In Nordic countries 30-day mortality rate is half that estimated with EuroSCORE II in high-risk adult patients given aprotinin and undergoing mainly complex cardiac procedures.

Objectives. To describe current on- (isolated coronary arterty bypass grafting, iCABG) and off-label (non-iCABG) use of aprotinin and associated safety endpoints in adult patients undergoing high-risk cardiac surgery in Nordic countries. Design. Data come from 10 cardiac surgery centres in Finland, Norway and Sweden participating in the European Nordic aprotinin patient registry (NAPaR). Results. 486 patients were given aprotinin between 2016 and 2020. 59 patients (12.1%) underwent iCABG and 427 (87.9%) non-iCABG, including surgery for aortic dissection (16.7%) and endocarditis (36.0%). 89.9% were administered a full aprotinin dosage and 37.0% were re-sternotomies. Dual antiplatelet treatment affected 72.9% of iCABG and 7.0% of non-iCABG patients. 0.6% of patients had anaphylactic reactions associated with aprotinin. 6.4% (95 CI% 4.2%-8.6%) of patients were reoperated for bleeding. Rate of postoperative thromboembolic events, day 1 rise in creatinine >44µmol/L and new dialysis for any reason was 4.7% (95%CI 2.8%-6.6%), 16.7% (95%CI 13.4%-20.0%) and 14.0% (95%CI 10.9%-17.1%), respectively. In-hospital mortality and 30-day mortality was 4.9% (95%CI 2.8%-6.9%) and 6.3% (95%CI 3.7%-7.8%) in all patients versus mean EuroSCORE II 11.4% (95%CI 8.4%-14.0%, p < .01). 30-day mortality in patients undergoing surgery for aortic dissection and endocarditis was 6.2% (95%CI 0.9%-11.4%) and 6.3% (95%CI 2.7%-9.9%) versus mean EuroSCORE II 13.2% (95%CI 6.1%-21.0%, p = .11) and 14.5% (95%CI 12.1%-16.8%, p = .01), respectively. Conclusions. NAPaR data from Nordic countries suggest a favourable safety profile of aprotinin in adult cardiac surgery.

Albumin and Cardioprotection in On-Pump Cardiac Surgery-A Post Hoc Analysis of a Randomized Trial.

OBJECTIVES: To study the quantitative potency of plasma albumin on cardioprotection in terms of creatinine kinase-myocardial band mass (CK-MBm) in on-pump cardiac surgery. DESIGN: Post hoc analysis of a double-blinded randomized clinical trial. SETTING: Single-center study in the Helsinki University Hospital. PARTICIPANTS: A total of 1,386 adult on-pump cardiac surgical patients. INTERVENTION: Administration of 4% albumin (n = 693) or Ringers acetate (n = 693) for cardiopulmonary bypass priming and volume replacement intraoperatively and postoperatively during the first 24 hours. MEASUREMENTS AND MAIN RESULTS: Albumin concentration was measured preoperatively and intraoperatively (after protamine administration), and CK-MBm on the first postoperative morning. Multivariate linear regression analyses were measured in the whole cohort and the Ringer group. Plasma albumin concentration did not differ between the groups preoperatively (Ringer v albumin: 38.3 ± 5.0 g/L v 38.6 ± 4.5 g/L; p = 0.171) but differed intraoperatively (29.5 ± 5.2 g/L v 41.5 ± 6.0 g/L; p < 0.001). Creatinine kinase-myocardial band mass was higher in the Ringer (32.0 ± 34.8 µg/L) than in the albumin group (24.3 ± 33.0 µg/L) (p < 0.001). Aortic cross-clamping time associated with CK-MBm in the whole cohort (standardized ß = 0.376 [95% CI 0.315-0.437], p < 0.001) and the Ringer group (ß = 0.363 [0.273-0.452]; p < 0.001). Albumin administration in the whole cohort (ß = -0.156 [-0.201 to -0.111]; p < 0.001) and high intraoperative albumin concentration in the Ringer group (ß = -0.07 [-0.140 to -0.003]; p = 0.04) associated with reduced CK-MBm. Compared with ischemia-induced increase in CK-MBm, albumin's potency to reduce CK-MBm was 41% in the whole cohort (ß-value ratio of -0.156/0.376) and 19% in the Ringer group (ß-value ratio of -0.07/0.363). CONCLUSION: Both endogenous and exogenous albumin appear to be cardioprotective regarding CK-MBm release in on-pump cardiac surgery.

Albumin Infusion and Blood Loss After Cardiac Surgery.

