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First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.

Objectives:To assess the feasibility and efficacy of implementing “Family Care Rituals” as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members.Design:Prospective, before-and-a

Additional file 1: Table S1. BPI score in patients with pain at 3 months.

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.

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.

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.Prospective interventional study.Surgical ICU. February 2016 to December 2016.Postsurgical patients requiring ICU admission, mechanical ventilation, and sedation.Sevoflurane was administered with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to -5 by adaptation of minimum alveolar concentration.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.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.

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.

Sleep disturbances are very common and associated with severe complications in patients admitted to intensive care units (ICU). Commonly, sedatives like propofol or benzodiazepines have been demonstrated to increase sleep duration but worsen sleep architecture. Dexmedetomidine seems to positively affect both sleep aspects.The present study aimed to investigate sleep characteristics in non-intubated patients admitted to intensive care unit. The subgroups consisted of those without sedation (NO-DEX), and those which received dexmedetomidine infusion (DEX), titrated to a Richmond Agitation-Sedation Scale target of -1/-2, were also explored. An auto-staged electroencephalographer was used to measure sleep duration and architecture. The Richard-Campbell-Sleep questionnaire was administered to all patients.A multivariate analysis conducted in the overall population showed that dexmedetomidine infusion was the only variable independently associated with N2 increase (p 0.001). DEX (n = 36) versus NO-DEX (n = 36) group showed longer N2 stage [68.9% (57.5-80.9) versus 49.5% [35.7-61.4]; p 0.0003]; longer Total Sleep Time [6.5 h (5.7-7.7) versus 3.4 h (1.8-4.9); p 0.0001, and higher Sleep Efficiency [84.2% (71.3-92.6) versus 47.7% (23.4-60.9); p 0.0001]; shorter N1 (percentage of Total Sleep Time) [10.5% (7.8-20.0) and 38.8% (25.6-50.3); p 0.0001]; longer N3 stage [13.6% (1.9-23.3) versus 4.3% (0.4-14.0); p = 0.058]; fewer Cortical Arousals [15 episodes/hour (8.1-24.6) versus 48.7 episodes/hour (29.7-80.4); p 0.0001]. The questionnaire showed better values in DEX-group in all explored items (p 0.0001).Abnormal sleep is common in intensive care unit patients who have not received sedation. Dexmedetomidine, titrated to reach an appropriate sedation level, may optimize sleep duration and architecture.

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.

Worldwide, the widespread use of extracorporeal blood purification therapies (EBPTs) is progressively increasing in everyday clinical practice, particularly in critical care settings. The efficacy of EBPTs on removal of inflammatory mediators is already well established in the literature. Nonetheless, clinical research is particularly cumbersome in this setting, and many clinical trials aiming at exploring the effect of EBPTs on outcomes have failed in demonstrating consistent results regarding 28-day- or hospital-mortality rates. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of EBPTs. The philosophy behind this Italian Registry is a renewal of the concept of “clinical research” in the field of EBPTs applied to critically ill, septic patients with or without acute kidney injury. The platform used for the registry – specifically designed for research purposes and fed by clinical data prospectively observed – promotes good practice with a positive and active interaction with the physician/researcher. This interaction has favorable real-time effects for the specific patient, providing “bed-side clinical feedbacks,” similarly to the decision support system. Examples of these issues are bundles reminders, suggestions for drug adjustment according to the extracorporeal clearance, clinical calculator for body mass index, or mechanical ventilation setting. The platform-physician interaction has additional useful effects on the single utilizing center, providing “mid-term, center-specific clinical feedbacks.” These generally consist of clusters of data taken over a certain period, for example, regarding patients’ outcome, microbiological data, or use of disposable for EBPTs.

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.

