Potential benefits of using an energy-dense, high-protein formula enriched with ß-hydroxy-ß-methylbutyrate, fructo-oligosaccharide, and vitamin D for enteral feeding in the ICU: A pilot case-control study in COVID-19 patients.

OBJECTIVES: The aim of this study was to investigate the potential benefits of using an energy-dense, high-protein (HP) formula enriched with ß-hydroxy-ß-methylbutyrate (HMB), fructo-oligosaccharide (FOS), and vitamin D (VitD) for enteral feeding in the intensive care unit (ICU). METHODS: This was a nested case-control multicenter study. Mechanically ventilated patients with COVID-19 in whom enteral nutrition was not contraindicated and receiving an energy-dense, HP-HMB-FOS-VitD formula (1.5 kcal/mL; 21.5% of calories from protein; n = 53) were matched (1:1) by age (±1 y), sex, body mass index (±1 kg/m2) and Sequential Organ Failure Assessment score (±1 point) and compared with patients fed with a standard HP, fiber-free formula (1.25-1.3 kcal/mL; 20% of calories from protein; n = 53). The primary end point was daily protein intake (g/kg) on day 4. Protein-calorie intake on day 7, gastrointestinal intolerance, and clinical outcomes were addressed as secondary end points. RESULTS: The use of a HP-HMB-FOS-VitD formula resulted in higher protein intake on days 4 and 7 (P = 0.006 and P = 0.013, respectively), with similar energy intake but higher provision of calories from enteral nutrition at both times (P <0 .001 and P = 0.017, respectively). Gastrointestinal tolerance was superior, with fewer patients fed with a HP-HMB-FOS-VitD formula reporting at least one symptom of intolerance (55 versus 74%; odds ratio [OR], 0.43; 95% confidence interval [CI], 0.18-0.99; P = 0.046) and constipation (38 versus 66%; OR, 0.27; 95% CI, 0.12-0.61; P = 0.002). A lower rate of ICU-acquired infections was also observed (42 versus 72%; OR, 0.29; 95% CI, 0.13-0.65; P = 0.003), although no difference was found in mortality, ICU length of stay, and ventilation-free survival. CONCLUSIONS: An energy-dense, HP-HMB-FOS-VitD formula provided a more satisfactory protein intake and a higher provision of caloric intake from enteral nutrition than a standard HP formula in mechanically ventilated patients with COVID-19. Lower rates of gastrointestinal intolerance and ICU-acquired infections were also observed.

A Role of Circuit Clotting and Strategies to Prevent It during Blood Purification Therapy with oXiris Membrane: An Observational Multicenter Study.

INTRODUCTION: Membrane fouling is a significant complication potentially reducing clinical effects of extracorporeal blood purification (EBP) in critically ill septic patients with acute kidney injury. Although fascinating, the effect of heparin coating in preventing membrane fouling is currently unknown. This multicenter prospective study aims to preliminary describe the incidence, associated factors, and clinical consequences of premature circuit clotting in a cohort of adult critically ill septic patients treated with EBP using a high biocompatible heparin-coated hemodiafilter characterized by advanced adsorption properties. METHODS: This study was a retrospective analysis of prospectively entered data in the oXirisNet Registry; overall, 97 septic patients undergoing EBP with oXiris between May 2019 and March 2020 were enrolled in this study. Patients were divided into two groups according to the occurrence of filter clotting (premature vs. nonpremature). Logistic regression analysis was used to identify factors associated with premature circuit clotting. RESULTS: Premature clotting occurred in 18 (18.6%) patients. Results of the multivariate logistic regression analysis demonstrated that hematocrit (p = 0.02, odds ratio [OR] 1.15 [1.05; 1.30]), serum procalcitonin (PCT) (p = 0.03, OR 1.1 [1.05; 1.2]), and anticoagulation strategy (p = 0.05 at Wald's test) were independent predictors of circuit clotting. Systemic anticoagulation (p = 0.02, OR 0.03 [0.01; 0.52]) and regional citrate anticoagulation (p = 0.10, OR 0.23 [0.04; 1.50]) were both protective factors if compared to no-anticoagulation strategy. Patients with nonpremature circuit clotting showed more rapid recovery from hemodynamic instability, pulmonary hypo-oxygenation, and electrolyte disorders and greater improvement of inflammatory markers and SOFA scores. CONCLUSION: Although in this study the incidence of premature circuit clotting was relatively low (18.6%) compared to previously reported values (54%), membrane clotting in adult critically ill septic patients could cause clinically relevant interferences with treatment performances. Prevention of clotting should be based on avoiding higher patients' hematocrit, high serum PCT, and no-anticoagulation strategy which resulted as independent predictors of circuit clotting.

Minimally invasive esophagectomy for cancer in COVID hospitals and oncological hubs: are the outcomes different?

Introduction: The outbreak of coronavirus disease 2019 (COVID-19) has caused significant delays in oncological care worldwide due to restriction of elective surgery and intensive care unit capacity. It has been hypothesized that COVID-free oncological hubs can provide safer elective cancer surgery compared to COVID hospitals. The primary aim of the present study was to analyze the outcomes of minimally invasive esophagectomy for cancer performed in both hospital settings by the same surgical staff. Methods: All esophagectomies for cancer performed during the pandemic by a single team were reviewed and data were compared with control patients operated during the preceding year. Screening for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was performed prior to surgery, and special precautions were taken to mitigate hospital-related transmission of COVID-19 among patients and healthcare workers. Results: Compared to the prepandemic period, the esophagectomy volume decreased by 64%. Comorbidities, time from onset of symptoms to first visit, waiting time between diagnosis and surgery, operative approach and technique, and the pathological staging were similar. None of the patients tested positive for COVID-19 during in-hospital stay, and esophagectomy was associated with similar outcomes compared to control patients. Conclusion: Outcomes of minimally invasive esophagectomy for cancer performed in a COVID hospital after implementation of a COVID-free surgical pathway did not differ from those obtained in an oncological hub by the same surgical team.

