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Background Postoperative acute kidney injury (PO-AKI) is a leading cause of short- and long-term morbidity and mortality, as well as progression to chronic kidney disease (CKD). The aim of this study was to explore the physicians’ attitude toward the use of perioperative serum creatinine (sCr) for the identification of patients at risk for PO-AKI and long-term CKD. We also evaluated the incidence and risk factors associated with PO-AKI and renal function deterioration in patients undergoing major surgery for malignant disease. Methods Adult oncological patients who underwent major abdominal surgery from November 2016 to February 2017 were considered for this single-centre, observational retrospective study. Routinely available sCr values were used to define AKI in the first three postoperative days. Long-term kidney dysfunction (LT-KDys) was defined as a reduction in the estimated glomerular filtration rate by more than 10 ml/min/m2 at 12 months postoperatively. A questionnaire was administered to 125 physicians caring for the enrolled patients to collect information on local attitudes regarding the use of sCr perioperatively and its relationship with PO-AKI. Results A total of 423 patients were observed. sCr was not available in 59 patients (13.9%); the remaining 364 (86.1%) had at least one sCr value measured to allow for detection of postoperative kidney impairment. Among these, PO-AKI was diagnosed in 8.2% of cases. Of the 334 patients who had a sCr result available at 12-month follow-up, 56 (16.8%) developed LT-KDys. Data on long-term kidney function were not available for 21% of patients. Interestingly, 33 of 423 patients (7.8%) did not have a sCr result available in the immediate postoperative period or long term. All the physicians who participated in the survey (83 out of 125) recognised that postoperative assessment of sCr is required after major oncological abdominal surgery, particularly in those patients at high risk for PO-AKI and LT-KDys. Conclusion PO-AKI after major surgery for malignant disease is common, but clinical practice of measuring sCr is variable. As a result, the exact incidence of PO-AKI and long-term renal prognosis are unclear, including in high-risk patients. Trial registration ClinicalTrials.gov, NCT04341974.

Background: International data on the epidemiology, ventilation practice, and outcomes in patients undergoing abdominal robotic-assisted surgery (RAS) are lacking. The aim of the study was to assess the incidence of postoperative pulmonary complications (PPCs), and to describe ventilator management after abdominal RAS. Methods: This was an international, multicentre, prospective study in 34 centres in nine countries. Patients ≥18 yr of age undergoing abdominal RAS were enrolled between April 2017 and March 2019. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score was used to stratify for higher risk of PPCs (≥26). The primary outcome was the incidence of PPCs. Secondary endpoints included the preoperative risk for PPCs and ventilator management. Results: Of 1167 subjects screened, 905 abdominal RAS patients were included. Overall, 590 (65.2%) patients were at increased risk for PPCs. Meanwhile, 172 (19%) patients sustained PPCs, which occurred more frequently in 132 (22.4%) patients at increased risk, compared with 40 (12.7%) patients at lower risk of PPCs (absolute risk difference: 12.2% [95% confidence intervals (CI), 6.8–17.6%]; P

Background: The current effective delivered dose is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the current effective delivered dose using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. Methods: We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. Results: In CVVH, the median SC values were 1.06 (1.02–1.07) and 1.02 (1.01–1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01–31.31) mL/kg/h and 30.30 (29–31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96–1.02) and 1 (0.95–1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52–31.32) mL/kg/h and 31.16 (30–31.75) mL/kg/h (discrepancy of –2.97%), respectively. Conclusion: Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the current effective delivered dose during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.

OBJECTIVES The aim of this prospective observational study was to evaluate the influence of OPRM1 polymorphism on the analgesic efficacy (including visual analog scale [VAS] scores and requirement for rescue analgesia) of a standard dose of intrathecal morphine. MATERIALS AND METHODS An Italian cohort of 63 parturients, scheduled for elective cesarean section at a tertiary University Hospital, received spinal anesthesia with hyperbaric bupivacaine and morphine 100 mcg. For the first 48 hours in the postoperative period the patients received acetaminophen 1 g IV q6hr. Incident pain was treated with ketorolac 30 mg IV. Every 6 hours the following parameters were registered: VAS at rest, VAS during movements, postoperative nausea and vomiting, pruritus, and rescue analgesic medications requirements. Age and anthropometric data, number of pregnancies, educational level, OPRM1 genotype, were also obtained. RESULTS Of the 63 patients enrolled, 45 (71%) were homozygous genotype A/A (118A group), whereas 18 carried the G variants of OPRM1 (A/G or G/G) (118G group). No significant differences in analgesic rescue doses' administration and in incidence of moderate/severe postoperative pain (VAS>3) between the 2 groups were observed. Pruritus was more frequent in the 118A group than in the 118G group in the first 24 hours of the postoperative period. DISCUSSION In the Italian population participating in this study there was a different incidence of pruritus in the postcesarean period in response to intrathecal opioids related to OPRM1 gene polymorphism, but not of postoperative pain.

