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The issue of acute dialysis dose prescription has undergone significant revision in the last 10 years. The previous idea that critically ill patients' survival was proportional to delivered dialysis being the highest with the highest dose has been downplayed. The best evidence supports a continuous renal replacement therapy dose of at least 25 mL/kg/hr of effluent flow rate, for venovenous hemofiltration, hemodialysis, or hemodiafiltration. However, if standard dose prescription may be recommended at the start of an acute dialytic treatment, strict control of delivered dose is recommended for adequate delivery of the prescribed dose. Furthermore, prescription and delivery should be reassessed frequently to meet the patients' needs, tailoring the removal of solutes to the complex and rapidly changing metabolism of different patients.

Extracorporeal life support (ECLS) (commonly named venoarterial extracorporeal membrane oxygenation, VA-ECMO) allows cardiocirculatory assistance and blood decarboxylation and oxygenation in patients with cardiac or cardiorespiratory failure. Blood is drained from the venous system, pushed through an artificial lung for CO2 removal and oxygenation, and then backs into the systemic circulation via an artery (VA configuration). Common indications for VA-ECMO are reversible causes of cardiac failure (myocardial infarction, cardiomyopathy, myocarditis, postcardiotomy cardiac failure, or cardiac arrest) or bridge to long-term therapy (ventricular assist devices or cardiac transplantation). Over the last 10 years, VA-ECMO application has been progressively increasing with significant improvement in the outcome of patients with acute cardiocirculatory failure.

Echocardiography, either transthoracic (TTE) or transesophageal (TEE), is the most powerful cardiovascular diagnostic technique available for perioperative hemodynamic assessment. With the information provided by echocardiography, the anesthesiologists, surgeons, and intensivists can manage the perioperative course of surgical patients and contribute to improve their outcome. The European Society of Cardiology/European Society of Anesthesiology guidelines have provided clear indications on the use of TTE and TEE in the perioperative setting for non-cardiac surgery. In addition, the use of thoracic ultrasound in everyday clinical practice has become increasingly common in non-cardiac surgery patients. An integrated thoracic-pulmonary-heart ultrasound examination represents an important diagnostic tool to diagnose and treat postoperative pulmonary complications, including pneumothorax, endobronchial intubation, bronchospasm, atelectasis, pulmonary edema, and pulmonary embolism. Importantly, although basic skills in ultrasound are relatively easy to achieve, clinicians need adequate training on cardiothoracic echography and need to be aware of the learning curve. Today, chest echography is regarded as a mandatory part of perioperative and critical care training.

Lungs and kidneys frequently are involved in critically ill patients with multi-organ failure syndrome, and many of these patients need respiratory support and renal replacement therapy (RRT). Technologic improvement has led to the capacity to support multiple organs through extracorporeal techniques in the context of the multi-organ support therapy. In this context, extracorporeal membrane oxygenation (ECMO) circuit, applied for lung support, may serve as a platform for additional organ support therapies in adults and children. Because acute kidney injury (AKI) is a major comorbid condition in patients undergoing respiratory extracorporeal support, the combination of ECMO and continuous RRT (CRRT) is a common practice. ECMO and CRRT can be assembled together in different ways with advantages and limitations for each. The most frequent indications for CRRT started in patients under respiratory support are, mainly, the treatment and prevention of fluid overload, the management of AKI, and electrolyte disturbances. Although precise comparisons among heterogeneous studies are complex, the majority of them indicate that CRRT can be applied safely in patients under ECMO support with and without AKI, and it may help to optimize patient status without independently increasing the risk of mortality and generally improving fluid balance and electrolyte disturbances.

