Temporary mechanical circulatory support with Impella in cardiac surgery: A systematic review.

INTRODUCTION: Perioperative cardiogenic shock (CS) in cardiac surgery is still burdened by a high mortality risk. The introduction of Impella pumps in the therapeutic armory of temporary mechanical circulatory support (tMCS) has potential implications to improve the management of complex cases, although it has never been systematically addressed. We performed a systematic review of the reported use of tMCS with Impella in cardiac surgery. METHODS: We searched PubMed for all original studies on the Impella use in adult patients in cardiac surgery. RESULTS: Nineteen studies (out of 151 identified by search string) were included. All studies were observational and all but one (95%) were retrospective. Seven studies focused on the implantation of Impella in the pre-operative setting (coronary or valvular surgery), either as a prophylactic device in high-risk cases (3 studies) or in patients with CS as stabilization tool prior to cardiac surgery procedure (4 studies). Three studies reported the use of Impella as periprocedural support for percutaneous valvular procedure, three as bridge to heart replacement, and six for postcardiotomy CS. Impella support had a low complication rate and was successful in supporting hemodynamics pre-, intra- and postoperatively. Most consistently reported data were left-ventricular ejection fraction at implant, short-term survival and weaning rate. CONCLUSIONS: tMCS with Impella in cardiac surgery patients is feasible and successful. It can be applied in selected cardiac surgery patients and presents advantages over other types of support. Systematic prospective studies are needed to standardize indications for implant and management of surgical issues, and to identify which patients may benefit.

Extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: 10-year experience in a metropolitan cardiac arrest centre in Milan, Italy.

Introduction: Growing evidence supports extracorporeal cardiopulmonary resuscitation (ECPR) for refractory out-of-hospital cardiac arrest (OHCA) patients, especially in experienced centres. We present characteristics, treatments, and outcomes of patients treated with ECPR in a high-volume cardiac arrest centre in the metropolitan area of Milan, Italy and determine prognostic factors. Methods: Refractory OHCA patients treated with ECPR between 2013 and 2022 at IRCCS San Raffaele Scientific Institute in Milan had survival and neurological outcome assessed at hospital discharge. Results: Out of 307 consecutive OHCA patients treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58-81] minutes), 17% survived and 9.4% had favourable neurological outcome. Survival and favourable neurological outcome increased to 51% (OR = 8.7; 95% CI, 4.3-18) and 28% (OR = 6.3; 95% CI, 2.8-14) when initial rhythm was shockable and low-flow (time between CPR initiation and ROSC or ECMO flow) ≤60 minutes and decreased to 9.5% and 6.3% when low-flow exceeded 60 minutes (72% of patients). At multivariable analysis, shockable rhythm (aOR for survival = 2.39; 95% CI, 1.04-5.48), shorter low-flow (aOR = 0.95; 95% CI, 0.94-0.97), intermittent ROSC (aOR = 2.5; 95% CI, 1.2-5.6), and signs of life (aOR = 3.7; 95% CI, 1.5-8.7) were associated with better outcomes. Survival reached 10% after treating 104 patients (p for trend <0.001). Conclusions: Patients with initial shockable rhythm, intermittent ROSC, signs of life, and low-flow ≤60 minutes had higher success of ECPR for refractory OHCA. Favourable outcomes were possible beyond 60 minutes of low-flow, especially with concomitant favourable prognostic factors. Outcomes improved as the case-volume increased, supporting treatment in high-volume cardiac arrest centres.

Extracorporeal Membrane Oxygenation Without Invasive Ventilation for Respiratory Failure in Adults: A Systematic Review.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an advanced treatment for acute severe respiratory failure. Patients on ECMO are frequently maintained sedated and immobilized until weaning from ECMO, first, and then from mechanical ventilation. Avoidance of sedation and invasive ventilation during ECMO may have potential advantages. We performed a systematic literature review to assess efficacy and safety of awake ECMO without invasive ventilation in patients with respiratory failure. DATA SOURCES: PubMed, Web of Science, and Scopus were searched for studies reporting outcome of awake ECMO for adult patients with respiratory failure. STUDY SELECTION: We included all studies reporting outcome of awake ECMO in patients with respiratory failure. Studies on ECMO for cardiovascular failure, cardiac arrest, or perioperative support and studies on pediatric patients were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of awake ECMO failure, and mortality. Primary outcome was rate of awake ECMO failure (need for intubation). Pooled estimates with corresponding 95% CIs were calculated. Subgroup analyses by setting were performed. DATA SYNTHESIS: A total of 57 studies (28 case reports) included data from 467 awake ECMO patients. The subgroup of patients with acute respiratory distress syndrome showed a pooled estimate for awake ECMO failure of 39.3% (95% CI, 24.0-54.7%), while in patients bridged to lung transplantation, pooled estimate was 23.4% (95% CI, 13.3-33.5%). Longest follow-up mortality was 121 of 439 (pooled estimate, 28%; 95% CI, 22.3-33.6%). Mortality in patients who failed awake ECMO strategy was 43 of 74 (pooled estimate, 57.2%; 95% CI, 40.2-74.3%). Two cases of cannula self-removal were reported. CONCLUSIONS: Awake ECMO is feasible in selected patients, although the effect on outcome remains to be demonstrated. Mortality is almost 60% in patients who failed awake ECMO strategy.