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.

BACKGROUND Postoperative residual curarisation (PORC) is a risk directly related to the use of neuromuscular blocking agents during surgical procedures. Acceleromyography is distressing for conscious patients when assessing PORC. Diaphragm ultrasonography could be a valid alternative. OBJECTIVES The primary objective was to achieve a 28% lower incidence of PORC in patients who, after rocuronium administration, received neostigmine or sugammadex at 30 min after surgery. To assess PORC, diaphragm ultrasonography was used, and thickening fractioning [the difference of thickness at the end of inspiration (TEI) and at the end of expiration (TEE), normalised for TEE (TEI - TEE/TEE)] was measured. PORC was defined as thickening fractioning of 0.36 or less. The secondary object was the comparison, in the two treatment groups, of the return to baseline thickening fractioning at 30 min after surgery (ΔTF30). DESIGN Randomised, double-blind, single-centre study. SETTING University Hospital Careggi, Florence, Italy. PATIENTS Patients of American Society Anesthesiologists' physical status 1 or 2, 18 to 80 years, receiving rocuronium during microlaryngeal surgery. INTERVENTIONS At the end of surgery participants were randomised to receive neostigmine (NEO group) or sugammadex (SUG group) as the reversal drug. Thickening fractioning and ΔTF30 were evaluated at baseline and at 0, 10 and 30 min after surgery. MAIN OUTCOME MEASURES TEE and TEI at each time point. RESULTS A total of 59 patients with similar demographic characteristics were enrolled. An association between lack of recovery (thickening fractioning ≤0.36) and drug treatment was only observed at 0 min (SUG vs. NEO, P

BACKGROUND The control of postoperative pain (POP) is a key component of perioperative care. POP after vitreo-retinal surgery (VRS) has been under-investigated, and its incidence remains elusive. METHODS In order to assess POP after VRS, the associated risk factors and efficacy of the analgesic protocol in use at our institution, we made a one-year retrospective study on patients undergoing VRS. Patients aged >18 years, ASA Class I-III undergoing VRS entered the study. POP was evaluated by measuring a Numerical Rating Scale (NRS), and analgesic consumption. RESULTS A total of 782 patients entered the study. Patients received locoregional (LRA) or general anesthesia (GA) with supplemental block. Twenty-two percent of patients needed analgesics (acetaminophen in 97% of cases), mostly between two and six hours after surgery. The univariate analysis showed a positive association between POP and duration of surgery (P

Background: Technical factors at the moment of catheter insertion might have a role in peripherally inserted central catheter–related thrombotic risk. We performed a systematic review and meta-analysis to define the actual rate of peripherally inserted central catheter–related symptomatic deep vein thrombosis in patients in whom catheter insertion was performed according to ultrasound guidance, appropriate catheter size choice, and proper verification of tip location. Methods: We searched Medline, Embase, and Cochrane Library. Only prospective observational studies published in peer-reviewed journals after 2010 up to November 2018 reporting peripherally inserted central catheter–related deep vein thrombosis rate were included. All studies were of adult patients who underwent peripherally inserted central catheter insertion. Results were restricted to those studies which included in their methods ultrasound guidance for venipuncture, catheter tip location, and a catheter size selection strategy. Random-effect meta-analyses and arcsine transformation for binomial data were performed to pool deep vein thrombosis weighted frequencies. Results: Of the 1441 studies identified, 15 studies involving 5420 patients and 5914 peripherally inserted central catheters fulfilled our inclusion criteria. The weighted frequency of peripherally inserted central catheter–related deep vein thrombosis was 2.4% (95% confidence interval = 1.5–3.3) and remained low in oncologic patients (2.2%, 95% confidence interval = 0.6–3.9). Thrombotic rate was higher in onco-hematologic patients (5.9%, 95% confidence interval = 1.2–10). Considerable heterogeneity (I2 = 74.9) was observed and all studies were considered at high risk of attrition bias. Conclusions: A proper technique is crucial at the moment of peripherally inserted central catheter insertion. Peripherally inserted central catheter–related deep vein thrombosis rate appears to be low when evidence-based technical factors are taken into consideration during the insertion procedure.

Background Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics–pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. Methods A prospective, experimental, randomized study was carried out in adult male Sprague–Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP). Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans) was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC). The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90%) for 80 and 100% of Tfree > minimum inhibitory concentration (MIC) for 80 and 100% of dosing interval. Measurements and main results After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104–1 × 105 CFU in CLP rats). CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004), while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p 90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. Conclusions Sepsis causes changes in the PK of CTX and an alteration in the sialic components of the GFB, with consequent loss of protein-bound CTX. Among factors that can affect drug pharmacokinetics during the early phases of sepsis, urinary loss of both free and albumin–bound antimicrobials should be considered.