Circulatory shock is a leading cause of tissue hypoperfusion and multiple organ dysfunction in critically ill patients. An appropriate cardiovascular support is required when circulatory shock occurs, in order to limit cellular hypoxia by increasing the oxygen delivery. The optimization of the different components involved in cellular oxygenation requires accurate monitoring, and represents the target for pharmacological and mechanical hemodynamic support therapies in critically ill patients with shock. Both invasive and non-invasive systems for hemodynamic monitoring allow the physician to identify the pathophysiological mechanisms sustaining shock, to target therapy delivery on the pathogenesis of the disease, and to evaluate the effects of treatments over time. The hemodynamic monitoring systems have their own advantages and limitation, and the most appropriate system will depend on the individual patient, on device and on local expertise available at each institution. A personalized pharmacological treatment with fluids and vasoactive/inotropic drugs, guided by appropriate monitoring, is crucial in the management of hemodynamic instability. Many drugs administered to critically ill patients have both cardiac and vascular effects depending on the dose and on density and distribution of their target receptors, e.g. catecholamines, vasopressin, inhibitors of phosphodiesterase type III or calcium sensitizer. When the pharmacologic vasoactive and inotropic therapy, even at maximal doses, is insufficient to prevent tissue hypoxia and organ damage, or patients ae becoming refractory to ongoing drug administration due to the prolonged illness, mechanical circulatory support (MCS) can be considered.

Sepsis-induced acute kidney injury (AKI) represents the leading cause of AKI in the intensive care unit (ICU). This syndrome is characterized by an acute deterioration of renal function and glomerular filtration in the context of sepsis and multiple organ damage. Sepsis-induced AKI is diagnosed in almost 50% of critically ill septic patients and 15–20% of them require renal replacement therapy (RRT) [1]. Moreover the syndrome is associated with short and long-term adverse outcomes including mortality and the development of chronic kidney disease [2]. Hemodynamic support and avoidance of toxic drugs (contrast media, non-steroidal anti-inflammatory drugs, antibiotics) still remain the most efficient strategies aimed at preventing or treating sepsis-induced AKI together with the administration of diuretics to balance fluid administration and the application of RRT in oligoanuric patients and/or those with severe acid base and electrolyte derangements [3]. Fifty to 60% of patients with sepsis-induced AKI receiving RRT in the ICU do not survive the hospital admission as also remarked in the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study in which patients with sepsis-induced AKI receiving continuous RRT (CRRT) had a longer hospital length of stay and higher mortality (70%) compared with those who received RRT outside the septic syndrome (52%) [4].

OBJECTIVES Our aim was to verify whether the cardiac index (CI) estimated by the pressure recoding analytical method (PRAM) was associated with clinical metabolic indexes of tissue perfusion and mechanical ventilation duration in paediatric patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) for congenital heart disease and whether it could therefore be considered a clinically reliable monitoring method. METHODS A retrospective study was conducted in a paediatric cardiac intensive care unit (PCICU), applying PRAM, a minimally invasive advanced haemodynamic monitoring system (MostCare®, Vygon, Vytech), for the first 24 postoperative hours. Haemodynamic and clinical average values were analysed as time-weighted average values at four postoperative time points (during the first 2 h from PCICU admission, from the 3rd to the 6th, from the 7th to the 12th and from the 13th to the 24th postoperative hours) and correlated with respective variables recorded and averaged at the same time points. RESULTS Forty consecutive patients were enrolled. Median (interquartile range) age, CPB time and Aristotle score were 85 (47-200) days, 157 (112-185) minutes and 8.9 (7.5-10), respectively. CI values at the four time points were 2.89 (2.67-3.19), 2.94 (2.60-3.17), 2.84 (2.64-3.26) and 2.93 (2.58-3.46) l/min/m2, respectively. CI values correlated with lactate levels (r: -0.2; P = 0.01), systolic pressure (r: 0.34, P = 0.0001), heart rate (r: -0.4; P = 0.0001), vasoactive inotropic score (r: -0.3; P = 0.0001) and diuretic dose (r: -0.2; P = 0.01). In patients with low cardiac output syndrome (diagnosed according to clinical metabolic indexes), CI values estimated by PRAM were significantly lower than those of patients without signs of low cardiac output syndrome (P = 0.0001): 3.0 vs 2.8 (95% CI of difference -0.05 to 0.67), 3.1 vs 2.7 (95% CI of difference 0.13-0.85), 3.2 vs 2.7 (95% CI of difference 0.11-0.83) and 3.2 vs 2.7 (95% CI of difference 0.08-0.81) l/min/m2, respectively. Patients with a CI equal to or above 3 l/min/m2, compared with others, showed a significantly lower increase in creatinine levels from PCICU arrival to postoperative day 1: 0.07 (-0.1 to 0.2) vs 0.21 (0.05-0.3) mg/dl (P = 0.0016). Prediction of mechanical ventilation duration was independently associated only with CI (b: -3.4; r: -0.39; P = 0.04) in a multivariable model after adjustment for Aristotle score, vasoactive inotrope score, cross-clamp time, creatinine levels at PCICU admission and patient's age. CONCLUSIONS CI estimated by PRAM after paediatric cardiac surgery was reliably associated with clinical indicators of tissue perfusion, with vasoactive and diuretic drug requirements, and predicted longer mechanical ventilation duration.

