systemic blood pressure. Twenty-eight day mortality was 44.3% in the pyridoxalated hemoglobin polyoxyethylene group versus 37.6% in the placebo group, p=0.227. Survivors who had received pyridoxalated hemoglobin polyoxyethylene had a longer vasopressor-free time (21.3 vs 19.7, p=0.035) than did survivors treated with placebo. Conclusions: In this phase III prospective, randomized, controlled trial, the administration of a pyridoxalated hemoglobin solution in patients with septic shock was not beneficial.
It is evident that the patient with sepsis needs immediate attention to allow rapid and effective intervention. Recently, the Sepsis-3 Definitions task force used multivariable logistic regression to develop the qSOFA—a short sequential organ failure assessment (SOFA) score that incorporates a systolic blood pressure of 100 mmHg or less, a respiratory rate of 22/min or greater and/or an acute alteration in mentation—to be used as a means of identifying infected patients on the general ward who may need urgent attention and further workup for possible sepsis (1,2).
Cathepsin B is an ancient family of eukaryotic cysteine proteases. We describe PsCat1, a plant cathepsin B-like transcript, identified as an expressed sequence in Rhizobium-induced, nitrogen-fixing root nodules of pea. In situ hybridization studies in root nodules showed strong, extremely localized expression of PsCat1 in individual cells associated with the central infected tissue. Restriction fragment polymorphism mapping of the PsCat1 locus in pea shows no correlation with existing mutant lines defective in symbiosis.
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Our literature review reaffirms the continued common occurrence of septic shock and estimates a high mortality of around 38%. The high level of heterogeneity observed in this review may be driven by variability in defining and applying the diagnostic criteria, as well as differences in treatment and care across settings and countries.