Prone positioning (PP) is necessary for surgical access during posterior spine procedure. However, physiological changes occur in the PP. Typical findings are a decrease in arterial blood pressure and in cardiac output that could potentially lead to an alteration in cerebral perfusion. Therefore, we decided to study cerebral blood flow velocity (CBFV) with transcranial Doppler ultrasonography to evaluate the effect of the PP on cerebral hemodynamics.Twenty-two patients undergoing spine surgery in the PP were studied. General anesthesia was induced using 250 μg of fentanyl, 2 mg/kg of propofol, and 0.1 mg/kg of vecuronium, and was maintained with 0.25%-0.5% isoflurane, 50% nitrous oxide in oxygen, continuous infusion of 100 μg/kg/min of propofol, 1.5 μg/kg/h of fentanyl, and 0.15 mg/kg/h of ketamine. Continuous invasive arterial blood pressure, heart rate, electrocardiogram, and end-tidal carbon dioxide were monitored. CBFV with transcranial Doppler in the middle cerebral artery was first measured with the patients under general anesthesia in the supine position. Patients were then placed in the PP and remained in this position throughout surgery. CBFV, end-tidal carbon dioxide, heart rate, and blood pressure were measured continuously for 75 minutes after initiation of PP. This coincided with surgical exposure and minimal blood loss. Data were analyzed every 15 minutes for statistical significant change over time.Mean arterial blood pressure decreased 15 minutes after the installation of the PP and onward, but this decrease was not statistically significant. CBFVsyst (the maximal CBFV during the systolic phase of a cardiac cycle) and CBFVmean (the time averaged value of the maximal velocity envelope over 1 cardiac cycle) did not vary at any time points. CBFVdiast (the CBFV just before the acceleration phase [systole] of the next waveform) was lower at T3 (30 minutes after PP) compared to T1 (value derived averaging the first measure in the PP with the ones at 5 and 10 minutes) (P = .01), and the pulsatility index was higher at T5 (60 minutes after PP) compared to T0 (baseline, patient supine under general anesthesia) (P = .04). Data were analyzed at specific time points (T0 and T1). This value was derived by computing an average of the CBFV values collected at the first measure in the PP and at 5 and 10 minutes thereafter: T2, 15 minutes after PP; T3, 30 minutes after PP; T4, 45 minutes after PP; T5, 60 minutes after PP; and T6, 75 minutes after PP.Our data on CBFV during PP for spine surgery demonstrate preservation of cerebral perfusion during stable systemic hemodynamic conditions. The present results do not allow us to determine whether the PP would be similarly tolerated with increasing length of surgery, variations in systemic hemodynamics, and in different patient populations.

Background Continuous popliteal nerve block is utilized for postoperative analgesia after foot and ankle surgery. Whether only the total dose of local anesthetic or the combination of concentration and volume determine the characteristics of a continuous popliteal nerve infusion remains currently unknown. We hypothesized a reduction of the incidence of insensate extremity in patients given ropivacaine 0.4% at 4 mL/h compared to patients given ropivacaine 0.2% at 8 mL/h. Methods Sixty-four patients scheduled for major foot and ankle surgery requiring a continuous popliteal catheter infusion for postoperative analgesia were studied. Thirty-three patients were randomized to receive a continuous popliteal nerve block with 0.2% (basal 8 mL/h) and thirty-one with 0.4% (basal 4 mL/h) ropivacaine, reaching the same total dose (16 mg/h). The primary outcome was the incidence of persistent sensory block in the distal sciatic nerve distributions in the postoperative period. Secondary outcomes were the incidence of motor block, NRS pain scores at rest in the postoperative period up to 48 hours after surgery, opioid use and related side effects, patients' satisfaction. Results The incidence of persistent sensory block was similar in patients given 0.2% and in patients receiving 0.4% ropivacaine. The incidence of motor block, postoperative pain scores at rest, use of oral opioids, side effects and patients' satisfaction with the quality of recovery were also similar in both groups. Conclusions Our results suggest that local anesthetic total dose is the primary determinant of continuous popliteal perineural infusion effects.

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.

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.

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.

Trauma, surgery, and infection represent a common source of stress in critically ill patients admitted in intensive care units (ICUs). Although the consequences of stress response in critical illness are still debated and not well understood, many neural and hormonal responses have been recognized to activate homeostatic mechanisms aimed at favoring survival and healing. These responses develop toward three different phases: the first immediate and short (24 h) phase, termed ebb, is directed to immediate survival; the second longer phase (6–7 days), termed flow, is characterized by an increase in total body oxygen consumption and carbon dioxide production with hypermetabolism; the third phase, termed chronic, may last some months and identifies the post-stress period of critical illness. Although the effects of sedatives (analgesics and hypnotics) on tissue metabolic demand of critically ill patient remain difficult to be adequately defined, these drugs commonly delivered in intensive care units actually influence the stress response by decreasing neurohumoral reactions, involving the sympathetic system, and affecting the inflammatory mechanisms. After the neuroendocrine activation, uncontrolled metabolic reactions, characterized by catabolism and the resistance to anabolic signals as insulin, develop. Secondary negative effects (infections, muscle atrophy and weakness, respiratory insufficiency, delayed wound healing) can occur as direct consequences of metabolic phenomena that are clearly difficult to monitor. Finally, sedatives administered to control stress response clearly have detrimental effects (hemodynamic alterations, immunosuppression, delirium) that should be carefully evaluated in the context of a balance between benefits and damages.

