Treating periprocedural bleeding in patients with cirrhosis.

Patients with cirrhosis are known to have an abnormal coagulation status, which is a particular concern when planning invasive procedures in which blood loss is possible or predictable. Careful consideration must be given to the bleeding risk for each individual patient and coagulation management strategies should be established in advance of procedural interventions, where possible. Perioperative clinical decision-making should utilize viscoelastic testing in addition to usual assessments, where possible, and focus on the well-established three pillars of patient blood management: optimization of erythropoiesis, minimization of bleeding and blood loss, and management of anemia. Restrictive transfusion policies, careful hemostatic monitoring, and a proactive approach to predicting and preventing bleeding on an individual patient basis should be central to managing perioperative bleeding in the fragile patient population with cirrhosis. This review discusses coagulation assessments and bleeding management techniques necessary before, during, and after surgical interventions in patients with cirrhosis, and provides expert clinical opinion and physician experience on the perioperative management of these patients.

Population pharmacokinetic modelling of fibrinogen in patients with congenital or acquired-chronic or acute-hypofibrinogenaemia.

AIMS: Fibrinogen is the key substrate for coagulation. Fibrinogen pharmacokinetics (PK) after single doses of fibrinogen concentrate (FC), using modelling approaches, has only been evaluated in congenital afibrinogenaemic patients. The aims of this study are to characterize the fibrinogen PK in patients with acquired-chronic (cirrhosis) or acute-hypofibrinogenaemia (critical haemorrhage), showing endogenous production. Influencing factors of differences on the fibrinogen PK between subpopulations will be identified. METHODS: A total of 428 time-concentration values from 132 patients were recorded. Eighty-two out of 428 values were from 41 cirrhotic patients administered with placebo and 90 out of 428 were from 45 cirrhotic patients that were given FC, 161 out of 428 values were from 14 afibrinogenaemic patients and 95 out of 428 values were from 32 severe acute trauma haemorrhagic patients. A turnover model that accounted for endogenous production and exogenous dose was fitted using NONMEM74. The production rate (Ksyn), distribution volume (V), plasma clearance (CL) and concentration yielding to 50% of maximal fibrinogen production (EC50) were estimated. RESULTS: Fibrinogen disposition was described by a one-compartment model with CL and V values of 0.0456 L·h-1 and 4.34 L·70 kg-1 , respectively. Body weight was statistically significant in V. Three different Ksyn values were identified that increased from 0.00439 g·h-1 (afibrinogenaemia), to 0.0768 g·h-1 (cirrhotics) and 0.1160 g·h-1 (acute severe trauma). EC50 was of 0.460 g·L-1 . CONCLUSIONS: This model will be key as a support tool for dose calculation to achieve specified target fibrinogen concentrations, in each of the studied populations.

Factors associated with mechanical ventilation longer than 24 h after liver transplantation in patients at risk for bleeding.

BACKGROUND: This risk analysis aimed to explore all modifiable factors associated with prolonged mechanical ventilation (lasting > 24 h) after liver transplantation, based on prospectively collected data from a clinical trial. METHODS: We evaluated 306 candidates. Ninety-three patients were excluded for low risk for transfusion (preoperative haemoglobin > 130 g.l-1), and 31 patients were excluded for anticoagulation therapy, bleeding disorders, familial polyneuropathy, or emergency status. Risk factors were initially identified with a log-binomial regression model. Relative risk was then calculated and adjusted for age, sex, and disease severity (Model for End-Stage Liver Disease [MELD] score). RESULTS: Early tracheal extubation was performed in 149 patients (84.7%), and 27 patients (15.3%) required prolonged mechanical ventilation. Reoperations were required for 6.04% of the early extubated patients and 44% of patients who underwent prolonged ventilation (p = 0.001). A MELD score > 23 was the main risk factor for prolonged ventilation. Once modifiable risk factors were adjusted for MELD score, sex, and age, three factors were significantly associated with prolonged ventilation: tranexamic acid (p = 0.007) and red blood cell (p = 0.001) infusion and the occurrence of postreperfusion syndrome (p = 0.004). The median (IQR) ICU stay was 3 (2-4) days in the early extubation group vs. 5 (3-10) days in the prolonged ventilation group (p = 0.001). The median hospital stay was also significantly shorter after early extubation, at 14 (10-24) days, vs. 25 (14-55) days in the prolonged ventilation group (p = 0.001). Eight patients in the early-extubation group (5.52%) were readmitted to the ICU, nearly all for reoperations, with no between-group differences in ICU readmissions (prolonged ventilation group, 3.7%). CONCLUSION: We conclude that bleeding and postreperfusion syndrome are the main modifiable factors associated with prolonged mechanical ventilation and length of ICU stay, suggesting that trials should explore vasopressor support strategies and other interventions prior to graft reperfusion that might prevent potential fibrinolysis. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT 2018-002510-13,) and on ClinicalTrials.gov (NCT01539057).