PERIOPERATIVE FLUID MANAGEMENT has been studied extensively, especially in noncardiac surgery populations, and hypovolemia and hypervolemia clearly have been identified as major contributors of morbidity and mortality. It has been demonstrated that both hypovolemia, eventually leading to inadequate oxygen delivery (DO2), and hypervolemia, which causes tissue edema, organ dysfunction, and coagulation system alterations, are associated with increased perioperative morbidity risk that has been welldescribed as a “parabolic-U-shape” relationship. Nonetheless, to date, the optimal regimen of fluids administration still is a matter of debate, and great concerns remain about the type (colloids v crystalloids), the ideal composition, and the amount of fluids that should be administered. Whereas in low-risk patients undergoing minor surgery, “liberal” fluid administration (or “nonrestrictive”) seems to improve outcome, reducing complications and length of stay, but in high-risk and pediatric surgeries, the issue is much more complex and individualized fluid administration (goaldirected therapy [GDT]) seems to be reasonable. In cardiac surgery patients, the distribution of fluids in the intravascular or extravascular spaces depends on a number of intraoperative and postoperative factors that highly influence the pathophysiology of body fluid kinetics, including the patients’ body surface area; cardiopulmonary bypass (CPB) (starting, conducting, and weaning); CPB priming solution (volume and composition); cardioplegic solutions (volume, composition, and temperature); CPB circuits and artificial lungs; thermal management; and vasoactive and inotropic drugs. Patient age is another key factor determining different fluid kinetics during cardiac surgery. This review is the first of 2 concerning fluid management during and after adult and

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.

Objectives Gonadotropin-releasing hormone (GnRH) agonists like deslorelin are being increasingly used in tom cats for their efficacy in controlling reproductive behaviour and fertility. Deslorelin implants have been widely available in Europe since 2008. Little, if anything, is known about the interval between treatment and onset of sterility, as well as semen quality, after treatment in tom cats. The purpose of this study was to investigate semen quality and interval to sterility in tom cats treated with a 9.4 mg deslorelin implant. Methods Fifteen healthy adult tom cats were treated with a 9.4 mg deslorelin implant (Suprelorin 12). For each cat, semen collection and a GnRH stimulation test (intramuscular administration of 50 μg gonadorelin [Fertagyl], followed by blood sampling 1 h later, to assay serum testosterone) were performed on the first consultation and then repeated every 15 days until complete sterility was achieved. Semen collection was performed by introducing a 14 cm, open-end feline catheter (Argyle) 9 cm into the distal urethra 10 mins after sedation by intramuscular injection of 100 μg/kg medetomidine (Domitor). Results Semen collection was not successful in all cats at each attempt. In the first month after treatment, the semen of only four cats could be evaluated, while the semen of eight cats could be evaluated during the second and third months of the study. Semen quality (ejaculate volume, progressive motility and morphological abnormalities) improved slightly during the first 19–25 days in 2/4 cats, and in 1/4 cats motility was still very high (80%) 25 days post-treatment (PT), but we have no data regarding fertility prior to treatment in this cat. The last cat never produced spermatozoa. Subsequently, semen quality gradually worsened in all cats from 30 days onwards. At 70 days PT, one cat was still potentially fertile. After 72 days all cats were sterile. Conclusions and relevance Semen quality increased slightly in treated cats during the first month after treatment, and then gradually decreased over the following months. Complete sterility was reached within 40–72 days following implantation.

An amendment to this paper has been published and can be accessed via the original article.

