Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; A prospective randomized study.

INTRODUCTION: Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented. METHODS: This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300 s and the rest (non-CABG) patients operated with a target ACT >400 s, respectively. RESULTS: Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24 mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46 mg vs 197 ± 45 mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products. CONCLUSIONS: Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy. TRIAL REGISTRATION: clinicaltrials.gov; NCT04215588.

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

Impact of secondary sepsis on mortality in adult intensive care unit patients.

RATIONALE: Septic patients admitted to the intensive care unit (ICU) suffer from immune dysregulation, potentially leading to a secondary sepsis episode. This study aims to (i) assess the secondary sepsis rate, (ii) compare the second with the first episodes in terms of demographics, clinical and laboratory characteristics, and outcomes, and iii) evaluate the outcome of secondary sepsis. METHODS: A single-center, retrospective study (2014-2017) was conducted in a Greek ICU, including consecutive cases of adult patients admitted to the ICU for at least 48 h with a principal admission diagnosis of sepsis and stayed for at least 48 h. We searched for a secondary episode of sepsis following the primary-one. We performed survival analyses with Cox proportional hazard, Fine-Gray, and multistate models. RESULTS: In this study, 121 patients that fulfilled the eligibility criteria were included. The secondary sepsis group included 28 (23.1 %) patients, with episode onset, median (interquartile range), 9.5 (7.7-16.2) days after ICU admission, who had less frequently had a medical admission diagnosis, a microbiologically confirmed first episode, and the C-reactive protein was lower. The overall ICU mortality of the cohort was 44.6 %. The group that developed secondary sepsis had higher mortality, but significance was lost in Cox regression [Hazard ratio (95 % CI) 0.59(0.31-1.16)]. However, after multistate modeling adjustment, the attributable mortality was estimated at 43.9 % (95 %CI ± 14.8 %). CONCLUSION: Secondary sepsis was evident in a quarter of the study participants and may be associated with an increased risk of death.

Minimal invasive extracorporeal circulation preserves coagulation integrity.

INTRODUCTION: Coagulopathy after cardiac surgery is a serious multifactorial complication that results in postoperative bleeding requiring transfusion of red blood cells and procoagulant products. Use of cardiopulmonary bypass represents the major contributing factor affecting coagulation. We sought to prospectively investigate the effect of contemporary minimal invasive extracorporeal circulation (MiECC) on coagulation parameters using point-of-care (POC) rotational thromboelastometry and the relation to postoperative bleeding. METHODS: Patients undergoing elective cardiac surgery on MiECC were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration. Rotational thromboelastometry testing was performed before induction of anesthesia and after aortic cross-clamp release. A strict POC-guided transfusion protocol was implemented. The primary endpoint was the assessment of viscoelastic properties of the coagulating blood at the end of surgery compared to preoperative values and the relation to postoperative bleeding and 24-hour transfusion requirements. RESULTS: Fifty patients were included in the study with a significant proportion having complex surgery. Thirteen patients (26%) required blood transfusion (mean rate: 0.5 ± 1 units per patient), 5/50 (10%) received coagulation factors while no patient received fresh frozen plasma, platelets or fibrinogen. Thromboelastometry analysis showed that the major derangement was CT EXTEM > 100 seconds in 28/50 (56%) and A10 EXTEM < 40 mm in one (2%) patient without clinical significance. Platelet function was preserved throughout surgery. A10-FIBTEM was found predictive of postoperative bleeding at 12 hours. CONCLUSIONS: MiECC preserves clot quality throughout surgery acting in both key determinants of clot strength; fibrinogen and platelets. This is clinically translated into minimal postoperative bleeding and restricted use of blood products and coagulation factors.

Gastroenterology and liver disease during COVID-19 and in anticipation of post-COVID-19 era: Current practice and future directions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.

Newly Diagnosed Acute Myeloid Leukemia in a Patient With Severe SARS-CoV-2 Infection.