Background The extensive use of neuromuscular blocking agents (NMBAs) during surgical procedures still leads to potential residual paralyzing effects in the postoperative period. Indeed, neuromuscular monitoring in an intra-operative setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle block, but their short half-life may lead to residual curarization in the ward, especially when intermediate or long-acting NMBAs have been administered. Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been shown to give full and rapid recovery of muscle strength, thus minimizing the occurrence of residual curarization. Acceleromyography of the adductor pollicis is the gold standard for detecting residual curarization, but it cannot be carried out on conscious patients. Ultrasonography of diaphragm thickness may reveal residual effects of NMBAs in conscious patients. Methods/design This prospective, double-blind, single-center randomized controlled study will enroll patients (of American Society of Anesthesiologists physical status I–II, aged 18–80 years) who will be scheduled to undergo deep neuromuscular block with rocuronium for ear, nose, or throat surgery. The study’s primary objective will be to compare the effects of neostigmine and sugammadex on postoperative residual curarization using two different tools: diaphragm ultrasonography and acceleromyography of the adductor pollicis. Patients will be extubated when the train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate the thickening fraction, which is the difference between the end expiratory thickness and the end inspiratory thickness, normalized to the end expiratory thickness. Ultrasonography will be performed before the initiation of general anesthesia, before extubation, and 10 and 30 min after discharging patients from the operating room. The secondary objective will be to compare the incidence of postoperative complications due to residual neuromuscular block between patients who receive neostigmine and those who receive sugammadex. Discussion Postoperative residual curarization is a topic of paramount importance, because its occurrence can cause complications and increase the length of stay in hospital and the related costs. Diaphragm ultrasound assessment may become a bedside integrative tool in the neuromuscular monitoring field to detect concealed residual curarization in surgical patients who have received paralyzing agents. Trial registration EudraCT, 2013-004787-62. Registered on 18 June 2014, as “Evaluation of muscle function recovery after deep neuromuscular blockade by acceleromyography of the adductor pollicis or diaphragmatic echography: comparison between sugammadex and neostigmine.” ClinicalTrials.gov, NCT02698969. Registered on 15 February 2016, as “Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs.” Electronic supplementary material The online version of this article (10.1186/s13063-018-2525-7) contains supplementary material, which is available to authorized users.

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.

Continuous venovenous haemodialysis with high cut-off membrane (HCO-CVVHD) is often used in critically ill septic patients with acute kidney injury (AKI) to sustain renal function and to remove circulating inflammatory mediators. The aim of this study was to analyse the extracorporeal removal of linezolid and related alterations in pharmacokinetic/pharmacodynamic (PK/PD) parameters during HCO-CVVHD. Three critically ill septic patients with AKI, treated with linezolid and HCO-CVVHD, were prospectively observed. To calculate the extracorporeal clearance of linezolid and the PK parameters, effluent, pre-filter and post-filter samples were contemporaneously collected before linezolid infusion, just after 1-h infusion (maximum serum concentration; C(max)), at 3 h and 6 h after dosing, and before the next dose (trough serum concentration; C(min)). Linezolid C(max) and C(min) (pre-filter) ranged from 10.4-23.5 mg/L and from 2.9-10.3 mg/L. The dialysate saturation coefficient was 0.66-0.85 and the extracorporeal clearance with a diffusive dose of 35 m L/kg/h ranged from 2.1-2.5 L/h. Total linezolid clearance was between 1.7 L/h and 6.3 L/h. The total area under the plasma concentration-time curve (AUC0-∞) ranged from 95.1 mgh/L to 352.9 mgh/L, in accordance with the different clinical conditions. AUCfree/MIC ratios were always

A new light has recently been shed on palliative care, especially, on its multidisciplinary approach developed to improve the Quality of life of seriously ill patients and their families. However, palliative care is still often mistakenly referred to as an end-of-life care and wrongly interchanged with hospice care. Nephropathic patients usually present a decrease in expectancy and Quality of life and may benefit from palliative care as opposed to hospice care. Palliative care requires a tight collaboration among different health care professionals, patients and their families, to share diagnosis, prognosis, realistic goals of treatment and therapeutic decisions. Several approaches may be attempted to improve the Quality of life of chronic nephropathic patients, such as palliative dialysis, conservative management and peritoneal dialysis. For example, personalized goals and a wider concept of adequacy of extracorporeal treatment are the bases of palliative dialysis. In specific subgroups of frail patients, the pharmacological conservative management could be more appropriate than extracorporeal treatment, as the former reduces the burdens derived from invasive procedures. Finally, peritoneal dialysis could be an important option for frail patients to avoid an aggressive extracorporeal treatment while maintaining a gentle solute and fluid control. However, only limited evidences are available on palliative and hospice care performed on patients with Acute Kidney Injury (AKI). Herein, the main variables affecting the medical decision-making on palliative care in nephropathic patients are described, and the different approaches available to improve quality of palliative care during Chronic and Acute Kidney Injury are analyzed.

