How early should be "Early Integrated Palliative Care"?

Palliative care, with its focus on comprehensive patient assessment encompassing physical, social, emotional, and spiritual pain, plays a crucial role in modern medicine. Despite its significance, integration with oncology and other healthcare specialties often occurs late in the disease trajectory. Strategies to bridge this gap include considering a "rebranding" of palliative care to "supportive care." Early initiation of palliative care, although challenging to define precisely, aims to improve the quality of life for patients and their families. Studies show some benefits, but the evidence remains limited. An embedded model that encourages interdisciplinary collaboration between oncologists and palliative care practitioners has shown promise. However, it raises questions about training and availability of palliative care specialists. A broader approach involves integrating palliative care principles into medical and nursing education to ensure early recognition of patient needs and empathetic communication. Regular monitoring of patients' physical and non-physical needs, along with appropriate interventions, can alleviate suffering and improve patient outcomes. Ultimately, the integration of palliative care into oncology and other disciplines focuses on addressing the individual's needs and understanding their unique experience of suffering.

Assessing suffering of patients on cancer treatment and of those no longer treated using ESAS-Total Care (TC).

AIM: The aim of the study was to assess the suffering of patients on oncologic treatment and of those no longer on treatment. Preliminarily, we aimed to confirm the psychometric properties of Edmonton Symptom Assessment System-Total Care (ESAS-TC) in different stages of the disease. The ESAS-TC screens physical and psychological symptoms, but also spiritual pain, discomfort deriving from financial problems associated with illness, and suffering related to social isolation. METHODS: A sample of consecutive advanced cancer patients on oncologic therapies treated at the Internistic and Geriatric Supportive Care Unit (IGSCU) of Istituto Nazionale dei Tumori, Milano, and of terminal patients no longer on treatment and cared for by the Fondazione ANT palliative home care team were asked to fill the ESAS-TC. In order to strengthen the previous validation study of the ESAS-TC, 3-ULS (to assess social isolation), JSWBS (to assess spiritual well-being), COST-IT (to assess financial distress), and KPS (to assess functional status) were administered too. RESULTS: The questionnaires were self-reported by 108 patients on treatment (52% >60 years old, female 53%, and 61% with KPS 90-100) and by 94 home care patients (71% >60 years old, female 51%, and 68% with KPS 10-50). The sound psychometric characteristics of ESAS-TC were confirmed. Patients on treatment showed lower total ESAS-TC score (19.3 vs 52.7, p<.001) after controlling for age and functional status, and lower financial distress (p.<001). Financial distress, spiritual suffering, and social isolation, after controlling for age, showed a significantly higher score in home care patients. CONCLUSIONS: Only through an adequate routine assessment with validated tools is it possible to detect total suffering, the "Total pain" of patients, and treat it through a multidisciplinary approach. The study confirms the reliability and validity of the Italian version of ESAS-TC and the importance of supportive and early palliative care fully integrated with oncological treatment.

The adult and pediatric palliative care: differences and shared issues.

Adult and pediatric palliative care (PC) share common aims and ethical principles but differ in many organizational and practical aspects. The aim of this narrative review is to analyze these differences and focus on which key aspects of pediatric palliative care could integrate adult services for a better care of suffering patients.Interventions which are peculiar of pediatric PC respect to adult PC include: an earlier referral to the PC service to identify the needs and plan the interventions at an earlier stage of the disease; consequently, a more systematic cooperation with the disease-specific physicians to reduce the burden of treatments; a better integration with the community and the social surroundings of the patients, to prevent social isolation and preserve their social role; a more dynamic organization of the PC services, to give patients the chance of being stabilized at in-hospital or residential settings and subsequently discharged and cared at home whenever possible and desired; the implementation of respite care for adults, to help the families coping with the burden of the disease of their beloved and promote the home-based PC.This review underlines the relevance of some key-aspects of pediatric PC that can be beneficial also within PC of adults. Its findings give the chance for a more dynamic and modern organization of adult PC services and may serve as a basis of future research for new interventions.

Multiple Electroencephalogram Recordings for Monitoring the Evolution of Neurological Complications during Baclofen Withdrawal Syndrome.

