Search

The intra-aortic balloon pump (IABP) is the most widely available mechanical support device, but its use has been disputed in recent decades. Although several efforts have been made to reduce the associated complication rate, contemporary data on this matter is lacking. The present study aims to evaluate the differences in vascular complications between the sheathless and the sheathed IABP implantation technique in cardiac surgery patients. A retrospective multi-center cohort, consisting of patients treated in 8 cardiac surgical centers, was evaluated. Patients who underwent cardiac surgery with peri-operative IABP support were included. Primary outcome was a composite end point of vascular complications. Propensity score matching (PSM) was performed, and a multivariable regression model was applied to evaluate predictors of vascular complications. The unmatched cohort consisted of 2,615 patients (sheathless n = 1,414, 54%, sheathed n = 1,201, 46%). A total of 878 patients were matched (n = 439 for both groups). The composite vascular complication end point occurred in 3% of patients in the sheathless group, compared with 8% in the sheathed group (p

Objectives: To compare heparin-based anticoagulation and bivalirudin-based anticoagulation within the context of critically ill patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design: An observational study. Setting: At the intensive care unit of a university hospital. Participants and interventions: Critically ill patients with a SARS-CoV-2 infection receiving full anticoagulation with heparin or bivalirudin. Measurements and main results: Twenty-three patients received full anticoagulation with bivalirudin and 60 with heparin. Despite patients in the bivalirudin group having higher mortality risk scores (SAPS II 60 ± 16 v 39 ±7, p < 0.001) and a higher need for extracorporeal support compared to the heparin group, hospital mortality was comparable (57% v 45, p=0.3). No difference in thromboembolic complications was observed, and bleeding events were more frequent in patients treated with bivalirudin (65% v 40%, p=0.01). Similar results were confirmed in the subgroup analysis of patients undergoing intravenous anticoagulation; in addition to comparable thrombotic complications occurrence and thrombocytopenia rate, however, no difference in the bleeding rate was observed (65% v 35%, p=0.08). Conclusions: Although heparin is the most used anticoagulant in the intensive care setting, bivalirudin-based anticoagulation was safe and effective in a cohort of critically ill patients with SARS-CoV-2. Bivalirudin may be given full consideration as an anticoagulation strategy for critically ill patients with SARS-CoV-2, especially in those with thrombocytopenia and on extracorporeal support.

Objective Current evidence supports centralization of patients with refractory acute respiratory distress syndrome (ARDS) to institutions with a high level of expertise and with extracorporeal membrane oxygenation (ECMO) capabilities. The aim of this study was to analyze and report the data of transferred refractory ARDS patients managed with venovenous (VV) ECMO at a national referral center over the last 11 years. Design Observational study. Setting Referral center in Italy. Participants The study comprised 100 patients treated from May 2009–November 2020. Interventions None. Measurements and Main Results The mean age was 54 ± 14 years, and 65% of patients were male. Patients were treated throughout the year, with seasonal peaks in the winter months. The majority of patients were referred from hospitals within the Lombardia region (81%), mainly from the city of Milan and surrounding area (36% of the total). The most common etiology of refractory ARDS was H1N1 influenza A (42 patients [42%]), followed by bacterial pneumonia (35 patients [35%]), and severe acute respiratory syndrome due to Sars-CoV-2 infection (five patients [5%]). All patients were severely hypoxic at the time of VV ECMO treatment. No transport-related complication was recorded. The most common configuration used in the authors’ clinical practice was a bicaval dual-lumen configuration (61 patients [61%]), followed by a femoro-jugular configuration (38 patients [38%]). The intensive care unit survival rate was 55%. Conclusions Referral to a specialized center for VV ECMO treatment should be considered expeditiously in case of refractory ARDS, which often is lethal. Transport of patients with an unstable condition, although challenging, is feasible, and centralization of patient care is associated with good outcomes.

Purpose: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). Materials and methods: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020–December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. Results: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1–18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6–96.9), a specificity of 95.6% (95% CI: 90.6–98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3–92.3), a negative PV of 97.1% (95% CI: 74.6–96.9) and an accuracy of 94.2% (95% CI: 89.6–97.2) in predicting PMD/PNX (AUC:0.924). Conclusions: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.