Near-infrared spectroscopy (NIRS) has been used to detect in vivo microvascular alterations by means of a vascular occlusion test. We sought to analyse by NIRS the microcirculatory profile of patients undergoing prolonged tourniquet-induced bloodless condition for extremity surgery, and compare the results with time of ischemia and comorbidities. We conducted a prospective observational study on 42 patients undergoing upper limb surgery. Regional anaesthesia was achieved and ischemia was induced by a tourniquet cuffed at 250 mmHg. The probe of a NIRS monitor (InSpectra 325, Hutchiston, USA) was placed on the brachial muscle, and muscle oxygen saturation (StO2) was recorded continuously before anaesthesia, during and after surgery. The following variables were recorded: baseline StO2, StO2 desaturation slope during occlusion (dSlope, units/s), resaturation rate following ischemia (RR, units/s), hyperaemic peak (peak, units), and duration of the hyperaemic period following ischemia (hyperaemic time, s). Values of dSlope were similar among all patients. RR and hyperaemic time were significantly correlated with the duration of ischemia, but not with comorbidities [p = 0.007 CI (−35.64 to −13.1), and p

Objective The development of sepsis in patients with traumatic brain injury increases mortality, exacerbates morphological and functional cerebral damage, and causes persistent neuroinflammation, including microglial activation. The administration of antibiotics possessing both antimicrobial and immunomodulatory activity might attenuate both sepsis and posttraumatic cerebral inflammation. We compared the potential therapeutic efficacy of two tetracyclines, minocycline and the newer generation tigecycline, on functional neurobehavioral impairment and regional histopathological damage in an experimental model of combined traumatic brain injury and sepsis. Design Prospective, experimental animal study. Setting University Research Laboratory. Subjects Adult male Sprague-Dawley rats. Interventions Controlled cortical impact was used to induce traumatic brain injury and cecal ligation and puncture for sepsis. Immediately following injury, animals were treated with minocycline (45 mg/kg intraperitoneal), tigecycline (7.5 mg/kg intraperitoneal), or saline every 12 hours for 3 days. Measurements and main results The development of sepsis and cerebral inflammatory response were evaluated, respectively, by 1) growth of peritoneal microorganisms and clinical variables and 2) tumor necrosis factor-α expression in the perilesional cortex. To assess posttraumatic outcome, vestibulomotor and cognitive function were evaluated at different time points for 14 days post injury whereupon animals were killed and cerebral tissue analyzed for lesion volume, regional hippocampal (CA1/CA3) cell death, and microglial activation in the perilesional cortex, lesion core zone, and choroid plexus. Treatment with both antibiotics reduced microorganism growth, body weight loss, and mortality but had no effect on vestibulomotor or cognitive function. Minocycline alone attenuated postinjury cortical lesion volume, hippocampal CA3 neuronal cell loss, tumor necrosis factor-α expression, and the extent of microglial activation and infiltration. Conclusions The significantly heightened mortality caused by the superimposition of sepsis upon traumatic brain injury can be reduced by administration of both antibiotics but only minocycline can decrease the extent of cell death in selectively cortical and hippocampal brain regions, via, in part, a reduction in cerebral inflammation.

Summary The progressive opening up of Intensive Care Units (ICUs) has brought about a series of questions regarding the presence of relatives alongside patients in intensive care, also for extended periods of time. The presence of visitors in the ward would appear to exacerbate the situation, while at the same time opening up communicative, relational and ethical issues regarding the experience of critical illness, as lived by patients, families or health care professionals (HCPs). Due to the opening up of ICUs, it seemed necessary to take into greater consideration the access of minors in particular, whether infants, children or adolescents. The reason for this particular interest lies in the fact that minors are relatives of a various degree from that of the hospitalised patient. The access of minors in ICUs appears to be an aspect that should not be neglected, but should instead be managed with great care when suggested and planned by the ward staff. Following these observations, an operational protocol was written, which could determine the access of minors and then guide them with the family and HCPs through the various phases of their visits to ICUs. The execution of the procedure also proved to stimulate more in-depth training and greater professionalism on the part of the HCPs and provided them with practical guidance, thus resolving their previous sensations of unease and of being ill-prepared with respect to conducting a minor through the experience of illness.

Summary Biomarkers are quantifiable indicators of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. They have been recently introduced into clinical practice as a means for risk assessment, screening, diagnosis, staging, and prognosis. Some of them (cardiac and kidney biomarkers) have already found a precise role as the leading actor and actress in clinical medicine while others (pulmonary biomarkers) are still under evaluation in the different settings. Together with their invaluable properties, biomarkers have some important characteristics that should never be underestimated. A single biomarker rarely seems to have all the characteristics required to meet the clinical needs for a complete organ failure assessment, every biomarker seems to show different behaviour in different kinds of diseases, and several confounding factors have to be considered when interpreting biomarkers used for clinical assessment. The research on biomarkers is running fast and it is likely that a panel of biomarkers may be the best approach for achieving a complete patient assessment together with an adequate clinical evaluation and monitoring.

