Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study

INTRODUCTION: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown. METHODS: In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg. RESULTS: ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00). CONCLUSION: Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min. TRIAL REGISTRATION: Clinicaltrials.gov NCT01393782. Registered 12 July 2011

Lisinopril Overdose and Management with Intravenous Angiotensin II

OBJECTIVE: This report describes a case of lisinopril overdose managed in part with an infusion of angiotensin II in a patient with dilated cardiomyopathy and reviews other literature reporting angiotensin-converting enzyme (ACE) inhibitor overdose. DATA SOURCES: Information concerning this patient was obtained through review of the medical chart, conversation with the attending physician, and personal involvement late in the course of the patient's therapy. We conducted MEDLINE and PAPERCHASE searches of the English language literature (restricted to human studies) from 1976 to the present, manually searched Current Contents and references from each publication reviewed, and contacted the manufacturer of lisinopril for any further references they could provide. STUDY SELECTION: All case reports that described an ACE inhibitor overdose. DATA EXTRACTION: Case reports were evaluated for the ACE inhibitor involved, amount ingested, and therapeutic management. DATA SYNTHESIS: Ten patients with ACE inhibitor overdose have been reported, most of whom required only intravenous fluids for blood pressure support. The case presented here is the second report in which the patient's blood pressure was not adequately controlled with fluid and traditional vasopressors and required an infusion of angiotensin II. CONCLUSIONS: Although only a few cases of ACE inhibitor overdose have been reported, it is possible that with widespread use of these agents, overdose may become a more common problem. Management of ACE inhibitor overdose should include general supportive care, gut decontamination when possible, intravenous fluids, and vasopressors if necessary. Intravenous angiotensin II may be effective in situations in which traditional vasopressors fail, and is a physiologically rational treatment. </jats:sec

Near-infrared spectroscopy: a tool for monitoring submerged fermentation processes using an immersion optical-fiber probe

Near-infrared (NIR) spectroscopy has been developed as a noninvasive tool for the direct, real-time monitoring of glucose, lactic acid, acetic acid, and biomass in liquid cultures of microrganisms of the genera Lactobacillus and Staphylococcus. This was achieved employing a steam-sterilizable optical- ber probe immersed in the culture (In-line Interactance Systemt ). Second-derivative spectra obtained were subjected to partial least-squares (PLS) regression and the results were used to build predictive models for each analyte of interest. Multivariate regression was carried out on two different sets of spectra, namely whole broth minus the spectral subtraction of water, and raw spectra. A comparison of the two models showed that the rst cannot be properly applied to real-time monitoring, so this work suggests calibration based on non-difference spectra, demonstrating it to be suf ciently reliable to allow the selective determination of the analytes with satisfactory levels of prediction (standard error of prediction (SEP) , 10%). Direct interfacing of the NIR syst em to the bioreactor control system allowed the implementation of completely automated monitoring of different cultivation strategies (continuous, repeated batch). The validity of the in-line analyses carried out was found to depend crucially on maintaining constant hydrodynamic conditions of the stirred cultures because both gas ow and stirring speed variations were found to markedly in fluence the spectral signal

Effect of Process Conditions on the Growth of Three-Dimensional Dermal-Equivalent Tissue Obtained by Microtissue Precursor Assembly

Bottom-up approach is an appealing strategy to build complex three-dimensional (3D) viable tissues in vitro starting from microtissue precursors (μTP). In this work we biofabricated a thick dermal-like tissue by sequentially combining two steps: a μTPs production and assembly followed by tissue maturation in a purpose-built bioreactor. The μTPs were produced by first seeding bovine primary fibroblasts on gelatine microparticles and then cultivating them in stirring conditions until a thick layer of ∼80μm of de novo synthesized extracellular matrix uniformly covered the microparticle surface. The μTPs were then loaded into a cylindrical chamber (2mm in depth and 35mm in diameter) and let to maturate and assemble into a 3D viable biohybrid tissue under specific fluid flow conditions. Several combinations of perfusion and/or tangential fluid flow were applied and their effect on the tissue formation and maturation was assessed. Results show that structural composition and mechanical features of the final 3D bioengineered tissue are strongly affected by the hydrodynamic environment and demonstrate that by optimizing culture conditions a 3D viable tissue with properties similar to that of native derma could be produced. © 2011 Mary Ann Liebert, Inc

Enhanced production of L-(+) lactic acid in chemostat by Lactobacillus casei DSM20011 using anion-exchange resins and cross-flow filtration in a fully automated pilot plant controlled via NIR.3

Due to the lack of suitable in-process sensors, on-line monitoring of fermentation processes is restricted almost exclusively to the measurement of physical parameters only indirectly related to key process variables, i.e., substrate, product, and biomass concentration. This obstacle can be overcome by near infrared(NIR) spectroscopy, which allows not only real-time process monitoring, but also automated process control, provided that NIR-generated information is fed to a suitable computerized bioreactor control system. Once the relevant calibrations have been obtained, substrate, biomass and product concentration can be evaluated online and used by the bioreactor control system to manage the fermentation. In this work, an NIR-based controlsystem allowed the full automation of a small-scale pilot plant for lactic acid production and provided an excellent tool for process optimization. The growth-inhibiting effect of lactic acid present in the culture broth is enhanced when the growth-limiting substrate, glucose, is also present at relatively high concentrations. Both combined factors can result in a severe reduction of the performance of the lactate production process. A dedicated software enabling on-line NIR data acquisition and reduction,and automated process management through feed addition, culture removal and/or product recovery by microfiltration was developed in order to allow the implementation of continuous fermentation processes with recycling of culture medium and cell recycling. Both operation modes were tested at different dilution rates and the respective cultivation parameters observed werecompared with those obtained in a conventional continuous fermentation. Steady states were obtained in both modes with high performance on lactate production. The highest lactate volumetric productivity, 138 g L−1 h−1, was obtained in continuous fermentation with cell recycling