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Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg −1 bodyweight −1 . Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia–reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min −1 ) 1.68 (1.02–2.35) versus 2.84 (2.15–3.53), p  = 0.002, mean arterial pressure (mmHg) 29.89 (21.65–38.12) versus 52.34 (43.55–61.14), p  < 0.001, pulse pressure variation (%) 24.84 (17.45–32.22) versus 9.59 (1.68–17.49), p  = 0.004, mean Flux (p.u.) 414.95 (295.18–534.72) versus 327.21 (206.95–447.48), p  = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73–1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.

IntroductionChronic lower back pain (CLBP) is a frequent cause of medical consultations worldwide, and it results in decreased quality of life and disability. Current treatments for CLBP are often not effective, and alternatives are urgently needed. Three promising possibilities have emerged: (1) open-label placebo treatment reduces chronic pain, (2) placebo treatment is as efficacious as opioid treatment with a high correlation between patient expectation and treatment outcome, and (3) observing positive effects in another patient can improve functional capacity. We hypothesise that treatment expectations can be positively influenced through social observation and improve treatment outcome.Methods and analysisIn our clinical trial, we will randomise patients with CLBP into five groups. Two groups receive either a 3 week course of treatment with an analgesic (ANA) (metamizole/dipyrone) or with open-label placebos (OLP). For one of each group, we will build treatment expectations through observational learning and assess its impact on the treatment. For this purpose, one group each will watch either a positive or a neutral video. The intervention groups will be compared with a control group that will not be given any medication or observational learning. Participants will be recruited via all institutions in the Hamburg metropolitan area that treat patients with CLBP. Patients are eligible for inclusion if they are at least 18 years or older, have CLBP (of at least 3 months duration), and agree to potentially receive an active ANA or an OLP. Patients with pain-related “red flags” will be excluded. The study requires 150 participants (30 participants per group) to assess the differences in the primary outcome, pain intensity. Secondary outcomes include changes in treatment expectations, anxiety, comorbid depression, stress-related neuroendocrine measures, functional and structural connectivity, functional capacity, and ANA consumption. All outcomes and treatment expectations will be measured before and after the intervention and 3 months post-intervention.Ethics and disseminationEthical approval was obtained in January 2020 from the Hamburg Medical Ethics Council (ref number PV7067). Outcomes will be disseminated through publications in peer-reviewed journals and presentations at national and international conference meetings.Trial registration numberThe approved trial protocol was registered at the German Clinical Trials Register (DRKS) and can be found at drks.de (Identifier: DRKS00024418).

Purpose Severe acute pancreatitis (SAP) remains a life-threatening disease with classic etiology of systemic inflammatory response and mortality between 30 and 50 %. The aim of the present study is to compare two different treatment strategies of goal-directed hemodynamic management and evaluate their impact on survival, microcirculation, tissue oxygenation, and histopathologic damage in acute pancreatitis in a prospective animal study. Methods Thirty-four domestic pigs were randomly assigned to two different treatment groups. After induction of acute pancreatitis, in group 1 volume administration was guided by central venous pressure (CVP >12 mmHg) and mean arterial pressure (MAP). In group 2, hemodynamic management was guided primarily by left-ventricular stroke volume variation (SVV <10 %), MAP, and cardiac output (CO). Treatment according to randomization was performed for 6 h, and tissue oxygen tension in the pancreas and pancreatic microcirculation were evaluated. Thereafter, animals were observed for 7 days and then sacrificed. Standardized tissue specimens were taken post mortem, and histopathologic scoring was performed. Results Survival after 7 days was 29.4 % in group 2 versus 11.8 % in group 1 ( p  < 0.05). Pancreatic oxygen tension (138.0 ± 89.5 mmHg versus 71.1 ± 35.3 mmHg; p  < 0.05) and pancreatic microcirculation (1,209.9 ± 630 AU versus 732 ± 315 AU; p  < 0.05) were significantly higher in group 2. Significantly less histopathologic damage within the pancreas could be analyzed post mortem in group 2. Conclusions Goal-directed hemodynamic management guided by stroke volume variation led to improved survival, tissue oxygenation, and microcirculatory perfusion, as well as less histopathologic damage in an animal model of severe acute pancreatitis.