Sleep is a complex process related to biologic and environmental factors essential to maintaining physiological and emotional well-being. Sleep disturbances and deprivation, and abnormal sleep architecture (prolonged sleep latency, sleep fragmentation, continuous arousals, a preponderance of inefficient sleep stages), frequently occur in critically ill patients, leading to adverse outcomes. Survivors of critical illness frequently refer to sleep deprivation as a major stressor associated with their admission. The following environmental (clinical and nonclinical) factors contribute to sleep disturbances in these patients: mechanical ventilation, drainage positioning and maintenance, bronchial aspiration, hygiene, nursing care, pain, light, and noise. Sleep duration in critically ill patients is shortened and fragmented, and sleep is essential for restoring energy and equilibrating the mind. Sleep deprivation hence alters cognition, leading to apathy, confusion, and delirium, all of which may increase morbidity and mortality. Sedatives are commonly given to critically ill patients to promote sleep, although physiological sleep and sedation may be significantly different. While patients may achieve an acceptable amount of sleep over a 24-h period, this sleep is both discontinuous and abnormally structured. Clinical guidelines strongly support and recommend the application of a multimodal approach aimed at promoting sleep that includes both environmental regulations and clinical assistance.

Critically ill patients often require sedative and analgesic drugs to optimize patient comfort, facilitate patient-ventilator synchrony, and allow tolerance to procedures. The level of sedation can change during a patient’s stay and an optimal degree of sedation is necessary to avoid the risk of oversedation and to reduce the risk of delirium, the length of mechanical ventilation, and the length of stay in the ICU.

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.

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 Organ dysfunction is common in ICU, and it is associated with high mortality rates, particularly among septic or complicated surgical patients. Scoring systems for organ dysfunction have a fourfold purpose: quantifying the entity and severity of organ dysfunction, stratifying and comparing patients as to morbidity and risk of mortality, tracking progression of critical illness in ICU and identifying patients who are unresponsive to therapies. The degree of organ dysfunction is strongly correlated with outcome, though in general the performance of organ dysfunction scores in terms of outcome prediction is inferior to that of classical severity scores, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II. Scoring systems for organ dysfunction can be divided into multiple organ dysfunction and single organ failure scores. The aim of this review is to summarize and compare the most commonly used organ dysfunction scores.

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.

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.

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.

Background: We report here a case of a woman affected by fever, weight loss, splenomegaly, and leucopenia associated with trombocytopenia, transferred to the intensive care unit with acute kidney injury and septic shock. Methods: Patient was treated with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD). Results: During treatment, the patient experienced a stable improvement in the hemodynamic, pulmonary function and tissue perfusion parameters. After 48 h of treatment, significant reductions in SOFA score (from 12, before starting the procedure, to 6) and in serum inflammatory mediators (as IL-6, from 599-568 pg/ml) were observed. Leishmania infection was identified as responsible of the septic condition only 48 h after removing hemodialysis. Antiprotozoal therapy was begun and the patient discharged. Conclusions: By supporting the renal function and reducing systemic inflammation, HCO-CVVHD could be a useful bridge therapy. This procedure allowed the medical team to gain sufficient time to diagnose the type of infection and begin an etiological therapy.

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.

Pharmacokinetics and pharmacodynamics are significantly altered in critically ill septic patients and the risk of prolonged periods with concentrations below the minimum inhibitory concentration (MIC) and of low area under the serum concentration-time curve/MIC (AUC/MIC) ratios is of concern. We compared the pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid administered by intermittent or continuous infusion in critically ill septic patients. Patients were divided into two groups: intermittent infusion (Group I) (600mg/12h); or continuous infusion (Group C) (300mg intravenous loading dose +900mg continuous infusion on Day 1, followed by 1200mg/daily from Day 2). Linezolid serum levels were monitored for 72h and microbiological data were collected. The clinical outcome was monitored. Sixteen patients completed the study. MICs of susceptible pathogens were 2mg/L for 80% of the isolates. In Group I, linezolid trough serum levels (C(min)) varied widely and were below the susceptibility breakpoint (4mg/L) during the study period; in 50% of patients C(min) was1mg/L. In Group C, mean linezolid serum levels were more stable and, starting from 6h, were significantly higher than C(min) levels observed in Group I and were always above the susceptibility breakpoint. Time that the free drug concentration was above the MIC (T(free)MIC) of85% was more frequent in Group C than in Group I (P0.05). Finally, with continuous infusion it was possible to achieve AUC/MIC values of 80-120 more frequently than with intermittent infusion (P0.05). According to PK/PD parameters, continuous infusion has theoretical advantages over intermittent infusion in this population of patients.