Objective: To describe the experience with CytoSorb treatment in patients with refractory acute respiratory distress syndrome (ARDS) following SARS-CoV-2 infection. Methods: Retrospective observational study on 15 patients treated in a University Hospital. Results: All patients were male, with a mean age of 55 ± 14 years; eight patients (53%) were on venovenous extracorporeal membrane oxygenation (VV ECMO) due to refractory ARDS and all (100%) under mechanical ventilation at the time of CytoSorb use. We observed reduction in the level of C reactive protein (−52%, p = 0.002), total bilirubin (−46%, p = 0.03), direct bilirubin (−50%, p = 0.02), and D-dimers (−39%, p = 0.04) during CytoSorb treatment and a trend toward reduction in lactate dehydrogenase (−20%, p = 0.2), creatine phosphokinase (−38%, p = 0.1), and fibrinogen (−15%, p = 0.07). Eight patients died (53%) and seven (47%) were discharged from the ICU, of which five had recovery of the native lung function and two were successfully bridged to lung transplantation on VV ECMO support. No difference between survivors and non-survivors was present at baseline. Patients received three CytoSorb cycles on average: mean duration of CytoSorb cycle was 17 h 21 min, but premature circuit clotting despite appropriate level of systemic anticoagulation was frequently observed. Conclusions: CytoSorb treatment was effective in improving several laboratory parameters and inflammation in our experience and no treatment-related adverse effects were recorded. In the light of the unique pathophysiology of SARS-CoV-2 infection, CytoSorb treatment is extremely promising, since it might both reduce inflammation and activation of coagulation.

VA-ECMO is commonly used for patients in cardiogenic shock (CS) or refractory cardiac arrest (CA) undergoing PCI for ACS. In this setting at high risk of both thrombotic and hemorrhagic complications, optimal anti-thrombotic therapy remains ill-defined. We hypothesized that an anti-thrombotic therapy comprising a parenteral anticoagulant (bivalirudin) and a parenteral anti-platelet agent (cangrelor) may prove safe and effective in this scenario. From November 2019 to December 2021, 14 patients received at least one dose of cangrelor (starting dose: 0.125 μg/kg/min) plus bivalirudin, without background aspirin, in the context of PCI and VA-ECMO for ACS-related CS/CA, and were included in this study. Efficacy endpoint was occurrence of thrombotic events and safety endpoint was major bleeding occurrence. Median age was 58 years. The majority (64%) presented with refractory CA. A thrombotic event occurred in 14%, while major bleeding occurred in 21% patients. One patient experienced arterial thrombosis after VA-ECMO arterial cannula removal, another experienced ischemic cerebellar stroke without functional sequelae. Bleeding events were: 29% BARC 3a, 14% BARC 3b, and 7% BARC 5b. Overall in-hospital mortality was 50%. Cangrelor was continued for 5 (4-10) days; temporary discontinuation was necessary in 36%, either for VA-ECMO cannula removal or for bleeding events. A low dose of cangrelor, associated with standard-intensity anticoagulation with bivalirudin was a feasible anti-thrombotic strategy in patients undergoing PCI during VA-ECMO support for ACS-related CS/CA. Bleeding events rates outweighed thrombotic events rates in this critically-ill population, although the observed rates were lowest among available studies.

OBJECTIVE: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. PARTICIPANTS: Adult patients receiving mechanical ventilation due to COVID-19. INTERVENTIONS: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. MAIN OUTCOME MEASURES: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. RESULTS: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87–16.22; P = 0.013) and the Pao2/Fio2 ratio (median difference, 23.17; 95% CI, 3.46–42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09–0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). CONCLUSIONS: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and Pao2/Fio2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366.