C-reactive protein (CRP) is one of the major acute phase proteins in dogs. It is produced by the liver and rapidly increases in response to an inflammatory stimulus. The aim of this study was to measure CRP concentrations around parturition and to verify whether this protein could be useful, together with progesterone (P), to detect the onset of parturition in bitches. The CRP and P concentrations were measured in 66 serum samples from 28 healthy pregnant bitches, collected between -5 and +2 days from parturition (day of parturition = day 0). The effect of ‘days from parturition’, parity, and litter size on P and CRP concentration was analyzed and the correlation between CRP and P values was calculated. The P and CRP values were affected by ‘days from parturition’. While P decreased during the last days of pregnancy, CRP concentration was greater than the normal range (0–1.07 mg/dl) starting the parturition day with the increase starting on day -1. The CRP concentration profiles during the days around parturition have not been previously reported in dogs. The increase in CRP very near the time of parturition and the low magnitude of the increase do not allow for it to be useful in clinical practice to assess the onset of parturition in the bitch.

Introduction Side effects of traditional analgo-sedative agents call the attention to alternative strategies of sedation for critically ill patients; volatile anaesthetics (VAs) are considered potential substitutes in selected categories of patients. MIRUS™ (Pall Corporation and TIM Germany) is an innovative system for the administration of VAs to these patients admitted in intensive care unit (ICU). Methods The aim of this study was to analyse the clinical and economical characteristics of MIRUS™, following the Health Technology Assessment principles (HTA); in particular, the study was focused on defining a cost/efficacy ratio of the use of MIRUS™ in an ICU with 8 beds and 80 procedures/year. HTA allows predicting the system impact in the clinical pathway before material introduction. Results The assessment showed that MIRUS™ could be innovative, safe and efficient, especially when applied to critically ill patients with compromised organ function. For the purposes of assessment, three classes of ICU treatments have been defined: short- (6–24 h), medium- (24–96 h) and long-term (>96 h) sedation (SS, MS, LS). Based on the technical characteristics of system, MIRUS™ could be considered unfit for LS. Considering clinical characteristics, effects on patients, sedation times and costs, the HTA shows how the procedure costs are different for each class. Conclusions In conclusion, the use of MIRUS™ could be useful and effective for critically ill patients, in which standard sedation may be associated with drug hangover. This assessment seems economically advantageous for SS, where cost/efficacy ratios are positive performing 400 procedures/year, while for MS the cost of drugs impacts on the procedure cost. Therefore, looking at the potential clinical benefits on all potential treatable patients, the best addition strategy of the system in the hospital should be evaluated to optimize the cost/efficacy ratio.

Background: Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgery. AKI is independently associated with morbidity, mortality, and long-term adverse events including chronic kidney disease in postsurgical patients. Since specific treatment options for kidney failure are very limited, early identification, diagnosis, and renal support strategies are key steps to improve patients’ outcome. Summary: According to current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on 2 functional markers, serum creatinine increase and urine output decrease, that are not renal-specific and have important limitations. However, preoperative risk stratification for postoperative AKI and/or early diagnosis after surgery could be the best way to apply preventive or timely supportive therapeutic measures. Clinical prediction scores, renal functional reserve assessment, and new biomarkers of kidney stress (suppression of tumorigenicity-2, insulin-like growth factor binding protein-7, tissue inhibitor metalloproteinase-2) may help the clinicians to identify patients at risk of AKI and that could benefit from the application of nephroprotective bundles suggested by the KDIGO guidelines. In severe AKI patients with oligoanuria and fluid accumulation, renal replacement therapy is the only supportive measure even if mode and timing remain open to investigation. Key messages: Perioperative AKI is an important and underdiagnosed complication. Identifying patients at high risk of AKI and diagnosing AKI early are major goals. Preventive interventions are mainly based on the KDIGO guidelines and bundles. Furthermore, a personalized multidisciplinary approach should always be considered to minimize the progression of disease and the complications related to kidney damage.

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

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.