Baclofen withdrawal syndrome represents a clinical emergency that can lead to life-threatening complications. It is often a diagnostic challenge because of its nonspecific nature of presentation and degree of symptom overlap with other clinical diseases. Electroencephalography (EEG) might provide important supporting evidence when neurological complications are involved. We present the case of a 55-year-old woman with sudden onset of motor manifestations at the limbs and an altered mental status 24 hours after cessation of intrathecal baclofen administration, following the removal of the pump due to infection, in whom a computed tomography did not show any acute-onset brain injuries, and multiple EEG recordings were performed. The first EEG showed the presence of bilateral sharply contoured waves, in the absence of epileptic discharges and seizures. No correlation between motor manifestations and EEG changes were detected. This EEG pattern was considered to be the expression of an overexcitation of the central nervous system (CNS) due to the loss of baclofen inhibitory effects, excluding an epileptic origin of motor manifestations. Another EEG, performed 24 hours later, showed the presence of triphasic waves with severe generalised slowing, suggesting the presence of encephalopathy. The last EEG, performed 48 hours after the previous recording, when a recovered state of consciousness was already present, showed regression of the triphasic waves and a reorganisation of the background activity. In our case, repeated EEG evaluation allowed monitoring the evolution of acute encephalopathy developed during baclofen withdrawal syndrome, from the initial phase of CNS hyperexcitability, through the phase of metabolic encephalopathy, and to its resolution. This modality allowed for optimising the diagnostic-therapeutic management of the patient during her stay in the intensive care unit.

The new SUMPOT to predict postoperative complications using an Artificial Neural Network.

An accurate assessment of preoperative risk may improve use of hospital resources and reduce morbidity and mortality in high-risk surgical patients. This study aims at implementing an automated surgical risk calculator based on Artificial Neural Network technology to identify patients at risk for postoperative complications. We developed the new SUMPOT based on risk factors previously used in other scoring systems and tested it in a cohort of 560 surgical patients undergoing elective or emergency procedures and subsequently admitted to intensive care units, high-dependency units or standard wards. The whole dataset was divided into a training set, to train the predictive model, and a testing set, to assess generalization performance. The effectiveness of the Artificial Neural Network is a measure of the accuracy in detecting those patients who will develop postoperative complications. A total of 560 surgical patients entered the analysis. Among them, 77 patients (13.7%) suffered from one or more postoperative complications (PoCs), while 483 patients (86.3%) did not. The trained Artificial Neural Network returned an average classification accuracy of 90% in the testing set. Specifically, classification accuracy was 90.2% in the control group (46 patients out of 51 were correctly classified) and 88.9% in the PoC group (8 patients out of 9 were correctly classified). The Artificial Neural Network showed good performance in predicting presence/absence of postoperative complications, suggesting its potential value for perioperative management of surgical patients. Further clinical studies are required to confirm its applicability in routine clinical practice.

Effects of psychological interventions on anxiety and pain in patients undergoing major elective abdominal surgery: a systematic review.

A maladaptive response to surgical stress might lead to postoperative complications. A multidisciplinary approach aimed at controlling the surgical stress response may reduce procedural complications and improve patients' quality of life in the short and long term. Several studies suggest that psychological interventions may interact with the pathophysiology of surgical stress response, potentially influencing wound repair, innate and adaptive immunity, inflammation, perception of pain, and patients' mood. The aim of this systematic review is to summarise the effects of perioperative psychological interventions on surgical pain and/or anxiety in adult patients scheduled for elective general abdominal and/or urologic surgery.We conducted a systematic review of controlled clinical trials and observational studies involving psychological interventions for adult patients scheduled for elective general abdominal and/or urologic surgery. Only studies reporting pain and/or anxiety among outcome measures were included in the systematic review. The following psychological interventions were considered: (1) relaxation techniques, (2) cognitive-behavioural therapies, (3) mindfulness, (4) narrative medicine, (5) hypnosis and (6) coping strategies.We examined 2174 papers. Among these, 9 studies were considered eligible for inclusion in this systematic review (1126 patients cumulatively): 8 are randomised controlled trials and 1 is an observational prospective pre/post study.Psychological characteristics widely influence the pathophysiological mechanisms underlying the neuroendocrine and inflammatory response to surgical stress, potentially interfering with surgical outcomes. Psychological interventions are technically feasible and realistically applicable perioperatively during abdominal and/or urologic surgery; they influence the pathophysiological mechanisms underlying maladaptive surgical stress response and might have positive effects on patients' surgical outcomes, such as pain and anxiety.

Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis.

BACKGROUND: The "END-of-Life ScorING-System" (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients. MATERIALS AND METHODS: Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient's ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis. RESULTS: Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort. CONCLUSIONS: ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.