Background Bedside insertion of Impella percutaneous ventricular assistant device (pVAD) (Abiomed, Danvers, MA) under transesophageal echocardiographic (TEE) guidance is an attractive strategy enabling lifesaving treatment in patients with cardiogenic shock and who cannot to be transported promptly to the catheterization laboratory (Cathlab). Methods In this retrospective, single-center study, we reviewed all consecutive patients supported with Impella pVAD for CS. We compared the characteristics and outcomes of those who underwent Impella pVAD insertion under fluoroscopic guidance (Fluoro group) in the Cathlab with those who underwent insertion under TEE guidance at bedside (TEE group). Results: Between February 2013 and April 2018, a total of 150 consecutive patients with CS were supported with Impella. Fifty-five (38%) were in TEE group and 95 (62%) in Fluoro group. Impella insertion was successful in all the patients. At the time of Impella insertion patients among the TEE group had higher incidence of refractory hemodynamic collapse (87% vs 53%; p < 0.001) and venoarterial extracorporeal membrane oxygenation (62% vs 35%, p=0.002). In-hospital mortality was significantly higher in the TEE group (55% vs. 31%, p=0.04). Rates of Impella-related complications were not different between the two groups, except for higher requirement for renal replacement therapy in the TEE group (35% vs 17%; p = 0.004). Conclusions Emergent Impella insertion with TEE guidance is feasible, safe and effective in critically ill patients with cardiogenic shock.

Objective Despite growing expertise and wide application of venovenous extracorporeal membrane oxygenation (VV ECMO) treatment for acute respiratory distress syndrome (ARDS) of different origin and during pandemics (H1N1 Influenza A virus and SARS-CoV-2), large reports are few and pertain mostly to multicenter registries, and randomized trials are difficult to perform. The aim of this study was to report outcomes, trends, and innovations of VV ECMO treatment over the last 11 years. Design, Setting, and Participants Observational study on 142 patients treated at the IRCCS San Raffaele Hospital in Milan from June 2009 (year of the H1N1 pandemic) to May 2020 (SARS-CoV-2 pandemic). Interventions None. Measurements and Main Results The main causes of ARDS were H1N1 pneumonia in 36% of patients, bacterial pneumonia in 17%, and SARS-CoV-2 in 9%. Seventy-two percent of patients were centralized from remote hospitals, of whom 33% had implanted VV ECMO before transport. The most common cannulation strategy was the dual-lumen catheter cannulation system (55%), and anticoagulation was performed with bivalirudin in most patients (79%). Refractory hypoxia was treated with intravenous beta-blockers (64%), nitric oxide (20%), and pronation (8%). Almost one-third of patients (32%) were extubated while on ECMO. Forty-nine percent of patients were discharged from the intensive care unit, and hospital discharge was 46%; survival was lower in patients requiring VV ECMO for more than three weeks compared with shorter support duration (23% v 56%, p = 0.007). Anticoagulation with bivalirudin was associated with higher survival, compared with heparin (55% v 31%, p = 0.03), and lower thrombocytopenia incidence (69% v 35%, p = 0.003). Conclusion VV ECMO is the pivotal rescue treatment for refractory ARDS—timely treatment and optimal care are needed to optimize therapy, as duration of support is associated with outcome. Anticoagulation with bivalirudin may improve outcome.

OBJECTIVES To evaluate the competing pro-haemorrhagic contribution of acquired von Willebrand (vW) disease and antithrombotic therapy in patients implanted with continuous-flow left ventricular assist devices (LVADs). METHODS We compared the extent of vW factor (vWf) degradation [vWf antigen (vWf:Ag)] and a decrease of functional activity of large vWf multimers [vWf collagen binding (vWf:CB)] in LVAD patients who did and did not suffer from bleeding. Data were measured pre-implant, at short-term (t1: 12 months) follow-up. The occurrence of primary bleeding events, as well as bleeding recurrence, was correlated with patient-specific vWf profile and antithrombotic regimen. Indeed, patients were discharged on warfarin (international normalized ratio: 2–2.5) and aspirin, with the latter withhold after a first bleeding episode. RESULTS Fifty-three patients were enrolled. The median follow-up was 324 (226–468) days. We recorded 25 primary bleeding events (47% of patients). All primary events occurred in patients on warfarin and aspirin. Both vWf:Ag and vWf:CB decreased significantly post-implant (P = 0.0003 and P < 0.0001), and patients showing pathological vWf:CB/vWf:Ag ratio ( CONCLUSIONS Aspirin contributes significantly to haemorrhagic events in the background of acquired vW disease; its discontinuation significantly reduces bleeding recurrence. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT03255928; ClinicalTrials.gov Identifier: NCT03255928.

BACKGROUND: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls. METHODS: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders. RESULTS: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P

BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.