Myocardial protection with phosphocreatine in high-risk cardiac surgery patients: a randomized trial.

BACKGROUND: This study was conducted to test the hypothesis that phosphocreatine (PCr), administered intravenously and as cardioplegia adjuvant in patients undergoing cardiac surgery with prolonged aortic cross clamping and cardiopulmonary bypass (CPB) time, would decrease troponin I concentration after surgery. METHODS: In this randomized, double-blind, placebo-controlled pilot study we included 120 patients undergoing double/triple valve repair/replacement under cardiopulmonary bypass in the cardiac surgery department of a tertiary hospital. The treatment group received: intravenous administration of 2 g of PCr after anesthesia induction; 2.5 g of PCr in every 1 L of cardioplegic solution (concentration = 10 mmol/L); intravenous administration of 2 g of PCr immediately after heart recovery following aorta declamping; 4 g of PCr at intensive care unit admission. The control group received an equivolume dose of normosaline. RESULTS: The primary endpoint was peak concentration of troponin I after surgery. Secondary endpoints included peak concentration of serum creatinine, need for, and dosage of inotropic support, number of defibrillations after aortic declamping, incidence of arrhythmias, duration of Intensive Care Unit (ICU) stay, length of hospitalization. There was no difference in peak troponin I concentration after surgery (PCr, 10,508 pg/ml [IQR 6,838-19,034]; placebo, 11,328 pg/ml [IQR 7.660-22.894]; p = 0.24). There were also no differences in median peak serum creatinine (PCr, 100 µmol/L [IQR 85.0-117.0]; placebo, 99.5 µmol/L [IQR 90.0-117.0]; p = 0.87), the number of patients on vasopressor/inotropic agents (PCr, 49 [88%]; placebo, 57 [91%]; p = 0.60), the inotropic score on postoperative day 1 (PCr, 4.0 (0-7); placebo, 4.0 (0-10); p = 0.47), mean SOFA score on postoperative day 1 (PCr, 5.25 ± 2.33; placebo, 5,45 ± 2,65; p = 0.83), need for defibrillation after declamping of aorta (PCr, 22 [39%]; placebo, 25 [40%]; p = 0.9),, duration of ICU stay and length of hospitalization as well as 30-day mortality (PCr, 0 (0%); placebo,1 (4.3%); p = 0.4). CONCLUSION: PCr administration to patients undergoing double/triple valve surgery under cardiopulmonary bypass is safe but is not associated with a decrease in troponin I concentration. Phosphocreatine had no beneficial effect on clinical outcomes after surgery. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov with the Identifier: NCT02757443. First posted (published): 02/05/2016.

Extracorporeal Blood Purification with CytoSorb in 359 Critically Ill Patients.

INTRODUCTION: Critically ill patients with inflammatory dysregulation and organ disfunction may benefit from blood purification, although the use of this technique has not been described in large case series. We evaluated clinical outcomes and survival in high-risk intensive care unit (ICU) patients who underwent extracorporeal blood purification. METHODS: 359 consecutive ICU patients treated with CytoSorb were included. RESULTS: Main admission diagnoses were 120 (34%) refractory cardiac arrest under mechanical chest compression; 101 (28%) profound cardiogenic shock; 81 (23%) post-cardiotomy cardiogenic shock; and 37 (10%) respiratory failure. Fifteen patients (4%) were positive for SARS-CoV-2 infection. We observed 49% 30-day mortality, 57% ICU mortality, and 62% hospital mortality, all lower than the 71% mortality predicted by SAPS II and 68% predicted by SOFA score. Parameters of shock and organ failure, above all vasoactive inotropic score, reduced during CytoSorb treatment. Multivariable analysis identified SAPS II, lactate dehydrogenase, ICU stay duration, vasoactive inotropic score, lactates, intra-aortic counterpulsation on top of VA-ECMO, and total bilirubin as predictors of mortality. No CytoSorb-related complications occurred. CONCLUSION: CytoSorb treatment was effective in reducing laboratory parameters of shock and vasoactive inotropic score with possible survival implications in a large population of critically ill patients.

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study.

BACKGROUND: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. METHODS: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. RESULTS: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. CONCLUSION: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.

Intraoperative hypotension and postoperative outcomes: a meta-analysis of randomised trials.

