Sharing Mechanical Ventilator: In Vitro Evaluation of Circuit Cross-Flows and Patient Interactions.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30-50 mL × cmH2O-1) and resistances (5-20 cmH2O × L-1 × s-1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O-1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L-1 × s-1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p < 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient's needs and has a high risk of cross-interference.

Recognition in Emergency Department of Septic Patients at Higher Risk of Death: Beware of Patients without Fever.

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed.

Risk of Atypical HUS Among Family Members of Patients Carrying Complement Regulatory Gene Abnormality.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is mainly due to complement regulatory gene abnormalities with a dominant pattern but incomplete penetrance. Thus, healthy carriers can be identified in any family of aHUS patients, but it is unpredictable if they will eventually develop aHUS. METHODS: Patients are screened for 10 complement regulatory gene abnormalities and once a genetic alteration is identified, the search is extended to at-risk family members. The present cohort study includes 257 subjects from 71 families: 99 aHUS patients (71 index cases + 28 affected family members) and 158 healthy relatives with a documented complement gene abnormality. RESULTS: Fourteen families (19.7%) experienced multiple cases. Over a cumulative observation period of 7595 person-years, only 28 family members carrying gene mutations experienced aHUS (overall penetrance of 20%), leading to a disease rate of 3.69 events for 1000 person-years. The disease rate was 7.47 per 1000 person-years among siblings, 6.29 among offspring, 2.01 among parents, 1.84 among carriers of variants of uncertain significance, and 4.43 among carriers of causative variants. CONCLUSIONS: The penetrance of aHUS seems a lot lower than previously reported. Moreover, the disease risk is higher in carriers of causative variants and is not equally distributed among generations: siblings and the offspring of patients have a much greater disease risk than parents. However, risk calculation may depend on variant classification that could change over time.

Perioperative management of children with neuromuscular disorders based on a common protocol: A prospective, national study in Italy.

BACKGROUND: Children with neuromuscular diseases (NMDs) often display respiratory muscle weakness which increases the risk of postoperative pulmonary complications (PPCs) after general anaesthesia. Non-invasive ventilation (NIV) associated with mechanical insufflation-exsufflation (MI-E) can reduce the incidence and severity of PPCs. The aim of this study was to report our experience with a shared perioperative protocol that consists in using NIV combined with MI-E to improve the postoperative outcome of NMD children (IT-NEUMA-Ped). METHOD: We conducted a multicentre, observational study on 167 consecutive paediatric patients with NMDs undergoing anaesthesia from December 2015 to December 2018 in a network of 13 Italian hospitals. RESULTS: We found that 89% of the 167 children (mean age 8 years old) were at high risk of PPCs, due to the presence of at least one respiratory risk factor. In particular, 51% of them had preoperative ventilatory support dependence. Only 14 (8%) patients developed PPCs, and only two patients needed tracheostomy. Average hospital length of stay (LOS) was 6 (2-14) days. The study population was stratified according to preoperative respiratory devices dependency and invasiveness of the procedure. Patients with preoperative ventilatory support dependence showed significantly higher intensive care unit (ICU) admission rate and longer hospital LOS. CONCLUSION: Disease severity seems to be more related to the outcome of this population than invasiveness of procedures. NIV combined with MI-E can help in preventing and resolve PPCs.

Assessing anaesthesiology and intensive care specialty physicians: An Italian language multisource feedback system.

BACKGROUND: Physician professionalism, including anaesthesiologists and intensive care doctors, should be continuously assessed during training and subsequent clinical practice. Multi-source feedback (MSF) is an assessment system in which healthcare professionals are assessed on several constructs (e.g., communication, professionalism, etc.) by multiple people (medical colleagues, coworkers, patients, self) in their sphere of influence. MSF has gained widespread acceptance for both formative and summative assessment of professionalism for reflecting on how to improve clinical practice. METHODS: Instrument development and psychometric analysis (feasibility, reliability, construct validity via exploratory factor analysis) for MSF questionnaires in a postgraduate specialty training in Anaesthesiology and intensive care in Italy. Sixty-four residents at the Università del Piemonte Orientale (Italy) Anesthesiology Residency Program. Main outcomes assessed were: development and psychometric testing of 4 questionnaires: self, medical colleague, coworker and patient assessment. RESULTS: Overall 605 medical colleague questionnaires (mean of 9.3 ±1.9) and 543 coworker surveys (mean 8.4 ±1.4) were collected providing high mean ratings for all items (> 4.0 /5.0). The self-assessment item mean score ranged from 3.1 to 4.3. Patient questionnaires (n = 308) were returned from 31 residents (40%; mean 9.9 ± 6.2). Three items had high percentages of "unable to assess" (> 15%) in coworker questionnaires. Factor analyses resulted in a two-factor solution: clinical management with leadership and accountability accounting for at least 75% of the total variance for the medical colleague and coworker's survey with high internal consistency reliability (Cronbach's α > 0.9). Patient's questionnaires had a low return rate, a limited exploratory analysis was performed. CONCLUSIONS: We provide a feasible and reliable Italian language MSF instrument with evidence of construct validity for the self, coworkers and medical colleague. Patient feedback was difficult to collect in our setting.