The role of endogenous H

Background: Hemodialysis with high cut-off continuous veno-venous hemodialyzer (HCO-CVVHD) removes mediators of organ dysfunction during sepsis. This study assessed the clinical effects of HCO-CVVHD as compared to high-flux (HF) membranes during gram-negative sepsis. Methods: Intensive care unit (ICU), septic patients treated with HCO-CVVHD or HF-CVVHDF for AKI were retrospectively observed (January 2013-December 2014). Mechanical ventilation, vasopressors' requirements, ICU length of stay (LOS) and ICU in-hospital mortality were compared between groups. Results: Sixteen HCO and 8 HF patients were observed. Isolated pathogens included Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa. Median ratios of days-on-vasopressors and days-on-mechanical ventilation/ICU-LOS were 0.5, 1 and 0.8, 1 for HCO and HF groups (p < 0.03), respectively. ICU-LOS was 16 and 9 days (HCO- and HF-group, p = 0.03). ICU mortality rates were 37.5 and 87.5% for HCO and HF groups, respectively (p = 0.03). No statistical difference was found in in-hospital morality. Conclusion: Patients in HCO-CVVHD group spent lesser number of days on vasopressors and mechanical ventilation as a ratio to total ICU-LOS. In the same group, a reduction in ICU mortality was observed.

Background The benefits of an Acute Pain Service (APS) for pain management have been widely reported, but its diffusion is still limited. There are two APS models: anesthesiologist-based and a nurse-based model. Here we describe the development of a different APS model managed by anesthesia residents, and we report the first year of activity in a tertiary Italian university hospital (Careggi University Hospital, Florence, IT). Methods Patients were included in the APS were those undergoing abdominal and urologic surgery causing moderate or severe postsurgical pain. The service was provided for patients, beginning upon their exit from the operating room, for 4, 12, 24 and 48 h for iv, and up to 72 h for epidural therapy. Vital signs, static/dynamic VAS, presence of nausea/vomiting, sedation level, and Bromage scale in case of epidural catheter, were monitored. Results From September 2013 to April 2015, a total of 1054 patients who underwent major surgery were included in the APS: 542 from abdominal surgery and 512 from urological surgery. PCA and epidural analgesia were more adopted in general surgical patients than in urology (48 % vs 36 % and 15 % vs 2 %, respectively; P

Purpose Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs. Materials and methods A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model. Results Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P=0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m 2 ). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P = .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 ( P = .0486), 48 ( P = .0011) and 72 hours ( P = .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P = .002) and BMI (OR 1.124; P = .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P = .019). Conclusions Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay.

In patients with severe acute pancreatitis (SAP) early and persistent elevated circulating levels of interleukins (IL)-1, 2 and 6 and tumor necrosis factor (TNF)-α are linked to severity of disease and early multiple organ failure (MOF), while persistently elevated serum IL-10 is linked to immune paralysis and infectious complications. Although experimental and clinical evidence exists that continuous venovenous hemodiafiltration with high cutoff membranes (HCO-CVVHDF) efficiently removes inflammatory mediators from blood of patients with severe sepsis or septic shock, data are lacking on the subset of patients with SAP, particularly in cases with uninfected necrosis. We treated with HCO-CVVHDF a 59-year-old man admitted to our intensive care unit (ICU) with SAP inducing early-onset cardiovascular, respiratory and renal dysfunctions associated with high circulating levels of IL-6 and TNF-α and without overt clinical or laboratory signs of infection. During the treatment, cardiovascular, respiratory and renal functions rapidly normalized and circulating levels of IL-6 and TNF-α consistently decreased. The patient was discharged from ICU on day 20.

Purpose Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009. Materials and Methods The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out. Results Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy. Conclusions Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported.

Over the last 5 y, clinical trials investigating products, procedures, and treatments aimed at preventing infections in the intensive care unit have been described. The findings of these studies appear to confirm the effectiveness of certain preventive procedures. With regard to ventilator-associated pneumonia, the efficacies of decontamination of the oral cavity, continuous suction of subglottic secretions, positioning of the patient, selective decontamination of the digestive tract, and (for higher-risk patients) endotracheal tubes coated with silver, have been demonstrated. Medicated catheters and chlorhexidine-based dressings have been found useful for catheter-related bloodstream infections, and medical catheters have also been shown to be efficacious against urinary tract infections. All these procedures can be incorporated into departmental protocols for the prevention of nosocomial infections in the intensive care unit.