CytoSorb is a promising tool to treat severe inflammatory status with multiple mechanisms in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although removal of small molecules might translate into decreased blood levels of life-saving medications. The aim of this study was to assess the impact of CytoSorb on vancomycin and bivalirudin clearance in a large population of critically ill patients. We performed a single-center analysis of CytoSorb treatments performed between January 2018 and March 2019 in critically ill patients admitted to our intensive care unit. A total of 109 CytoSorb treatments were performed in 89 patients. A decrease in lactate dehydrogenase (P = .007), troponin T (P = .022), and creatine phosphokinase (P = .013) was reported during treatment. Vancomycin dose required significant adjustments during treatment (P < .001), but no significant change was necessary after the first 3 days. Similarly, the requirements of bivalirudin significantly changed over days (P < .001), but no dose adjustment was needed after the first 3 days of treatment. No differences in terms of vancomycin and bivalirudin dose need was observed between patients on extracorporeal membrane oxygenation and those who were not (P = .6 and P = .6, respectively), between patients with and without continuous veno-venous hemofiltration (P = .9 and P = .9, respectively), and between CytoSorb responders or not (P = .4 and P = .7, respectively). CytoSorb is effective in mitigating the systemic inflammatory response and safe with respect to vancomycin and bivalirudin administration. These preliminary data further support the use of CytoSorb as adjunct therapy in critically ill patients.

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. Methods: Observational study in a tertiary care hospital in Milan, Italy. Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Objective Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients. Design Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio). Setting Tertiary and University hospitals. Interventions 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h). Measurements The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group. Conclusions The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs, or both. Despite being employed clinically first in the 1970s [1], the more widespread use of ECMO in critically ill adult patients is a recent phenomenon [2], and the number of centers offering ECMO has grown rapidly. During the same period, the indications for ECMO in adults have expanded from refractory severe respiratory and cardiac failure [3] to extracorporeal cardiopulmonary resuscitation (ECPR) [4] and as a bridge to lung transplantation [5]. Furthermore, the use of ECMO is strongly established in neonatal and pediatrics populations [6].

Background: The use of angiotensin II (ANGII) in invasively ventilated COVID-19 patients is controversial. Its effect on markers of organ function is unknown.Methods: We used ANGII either as rescue vasopressor agent or as low dose vasopressor support. Patients treated before ANGII availability or in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of ANG on markers of organ function.Results: We compared 46 ANGII patients with 53 controls. Compared with controls, ANGII increased MAP (median difference, 9.05 mmHg [95% confidence interval, 1.87 to 16.22]; p = 0.013) and PaO2/FiO2 ratio (median difference, 23.17 [95% confidence interval, 3.46 to 42.88]; p = 0.021). ANGII had no effect on lactate, urinary output, serum creatinine, C-Reactive protein, platelet count, or thromboembolic complications. However, it significantly decreased the odd ratio of liver dysfunction (odds ratio: 0.32; 0.09 to 0.94) and, on Bayesian modelling, in patients with abnormal baseline serum creatinine, ANGII carried a 95.7% probability of decreasing renal replacement therapy use. Conclusions: In ventilated COVID-19 patients, ANGII therapy was associated with increased blood pressure and PaO2/FiO2 ratios, decreased odds ratio of liver dysfunction, and a high probability of decreasing renal replacement therapy use in patients with abnormal baseline serum creatinine.

Objectives The aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19). Methods This was a cohort study of patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine–Gray models to assess factors associated with risk of secondary infections. Results Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4–21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 109/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11–3.35), baseline PaO2/FiO2 (per 100 points lower: sdHRs 1.56, 95%CI 1.21–2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04–6.05). Conclusions Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections.

Monitoring the coagulation time and regulating the administration of unfractionated heparin (UFH) during cardiopulmonary bypass (CPB) are challenging activities. The manuscript focuses on the development of a mathematical model to predict the activated clotting time (ACT) during CPB following an intravenous administration of heparin. The overall mathematical tool features a physiologically-based pharmacokinetic (PBPK) model and a pharmacodynamic (PD) model. The PBPK model describes the human circulatory system and employs correlations from the literature to estimate its physiological parameters from individual characteristics (i.e. age, sex, race, weight, height, serum creatinine, and hematocrit) to yield a prediction of heparin plasma concentration as a function of time. The PD model predicts the ACT as a function of heparin concentration thanks to several differential equations that describe the coagulation cascade. The combined PBPK/PD model produces, for each patient, an individualized prediction of the resulting ACT dynamics, using either a population or an individualized approach. The model can be used to help monitoring the ACT trend during CPB and to optimize heparin administration in order to reach and maintain the therapeutic goal of 480 s.