Use of backboards in cardiopulmonary resuscitation: a systematic review and meta-analysis.

To achieve optimal chest compression depth, victims of cardiac arrest should be placed on a firm surface. Backboards are usually placed between the mattress and the back of a patient in the attempt to increase cardiopulmonary resuscitation (CPR) quality, but their effectiveness remains controversial. A systematic search was performed to include studies on humans and simulation manikins assessing CPR quality with or without backboards. The primary outcome of the meta-analysis was the difference in chest compression depth between these two conditions. Out of 557 records, 16 studies were included in the review and all were performed on manikins. The meta-analysis, performed on 15 articles, showed that the use of backboards during CPR increases chest compression depth by 1.46 mm in manikins. Despite statistically significant, this increase could have a limited clinical impact on CPR, due to the substantial heterogeneity of experimental conditions and the scarcity of other CPR quality indicators.

Potential harm caused by physicians' a-priori beliefs in the clinical effectiveness of hydroxychloroquine and its impact on clinical and economic outcome - A simulation approach.

BACKGROUND: Despite growing controversies around Hydroxychloroquine's effectiveness, the drug is still widely prescribed by clinicians to treat COVID19 patients. Therapeutic judgment under uncertainty and imperfect information may be influenced by personal preference, whereby individuals, to confirm a-priori beliefs, may propose drugs without knowing the clinical benefit. To estimate this disconnect between available evidence and prescribing behavior, we created a Bayesian model analyzing a-priori optimistic belief of physicians in Hydroxychloroquine's effectiveness. METHODOLOGY: We created a Bayesian model to simulate the impact of different a-priori beliefs related to Hydroxychloroquine's effectiveness on clinical and economic outcome. RESULTS: Our hypothetical results indicate no significant difference in treatment effect (combined survival benefit and harm) up to a presumed drug's effectiveness level of 20%, with younger individuals being negatively affected by the treatment (RR 0.82, 0.55-1.2; (0.95 (1.1) % expected adverse events versus 0.05 (0.98) % expected death prevented). Simulated cost data indicate overall hospital cost (medicine, hospital stay, complication) of 18.361,41€ per hospitalized patient receiving Hydroxychloroquine treatment. CONCLUSION: Off-label use of Hydroxychloroquine needs a rational, objective and datadriven evaluation, as personal preferences may be flawed and cause harm to patients and to society.

Augmented Reality Learning Environment for Basic Life Support and Defibrillation Training: Usability Study.

BACKGROUND: Basic life support (BLS) is crucial in the emergency response system, as sudden cardiac arrest is still a major cause of death worldwide. Unfortunately, only a minority of victims receive cardiopulmonary resuscitation (CPR) from bystanders. In this context, training could be helpful to save more lives, and technology-enhanced BLS simulation is one possible solution. OBJECTIVE: The aim of this study is to assess the feasibility and acceptability of our augmented reality (AR) prototype as a tool for BLS training. METHODS: Holo-BLSD is an AR self-instruction training system, in which a standard CPR manikin is "augmented" with an interactive virtual environment that reproduces realistic scenarios. Learners can use natural gestures, body movements, and spoken commands to perform their tasks, with virtual 3D objects anchored to the manikin and the environment. During the experience, users were trained to use the device while being guided through an emergency simulation and, at the end, were asked to complete a survey to assess the feasibility and acceptability of the proposed tool (5-point Likert scale; 1=Strongly Disagree, 5=Strongly Agree). RESULTS: The system was rated easy to use (mean 4.00, SD 0.94), and the trainees stated that most people would learn to use it very quickly (mean 4.00, SD 0.89). Voice (mean 4.48, SD 0.87), gaze (mean 4.12, SD 0.97), and gesture interaction (mean 3.84, SD 1.14) were judged positively, although some hand gesture recognition errors reduced the feeling of having the right level of control over the system (mean 3.40, SD 1.04). CONCLUSIONS: We found the Holo-BLSD system to be a feasible and acceptable tool for AR BLS training.

Cognitive appraisals and team performance under stress: A simulation study.