In-line filtration reduced phlebitis associated with peripheral venous cannulation: Focus on cost-effectiveness and patients' perspectives.

BACKGROUND: In a previous trial, in-line filtration significantly prevented postoperative phlebitis associated with short peripheral venous cannulation. This study aims to describe the cost-effectiveness of in-line filtration in reducing phlebitis and examine patients' perception of in-hospital vascular access management with and without in-line filtration. METHODS: We analysed costs associated with in-line filtration: these data were prospectively recorded during the previous trial. Furthermore, we performed a follow-up for all the 268 patients enrolled in this trial. Among these, 213 patients responded and completed 6 months after hospital discharge questionnaires evaluating the perception of and satisfaction with the management of their vascular access. RESULTS: In-line filtration group required 95.60€ more than the no-filtration group (a mean of € 0.71/patient). In terms of satisfaction with the perioperative management of their short peripheral venous cannulation, 110 (82%) and 103 (76.9%) patients, respectively, for in-line filtration and control group, completed this survey. Within in-line filtration group, 97.3% of patients were satisfied/strongly satisfied; if compared with previous experiences on short peripheral venous cannulation, 11% of them recognised in-line filtration as a relevant causative factor in determining their satisfaction. Among patients within the control group, 93.2% were satisfied/strongly satisfied, although up to 30% of them had experienced postoperative phlebitis. At the qualitative interview, they recognised no difference than previous experiences on short peripheral venous cannulation, and mentioned postoperative phlebitis as a common event that 'normally occurs' during a hospital stay. CONCLUSION: In-line filtration is cost-effective in preventing postoperative phlebitis, and it seems to contribute to increasing patient satisfaction and reducing short peripheral venous cannulation-related discomfort.

Albumin Loss and Citrate Load in Pre-Dilution High Cut-Off-CVVHDF with Regional Citrate (18 mmol/L) and High Cut-Off CVVHD with Systemic Heparin: An in vitro Study.

BACKGROUND: Convective therapies with high cut-off membranes (HCO) are usually not recommended because of theoretical excessive albumin loss. The aim of this in vitro study is to demonstrate the noninferior safety of pre-dilution hemodiafiltration with HCO (HCO-CVVHDF) with isotonic citrate anticoagulation (18 mmol/L) with respect to heparin anticoagulated hemodialysis with HCO (HCO-CVVHD) in terms of albumin removal and citrate load. METHOD: -Albumin removal was compared in vitro between 3 pre--dilution-HCO-CVVHDF with citrate anticoagulation and 3 -HCO-CVVHD with heparin anticoagulation during 30-min single-pass and 180-min recirculation phases. RESULTS: Considering concentrations and flows in the extracorporeal circuit, the transmembrane albumin removal was 2.06 (1.51; 2.09) g and 2.09 (1.9; 2.8) g respectively for HCO-CVVHDF and HCO-CVVHD, during the single-pass phase; 2.8 (2.67; 4.59) g and 2.54 (2.35; 4.67) g, respectively, for HCO-CVVHDF and HCO-CVVHD during the recirculation phase. Based on the citrate saturation coefficients, a citrate metabolic load of 8.86 mmol/h has been calculated for HCO-CVVHDF. CONCLUSION: HCO-CVVHDF performed with regional anticoagulation with 18 mmol/L citrate solution does not induce higher -albumin transmembrane removal compared to HCO-CVVHD.

In-Line Filtration Reduces Postoperative Venous Peripheral Phlebitis Associated With Cannulation: A Randomized Clinical Trial.

