Impact of the FloTrac/VigileoTM Monitoring on Intraoperative Fluid Management and Outcome after Liver Resection.

BACKGROUNDS: Perioperative fluid-therapy is a still a debated issue. In hepatic surgery, volume load must be strictly monitored to assure both a safe hemodynamics and low central venous pressure (CVP) to limit the backflow bleeding. Retrospectively, we compared intraoperative fluid management before and after the adoption of a semi-invasive hemodynamic monitoring. METHODS: We compared patients submitted to liver resection monitored by FloTrac/VigileoTM (group A) vs. patients who did not (group B). We searched for differences about hemodynamics, fluid therapy and outcome. RESULTS: Three hundred fifty-five patients underwent hepatic resection due to neoplasm: group A - n = 179 and group B - n = 176. At the end of the resection, patients of group A showed a higher mean arterial pressure (MAP) than group B (74 ± 12 vs. 49.4 ± 8 mm Hg, respectively; p < 0.001). Cardiac index and stroke volume variation in group A were within a normal range. Fluid input was higher in group B than in group A (12.0 ± 3.4 vs. 7.6 ± 3.1 mL/kg/h, respectively; p < 0.001) and fluid balance was significantly different: group A -400 ± 1,527 vs. group B 326 ± 1,527 mL (p < 0.001). Group B showed a greater number of cases complicated outcomes (36 vs. 20; p = 0.014). Considering only those subjects who were able to reach their hemodynamic targets (MAP ≥65 mm Hg and CVP ≤7 mm Hg), we found similar data. CONCLUSIONS: Patients who received a monitored fluid therapy experienced a safer outcome.

Prolonged continuous wound infusion of local anesthetic and steroid after major abdominal surgery to reduce opioid consumption: a randomized, double-blind trial.

BACKGROUND: Continuous wound infusion (CWI) is effective for post-operative pain management, but the effect of prolonged infusions and the use of steroids in the infused mixture have never been addressed. We investigate the effect of prolonged CWI with ropivacaine 0.2% (R) over seven days and methylprednisolone (Mp) 1 mg/kg infused in the wound in the first 24 hours. METHODS: This is a randomized, double blind, phase III trial (RCT) in major abdominal surgery with laparotomy. After a 24-hours pre-peritoneal CWI of R-Mp, patients were randomized to receive either R-Mp or placebo for the next 24 hours. Then, patient-controlled CWI with only ropivacaine 0.2% or placebo (according to the randomization group) was planned between 48 hours and seven days after surgery. Morphine equivalents at seven days were analyzed, together with any catheter- or drug-related side effect and PPSP at 3 months. RESULTS: We enrolled 120 patients (63 in the CWI group, 57 in the placebo group). Prolonged CWI did not reduce opioid consumption in the first seven postoperative days (P=0.08). CWI was associated with reduced consumption of non-opioid analgesics (P=0.03). Most of the patients continued to require bolus in the surgical wound beyond 48 hours. PPSP prevalence was not different between groups. CONCLUSIONS: Prolonged infusion with R-Mp is safe and effective but did not reduce opioid consumption in the seven days after surgery or PPSP prevalence.

The number of people exposed to water stress in relation to how much water is reserved for the environment: a global modelling study.

BACKGROUND: Increasing human demand for water and changes in water availability due to climate change threatens water security worldwide. Additionally, exploitation of water resources induces stress on freshwater environments, leading to biodiversity loss and reduced ecosystem services. We aimed to conduct a spatially detailed assessment of global human water stress for low to high environmental flow (EF) protection. METHODS: In this modelling study, we used the LISFLOOD model to generate daily natural flows without anthropogenic water use for 1980-2018. On the basis of these flows, we selected three EF methods (EF with high ecological protection [EFPROT], EF with minimum flow requirements [EFMIN], and variable monthly flow [EFVMF]) to calculate monthly EFs. We assessed monthly consumptive water use for industry, agricultural crops, livestock, municipalities, and energy production for 2010. We then estimated the corresponding number of people under water stress per month on a global and national level using a spatially detailed population database for 2010. FINDINGS: We estimate that 3·2 billion (EFPROT), 2·4 billion (EFVMF), and 2·2 billion (EFMIN) people lived under water stress for at least 1 month per year, corresponding to 46%, 35%, and 32% of the world's population in 2010, respectively. Around 80% of people living under water stress lived in Asia; in particular, India, Pakistan, and northeast China. Compared with EFMIN, imposing EFPROT globally would have put between 710 million (March) to 1 billion (June) additional people under water stress on a monthly basis, whereas this would have been 72 million (August) to 218 million (April) additional people if EFVMF were imposed. INTERPRETATION: Ensuring high ecological protection would put nearly half of the world's population (3·2 billion people) under water stress for at least 1 month per year. Policy makers and water managers have to make an important trade-off when allocating limited water resources between direct human needs and the environment. A better understanding of local ecosystem needs is crucial to alleviating current and future human water stress, while sustaining healthy ecosystems. FUNDING: None.