Pain can play an important role at the social and psychological level; hence one of the major goals of anaesthesia is to control and reduce the incidence of postoperative pain. The use of an analgesia before surgical incision may offer one of the most innovative and promising strategies for better pain control throughout the perioperative period. Pre-emptive analgesia refers to pharmacological intervention initiated prior to a painful stimulus in order to inhibit nociceptive mechanisms before they are triggered. Pre-emptive analgesia has three objectives: to reduce pain resulting from the activation of inflammatory mechanisms triggered by surgical incision; to hinder the pain memory response of the central nervous system; and to ensure a good control of postoperative pain in order to avoid the development of chronic pain. The following provides an overview of the scientific rationale for pre-emptive analgesia alongside an overview of published systematic reviews and randomized clinical trials related to this topic.

The development of sepsis in patient suffering from traumatic brain injury (TBI) represents a frequent complication that has been associated with worsened global and neurological outcome. In an effort to better characterize the influence of sepsis following TBI, we developed an in vivo model of combined TBI and sepsis in the rat by coupling two validated models: (1) Controlled Cortical Impact (CCI) and (2) Cecal Ligation and Puncture (CLP). Possible contributing effects of sepsis on post-traumatic outcome were evaluated as mortality rate, body weight change, neurological motor (beam balance), cognitive (Morris water maze [MWM] for memory and learning) function, histopathological damage (lesion volume, cell counts in the CA1 and CA3 hippocampal areas), and morphological indices of inflammation (activated microglia and astrocytes) for the 14-day study period. In this study, we produced a mild TBI characterized by a low mortality rate, a transient delay in weight gain, and a transient impairment in motor and cognitive functions. The histological counterpart was represented by a cortical lesion in the area of impact at 14 days post-injury, associated with cell loss in the CA1 and CA3 hippocampal regions, and scarce infiltration of microglia. The superimposition of sepsis on this mild TBI model resulted in worsening of post-injury mortality and weight loss, significant exacerbation of post-injury motor deficit and cognitive impairments, and further exacerbation of neuronal cell death in the CA3 area together with over-expression and activation of microglial cells in the peri-lesional area. Altogether, our findings indicate that sepsis, when superimposed on TBI, exerts a negative effect on the evolution of post-traumatic damage.

To evaluate and compare the pharmacokinetic profiles of imipenem and meropenem in a population of critically ill patients with sepsis to find possible differences that may help in selecting the most appropriate drug and/or dosage in order to optimise empiric antimicrobial therapy.This was a single-centre, randomised, nonblind study of the pharmacokinetics of both intravenous imipenem 1g and meropenem 1g in 20 patients admitted to an intensive care unit with sepsis in whom antimicrobial therapy was indicated on clinical grounds. Patients were divided into two groups: group I received intravenous imipenem 1g plus cilastatin 1g, and group II received intravenous meropenem 1g over 30 minutes. Peripheral blood samples were collected at 0, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hours after the first dose and were centrifuged for 10 minutes at 4 masculineC. Urine samples were collected during the 8 hours after antimicrobial administration at 2-hour intervals: 0-2, 2-4, 4-6 and 6-8 hours. The total volume of urine was recorded; the serum and urine samples were immediately frozen and stored at -80 masculineC until assayed. Pharmacokinetic analysis was carried out through computerised programs using the least-square regression method and a two-compartment open model. Statistical differences were evaluated by means of one-way ANOVA.The following pharmacokinetic differences between the two drugs were observed: the imipenem mean peak serum concentration was significantly higher than for meropenem (90.1 +/- 50.9 vs 46.6 +/- 14.6 mg/L, p0.01); the area under the serum concentration-time curve was significantly higher for imipenem than for meropenem (216.5 +/- 86.3 vs 99.5 +/- 23.9 mg . h/L, p0.01), while the mean volume of distribution and mean total clearance were significantly higher for meropenem than for imipenem (25 +/- 4.1 vs 17.4 +/- 4.5L, p0.01 and 191 +/- 52.2 vs 116.4 +/- 42.3 mL/min, p0.01, respectively).The more favourable pharmacokinetic profile of imipenem compared with meropenem in critically ill patients with sepsis might balance the possibly greater potency demonstrated in vitro for meropenem against Gram-negative strains. Hence, the clinical efficacy of the two carbapenems depends mostly on their correct dosage.

Purpose Totally implantable venous access devices (Ports) represent the mainstay for infusion therapy in patients undergoing chemotherapy, total parenteral nutrition and/or long-term antibiotic treatment. Amongst mechanical complications, lesions of the catheter wall represent a rare but potentially severe condition. We report our experience with the accidental detection of catheter ruptures in a series of ports removed for complication or for end of use. Methods All ports removed from January 2011 to June 2013 were considered. All removed ports had been inserted according to a standardized protocol including ultrasound-guided percutaneous venipuncture (out-of-plane or in-plane approaches) and electrocardiogram-guided positioning of the tip. Once removed, each catheter was checked by inspection and saline instillation in order to evaluate the integrity of the device itself and rule out possible ruptures. Results In over 338 removed ports, 12 Groshong catheters out of 65 (18.5%) had evidence of partial rupture of the catheter wall. Amongst considered variables, “out-of-plane” approach and type of port (silicon, closed tip with Groshong valve) were the only ones significantly associated with catheter ruptures (p=0.0003 and 0.0008, respectively). We could detect no evidence of rupture in any silicon open-ended catheter (Celsite ports) or in any catheter inserted by “in-plane” approach to the vein. Conclusions The actual advantage of using port connected with Groshong silicon catheters should be questioned, since apparently they are more fragile than standard catheters. Furthermore, ultrasound-guided “out-of-plane” puncture of the internal jugular vein should be discouraged.