The acute reduction of kidney function in critically and noncritically ill patients (regardless of their age) is one of the deadliest clinical conditions ever reported in modern medicine. Acute kidney injury (AKI) symptoms are sneaky and potentially difficult to be identified at the right time at the bedside. One of the greatest efforts of the recent history of critical care nephrology has been to find a common classification for AKI definition and staging with the purpose of allowing a timely diagnosis and push forward epidemiologic research.AKI is currently defined by the Kidney Disease Improving Global Outcomes (KDIGO) consensus classification that applies conventional serum creatinine and urine output (UO) criteria. According to a recent large epidemiologic study, this classification led to the confirmation that AKI occurs in about half of adult critically ill patients admitted to the intensive care unit and that a stepwise increase in mortality is associated with the severity of AKI along KDIGO stages. Both serum creatinine and UO have inherent limitations in accurately diagnosing abrupt decreases of renal function, but their common and easy application in routine clinical practice is currently considered the standard of care for AKI diagnosis. Pediatric and neonatal AKI have recently been described and specific staging with KDIGO modification has been proposed. Key Messages: AKI is frequent in critically ill patients and significantly affects intensive outcomes independent of other clinical factors. AKI can be diagnosed and its severity accurately staged by the KDIGO classification and its modification for pediatric patients. Serum creatinine and UO criteria are applied in order to diagnose and stage AKI. Despite some significant limitations of these commonly applied biomarkers, their application has made it possible to clearly appraise the importance of accurate AKI identification in clinical practice in several studies for prognostic and therapeutic purposes.

Assessing the volemic status of patients undergoing surgery is part of the routine management for the anesthesiologist. This assessment is commonly performed by means of dynamic indexes based on the cardiopulmonary interaction during mechanical ventilation (if available) or by administering a fluid challenge (FC). The FC is used during surgery to optimize predefined hemodynamic targets, the so-called Goal-Directed Therapy (GDT), or to correct hemodynamic instability (non-GDT).In this systematic review, we considered the FC components in studies adopting either GDT or non-GDT, to assess whether differences exist between the 2 approaches. In addition, we performed a meta-analysis to ascertain the effectiveness of dynamic indexes pulse pressure variation (PPV) and stroke volume (SV) variation (SVV), in predicting fluid responsiveness.Thirty-five non-GDT and 33 GDT studies met inclusion criteria, including 5017 patients. In the vast majority of non-GDT and GDT studies, the FC consisted in the administration of colloids (85.7% and 90.9%, respectively). In 29 non-GDT studies, the colloid infused was the 6% hydroxyethyl starch (6% HES; 96.6% of this subgroup). In 20 GDT studies, the colloid infused was the 6% HES (66.7% of this subgroup), while in 5 studies was a gelatin (16.7% of this subgroup), in 3 studies an unspecified colloid (10.0% of this subgroup), and in 1 study albumin (3.3%) or, in another study, both HES 6% and gelatin (3.3%). In non-GDT studies, the median volume infused was 500 mL; the time of infusion and hemodynamic target to assess fluid responsiveness lacked standardization. In GDT studies, FC usually consisted in the administration of 250 mL of colloids (48.8%) in 10 minutes (45.4%) targeting an SV increase10% (57.5%). Only in 60.6% of GDT studies, a safety limit was adopted. PPV pooled area under the curve (95% confidence interval [CI]) was 0.86 (0.80-0.92). The mean (standard deviation) PPV threshold predicting fluid responsiveness was 10.5% (3.2) (range, 8%-15%), while the pooled (95% CI) sensitivity and specificity were 0.80 (0.74-0.85) and 0.83 (0.73-0.91), respectively. SVV pooled area under the curve (95% CI) was 0.87 (0.81-0.93). The mean (standard deviation) SVV threshold predicting fluid responsiveness was 11.3% (3.1) (range, 7.5%-15.5%), while the pooled (95% CI) sensitivity and specificity were 0.82 (0.75-0.89) and 0.77 (0.71-0.82), respectively.The key components of FC including type of fluid (colloids, often 6% HES), volume (500 and 250 mL in non-GDT studies and GDT studies, respectively), and time of infusion (10 minutes) are quite standardized in operating room. However, pooled sensitivity and specificity of both PPV and SVV are limited.

Continuous renal replacement therapy (CRRT) is commonly applied in critically ill patients affected by severe acute kidney injury for solute and volume control and to optimize acid-base and electrolytes balance. Although CRRT represents a life-saving procedure for these patients, it is a representation of a non-physiologic artificial kidney and the potential benefits of the treatment could be hampered by clinical and technical side effects. Different parts of the CRRT system can be a source of technical complications. Vascular access dysfunction, activation of the coagulation system, air embolism, heat loss and hypothermia, fluid balance errors, and immune system activation are some issues the medical and nurse staff have to face daily in patients undergoing CRRT. A detailed understanding of these complications and knowledge about the technology that the staff are dealing with are fundamental aspects for applying CRRT safely and efficaciously.