Altered Fibrinolysis during and after Surgery.

Major surgery induces hemostatic changes related to surgical stress, tissue destruction, and inflammatory reactions. These changes involve a shift of volume from extravascular space to intravascular and interstitial spaces, a "physiologic" hemodilution of coagulation proteins, and an increase of plasmatic fibrinogen concentration and platelets. Increases in fibrinogen and platelets together with a simultaneous dilution of pro- and anticoagulant factors and development of a hypofibrinolytic status result in a postoperative hypercoagulable state. This profile is accentuated in more extensive surgery, but the balance can shift toward hemorrhagic tendency in specific types of surgeries, for example, in prolonged cardiopulmonary bypass or in patients with comorbidities, especially liver diseases, sepsis, and hematological disorders. Also, acquired coagulopathy can develop in patients with trauma, during obstetric complications, and during major surgery as a result of excessive blood loss and subsequent consumption of coagulation factors as well as hemodilution. In addition, an increasing number of patients receive anticoagulants and antiplatelet drugs preoperatively that might influence the response to surgical hemostasis. This review focuses on those situations that may change normal hemostasis and coagulation during surgery, producing both hyperfibrinolysis and hypofibrinolysis, such as overcorrection with coagulation factors, bleeding and hyperfibrinolysis that may occur with extracorporeal circulation and high aortic-portal-vena cava clamps, and hyperfibrinolysis related to severe maintained hemodynamic disturbances. We also evaluate the role of tranexamic acid for prophylaxis and treatment in different surgical settings, and finally the value of point-of-care testing in the operating room is commented with regard to investigation of fibrinolysis.

Baseline haemoglobin and thromboelastometry are predictive of red blood cell requirements and one-year mortality in liver transplantation.

BACKGROUND: To determine the predictive capacity of baseline haemoglobin and maxim clot firmness (MCF) EXTEM thromboelastometry for intraoperative red blood cell (RBC) requirements and its influence on mortality. METHODS: 591 adult liver transplant (LT) recipients from ten Spanish centres were reviewed. The main outcomes were the percentage of patients who received RBC and massive transfusion (≥ 6 RBC units), RBC units transfused, and mortality. RESULTS: 76 % received a donor after brain death graft and 24 % a controlled donor after circulatory death graft. Median (interquartile ranges) RBC transfusion was 2 (0-4) units, and 63 % of patients were transfused. Comparing transfused and non-transfused patients, mean (standard deviation) for baseline haemoglobin was 10.4 (2.1) vs. 13.0 (1.9) g/dl (p = 0.001), EXTEM MCF was 51(11) vs. 55(9) mm (p = 0.001). Haemoglobin and EXTEM MCF were inversely associated with the need of transfusion odds ratio (OR) of 0.558 (95 % CI 0.497-0.627, p < 0.001) and OR 0.966 (95 % CI0.945-0.987, p = 0.002), respectively. Pre-operative baseline haemoglobin ≤ 10 g/dL predicted RBC transfusion, sensitivity of 93 % and specificity of 47 %. Massive transfusion (MT) was received by 19 % of patients. Haemoglobin ≤10 g/dL predicted MT with sensitivity 73 % and specificity of 52 %. One-year patient and graft survival were significantly lower in patients who required MT (78 % and 76 %, respectively) vs. those who did not (94 % and 93 %, respectively). DISCUSSION: whereas EXTEM MCF is less dreterminant predicting RBC requirements, efforts are required to improve preoperative haemoglobin up to 10 g/dl in patients awaiting LT.