Immune function after major surgical interventions: the effect of postoperative pain treatment.

INTRODUCTION: Impaired immune function during the perioperative period may be associated with worse short- and long-term outcomes. Morphine is considered a major contributor to immune modulation. PATIENTS AND METHODS: We performed a pilot study to investigate postoperative immune function by analyzing peripheral blood mononuclear cells' functionality and cytokine production in 16 patients undergoing major abdominal surgery. All patients were treated with intravenous (i.v.) patient-controlled analgesia with morphine and continuous wound infusion with ropivacaine+methylprednisolone for 24 hours. After 24 hours, patients were randomized into two groups, one continuing intrawound infusion and the other receiving only i.v. analgesia. We evaluated lymphoproliferation and cytokine production by peripheral blood mononuclear cells at the end of surgery and at 24 and 48 hours postoperatively. RESULTS: A significant reduction in TNF-α, IL-2, IFN-γ and lymphoproliferation was observed immediately after surgery, indicating impaired cell-mediated immunity. TNF-α and IFN-γ remained suppressed up to 48 hours after surgery, while a trend to normalization was observed for IL-2 and lymphoproliferation, irrespective of the treatment group. A significant inverse correlation was present between age and morphine and between age and lymphoproliferation. No negative correlation was present between morphine and cytokine production. We did not find any differences within the two groups between 24 and 48 hours in terms of morphine consumption and immune responses. CONCLUSION: A relevant depression of cell-mediated immunity is associated with major surgery and persists despite optimal analgesia. Even though morphine may participate in immunosuppression, we did not retrieve any dose-related effect.

Microevolution of Anthrax from a Young Ancestor (M.A.Y.A.) Suggests a Soil-Borne Life Cycle of Bacillus anthracis.

During an anthrax outbreak at the Pollino National Park (Basilicata, Italy) in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil-borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA) and next generation Whole Genome Sequencing (WGS). PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near-surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis.

Continuous wound infusion of local anesthetic and steroid after major abdominal surgery: study protocol for a randomized controlled trial.

BACKGROUND: Inflammatory response is one of the key components of pain perception. Continuous infusion (CWI) of local anesthetics has been shown to be effective in controlling pain and reducing postoperative morphine consumption, but the effect of adding a potent anti-inflammatory drug (such as a steroid) has never been addressed. In our study, we want to investigate the effect of CWI with local anesthetic + methylprednisolone on acute and persistent pain, correlating clinical data with biomarkers of inflammation and genetic background. METHODS/DESIGN: After approval by their institutional review board, three hospitals will enroll 120 patients undergoing major abdominal surgery in a randomized, double-blind, phase III study. After a 24-h CWI of ropivacaine 0.2 % + methylprednisolone 1 mg/kg, patients will be randomly assigned to receive either ropivacaine + steroid or placebo for the next 24 h. Then, patient-controlled CWI with only ropivacaine 0.2 % or placebo (according to the group of randomization) is planned after 48 h up to 7 days (bolus 10 ml, lock-out 1 h, maximum dose of 40 ml in 4 h). Morphine equivalent consumption up to 7 days will be analyzed, together with any catheter- or drug-related side effect. Persistent post-surgical pain (PPSP) incidence will also be investigated. Our primary endpoint is analgesic consumption in the first 7 days after surgery; we will evaluate, as secondary endpoints, any catheter- or drug-related side effect, genotype/phenotype correlations between some polymorphisms and postoperative outcome in terms of morphine consumption, development of the inflammatory response, and incidence of PPSP. Finally, we will collect, in a subgroup of patients, wound exudate samples by micro-dialysis, blood samples, and urine samples up to 72 h to investigate local and systemic inflammation and oxidative stress. DISCUSSION: This is a phase III trial to evaluate the safety and efficacy of wound infusion with steroid and local anesthetic. The study is aimed also to evaluate how long this infusion has to be maintained in order to maximize effectiveness. Our data are intended to quantify the amount of ropivacaine and methylprednisolone needed by patients undergoing major abdominal surgery, to be stored in a new nanotechnology device for sustained pain treatment after surgery. We also aim to clarify the roles of inflammatory response, oxidative stress, and genetic background on postoperative and persistent pain after major abdominal surgery. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT02002663 ) on 24 Oct. 2013.