The incidence of the multiple organ dysfunction syndrome (MODS) is rapidly increasing in intensive care units (ICU). It usually combines with sepsis and is the most frequent cause of death in the ICU patients. The nature of the ICU patients has changed in the last years. It includes a variety of patients with severe cases due to major surgical interventions, trauma, hemodynamic instability, sepsis, and so on but also older people than previous times. All these situations can easily lead to MODS. In the prior years, the only available and efficient therapy was renal replacement therapy (RRT) for treating acute renal failure, but the development of technology also gives us devices to support the other systems. The adequacy of any artificial organ support is evaluated by how closely it mimics the flexibility and efficacy of the organ systems it seeks to substitute or support. In a sequence of events, such as that created by sepsis and MODS, all these criteria should be applied at the same time but for different organs and different tasks. RRT and especially continuous renal replacement therapies (CRRT) allowed extracorporeal treatment in critically ill patients with hyper catabolism and fluid overload with excellent hemodynamic stability. New techniques in CRRT as high volume hemofiltration have been applied in septic patients with very promising results. In the light of these observations, a new thought arises: Can extracorporeal blood purification have a positive impact on different organ systems? A possible answer might come from the simple observation that all organs share one aspect in common: contact with blood. All extracorporeal therapies also have one aspect in common: treatment of blood. Based on these observations and knowledge of the molecular biology of sepsis, a "humoral" theory of MODS makes pathophysiological sense and its consequence triggers the need to consider extracorporeal therapies as multiple organ support therapies and not just as single organ support.

The incidence of the multiple organ dysfunction syndrome (MODS) is rapidly increasing in intensive care units (ICU). It usually combines with sepsis and is the most frequent cause of death in the ICU patients. The nature of the ICU patients has changed in the last years. It includes a variety of patients with severe cases due to major surgical interventions, trauma, hemodynamic instability, sepsis, and so on but also older people than previous times. All these situations can easily lead to MODS. In the prior years, the only available and efficient therapy was renal replacement therapy (RRT) for treating acute renal failure, but the development of technology also gives us devices to support the other systems. The adequacy of any artificial organ support is evaluated by how closely it mimics the flexibility and efficacy of the organ systems it seeks to substitute or support. In a sequence of events, such as that created by sepsis and MODS, all these criteria should be applied at the same time but for different organs and different tasks. RRT and especially continuous renal replacement therapies (CRRT) allowed extracorporeal treatment in critically ill patients with hyper catabolism and fluid overload with excellent hemodynamic stability. New techniques in CRRT as high volume hemofiltration have been applied in septic patients with very promising results. In the light of these observations, a new thought arises: Can extracorporeal blood purification have a positive impact on different organ systems? A possible answer might come from the simple observation that all organs share one aspect in common: contact with blood. All extracorporeal therapies also have one aspect in common: treatment of blood. Based on these observations and knowledge of the molecular biology of sepsis, a "humoral" theory of MODS makes pathophysiological sense and its consequence triggers the need to consider extracorporeal therapies as multiple organ support therapies and not just as single organ support.

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.