Ventral hernia repair under neuraxial anesthesia.

BACKGROUND: Acute strangulated ventral hernia is associated with operative morbidity and mortality. General anesthesia may increase the operative risk, especially in morbidly obese and COVID-19-positive individuals. METHODS: A 67-year-old woman with body mass index (BMI) 51 kg/m2, hospitalized for SARS-CoV-2-related interstitial pneumonia and renal failure, presented with acute abdominal pain, nausea, vomiting, and abdominal tenderness secondary to giant ventral hernia strangulation. RESULTS: Due to the suspicion of vascular bowel compromise at contrast-enhanced CT scan, urgent open surgical repair surgery was performed under spinal anesthesia and Venturi mask support. There was no need for an intensive care unit (ICU) stay. Postoperative course was uneventful, and the patient was transferred to a rehabilitation center on postoperative day 10. CONCLUSION: Although some anesthetists and surgeons may be reluctant to use regional anesthesia for both emergent and elective ventral hernia repair, this may represent an excellent option in obese patients with a high respiratory risk.

Combined Renal-Pulmonary Extracorporeal Support with Low Blood Flow Techniques: A Retrospective Observational Study (CICERO Study).

BACKGROUND: Critically ill patients with acute respiratory failure frequently present concomitant lung and kidney injury, within a multiorgan failure condition due to local and systemic mediators. To face this issue, extracorporeal carbon dioxide removal (ECCO2R) systems have been integrated into continuous renal replacement therapy (CRRT) platforms to provide a combined organ support, with efficient clearance of CO2 with very low extracorporeal blood flows (<400 mL/min). OBJECTIVES: To evaluate efficacy and safety of combined ECCO2R-CRRT support with PrismaLung®-Prismaflex® in patients affected by hypercapnic respiratory acidosis associated with AKI in a second level intensive care unit. METHODS: We carried out a retrospective observational study enrolling patients submitted to PrismaLung®-Prismaflex® due to mild to moderate acute respiratory distress syndrome (ARDS) or acute exacerbation of chronic obstructive pulmonary disease (aeCOPD). The primary endpoints were the shift to protective ventilation and extubation of mechanically ventilated patients and the shift to invasive mechanical ventilation of patients receiving noninvasive ventilation (NIV). Clinical-laboratoristic data and operational characteristics of ECCO2R-CRRT were recorded. RESULTS: Overall, 12/17 patients on mechanical ventilation shifted to protective ventilation, CO2 clearance was satisfactorily maintained during the whole observational period, and pH was rapidly corrected. Treatment prevented NIV failure in 4 out of 5 patients. No treatment-related complications were recorded. CONCLUSION: ECCO2R-CRRT was effective and safe in patients with aeCOPD and ARDS associated with AKI.

Hemodynamic Instability during Acute Kidney Injury and Acute Renal Replacement Therapy: Pathophysiology and Clinical Implications.

Hemodynamic instability associated with acute renal replacement therapy (aRRT, HIRRT) and/or with acute kidney injury (AKI) is frequently observed in the intensive care unit; it affects patients' renal recovery, and negatively impacts short- and long-term mortality. A thorough understanding of mechanisms underlying HIRRT and AKI-related hemodynamic instability may allow the physician in adopting adequate strategies to prevent their occurrence and reduce their negative consequences. The aim of this review is to summarize the main alterations occurring in patients with AKI and/or requiring aRRT of those homeostatic mechanisms which regulate hemodynamics and oxygen delivery. In particular, a pathophysiological approach has been used to describe the maladaptive interactions between cardiac output and systemic vascular resistance occurring in these patients and leading to hemodynamic instability. Finally, the potential positive effects of aRRT on these pathophysiological mechanisms and on restoring hemodynamic stability have been described.

Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study.

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.

The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES: Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS: Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS: At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 µg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2  = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). CONCLUSION: The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.

Calcium priming of the central venous catheter prevents a drop in ionized calcium concentration during Regional Citrate Anticoagulation.

During citrate-based Continuous Renal Replacement Therapy (CRRT), an infusion of calcium is necessary to replace the calcium lost in the effluent. The replacement takes place through a central venous catheter (CVC) that is primed with saline solution. Thus, we hypothesized a potential systemic anticoagulation caused by the unchelated citrate reaching the patient at the start of CRRT because of 0.42 ml of line dead space. In this pilot study, two subpopulations of 7 patients who underwent Continuous Veno-Venous Hemodiafiltration (150 ml/min of blood flow, 1500 ml/h dialysate flow, 1500 ml/h of citrate predilution) were studied. One had the CVC primed with saline, the second with calcium chloride 10%. Calcium replacement rate was 6.3 ± 0.2 ml/h. Ionized calcium concentration was studied over time in the two groups and in the group with saline priming we detected a transient period of hypocalcemia (ionized calcium concentration [iCa] < 1.00 mmol/l for the first 2 hours). In the subpopulation with the calcium priming, this was not present. No significant effect on filter life emerged. Priming of the catheter with calcium seems effective in avoiding a potential issue regarding citrate accumulation at the start of CRRT. More studies are needed to assess the clinical significance of this finding.