Background Delirium after cardiac surgery is associated with adverse outcomes, including prolonged hospital stay, prolonged intensive care unit stay, and increased mortality. Effective preventive interventions and treatments still are largely unknown. Aim This systematic review aimed to gather and summarize the existing evidence from randomized trials concerning interventions studied in the prevention or treatment of delirium in adult patients undergoing cardiac surgery. Methods A systematic review of the literature using a key word strategy and Boolean operators was performed. PubMed and the Cochrane and Scopus databases were searched for pertinent studies until July 2018 (no inception limit). Results Of 2,556 articles identified, 56 studies met the inclusion criteria and were included in the review—39 addressed pharmacologic strategies and 17 nonpharmacologic interventions. Interestingly, 51 (91%) trials focused on delirium prevention and only 5 (9%) on delirium treatment. Most of the analyzed studies were recent double-blind, single-center trials conducted in Europe or North America, with a low risk of bias. Overall, 38 different interventions were identified: 15 (26%) interventions were performed before surgery, 20 (36%) in the operating room, and 21 (38%) after surgery. The most frequently analyzed strategies were the administration of dexmedetomidine, ketamine, antipsychotics, glucocorticoids, propofol, opioids, volatile anesthetics, local anesthetics, and remote ischemic preconditioning. The analyzed strategies were extremely heterogenous, and dexmedetomidine was the most promising measure able to prevent the development of postoperative delirium. Conclusions In the present systematic review of 56 randomized controlled trials that examined 38 interventions, the authors found that dexmedetomidine was the most frequently studied agent and that it might reduce the occurrence of delirium after cardiac surgery.

Temporary mechanical circulatory support devices for the treatment of acute right ventricular failure represent crucial tools for clinical practice. Right ventricular failure presents specific treatment issues, and dedicated percutaneous devices are less in number compared to the left ventricle. Current data and insights on mechanical circulatory support for the right ventricle come mostly from the context of cardiac surgery, predominantly the setting of acute right ventricular failure after left ventricular assist device implantation.The Impella RP (Abiomed, Danvers, MA) is a minimally invasive temporary device that has gained application for the percutaneous treatment of right ventricular failure with positive clinical results. Even though treatment indications are clear, technical and management issues still are relevant because of the limited scientific data available. Appropriate positioning and repositioning, interaction with right ventricular valvular apparatus, anticoagulation management, weaning, and patient mobilization are examples of the open challenges. In line with the positive initial experience with this device, future research efforts should be focused on the improvement of device limitations and on providing additional data that might drive optimal clinical management. (C) 2018 Elsevier Inc. All rights reserved.

Background: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. Methods: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. Results: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P =0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P P =0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. Conclusions: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

Objective: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. Design: A systematic review of the literature followed by a consensus-based voting process. Setting: A web-based international consensus conference. Participants: Two hundred fifty-one physicians from 46 countries. Interventions: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. Measurements and main results: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma- derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. Conclusion: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

Objective Patients undergoing transapical cardiac procedure are a minority of cardiac surgery patients but represent a challenge for cardiac anesthesiologists because they generally are older and have more comorbidities than do open heart cardiac surgery patients. The aims of this study were to describe the anesthetic experience with transapical procedures in a single high-volume center and to analyze the most critical aspects for anesthetic management. Design Retrospective study. Setting IRCCS San Raffaele Scientific Institute, Milan, Italy. Participants All patients undergoing a cardiac transapical procedure from January 2009 to April 2018 were included in this case series. Interventions Patients were managed by a multidisciplinary heart team. The perioperative anesthetic approach and hemodynamic management were consistent and performed by a group of trained cardiac anesthesiologists. Measurements and Main Results The study population comprised 143 patients: 81 (57%) underwent an aortic valve procedure, 60 (42%) a mitral valve intervention, 1 patient underwent a procedure involving both the aortic and mitral valves, and 1 patient underwent correction of a congenital heart defect. A major intraoperative complication occurred in 5 (3.5%) patients, the procedure was not technically feasible because of unsuitable anatomy in 3 patients, and conversion to open heart surgery was needed in 2 patients. All patients were admitted to the intensive care unit. Intensive care unit stay was 1 (1-3) days, and hospital stay was 6 (5-8) days. Hospital survival was 94%. Conclusions Patients undergoing transapical cardiac procedures are a minority of cardiac surgery patients, but represent a high-risk population. A patient-tailored anesthetic approach, in the context of the therapeutic strategy shared by the heart team, is crucial to improve outcomes.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Background: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). Methods: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. Results: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group ; relative risk, 0.94 ; 95% confidence interval [CI], 0.69 to 1.29 ; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively ; relative risk, 1.11 ; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. Conclusions: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia.