Impact of the SARS-CoV-2 (COVID19) pandemic on the morbidity and mortality of high risk patients undergoing surgery: a non-inferiority retrospective observational study.

BACKGROUND: During the COVID-19 crisis it was necessary to generate a specific care network and reconvert operating rooms to attend emergency and high-acuity patients undergoing complex surgery. The aim of this study is to classify postoperative complications and mortality and to assess the impact that the COVID-19 pandemic may have had on the results. METHODS: this is a non-inferiority retrospective observational study. Two different groups of surgical patients were created: Pre-pandemic COVID and Pandemic COVID. Severity of illness was rated according to the Diagnosis-related Groups (DRG) score. Comparisons were made between groups and between DRG severity score-matched samples. Non-inferiority was set at up to 10 % difference for grade III to V complications according to the Clavien-Dindo classification, and up to 2 % difference in mortality. RESULTS: A total of 1649 patients in the PreCOVID group and 763 patients in the COVID group were analysed; 371 patients were matched for DRG severity score 3-4 (236 preCOVID and 135 COVID). No differences were found in relation to re-operation (22.5 % vs. 21.5 %) or late admission to critical care unit (5.1 % vs. 4.5 %). Clavien grade III to V complications occurred in 107 patients (45.3 %) in the PreCOVID group and in 56 patients (41.5 %) in the COVID group, and mortality was 12.7 % and 12.6 %, respectively. During the pandemic, 3 % of patients tested positive for Covid-19 on PCR: 12 patients undergoing elective surgery and 11 emergency surgery; there were 5 deaths, 3 of which were due to respiratory failure following Covid-19-induced pneumonia. CONCLUSIONS: Although this study has some limitations, it has shown the non-inferiority of surgical outcomes during the COVID pandemic, and indicates that resuming elective surgery is safe. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04780594 .

Blood component requirements in liver transplantation: effect of 2 thromboelastometry-guided strategies for bolus fibrinogen infusion-the TROMBOFIB randomized trial.

BACKGROUND: A low plasma fibrinogen level influences blood component transfusion. Thromboelastometry provides clinical guidance for fibrinogen replacement in liver transplantation (LT). OBJECTIVES: We hypothesized that infusions of fibrinogen concentrate to reach an A10FibTem value of 11 mm during LT could reduce red blood cell (RBC) and other component and fluid requirements in comparison to standard care. METHODS: This randomized, blinded, multicenter trial in 3 hospitals enrolled 189 LT-scheduled patients allocated to an intervention target (A10FibTem, 11 mm) or a standard target (A10FibTem, 8 mm); 176 patients underwent LT with fibrinogen replacement. Data were analyzed by intention-to-treat (intervention group, 91; control group, 85). Blood was extracted, and fibrinogen kits were prepared to bring each patient's fibrinogen level to the assigned target at the start of LT, after portal vein clamping, and after graft reperfusion. The main outcome was the proportion of patients requiring RBC transfusion during LT or within 24 hours. RESULTS: The proportion of patients requiring RBCs did not differ between the groups: intervention, 74.7% (95% CI, 65.5%-83.3%); control, 72.9% (95% CI, 62.2%-82.0%); absolute difference, 1.8% (95% CI, -11.1% to 14.78%) (P = .922). Thrombotic events occurred in 4% of the patients in both groups; reoperation and retransplantation rates and mortality did not differ. Nearly 70% of the patients in both groups required fibrinogen concentrate to reach the target. Using an 11-mm A10FibTem target increased the maximum clot firmness without affecting safety. However, this change provided no clinical benefits. CONCLUSION: The similar low plasma fibrinogen concentrations could explain the lack of significant between-group outcomes.

International Liver Transplantation Society/Society for Advancement of Transplant Anesthesia Consensus Statement on Essential Attributes of a Liver Transplant Anesthesiologist.