Peripheral venous cannulation is an everyday practice of care for patients undergoing anesthesia and surgery. Particles infused with intravenous fluids (eg, plastic/glass/drugs particulate) contribute to the pathogenesis of peripheral phlebitis. The aim of this study is to demonstrate the efficacy of in-line filtration in reducing the incidence of postoperative phlebitis associated with peripheral short-term vascular access.In this controlled trial, 268 surgical patients were randomly assigned to in-line filtration and standard care (NCT03193827). The incidence of phlebitis (defined as visual infusion phlebitis [VIP] score, ≥2) within 48 hours was compared between the 2 groups, as well as the onset and severity of phlebitis and the reasons for removal of the cannula. The lifespan of venous cannulae was compared for the in-line filter and no-filter groups through a Kaplan-Meier curve.The incidence of phlebitis within 48 hours postoperatively was 2.2% and 26.9% (difference, 25% [95% confidence interval {CI}, 12%-36%]; odds ratio, 0.05 [0.01-0.15]), respectively, for the in-line filter and no-filter groups (P.001). From 24 to 96 hours postoperatively, patients in the no-filter group had higher VIP scores than those in in-line filter group (P.001). Venous cannulae in the in-line filter group exhibited prolonged lifespan compared to those in the no-filter group (P = .01). In particular, 64 (47.8%) of cannulae in the in-line filter group and 56 (41.8%) of those in the no-filter group were still in place at 96 hours postoperatively. At the same time point, patients with a VIP score3 were 100% in the in-line filter group and only 50% for the no-filter group. In-line filtration was a protective factor for postoperative phlebitis (hazard ratio, 0.05 [95% CI, 0.014-0.15]; P.0001) and cannula removal (hazard ratio, 0.7 [95% CI, 0.52-0.96]; P = .02).In-line filtration has a protective effect for postoperative phlebitis and prolongs cannula lifespan during peripheral venous cannulation in surgical patients.

Minimally invasive surgical procedures have revolutionized the world of surgery in the past decades. While laparoscopy, the first minimally invasive surgical technique to be developed, is widely used and has been addressed by several guidelines and recommendations, the implementation of robotic-assisted surgery is still hindered by the lack of consensus documents that support healthcare professionals in the management of this novel surgical procedure. Here we summarize the available evidence and provide expert opinion aimed at improving the implementation and resolution of issues derived from robotic abdominal surgery procedures. A joint task force of Italian surgeons, anesthesiologists and clinical epidemiologists reviewed the available evidence on robotic abdominal surgery. Recommendations were graded according to the strength of evidence. Statements and recommendations are provided for general issues regarding robotic abdominal surgery, operating theatre organization, preoperative patient assessment and preparation, intraoperative management, and postoperative procedures and discharge. The consensus document provides evidence-based recommendations and expert statements aimed at improving the implementation and management of robotic abdominal surgery.

During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology.

Multisite near infrared spectroscopy (NIRS) monitoring during pediatric cardiopulmonary bypass (CPB) has not been extensively validated. Although it might be rational to explore regional tissue saturation at different body sites (namely brain, kidney, upper body, lower body), conflicting results are currently provided by experience in children. The aim of our study was to evaluate absolute values of multisite NIRS saturation during CPB in a cohort of infants undergoing pediatric cardiac surgery to describe average differences between cerebral, renal, upper body (arm), and lower body (thigh) regional saturation. Furthermore, the correlation between cerebral NIRS and cardiac index (CI) at CPB weaning was evaluated. Twenty-five infants were enrolled: their median weight, age, and body surface area were 3.9 (3.3-6) kg, 111 (47-203) days, and 0.24 (0.22-0.33) m(2) , respectively. Median Aristotle score was 8 (6-10), and vasoactive inotropic score at CPB weaning was 16 (14-25). A total of 17 430 data points were recorded by each sensor: two-way ANOVA showed that time (P < 0.0001) and site (P = 0.0001) significantly affected variations of NIRS values: however, if cerebral NIRS values are excluded, sensor site is no more significant (P = 0.184 in the no circulatory arrest [noCA] group and P = 0.42 in the circulatory arrest [CA] group). Analysis of NIRS saturation changes over time showed that, at all sites, average NIRS values increased after CPB start, even if the increase of cerebral saturation was less intense than other sites (P < 0.0001). Detailed analysis of interaction between site of NIRS measurement and time point showed that cerebral NIRS (ranging from 65 to 75%) was always significantly lower than that of other channels (P < 0.0001) that tended to be in the range of oversaturation (80-90%), especially during the CPB phase. Average cerebral NIRS values of patients who did not undergo circulatory arrest (CA) during CPB, 10 min after CPB weaning, were associated with average CI values with a significant correlation (r = 0.7, P = 0.003). In conclusion, during CPB, cerebral NIRS values are expected to remain constantly lower than somatic sensors, which instead tend to show similar elevated saturations, regardless of their position. Based on these results, positioning of noncerebral NIRS sensors during CPB without CA may be questioned.