Tracheal intubation is a common procedure in critically ill patients (1). Despite its frequent occurrence, tracheal intubation in this setting remains a risky procedure (2,3), mainly due to the combination of two synergistic and negative factors: the unique respiratory and hemodynamic instability of critically ill patients, and the high incidence of difficult airway in this population (4). Intubation-related life-threatening hypoxemia, hypotension, arrythmia, cardiac arrest and death are frequently reported (2,3). Recently, a multicenter retrospective trial on tracheal intubation in Intensive Care Unit (ICU) observed a 2.7% rate of cardiac arrest (strongly predicted by hypoxemia prior to intubation and lack of preoxygenation), with a high 28-day mortality in patients who had experienced an intubation-related cardiac arrest (5).

Mediastinitis is more frequent in patients with implantable ventricular assist devices (VADs) than in other cardiac surgery patients and carries significant mortality. We report our experience with a stepwise approach including aggressive debridement, jet lavage, vacuum assisted closure dressing, and finally coverage with well-vascularized and immune-active omental flaps in VAD patients with infective mediastinitis. We retrospectively collected and analyzed data of patients with continuous flow VAD who underwent plasty with the omental flap because of mediastinitis at Deutsches Herzzentrum Berlin between January 1, 2008 and October 30, 2015. Eight hundred forty-five patients underwent VAD implantation during the study period. Omentoplasty due to infective mediastinitis was performed in 17 cases. Nine had a HeartWare HVAD as left ventricular assist device (LVAD), three patients had two Heart-Ware HVAD as biventricular assist device (BIVAD), four had a HeartMate II LVAD device, and one patient had a Berlin Heart Incor LVAD. The microorganisms most frequently isolated from the sternal wound were Gram-positive Staphylococcus spp. Four cases of bleeding requiring surgical revision were recorded: three of intraabdominal and one of wound bleeding. Eight patients (47%) survived, whereas the other nine patients (53%) died. Sixteen (94%) required intensive care unit admission, and median hospital stay was 21 (1-182) days. Postoperative renal failure requiring dialysis and septic shock requiring vasopressors were associated with hospital mortality (p = 0.009 and p = 0.05, respectively). Early surgical treatment of mediastinitis after VAD implantation with omentoplasty is a valuable strategy in an otherwise dead-end situation. Bleeding should be meticulously controlled in these anticoagulated and fragile patients.

BACKGROUND AND AIM OF THE STUDY Driveline infections in patients with implantable left ventricular assist devices (VAD) carry increasing risk for pump infection, thromboembolic events, decreased quality of life, and increased hospitalization. We report our experience with a surgical technique for refractory driveline infections without mediastinitis consisting of translocation and wrapping of the driveline with greater omentum tissue. METHODS We retrospectively reviewed data of VAD patients who underwent surgical treatment by translocation and wrapping with omentum for severe chronic driveline infection. RESULTS Thirteen patients were treated between January 2010 and October 2015; 12 (92%) were male, and the mean age was 56 ± 14 years. Ten patients (77%) were managed with driveline sheathing with omentum and repositioning with a new exit site, and three (23%), suffering from driveline fistula, with driveline covering with omentum maintaining the previous exit site. Three episodes of postoperative bleeding (23%) required surgical revision. Twelve patients (92%) were discharged from the hospital and one (8%) died. Nine patients (69%) were free from infection at the time of discharge, and three (23%) had recurrence of infection within the first postoperative year. Only four patients (31%) required admission to the intensive care unit; overall median hospital stay was 23 days (range 7-205 days). CONCLUSIONS Driveline relocation with use of omentum is a feasible and effective procedure in selected cases of chronic severe driveline infection. The risk for perioperative bleeding should be taken into consideration and carefully monitored.