BACKGROUND: We sought to establish consensus on the essential skills, knowledge, and attributes that a liver transplant (LT) anesthesiologist should possess in a bid to help guide the further training process. METHODS: Consensus was achieved via a modified Delphi methodology, surveying 15 identified international experts in the fields of LT anesthesia and critical care. RESULTS: Key competencies were identified in preoperative management and optimization of a potential LT recipient; intraoperative management, including hemodynamic monitoring; coagulation and potential crisis management; and postoperative intensive and enhanced recovery care. CONCLUSIONS: This article provides an essential guide to competency-based training of an LT anesthesiologist.

Sugammadex ideal body weight dose adjusted by level of neuromuscular blockade in laparoscopic bariatric surgery.

BACKGROUND: Bariatric surgery patients are at risk of perioperative airway collapse. Neuromuscular blockade should be fully reversed before tracheal extubation. The optimal dosage of the reversal agent sugammadex in the morbidly obese is still unknown. This study explored the sugammadex dose adjusted according to train-of-four ratio (TOFR). METHODS: Prospective observational study of consecutive patients scheduled for laparoscopic bariatric surgery. To reverse a deep blockade (2 or fewer posttetanic twitches), a dose of sugammadex of 4 mg/kg ideal body weight (IBW) was followed by a second dose of 2 mg/kg IBW if the TOFR was less than 0.9 after 3 min. To reverse a moderate blockade (reappearance of the second twitch in the TOF), a 2 mg/kg IBW dose of sugammadex was followed by a second dose of 2 mg/kg IBW if the TOFR was less than 0.9 after 2 min. Sugammadex effectiveness was reflected by the time required to obtain a TOFr of 0.9 or more. RESULTS: A total of 120 patients were included. The blockade was deep at the end of surgery in 43 and moderate in 77. The median times (range) to TOFR of 0.9 or more were 167 (20-460) seconds and 113 (28-300) seconds in deep and moderate blockades, respectively (P < 0.05). The percentage of patients requiring a second dose of sugammadex were larger after deep blockades (39.5% [n = 17] vs. 23.4% [n = 18] after moderate blockades); the difference was not significant. CONCLUSION: A sugammadex dose calculated according to IBW is insufficient for reversing both deep and moderate blockades in morbidly obese patients.

[Incidence of surgical wound infection in elective colorectal surgery and its relationship with preoperative factors]. / Incidencia de la infección de la herida quirúrgica en cirugía colorrectal electiva y su relación con factores perioperatorios.

INTRODUCTION: Surgical wound infection in colorectal surgery has incidence rate of up to 26%. Peri-operative factors and those of the patients themselves play a part in these infections. The correct administration of the antibiotic, a normal temperature, and hyperoxygenation are a commonly applied triad. The primary aim of the study was to evaluate the incidence of surgical wound infection in patients subjective to colorectal surgery where a surgical infection prevention protocol was applied. The second objective was the relationship between surgical infection and peri-operative factors. MATERIAL AND METHODS: An observational study was conducted on 100 patients who had undergone elective colorectal surgery. Demographic data and related surgical and post-surgical data were recorded. A surgical wound infection was defined using the criteria of Disease Control and Prevention Hospital Infection Centres. RESULTS: The median age of the patients was 68 years (range 25-88), 65% were male, and 59% were ASA 3-4. There was more than 80% compliance to the protocol in its different sections. There was laparoscopic access in 31% of the cases. The incidence of superficial and deep surgical wound infection was 25%. The patients with an infection had a higher prevalence of diabetes (48% vs 24%), transfusion (56% vs 28%), paralytic ileum (48% vs 18.7%), and intra-abdominal abscess (16% vs 3%). The multivariate analysis associated, preoperative haemoglobin and blood glucose, and the duration of the surgery, with incisional infection. CONCLUSIONS: The prevention protocol did not have an impact on the incidence of surgical wound infection.

Clinical use of tranexamic acid: evidences and controversies.

Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

[Charlson index and the surgical risk scale in the analysis of surgical mortality]. / Valor de los índices de Charlson y la escala de riesgo quirúrgico en el análisis de la mortalidad operatoria.