BACKGROUND: Peripheral venous cannulation is an everyday practice of care for patients undergoing anesthesia and surgery. Particles infused with intravenous fluids (eg, plastic/glass/drugs particulate) contribute to the pathogenesis of peripheral phlebitis. The aim of this study is to demonstrate the efficacy of in-line filtration in reducing the incidence of postoperative phlebitis associated with peripheral short-term vascular access. METHODS: In this controlled trial, 268 surgical patients were randomly assigned to in-line filtration and standard care (NCT03193827). The incidence of phlebitis (defined as visual infusion phlebitis [VIP] score, ≥2) within 48 hours was compared between the 2 groups, as well as the onset and severity of phlebitis and the reasons for removal of the cannula. The lifespan of venous cannulae was compared for the in-line filter and no-filter groups through a Kaplan-Meier curve. RESULTS: The incidence of phlebitis within 48 hours postoperatively was 2.2% and 26.9% (difference, 25% [95% confidence interval {CI}, 12%-36%]; odds ratio, 0.05 [0.01-0.15]), respectively, for the in-line filter and no-filter groups (P < .001). From 24 to 96 hours postoperatively, patients in the no-filter group had higher VIP scores than those in in-line filter group (P < .001). Venous cannulae in the in-line filter group exhibited prolonged lifespan compared to those in the no-filter group (P = .01). In particular, 64 (47.8%) of cannulae in the in-line filter group and 56 (41.8%) of those in the no-filter group were still in place at 96 hours postoperatively. At the same time point, patients with a VIP score <3 were 100% in the in-line filter group and only 50% for the no-filter group. In-line filtration was a protective factor for postoperative phlebitis (hazard ratio, 0.05 [95% CI, 0.014-0.15]; P < .0001) and cannula removal (hazard ratio, 0.7 [95% CI, 0.52-0.96]; P = .02). CONCLUSIONS: In-line filtration has a protective effect for postoperative phlebitis and prolongs cannula lifespan during peripheral venous cannulation in surgical patients.

Infection of totally implantable venous access devices: A review of the literature.

Totally implantable venous access devices, or ports, are essential in the therapeutic management of patients who require long-term intermittent intravenous therapy. Totally implantable venous access devices guarantee safe infusion of chemotherapy, blood transfusion, parenteral nutrition, as well as repeated blood samples. Minimizing the need for frequent vascular access, totally implantable venous access devices also improve the patient's quality of life. Nonetheless, totally implantable venous access devices are not free from complications. Among those, infection is the most relevant, affecting patients' morbidity and mortality-both in the hospital or outpatient setting-and increasing healthcare costs. Knowledge of pathogenesis and risk factors of totally implantable venous access device-related infections is crucial to prevent this condition by adopting proper insertion bundles and maintenance bundles based on the best available evidence. Early diagnosis and prompt treatment of infection are of paramount importance. As a totally implantable venous access device-related infection occurs, device removal or a conservative approach should be chosen in treating this complication. For both prevention and therapy, antimicrobial lock is a major matter of controversy and a promising field for future clinical studies. This article reviews current evidences in terms of epidemiology, pathogenesis and risk factors, diagnosis, prevention, and treatment of totally implantable venous access device-related infections.

The Valsalva manoeuvre versus tourniquet for venipuncture.

BACKGROUND: During ultrasound-guided cannulation, venous filling is required for venipuncture. Tourniquet with an elastic tube at the axilla is the most common method to induce venous stasis for cannulation of the deep veins of the arm. Although effective, this method might be associated with short- and long-term complications. Valsalva manoeuvre has been used to produce venous filling in other extrathoracic veins. The aim of this observational study is to demonstrate the effect of Valsalva manoeuvre in respect of the elastic tourniquet on venous distention during echography-guided cannulation of the deep veins of the arm. METHOD: Sixty-nine patients scheduled for cannulation of basilic or brachial vein were prospectively observed. Vein diameters were recorded at rest and after 10 s of Valsalva or tourniquet placement. RESULTS: The mean difference between basilic vein diameters during tourniquet and Valsalva manoeuvre was 0.006 mm (95% confidence interval = -inf, 0.09) with a standard deviation of 0.5 mm (95% confidence interval = 0.5, 0.7; p > 0.01). The mean difference between brachial vein diameters during tourniquet and Valsalva manoeuvre was 0.04 mm (95% confidence interval = -0.23, 0.15) with a standard deviation of 0.8 mm (95% confidence interval = 0.7, 0.9; p > 0.01). DISCUSSION: This increase in cross-sectional basilic and brachial vein diameters was not different to that obtained with the elastic tube tourniquet.

Light sedation with dexmedetomidine: a practical approach for the intensivist in different ICU patients.

Light sedation, corresponding to a Richmond Agitation-Sedation Scale between 0 and -1 is a priority of modern critical care practice. Dexmedetomidine, a highly selective, central, α2-adrenoceptor agonist, is increasingly administered in the intensive care units (ICUs) as an effective drug to induce light sedation, analgesia and a quasi-physiological sleep in critically ill patients. Although in general dexmedetomidine is well tolerated, side effects as bradycardia, hypertension, and hypotension may occur. Although a general dosing range is suggested, different ICU patients may require different and highly precise titration that may significantly vary due to neurological status, cardio-respiratory function, base-line blood pressure, heart rate, liver efficiency, age and co-administration of other sedatives. This review analyzes the use of dexmedetomidine in different settings including pediatric, adult, medical and surgical patients starting with some considerations on delirium prevention and sleep quality in critically ill patients and how dexmedetomidine may contribute to these crucial aspects. Dexmedetomidine use in specific sub-populations with unique characteristics will be detailed, with a special attention to a safe use.