OBJECTIVES: The present study explored how challenge and threat responses to stress relate to performance, anxiety, confidence, team identity and team characteristics (time spent in training and postgraduate experience) in a medical simulation-based team competition. METHODS: The study was conducted during a national simulation-based training event for residents, the SIMCUP Italia 2018. The SIMCUP is a simulation competition in which teams of four compete in simulated medical emergency scenarios. Cross-sectional data were collected prior to the 3 days of the competition. Subjects included 95 participants on 24 teams. Before the competition on each day, participants completed brief self-report measures that assessed demands and resources (which underpin challenge and threat responses to stress), cognitive and somatic anxiety, self-confidence and team identification. Participants also reported time (hours) spent practising as a team and years of postgraduate experience. A team of referees judged each scenario for performance and assigned a score. A linear mixed model using demands and resources was built to model performance. RESULTS: The data showed that both demands and resources have positive effects on performance (31 [11-50.3] [P < .01] and 54 [25-83.3] [P < .01] percentage points increase for unitary increases in demands and resources, respectively); however, this is balanced by a negative interaction between the two (demands * resources interaction coefficient = -10 [-16 to -4.2]). A high level of resources is associated with better performance until demands become very high. Cognitive and somatic anxieties were found to be correlated with demands (Pearson's r = .51 [P < .01] and Pearson's r = .48 [P < .01], respectively). Time spent training was associated with greater perceptions of resources (Pearson's r = .36 [P < .01]). CONCLUSIONS: We describe a model of challenge and threat that allows for the estimation of performance according to perceived demands and resources, and the interaction between the two. Higher levels of resources and lower demands were associated with better performance.

Osteopontin in the Cerebrospinal Fluid of Patients with Severe Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. In SAH patients, plasma osteopontin (OPN) has been shown to independently predict poor outcome. The aim of the study is to investigate, in a selected population with severe SAH, OPN time course in cerebrospinal fluid (CSF) and plasma during the first week after aneurism rupture, and OPN prognostic value. We included 44 patients with the following criteria: (1) age 18 and 80 years, (2) diagnosis of SAH from cerebral aneurysm rupture, (3) insertion of external ventricular drain. Plasma and CSF were sampled at day 1, 4, and 8. OPN levels, in CSF and plasma, displayed a weak correlation on day 1 and were higher, in CSF, in all time points. Only in poor prognosis patients, OPN levels in CSF significantly increased at day 4 and day 8. Plasma OPN at day 1 and 4 was predictor of poor outcome. In conclusion, plasma and CSF OPN displays a weak correlation, on day 1. The higher levels of OPN found in the CSF compared to plasma, suggest OPN production within the CNS after SAH. Furthermore, plasma OPN, at day 1 and 4, seems to be an independent predictor of poor outcome.

Sodium removal and plasma tonicity balance are not different in hemodialysis and hemodiafiltration using high-flux membranes.

BACKGROUND: The clinical benefits of on-line hemodiafiltration (HDF) versus high-flux membranes hemodialysis (hf-HD) are still debated. In fact, although a superiority of one treatment over the other, especially in terms of mortality, did not emerge from the analysis of clinical trials, improved intradialytic vascular stability and cardiovascular mortality have been observed in patients undergoing HDF rather than hf-HD; the lower removal of sodium (Na+) during HDF seems to play a major role. The plasma concentration of Na+ is the major determinant of plasma tonicity, which, by determining the flow of water between the intracellular and the extracellular compartment, contributes to the vascular refilling process and the maintenance of blood pressure during the hemodialysis treatment. Plasma tonicity also depends on plasma glucose concentration, especially in patients with diabetes mellitus with hyperglycaemia at the start of hemodialysis treatment. MATERIALS AND METHODS: We evaluated the removal of Na+ and plasma tonicity balance during a 2-week period by performing 2-3 consecutive sessions of hf-HD followed by 2-3 consecutive sessions of HDF, or vice versa, in 47 patients (40% diabetics) on chronic hemodialysis. Identical parameters were used in all dialytic sessions. RESULTS: Na+ removal per session was - 224 ± 144 mmol and - 219 ± 152 mmol, respectively, in hf-HD and in HDF (p = 0.79). The plasma tonicity balance per session was - 575 ± 310 mOsm and - 563 ± 328 mOsm, respectively, in hf-HD and in HDF (p = 0.75). CONCLUSIONS: The removal of Na+ and plasma tonicity balance did not differ between hf-HD and HDF. This observation suggests that factors other than those assessed in our study might explain the improved cardiovascular stability reported in HDF.

Current and potential treatment options for hyperphosphatemia.