INTRODUCTION: Intraoperative hypotension is associated with adverse postoperative outcomes; however these findings are supported only by observational studies. The aim of this meta-analysis of randomised trials was to compare the postoperative effects permissive management with targeted management of intraoperative blood pressure. METHODS: We searched PubMed, Cochrane, and Embase up to June 2023 for studies comparing permissive (mean arterial pressure ≤60 mm Hg) with targeted (mean arterial pressure >60 mm Hg) intraoperative blood pressure management. Primary outcome was all-cause mortality at the longest follow-up available. Secondary outcomes were atrial fibrillation, myocardial infarction, acute kidney injury, delirium, stroke, number of patients requiring transfusion, time on mechanical ventilation, and length of hospital stay. RESULTS: We included 10 randomised trials including a total of 9359 patients. Mortality was similar between permissive and targeted blood pressure management groups (89/4644 [1.9%] vs 99/4643 [2.1%], odds ratio 0.88, 95% confidence interval [CI], 0.65-1.18, P=0.38, I2=0% with nine studies included). Atrial fibrillation (102/3896 [2.6%] vs 130/3887 [3.3%] odds ratio 0.71, 95% CI 0.53-0.96, P=0.03, I2=0%), and length of hospital stay (mean difference -0.20 days, 95% CI -0.26 to -0.13, P<0.001, I2=0%) were reduced in the permissive management group. No significant differences were found in subgroup analysis for cardiac and noncardiac surgery. CONCLUSION: Pooled randomised evidence shows that a target intraoperative mean arterial pressure ≤60 mm Hg is not associated with increased mortality; nevertheless it is surprisingly associated with a reduced rate of atrial fibrillation and of length of hospital stay. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023393725.

Plasma Transfusion and Procoagulant Product Administration in Extracorporeal Membrane Oxygenation: A Secondary Analysis of an International Observational Study on Current Practices.

OBJECTIVES: To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO. DESIGN: A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications. SETTING: Sixteen international ICUs. PATIENTS: Adult patients on VA-ECMO or VV-ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 420 VA-ECMO patients, 59% (n = 247) received plasma, 20% (n = 82) received fibrinogen concentrate, 17% (n = 70) received TXA, and 7% of patients (n = 28) received PCC. Fifty percent of patients (n = 208) suffered bleeding complications and 27% (n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p < 0.001), fibrinogen concentrate (28% vs 11%, p < 0.001), and TXA (23% vs 10%, p < 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% (n = 81) received plasma, 6% (n = 12) fibrinogen concentrate, 7% (n = 14) TXA, and 5% (n = 10) PCC. Thirty-nine percent (n = 80) of VV-ECMO patients suffered bleeding complications and 23% (n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p < 0.001), fibrinogen concentrate (13% vs 2%, p < 0.01), and TXA (11% vs 2%, p < 0.01). CONCLUSIONS: The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided.

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study.

BACKGROUND: Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. METHODS: This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·109/L), moderate (50-100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. RESULTS: Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360). CONCLUSIONS: Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI. METHODS: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis. DISCUSSION: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018.

Lung Transplant for ARDS after COVID-19: Long-Term Outcomes and Considerations about Detrimental Issues.

During the first outbreak of COVID-19 in Italy, based on the only few cases reported from a Chinese centre at the time, we performed lung transplantation in two patients with irreversible acute respiratory distress syndrome (ARDS) after COVID-19 at our centre. After two years, we report the outcomes of these cases and some considerations. The first patient, an 18-year-old male, is in excellent conditions twenty-four months after surgery. The second patient was a 48-year-old man; his airways were colonized by carbapenemase-producing klebsiella pneumoniae at the time of lung transplantation, and he had previously suffered from delirium and hallucinations in the intensive care unit. His postoperative clinical course was complicated by dysexecutive behaviour and then septic shock; he died 62 days after surgery. The recently reported experience of different transplantation centres has led to the inclusion of irreversible acute respiratory distress syndrome (ARDS) after COVID-19 among the indications for lung transplantation in carefully selected patients. Our results confirm the feasibility and the good long-term outcomes of lung transplantation for COVID-19-associated ARDS. Nonetheless, our experience corroborates the need for careful recipient selection: special attention must be paid to the single-organ dysfunction principle, the evaluation of any neuro-psychiatric disorder, and MDR germs colonization, before listing.

Anticoagulation Strategies in Critically Ill Patients With SARS-CoV-2 Infection: The Role of Direct Thrombin Inhibitors.

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.

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

One-Year Multidisciplinary Follow-Up of Patients With COVID-19 Requiring Invasive Mechanical Ventilation.

OBJECTIVES: Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. The authors investigated 1-year survival, quality of life, and functional recovery of patients with COVID-19 ARDS requiring invasive mechanical ventilation. DESIGN: Prospective observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: All patients with COVID-19 ARDS receiving invasive mechanical ventilation and discharged alive from hospital. INTERVENTIONS: Patients were contacted by phone after 1 year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS: The study included all adult (age ≥18 years) patients with COVID-19-related ARDS admitted to an ICU of the authors' institution between February 25, 2020, and April 27, 2020, who received at least 1 day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed 1 year after discharge and 56 completed a battery of tests of cognition, activities of daily living, and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by 5 (8.9%) patients. Comparing 2-month and 1-year data, the authors observed the most significant improvements in the areas of working status and exertional dyspnea. One-year chest CT scans were available for 36 patients; fibrotic-like changes were present in 4 patients. CONCLUSIONS: All patients who survived the acute phase of COVID-19 and were discharged from the hospital were alive at the 1-year follow up, and the vast majority of them had good overall recovery and quality of life.

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

CytoSorb purification in critically ill SARS-CoV-2 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.