Perioperative Levels of Adiponectin and Oxidative Stress in Patients Undergoing Laparoscopic Abdominal Surgery for Cancer.

BACKGROUND: Low circulating levels of adiponectin are associated with the occurrence of infection after surgery in patients with cancer. Data are lacking on whether surgical stress is associated with a reduction in circulating levels of adiponectin. Furthermore, the relationship between oxidative stress and postoperative complications has not been investigated. OBJECTIVE: The aim of this study was to evaluate the pre-, intra-, and postoperative levels of adiponectin in patients who underwent major abdominal surgery for malignancy and their association with postoperative complications. METHODS: An observational, prospective, single-center study was conducted in patients undergoing abdominal surgery for cancer. Circulating levels of adiponectin and of two biomarkers of oxidative stress were measured preoperatively, at the end of surgery, 24 and 48 hours after surgery. Patients were divided into two groups: complicated (CL+) and uncomplicated (CL-), according to the Clavien-Dindo classification. Temporal patterns of adiponectin and markers of oxidative stress were followed at different time points. RESULTS: Twelve patients were enrolled, seven with postoperative complications (CL+) and five without (CL-). The preoperative median levels of adiponectin were statistically different between CL+ and CL- groups (3.2 µg/ml vs 10.9 µg/ml; p=0.03). Levels of preoperative adiponectin were inversely related to the severity of postoperative complications (Rho= -0.68; p= 0.02). Pre-, intra- and postoperative levels of oxidative stress products were not statistically different between the two groups. Adiponectin levels decreased during surgery in both groups, while those of oxidative stress tended to increase. CONCLUSIONS: Preoperative adiponectin levels correlate with postoperative complications after cancer surgery.

The New MIRUS System for Short-Term Sedation in Postsurgical ICU Patients.

OBJECTIVES: To evaluate the feasibility and safety of the MIRUS system (Pall International, Sarl, Fribourg, Switzerland) for sedation with sevoflurane for postsurgical ICU patients and to evaluate atmospheric pollution during sedation. DESIGN: Prospective interventional study. SETTING: Surgical ICU. February 2016 to December 2016. PATIENTS: Postsurgical patients requiring ICU admission, mechanical ventilation, and sedation. INTERVENTIONS: Sevoflurane was administered with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to -5 by adaptation of minimum alveolar concentration. MEASUREMENTS AND MAIN RESULTS: Data collected included Richmond Agitation Sedation Scale, minimum alveolar concentration, inspired and expired sevoflurane fraction, wake-up times, duration of sedation, sevoflurane consumption, respiratory and hemodynamic data, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment, and laboratory data and biomarkers of organ injury. Atmospheric pollution was monitored at different sites: before sevoflurane delivery (baseline) and during sedation with the probe 15 cm up to the MIRUS system (S1) and 15 cm from the filter-Reflector group (S2). Sixty-two patients were enrolled in the study. No technical failure occurred. Median Richmond Agitation Sedation Scale was -4.5 (interquartile range, -5 to -3.6) with sevoflurane delivered at a median minimum alveolar concentration of 0.45% (interquartile range, 0.4-0.53) yielding a mean inspiratory and expiratory concentrations of 0.79% (SD, 0.24) and 0.76% (SD, 0.18), respectively. Median awakening time was 4 minutes (2.2-5 min). Median duration of sevoflurane administration was 3.33 hours (2.33-5.75 hr), range 1-19 hours with a mean consumption of 7.89 mL/hr (SD, 2.99). Hemodynamics remained stable over the study period, and no laboratory data indicated liver or kidney injury or dysfunction. Median sevoflurane room air concentration was 0.10 parts per million (interquartile range, 0.07-0.15), 0.17 parts per million (interquartile range, 0.14-0.27), and 0.15 parts per million (interquartile range, 0.07-0.19) at baseline, S1, and S2, respectively. CONCLUSIONS: The MIRUS system is a promising and safe alternative for short-term sedation with sevoflurane of ICU patients. Atmospheric pollution is largely below the recommended thresholds (< 5 parts per million). Studies extended to more heterogeneous population of patients undergoing longer duration of sedation are needed to confirm these observations.