We present a 68-year-old male patient with persistent and complicated SARS-CoV-2 infection who was diagnosed with acute myeloid leukemia (AML). The patient suffered from fever, cough and progressive dyspnea for 10 days and he was admitted to the intensive care unit due to respiratory failure and cytokine release syndrome (CRS). Despite a transient improvement of CRS by the implementation of supportive care, including also the administration of recombinant tissue plasminogen activator (rt-PA) and tocilizumab, his clinical course worsened over time. Thus, a bone marrow aspiration was performed revealing the presence of myeloblasts in a proportion of 32% and flow cytometry confirmed the diagnosis of AML-M1 according to FAB classification. Re-evaluation of peripheral blood tests revealed that the patient was admitted with anemia and thrombocytopenia that were never recovered during hospitalization. Due to the patient's poor clinical condition, no chemotherapy was applied, and he died of sepsis and multi-organ failure two days later. This case suggests that in all patients with a persistent and/or complicated infection, even during pandemics, the presence of an underlying hematologic malignancy should always be taken into consideration.

Minimal invasive extracorporeal circulation preserves platelet function after cardiac surgery: a prospective observational study.

INTRODUCTION: Cardiac surgery on conventional cardiopulmonary bypass induces a combination of thrombocytopenia and platelet dysfunction which is strongly related to postoperative bleeding. Minimal invasive extracorporeal circulation has been shown to preserve coagulation integrity, though effect on platelet function remains unclear. We aimed to prospectively investigate perioperative platelet function in a series of patients undergoing cardiac surgery on minimal invasive extracorporeal circulation using point-of-care testing. METHODS: A total of 57 patients undergoing elective cardiac surgery on minimal invasive extracorporeal circulation were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration performed in all patients with a specialized point-of-care device (Hemostasis Management System - HMS Plus; Medtronic, Minneapolis, MN, USA). Platelet function was evaluated with impedance aggregometry using the ROTEM platelet (TEM International GmbH, Munich, Germany). ADPtest and TRAPtest values were assessed before surgery and after cardiopulmonary bypass. RESULTS: ADPtest value was preserved during surgery on minimal invasive extracorporeal circulation (58.2 ± 20 U vs. 53.6 ± 21 U; p = 0.1), while TRAPtest was found significantly increased (90 ± 27 U vs. 103 ± 38 U; p = 0.03). Postoperative ADPtest and TRAPtest values were inversely related to postoperative bleeding (correlation coefficient: -0.29; p = 0.03 for ADPtest and correlation coefficient: -0.28; p = 0.04 for TRAPtest). The preoperative use of P2Y12 inhibitors was identified as the only independent predictor of a low postoperative ADPtest value (OR = 15.3; p = 0.02). CONCLUSION: Cardiac surgery on minimal invasive extracorporeal circulation is a platelet preservation strategy, which contributes to the beneficial effect of minimal invasive extracorporeal circulation in coagulation integrity.

Comparison of Laryngoscopic Views betweenC-MAC™ and Conventional Laryngoscopy in Patients with Multiple Preoperative Prognostic Criteria of Difficult Intubation. An Observational Cross-Sectional Study.

Background and Objectives: Video laryngoscopy has been proven useful under difficult airway scenarios, but it is unclear whether anticipated improvement of visualization is related to specific difficult intubation prognostic factors. The present study evaluated the change in laryngoscopic view between conventional and C-MAC® laryngoscopy and the presence of multiple difficult intubation risk factors. Materials and Methods: Patients scheduled for elective surgery with >2 difficult intubation factors, (Mallampati, thyromental distance (TMD), interinscisor gap, buck teeth, upper lip bite test, cervical motility, body mass index (BMI)) were eligible. Patients underwent direct laryngoscopy (DL) followed by C-MAC™ laryngoscopy (VL) and intubation. Change of view between DL and VL, time for best view, intubation difficulty scale (IDS) and correlation between prognostic factors, laryngoscopic view improvement, and IDS were measured. Results: One-hundred and seventy-six patients completed the study. VL lead to fewer Cormarck-Lehane (C/L) III-IV, compared to DL (13.6% versus 54.6%, p < 0.001). The time to best view was also shorter (VL: 10.82 s, DL: 12.08 s, p = 0.19). Mallampati III-IV and TMD ≤ 6 cm were related to improvement of C/L between DL and VL. Logistic regression showed these two factors to be a significant risk factor of the glottis view change (p = 0.006, AUC-ROC = 0.57, 95% CI: 0.47-0.66). 175/176 patients were intubated with VL. 108/176 were graded as 0 < IDS ≤ 5 and 12/176 as IDS > 5. IDS was only correlated to the VL view (p < 0.0001). Conclusion: VL improved laryngoscopic view in patients with multiple factors of difficult intubation. Mallampati and TMD were related to the improved view. However, intubation difficulty was only related to the VL view and not to prognostic factors.