Objective Central neuraxial techniques are typically avoided in patients with underlying coagulopathy or abnormal coagulation tests. Vertebral canal hematoma is a rare but devastating complication of those procedures. Although the sensitivity and specificity of standard laboratory tests in predicting this event are rather poor or unknown, these tests are commonly used to allow or advise against the insertion of an epidural or spinal catheter. Furthermore, the role of viscoelastic point-of-care tests, which are widely used to monitor coagulation in the perioperative setting, is unexplored. Case Report We report a patient presenting for endovascular repair of a dissecting thoracoabdominal aortic aneurysm, in which we placed a subarachnoid catheter for continuous cerebrospinal fluid drainage because of the high risk of spinal cord ischemia associated with the procedure. Unfortunately, the patient presented with an overt consumption coagulopathy that would have advised against performing any central neuraxial technique. Bedside monitoring, diagnosis, and goal-directed hemostatic therapy guided by thromboelastometry documented improved coagulation both at the time of insertion and removal of the subarachnoid device. No catheter-related complications occurred. Conclusions Thromboelastometry proved useful to guide hemostatic therapy before subarachnoid catheter placement and extraction in a patient with severe coagulopathy when standard coagulation tests were of less benefit.

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.

Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a significant proportion of critically ill patients. However, many questions remain about the optimal administration of RRT with regard to several important considerations, including treatment dose, timing of treatment initiation and cessation, therapy mode, type of anticoagulation, and management of fluid overload. While Level 1 evidence exists for RRT dosing in AKI, all the studies contributing to this evidence base employed fixed-dose regimens throughout a patient's continuous RRT (CRRT) course, without regard for the possibility of individualizing treatment dose according to the clinical status of a given patient at a specific time. As opposed to CRRT dose, no consensus about the timing of RRT in critically ill AKI patients exists currently. While numerous clinical trials over the past 40 years have attempted to assess "early" versus "late" initiation of RRT, they have been plagued by a myriad of methodological problems, including their largely observational nature and the widely varying definitions of early and late initiation. Although questions about the appropriate timing of CRRT discontinuation arise very frequently in clinical practice, even less information is available in the literature to guide this important decision. The aim of this review is to provide a comprehensive update on RRT delivery to critically ill AKI patients, with specific attention paid to treatment dose and timing and emphasis on addressing the practical questions that arise in daily clinical practice.

Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

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

Background There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. Methods/design The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2–3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3–5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2 ratio

In most mammals, the sex of an individual is genetically determined by the Y chromosome-specific SRY gene. The presence of at least one functional copy of this gene determines the development of the primordial gonads into testes. However, testicular tissue does develop in the absence of SRY, albeit rarely, which is the case in testicular XX (SRY-negative) disorder of sex development (DSD). This condition is very important for studying the process of sexual determination because it allows the identification of genetic factors that are able to promote the male developmental pathway in the absence of SRY and thereby enables a better understanding of this process. Until now, this condition has been identified in various animal species but has never been reported in cat. In this study, we describe the first case of an XX (SRY-negative) DSD cat. The cat possesses a tortoiseshell coat associated with male-like external genitalia, including normal scrotum with 2 palpably normal testicles. Histological analysis confirmed the presence of the testes, and cytogenetic and genetic analyses showed a female karyotype associated with the absence of the SRY gene. Finally, sequencing of the RSPO1 gene revealed no mutation, and FISH analysis of the SOX9 locus did not reveal any large abnormalities.

In the literature, the term “inoperable” mainly refers to two specific clinical aspects: cancer staging and technical difficulty/impossibility in performing. In light of this clarification, the statement “the patient cannot be anesthetized” has no medical foundation. On the contrary, the physicians have to carefully stratify the perioperative risk and optimize the patients’ preoperative clinical status. In order to perform a precise risk stratification, the European Society of Cardiology and the European Society of Anaesthesiology have joined and published the guidelines for the perioperative cardiovascular management of patients scheduled to undergo non-cardiac surgery. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) represents the most complete and accurate prediction tool so far. It includes 21 preoperative factors relating to demographics, comorbidities and procedures able to predict outcomes based on preoperative risk factors such as death, cardiac complications, pneumonia, and acute kidney injury. The present article will address aspects related to common aspects concerning modifiable and non-modifiable that should be addressed in every patient to whom elective surgery has been scheduled.