For an UltraSound guided Infraclavicular Block, a non-inferiority randomized study was conducted comparing two volumes of ropivacaine 0.75%: 35 ml vs 30ml. Fifty 18-70 years old patients undergoing upper limb surgery, ASA I-II were enrolled. Exclusion criteria included existing neurologic disease, coagulopathy, allergy, pregnancy, previous surgery in clavicular region, BMI more than 30 kg/m2 or patients unable to give written consent. Using US guidance, a 22 gauge/80 mm SonoPlex needle (Pajunk®) was advanced until the tip was located dorsally to the artery at a 6-o’clock position. Correct placement was ensuring by a “double bubble” sign. The block was performed by delivering ropivacaine 0.75% via an infusion pump (Alaris® PK) at 600 ml/h.

Since the initial use of prosthetic heart valves, the use of cardiac prosthesis and implantable devices has revolutionized the therapeutic options available to patients (de Oliveira et al.,2009). Cardiac Permanent PaceMakers (PPMs) have been implanted since the early 1960s. Over the past 50 years there have been tremendous advances in both the design of the device and the software employed. In the mid 1960s, transvenous leads were developed that could be inserted through a vein and thence into the heart, thus preventing the need for a thoracotomy. The development of ‘active fixation’ leads ensured a better contact with the endocardium and the presence of a steroid eluting tip helped to reduce any inflammation that might result. The introduction of the lithium iodine battery has dramatically increased the battery life to well over ten years. Radiofrequency programming became available in the 1970s, allowing simple adjustments to be made to pacemaker’s settings without the need for surgery. Today, permanent pacemakers and ICD (Implantable Cardiac Defibrillator), together with any adjustments, can be completed within minutes using a portable computer. Information regarding events such as periods of bradycardia, tachycardia or ventricular fibrillation can be stored within the memory of the device and accessed by the specialist during the routine checkup. To maintain atrio-ventricular synchrony, dual chamber pacing was then introduced. Moreover, in the late 1990s, pacemaker technology had improved to the extent that it became possible to increase the pacing rate to match the patient’s activity level (Allen et al., 2007). A wide range of cardiac implantable electronic devices (CIEDs) are now available, including ICDs and cardiac resynchronization systems. PPMs are commonly used in patients with atrioventricular conduction block, sick sinus syndrome, and symptomatic sinus bradycardia, whereas ICDs target primarily patients at risk for life-threatening ventricular arrhythmias. Since clinical trials have consistently demonstrated the ability of the ICD to reduce mortality in selected patients with moderate-to-severe left ventricular systolic

Purpose We aimed to compare the effects of a blood pressure transducer system specifically manufactured to limit underdamping artifacts with those of a standard system on hemodynamic parameter estimation and accuracy. Materials and Methods Forty-three consecutive patients undergoing vascular surgery at the University of Florence, Italy, were included. Arterial blood pressure signal was simultaneously registered with 2 MostCare monitors, connected to the artery either by a standard transducer or a specific transducer manufactured to avoid underdamping artifacts (Resonance Over-Shoot Eliminator [R.O.S.E.]; Becton Dickinson, Becton Drive, NJ). Patients were divided into 2 groups: absence (C group) or presence (R group) of underdamping/resonance artifacts of blood pressure signal. Systolic blood pressure, cardiac index, maximal pressure/time ratio (d P /d t MAX ), and cardiac cycle efficiency were recorded every 30 seconds for 30 minutes. A total of 2675 measurements were performed with 34.9% incidence of underdamping/resonance artifacts. Results All hemodynamic parameters showed clinically acceptable differences in the C group; in contrast, the results differed greatly in the R group between standard and R.O.S.E. transducer (systolic blood pressure bias, 16.7 mm Hg; cardiac index bias, 0.24 L min −1 m −2 ; d P /d t MAX bias, 0.92 mm Hg/ms; cardiac cycle efficiency bias, 0.018 units). Conclusions Underdamping/resonance artifacts frequently affect blood pressure measurement in operating rooms and intensive care units and cause severe overestimation of systolic blood pressure and incorrect estimation of hemodynamic parameters when the pulse contour method is used.