Aims Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support stabilizes patients with cardiogenic shock. Despite improved oxygenation and peripheral circulation, LV unloading may be impeded due to the increased afterload, resulting in a failing static left ventricle and in high mortality. Methods and results We describe for the first time a large series of patients treated with the combination of VA-ECMO and Impella® compared with patients with VA-ECMO only. We retrospectively collected data on patients from two tertiary critical care referral centres. We enrolled 157 patients treated with VA-ECMO from January 2013 to April 2015: 123 received VA-ECMO support and 34 had concomitant treatment with VA-ECMO and Impella. A propensity-matching analysis was performed in a 2:1 ratio, resulting in 42 patients undergoing VA-ECMO alone (control group) compared with 21 patients treated with VA-ECMO and Impella. Patients in the VA-ECMO and Impella group had a significantly lower hospital mortality (47% vs. 80%, P < 0.001) and a higher rate of successful bridging to either recovery or further therapy (68% vs. 28%, P < 0.001) compared with VA-ECMO patients. A higher need for continuous veno-venous haemofiltration (48% vs. 19%, P = 0.02) and increased haemolysis (76% vs. 33%, P = 0.004) were reported in the study group due to higher survival. There was no difference in major bleeding rates between the two groups (VA-ECMO and Impella 38% vs. VA-ECMO 29%, P = 0.6). Conclusions Concomitant treatment with VA-ECMO and Impella may improve outcome in patients with cardiogenic shock compared with VA-ECMO only. Nevertheless, randomized studies are needed to validate these promising results further.

Background Thrombosis is an uncommon, but severe complication of left ventricular assist devices (LVADs). Objectives This study analyzed experience with obstruction of blood flow through the LVAD with the purpose of developing optimal diagnosis and treatment of LVAD-related thrombosis. Methods Between October 2009 and July 2015, a total of 652 LVAD were implanted in 557 patients. Blood flow abnormalities in patients with LVAD (n = 524) were identified and classified as “high-power” and “low-flow” events. Results Three types of late blood flow obstructions were identified: 1) pre-pump via thrombus obstructing the inflow cannula (26 events; 0.037 events per patient-year); 2) intra-pump (70 events; 0.1 events per patient-year); and 3) post-pump via thrombosis of the outflow graft or stenosis of the anastomosis to the aorta (4 events; 0.006 events per patient-year). Pre-pump obstruction was treated by washout maneuver in 9 cases (success rate, 100%), thrombolysis in 9 patients (success rate, 56%), and pump exchange in 9 cases (success rate, 100%); 1 patient died without treatment and 2 were weaned from LVAD. Intra-pump obstruction was treated by thrombolysis (n = 9; success rate, 33%), pump exchange (n = 53; success rate, 94%), and removal due to myocardial recovery (n = 3; success rate, 100%); 7 patients died without treatment and parameters spontaneously normalized in 2 cases. Post-pump obstruction was treated in 2 patients by stenting (success rate, 100%), and was left untreated in 2 cases. Conclusions We identified 3 types of LVAD-related blood flow obstruction, and developed an algorithm for optimal diagnosis and treatment.

Purpose CytoSorb treatment is a promising tool to treat severe inflammatory status in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although unselective and unpredictable removal of small molecules might translate into decreased blood levels of potentially life-saving medications. The aim of this study was to assess the impact of Cytosorb treatment on clereance of small drug molecules, measured as dose adjustements need, in a large population of critically ill patients. Methods Single-center analysis of Cytosorb treatments performed between 01-2018 and 03-2019 in patients with cardiogenic shock of several origins. Results 109 Cytosorb treatments were performed in 86 patients. A decrease in LDH (p=0.007), troponin T (p=0.022) and CPK (p=0.013), together with a trend toward lower need of inotropes, was reported during treatment, supporting its clinical efficacy in the study population. Vancomycin dose was significantly changed during the days of treatment (p Conclusion Cytosorb therapy was effective in improving shock parameters in a large population of cardiogenic shock patients, without affecting the dose need of vancomycin and bivalirudin after reaching target concentration. The results of this study further support the role of Cytosorb in the treatment of critically ill.