INTRODUCTION: There is controversy over how to assess surgical mortality risks after different operations. The purpose of this study was to assess the surgical factors that influenced surgical mortality and the ability of the Charlson Index and The Surgical Risk Scale (SRS) to determine low risk patients. MATERIAL AND METHODS: All patients who died during the period 2004-2007 were included. The score of both indices (Charlson and SRS) were recorded. A score of «0¼ for the Charlson Index and «8¼ for the SRS were chosen as the cut-off point between a low and high probability of death. Three risk groups were established: Low when the Charlson was =0 and SRS was <8; Intermediate when the Charlson was >0 and the SRS <8 or Charlson=0 and SRS ≥8; and high when the Charlson was>0 and the SRS ≥8. The risks factors before, during and after surgery were compared between the groups. RESULTS: A total of 72,771 patients were surgically intervened, of which 7011 were urgent. One in every 1455 patients died during surgery and 1 in every 112 died during their hospital stay. Thirteen (2%) patients who died belonged to the low risk group, 199 (30.7%) to the intermediate risk group, and 434 (67.2%) to the high risk group. Heart disease was associated with the high risk group. The urgency of the operation was a determining factor associated with surgical complexity. Re-intervention and sepsis predominated as a cause of death in the low risk group, and in the rest of the groups a cardiac cause was the predominant factor. CONCLUSIONS: The combination of the Charlson Index and SRS detected those patients with a low risk of death, thus making it a useful tool to audit surgical results.

Impact of surgical technique and analgesia on clinical outcomes after lung transplantation: A STROBE-compliant cohort study.

There is paucity of data on the impact of surgical incision and analgesia on relevant outcomes.A retrospective STROBE-compliant cohort study was performed between July 2007 and August 2017 of patients undergoing lung transplantation. Gender, age, indication for lung transplantation, and the 3 types of surgical access (Thoracotomy (T), Sternotomy (S), and Clamshell (C)) were used, as well as 2 analgesic techniques: epidural and intravenous opioids. Outcome variables were: pain scores; postoperative hemorrhage in the first 24 hours, duration of mechanical ventilation, and length of stay at intensive care unit (ICU).Three hundred forty-one patients were identified. Thoracotomy was associated with higher pain scores than Sternotomy (OR 1.66, 95% CI: 1.01; 2.74, P: .045) and no differences were found between Clamshell and Sternotomy incision. The median blood loss was 800 mL [interquartile range (IQR): 500; 1238], thoracotomy patients had 500 mL [325; 818] (P < .001). Median durations of mechanical ventilation in Thoracotomy, Sternotomy, and Clamshell groups were 19 [11; 37] hours, 34 [IQR 16; 57.5] hours, and 27 [IQR 15; 50.5] hours respectively. Thoracotomy group were discharged earlier from ICU (P < .001).Thoracotomy access produces less postoperative hemorrhage, duration of mechanical ventilation, and lower length of stay in ICU, but higher pain scores and need for epidural analgesia.

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

Quality improvement: ultrasonography-guided venous catheterization in organ transplantation.

PURPOSE OF REVIEW: Central venous catheterization (CVC) is a procedure, not exempt of risk. Transplantation patients represent by themselves a high-risk group for CVC. Ultrasonography provides us of the exact localization of the target vein and its relationship with artery and nerve structures, detecting anatomic variations and thromboses of vessels. A description of technical skills, a review of the clinical evidence of ultrasonography-guided CVC and basic training guidelines are presented. RECENT FINDINGS: The internal jugular vein is the most common target vein selected because it is easier and safer, therefore it is the target vein recommended for learning the ultrasonography procedure. For subclavian-axillar vein insertion, the more distal (deltoid) access is the preferred approach; the supraclavicular access has been described with high success in paediatric patients. Anatomic variations of the venous system are not uncommon; small size, overlap artery and tissue oedema around the neck are the main causes of CVC failure. Training guidelines for ultrasound-guided vascular catheterization are necessary, and skill maintenance is crucial. SUMMARY: Ultrasonography-guided venous catheterization is an easily learned technique for internal jugular vein insertion, with significant improvements in overall success in those patients in whom a difficult vein access can be anticipated.