Treatment with analgesics before surgery may be effective in reducing post-operative pain. This approach is defined as "pre-emptive analgesia" and recent reviews show conflicting results.The aim of this study was to investigate the efficacy of pre-emptive analgesia with sublingual morphine sulphate, compared with sublingual midazolam in patients undergoing elective abdominal surgery.Prior to surgery, 29 patients were randomized and premedicated with sublingual morphine sulphate 0.5 mg/kg (Group A; n = 15) or with sublingual midazolam 0.03 mg/kg (Group B; n = 14). General anaesthesia was maintained with sevoflurane and fentanyl. Post-operatively, intravenous (IV) acetaminophen 0.02 mg/kg was given to all patients and a bolus of IV morphine 0.1 mg/kg was given to Group B patients. Post-operative pain was controlled by IV morphine via a patient-controlled analgesia (PCA) device. IV acetaminophen 0.02 mg/kg was also administered four times daily. Efficacy was assessed using static Visual Analogue Scale (sVAS) scores, dynamic VAS (dVAS) scores, number of PCA doses administered and number of failed doses registered from the PCA device at 4, 6, 24 and 48 hours after surgery. Results were statistically analysed using the Student t-test; a value of p0.05 was considered significant.Significantly lower sVAS and dVAS scores were observed in Group A patients than in Group B at all assessment periods (p0.05 for all time points). There were less PCA administered and failed doses in Group A, compared with Group B (all time points p0.05). There was no difference in the occurrence of common side effects between the two treatments.In patients undergoing elective abdominal surgery, premedication with sublingual morphine sulphate results in a better control of post-operative pain, compared to premedication with sublingual midazolam. The beneficial effect of pre-operative sublingual morphine sulphate was apparent in the immediate post-operative period and was sustained over the 48-hour assessment period.

Critically ill patients, not infrequently present alterations of physiological parameters that determine the success/failure of therapeutic interventions as well as the final outcome. Sepsis and polytrauma are two of the most common and complex syndromes occurring in Intensive Care Unit (ICU) and affect drug absorption, disposition, metabolism and elimination. Pharmacological management of ICU patients requires consideration of the unique pharmacokinetics associated with these clinical conditions and the likely occurrence of drug interaction. Rational adjustment in drug choice and dosing contributes to the appropriateness of treatment of those patients.

The hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms are implicated in endothelial damage and in multiple organ failure during septic shock. Many authors have proposed the use of antioxidants to decrease OFR damage. Glutathione (GSH) is one of the most important endogenous antioxidants. It plays the role of a sulphydryl group provider for scavenging reactions. N-Acetylcysteine (NAC) is an artificial precursor of GSH which both increases GSH levels and acts as OFR scavenger. The authors carried out a clinical trial to confirm the capacity of high doses of GSH and NAC to cooperate in reducing lipoperoxidative damage in patients with early septic shock. Patients were divided into three groups who received shock therapy only or shock therapy plus GSH or shock therapy plus GSH plus NAC. OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, complement activation and clinical scores. The study demonstrated that the group who received GSH and NAC showed a significant decrease in peroxidative indexes and an improvement of the clinical scores if compared with the other two groups. In conclusion the administration of high doses of NAC added to GSH significantly decreases the peroxidative stress of patients with early septic shock.

Background: Surgery is the standard of care in several oncologic diseases. However, when non-surgical candidates are not suitable for radical treatment, palliation must be achieved at least. High-intensity focused ultrasound uses ultrasound power that can be sharply focused for highly localised application, as it is a completely non-invasive procedure. Its non-invasiveness appears to be of paramount importance in critically ill patients. Case description: We describe the use of ultrasound-guided high-intensity focused ultrasound for a large liver metastasis from breast cancer causing gastric outlet obstruction in a metastatic disease. The left liver deposit did not allow the stomach to empty due to its large volume, and the patient was unable to eat properly. The tumour was metastatic, resistant to chemotherapy and had a size that contraindicated an ablation percutaneous technique. To improve the patient's quality of life, ultrasound-guided high-intensity focused ultrasound ablation seemed the only and most suitable option. Therefore, a high-intensity focused ultrasound treatment was performed, no complications occurred and the patient's general condition has improved since the early post-procedural period. Three months after treatment, two body mass index points were gained, and the lesion decreased by 72% in volume as detected through multi-detector computed tomography follow-up. Discussion and conclusion: Quality of life is an unquestionable goal to achieve, and palliation must be achieved while causing as little harm as possible. In this view, debulking surgery and percutaneous ablation technique seemed not appropriate for our patient. Instead, high-intensity focused ultrasound combined several advantages, no lesion size limit and a totally non-invasive treatment. Thus, this technique proved to be a clinically successful procedure, offering better disease control and quality of life. In circumstances where other alternatives clearly seem to fail or are contraindicated, high-intensity focused ultrasound can be used and can provide benefits. We recommend its use and development in several oncologic diseases, not only for therapeutic purposes but also for the improvement of patient's quality of life.