It is a common observation that many multicenter randomized controlled trials (mRCT) performed in critically ill patients do not achieve the positive findings often seen in single center studies (sRCT). This has, of course, relevant consequences for clinical practice, as mRCTs have higher scientific validity compared to sRCTs. The aim of this manuscript was to review and discuss the several potential causes of this phenomenon and to relate them to the future of mRCTs in critical care medicine. Overall, this seems to recall the old mythologic story of Achilles and the tortoise: although mRCTs (i.e. Achilles) are much more powerful, indeed, they always arrive later in time compared to the sRCTs (i.e. the tortoise) from which they were powered. However, sRCTs are more prone to several bias compared to mRCTs, such as local effect bias, selection and performance bias, detection and reporting bias, analysis and attrition bias, concomitant therapy bias, low fragility index and publication bias. In this sense, it is high time the critical care community should see the positive findings of sRTCs with a very high level of scientific caution, unless they are confirmed by mRCTs. MRCTs represent the final step of the process of evidence-based medicine and in the end (however slowly and painfully) such evidence catches up with sRCT and truly helps changes practice worldwide.

In this retrospective analysis we evaluated a standardized echocardiographic assessment and an invasive technique for patient selection for successful continuous-flow left ventricular assist device (CF-LVAD) explantation.Inclusion criteria for LVAD recovery assessment were: clinically stable condition; LVAD support for6 months; physical activity; normal echocardiography findings; and no more than mild valvular disease and aortic valve opening. In a second step, echocardiography was performed under CF-LVAD reduction and stop conditions (PStopE). In the third step, patients who presented with stable parameters underwent right heart catheterization under CF-LVAD stoppage and occlusion of the outflow graft with a balloon catheter. Criteria for explantation were normal pulmonary artery pressure and pulmonary capillary wedge pressure16 mmHg.Thirty-three of 424 patients entered the second step of evaluation and 20 entered the third step. Fourteen presented positive results and the pump was successfully explanted. The PCWP at baseline was 8.5 (2.8) mmHg in the explantation group and 10.6 (2.8) mmHg in the non-explantation group (p = 0.105). It increased to 10.9 (3.0) mmHg vs 20.8 (4.9) mmHg under outflow graft occlusion. The wedge pressure was significantly higher in the non-explantation group (p0.001). Median duration of follow-up after explantation was 9.74 (interquartile range 4.3 to 20.60) months, with survival of 93%.The protocol presented is feasible and safe. The criteria applied provide good patient selection for sustained mid-term myocardial recovery after LVAD explantation.

Objectives: Aim of the study was to assess in-hospital survival rate and the degree of myocardial recovery after MCS treatment (IABP or IMPELLA) at discharge and at 6 months in patients with AMI-CS and planned early percutaneous revascularization. Background: All studies on MCS for acute myocardial infarction related cardiogenic shock (AMI-CS) focused on its impact on in-hospital mortality; however, few data about its role on myocardial recovery are available. Methods: Retrospective study on 64 patients: 36 patients (56%) received IABP and 28 (44%) Impella 2.5/CP. Results: Patients treated with Impella were sicker compared to those treated with IABP as shown by a higher need of catecholamines (93% Impella vs 57% IABP, P = 0.002) and higher inotropic score before procedure: 8 (5-15) versus 4.5 (0-9), P = 0.02. In-hospital survival and MCS-related complications were comparable; hemolysis was more frequent in the Impella group (32% vs 0%, P < 0.0001). Myocardial damage was lower in those patients who were implanted with IMPELLA before PCI: lower troponin peak [3831 ng/dL (1441-8436) vs 16 581 (7802-23 675), P = 0.004] and lower CPK peak [893 UI/L (584-4082) vs 5797 (2483-9292) P = 0.04]. Impella patients had higher LVEF at 6 months [45 (38-52) vs 40 (33-45)%, P = 0.04]. LVEF increase at 6 months was statistically significant in both groups (P < 0.0001), with higher myocardial recovery in patients supported with Impella (absolute delta-LVEF increase 20% vs 10% P = 0.005). Conclusions: Cardiac unloading with IMPELLA in ACS-CS, especially if implanted before PCI, might provide lower myocardial damage and improved myocardial recovery which translates into significantly higher LVEF at 6 months.