Background Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear. Methods The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo. Results When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats. Conclusions These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.

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.

Objective: To investigate whether an inflammatory response occurs in patients undergoing infrarenal aortic abdominal aneurysm repair, the localization and timing (ischemia and/or reperfusion) of this activation, and finally whether it affects postoperative pulmonary function. Design: Prospective, observational study. Setting: Academic referral center in Italy. Patients: We included 12 patients undergoing infrarenal aortic abdominal aneurysm repair and 12 patients undergoing major abdominal surgery. Interventions: Timed measurement of gene activation (angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes) in muscle biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR), and prospective assessment of interleukin-6 plasma concentration and pulmonary function (Pao 2 /Fio 2 and Pao 2 /PAo 2 ratios). Measurements and Main Results: After 30 mins of aortic clamping, angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes were all over-expressed at RT-PCR studies in quadriceps muscle of patients undergoing aortic abdominal aneurysm repair, and the overex-pression persisted after reperfusion. In situ hybridization and immunohistochemistry revealed that the inflammatory response was localized in endothelial cells. A significant increase in plasma interleukin-6 concentrations was then detectable at 6 and 12 hrs after reperfusion in aortic abdominal aneurysm surgery compared with patients undergoing abdominal surgery (p

During the last decade, blood purification therapies have been proposed as an effective therapy to control the cytokines dysregulation in systemic inflammatory syndromes. Among them, the treatment with high cut-off membranes is characterized by larger pore size and more effective clearance for middle molecular weight molecules (cytokines). In this paper, we performed a thoughtful review of the literature on HCO being used for blood purification indications in all systemic inflammation syndromes. Clinical and experimental studies show that the use of high effluent flows in a pure diffusive treatment effectively removes serum cytokines with a safe profile in albumin clearance. In clinical studies, the removal of these inflammatory mediators is associated with a significant improvement in hemodynamic condition, oxygenation indices, and organ dysfunction. © 2014 S. Karger AG, Basel

Background: Differentiation syndrome is a life-threatening complication of therapy that is carried out with agents used for acute promyelocytic leukemia. Its physiopathology comprehends the production of inflammatory mediators by differentiating granulocytes, endothelial and alveolar cells due to stimulation by all-trans retinoic acid and leading to sustained systemic inflammation. Methods: Treatment with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD) was performed to reduce the circulating mediators of systemic inflammation. Results: After 52 h of treatment, an important reduction was observed in inflammatory mediators (IL-1β: from 10 to 2 pg/ml; IL-8: from 57 to 40 pg/ml; TNF-α: from 200 to 105 pg/ml; IL-6: from 263 to 91 pg/ml), as well as in anti-inflammatory mediators (IL-10: from 349 to 216 pg/ml). Conclusions: HCO-CVVHD should be explored as a part of treatment in systemic inflammation states other than sepsis (e.g., differentiation syndrome). Furthermore, its immunomodulatory effects could be particularly useful in immunocompromised patient treated with corticosteroids.

Invasive aspergillosis has been mainly reported among immunocompromised patients during prolonged periods of neutropenia. Recently, however, non-neutropenic patients in the ICU population have shown an increasing risk profile for aspergillosis. Associations with chronic obstructive pulmonary disease and corticosteroid therapy have been frequently documented in this cohort. Difficulties in achieving a timely diagnosis of aspergillosis in non-neutropenic patients is related to the non-specificity of symptoms and to lower yields with microbiological tests compared to neutropenic patients. Since high mortality rates are typical of invasive aspergillosis in critically ill patients, a high level of suspicion and prompt initiation of adequate antifungal treatment are mandatory. Epidemiology, risk factors, diagnostic algorithms, and different approaches in antifungal therapy for invasive aspergillosis in non-neutropenic patients are reviewed.

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.

Summary The famous military leader Giovanni de' Medici died in 1526, during a battle against the Emperor army. He was wounded in his right thigh and died after the surgical intervention, which was performed by Magister Abraham. His friends suspected that the surgeon had "poisoned" his instruments, but someone wrote that Magister Abraham had purposely left "too much wounded flesh". After five centuries it is now possible to confirm this rumour.