Organ dysfunction during continuous veno-venous high cut-off hemodialysis in patients with septic acute kidney injury: A prospective observational study.

BACKGROUND: Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI). METHODS: An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Thirty-eight patients with septic shock and AKI (KDIGO stage≥1) treated with HCO-CVVHD have been included in this study. Patients were divided into Survivors and non-Survivors according to mortality observed at 72nd hr of treatment. The variation of SOFA scores and clinical/biochemical parameters were described over time for the entire population and specifically for Survivors and non-Survivors. Similarly, circulating inflammatory mediators (as IL-6, TNF-a and IL-10) were described over time. A logistic regression analysis was used to identify the baseline clinical and biochemical parameters associated with 72 hrs-ICU mortality. RESULTS: Overall, the mean SOFA score was 12±3 at baseline, 10.9±3 at 6hrs, 9.8±3 at 12hrs, 8.9±3.3 at 24 hrs, and 8±3.5 at 48 hrs after HCO-CVVHD initiation; and 6.5±2.7 at 24 hrs and 6.6±3 at 48 hrs after HCO-CVVHD discontinuation. In the multivariate regression analysis, baseline serum lactate levels and AKI stage independently correlated with short-term mortality during HCO-CVVHD. A significant reduction was observed in circulating levels of TNFα and IL-6 among Survivors. CONCLUSIONS: SOFA score significantly decreased early after initiation of HCO-CVVHD in patients with septic AKI. Baseline lactate levels and the AKI stage resulted to be associated to 72 hrs-ICU-mortality.

Vasodilator activity of hydrogen sulfide (H2S) in human mesenteric arteries.

The role of endogenous H2S has been highlighted as a gaseous transmitter. The vascular smooth muscle inhibitory effects of H2S have been characterized in isolated aorta and mesenteric arteries in rats and mice. Our study was aimed at investigating the vascular effects of H2S on human isolated mesenteric arteries and examining the underlying mechanisms involved. All experiments were performed on rings (4-8mm long) of human mesenteric arteries obtained from patients undergoing abdominal surgery. Ethical approval was obtained from the Ethics Committee of the University Hospital of the University of Florence (app. N. 2015/0024947). The effect of NaHS, an H2S donor, was determined using noradrenaline pre-contracted human isolated mesenteric rings. NaHS evoked a concentration-dependent relaxation (EC50 57µM). In contrast, homocysteine, an endogenous precursor of H2S, failed to affect human isolated mesenteric rings. Vasorelaxant response to NaHS was reduced by endothelium removal, application of the nitric oxide synthase inhibitor L-NAME and ODQ inhibitor of cyclic GMP. SQ 22536, an adenylate-cyclase inhibitor, failed to block NaHS-induced vasorelaxation. Inhibition of endogenous prostanoid production by indomethacin significantly reduced NaHS induced vasorelaxation. The role of potassium channels was also examined: blockers of the Ca2+-dependent potassium channel, charybdotoxin and apamin, failed to have any influence on the relaxant response to NaHS on this vascular tissue. In summary, H2S induced relaxation of isolated rings of human mesenteric arteries. Endothelium-dependent related mechanisms with the stimulation of ATP-sensitive potassium channels represents important cellular mechanisms for H2S effect on human mesenteric arteries.

Cardiac output: a central issue in patients with respiratory extracorporeal support.

The iLA-activve® Novalung is a new extracorporeal device specifically designed for lung support in patients with hypercapnic and/or hypoxemic respiratory failure. To date, only low-flow applications for decompensated hypercapnic chronic obstructive pulmonary disease have been reported in the literature. Here, we briefly report three cases of iLA-activve use in patients with hypercapnic-hypoxemic acute lung failure assisted with mid-flow (up to 2.4 L/min) and different single/double venous cannulation. The main findings of our small case series were: firstly, extracorporeal blood flows over 2.0 L/min across the membrane provided clinically satisfying decarboxylation and improved oxygenation; secondly, the ratio between blood flow through the membrane and the patient's cardiac output (CO) was a major determinant for the oxygen increase. The latter could, therefore, be a useful indicator for understanding performance in the complex and multifactorial evaluation of patients with extracorporeal veno-venous lung support.