INTRODUCTION: Hyperphosphatemia is common in late stages of chronic kidney disease and is often associated with elevated parathormone levels, abnormal bone mineralization, extra-osseous calcification, and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control plasma phosphorus levels. Although effective at lowering serum phosphorus, they all have safety, tolerability, and compliance issues that need to be considered when selecting which one to use. AREAS COVERED: This paper reviews the most established treatment options for hyperphosphatemia, in patients with chronic kidney disease, focusing on the new inhibitors of active phosphate absorption. EXPERT OPINION: The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Nonetheless, an extending range of phosphate binders are now available. Aluminum has potentially serious toxic risks. Calcium-based binders are very effective but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, and long-term effects of tissue deposition seem clinically irrelevant. Sevelamer, appear to have profiles that would lead to pleiotropic effects and reduced progression of vascular calcification, and the main adverse events seen with these agents are gastrointestinal. Iron has a powerful capability of binding phosphate, thus numerous preparations are available, both with and without significant systemic absorption of the iron component. The inhibitors of active intestinal phosphate transport, with their very selective mechanism of action and low pill burden seem the most interesting approach; however, do not seem at present to be effective alone, in reducing serum phosphorus levels.

Haemodialysis or haemodiafiltration: that is the question.

Despite the technological and pharmacological advancements in the last 30 years, morbidity and mortality of dialysis patients are still astonishingly high. Today, convective treatments, such as high-flux haemodialysis (hf-HD) and haemodiafiltration (HDF), are established techniques; the online production of fresh pure dialysate has provided clinical and economic advantages. Nevertheless, the actual benefits of HDF, even with high-convective-volume treatments, are still debatable. Three recent, randomized controlled trials compared survival outcomes in prevalent patients receiving conventional HD or post-dilution HDF and reported conflicting results. The meta-analyses of the published trials were ultimately incapable of providing a clear and definitive answer on the possible beneficial effects of choosing one treatment over the other. All-cause mortality, anaemia, phosphate control and clearance of small molecules seemed to be unaffected by the treatment modality. On the other hand, cardiovascular mortality, intradialytic vascular stability and the clearance of protein-bound molecules fared better in patients treated with HDF. These results were not consistent between the studies. Thus, there is still no conclusive answer to the question that nephrologists would like to have answered: 'Which is the best treatment for my patient?' In the age of evidence-based medicine, we need strong data to support the superiority of a treatment in comparison with another, although theoretically plausible. There is the need for a well-designed clinical trial comparing outcomes for patients randomly assigned to high- or moderate-convection-volume HDF versus hf-HD to clearly prove the clinical superiority of HDF, including the effect of different infusion volumes.

Assessment of intradialysis calcium mass balance by a single pool variable-volume calcium kinetic model.

INTRODUCTION: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single-pool variable-volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. METHODS: Thirty-four patients on thrice-weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end-dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. FINDINGS: The difference between predicted and measured values was 0.02 mmol/L (range -0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD -0.84 ± 1.33 mmol, range -5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. DISCUSSION: The proposed single pool variable-volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.

Patient-specific modeling of multicompartmental fluid and mass exchange during dialysis.

BACKGROUND: Dialysis is associated with a non-negligible rate of morbidity, requiring treatment customization. Many mathematical models have been developed describing solute kinetics during hemodialysis (HD) for an average uremic patient. The clinical need can be more adequately addressed by developing a patient-specific, multicompartmental model. MATERIALS AND METHODS: The data from 148 sessions (20 patients), recorded at the Regional Hospital of Lugano, Switzerland, were used to develop and validate the mathematical model. Diffusive and convective interactions among patient, dialysate and substitution fluid were considered. Three parameters, related to mass transfer efficiency at the cell membrane, at the dialyzer and at the capillary wall, were used to tune the model. The ability of the model to describe the clinical evolution of a specific HD session was evaluated by comparing model outputs with clinically acquired data on solutes and catabolite concentrations. RESULTS: The model developed in this study allows electrolyte and catabolite concentration trends during each HD session to be described. The errors obtained before the estimation of the patient-specific parameters drastically decrease after their identification. With the optimized model, plasmatic concentration trends can be described with an average percent error lower than 2.1% for Na+, Cl-, Ca2+ and HCO3-, lower than 5% for K+ and lower than 8% for urea. CONCLUSIONS: The peculiarity of the proposed model is the possibility it offers to perform a real-time simulation enabling quantitative appraisal of hematochemical quantities whose direct measurement is prohibitive. These will be beneficial to dialysis therapy planning, reducing intradialysis complications and improving patients' quality of life.