BACKGROUND: In the recent ALBICS (ALBumin In Cardiac Surgery) trial, 4% albumin used for cardiopulmonary bypass priming and volume replacement increased perioperative bleeding compared with Ringer acetate. In the present exploratory study, albumin-related bleeding was further characterized. METHODS: Ringer acetate and 4% albumin were compared in a randomized, double-blinded fashion in 1386 on-pump adult cardiac surgery patients. The study end points for bleeding were the Universal Definition of Perioperative Bleeding (UDPB) class and its components. RESULTS: The UDPB bleeding grades were higher in the albumin group than the Ringer group: "insignificant" (albumin vs Ringer: 47.5% vs 62.9%), "mild" (12.7% vs 8.9%), "moderate" (28.7% vs 24.4%), "severe" (10.2% vs 3.2%), and "massive" (0.9% vs. 0.6%; P < .001). Patients in the albumin group received red blood cells (45.2% vs 31.5%; odds ratio [OR], 1.80; 95% CI, 1.44-2.24; P < .001), platelets (33.3% vs 21.8%; OR, 1.79; 95% CI, 1.41-2.28; P < .001), and fibrinogen (5.6% vs 2.6%; OR, 2.24; 95% CI, 1.27-3.95; P < .05), and underwent resternotomy (5.3% vs 1.9%; OR, 2.95; 95% CI, 1.55-5.60, P < .001) more often than patients in the Ringer group. The strongest predictors of bleeding were albumin group allocation (OR, 2.18; 95% CI, 1.74-2.74) and complex (OR, 2.61; 95% CI, 2.02-3.37) and urgent surgery (OR, 1.63; 95% CI, 1.26-2.13). In interaction analysis, the effect of albumin on the risk of bleeding was stronger in patients on preoperative acetylsalicylic acid. CONCLUSIONS: Perioperative administration of albumin, compared with Ringer's acetate, resulted in increased blood loss and higher UDBP class. The magnitude of this effect was similar to the complexity and urgency of the surgery.

Effect of 4% Albumin Solution vs Ringer Acetate on Major Adverse Events in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Randomized Clinical Trial.

Importance: In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. Objective: To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery. Design, Setting, and Participants: A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020). Interventions: The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively. Main Outcomes and Measures: The primary outcome was the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury. Results: Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P = .20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group). Conclusions and Relevance: Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02560519.

Heparin Dose and Point-of-Care Measurements of Hemostasis in Cardiac Surgery-Results of a Randomized Controlled Trial.

OBJECTIVE: High heparin doses during cardiopulmonary bypass (CPB) have been suggested to reduce thrombin activation and consumption coagulopathy and consequently bleeding complications. The authors investigated the effect of a high heparin dose during CPB on point-of-care measurements of coagulation. The authors hypothesized that during CPB a high heparin dose compared with a lower heparin dose would reduce thrombin generation and platelet activation and tested whether this would be reflected in the results of rotational thromboelastometry (TEM) and platelet aggregation, measured with multiple electrode aggregometry (MEA). DESIGN: Prospective, randomized, controlled, open single-center study. SETTING: University teaching hospital. PARTICIPANTS: Sixty-three consecutive patients undergoing elective coronary artery bypass grafting with CPB were enrolled. INTERVENTIONS: Patients were randomly assigned to receive either a high (600 IU/kg, n = 32) or a low (300 IU/kg, n = 31) initial dose of heparin. Target levels of activated clotting time during CPB were >600 seconds in the high heparin dose group and >400 seconds in the low heparin dose group. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected (1) preoperatively after induction of anesthesia, (2) 10 minutes after aortic declamping, (3) 30 minutes after protamine administration, and (4) 3 hours after protamine administration. TEM and MEA were then measured. There was no difference in blood loss up to 18 hours postoperatively (median 735 mL for high dose v 610 mL for low dose; p < 0.056) or transfusions between the groups. Total median heparin dose (54,300 IU v 27,000 IU; p = 0.001) and median antifactor Xa levels during CPB (9.38 U/mL v 5.04 U/mL; p = 0.001) were greater in the high than in the low heparin dose group. However, neither TEM nor MEA results differed significantly between the groups. CONCLUSIONS: Compared with a lower dose of heparin during CPB, a high dose of heparin had little effect on the point-of-care measurements of hemostasis, TEM, and MEA. Based on the similarity of platelet and coagulation activity assessments, the higher heparin dose does not appear to offer benefit during CPB.

Effect and safety of 4% albumin in the treatment of cardiac surgery patients: study protocol for the randomized, double-blind, clinical ALBICS (ALBumin In Cardiac Surgery) trial.

BACKGROUND: In cardiac surgery with cardiopulmonary bypass (CPB), large amounts of fluids are administered. CPB priming with crystalloid solution causes marked hemodilution and fluid extravasation. Colloid solutions may reduce fluid overload because they have a better volume expansion effect than crystalloids. The European Medicines Agency does not recommend the use of hydroxyethyl starch solutions (HES) due to harmful renal effects. Albumin solution does not impair blood coagulation but the findings on kidney function are conflicting. On the other hand, albumin may reduce endothelial glycocalyx destruction and decrease platelet count during CPB. No large randomized, double-blind, clinical trials have compared albumin solution to crystalloid solution in cardiac surgery. METHODS/DESIGN: In this single-center, double-blind, randomized controlled trial comprising 1386 adult cardiac surgery patients, 4% albumin solution will be compared to Ringer's acetate solution in CPB priming and volume replacement up to 3200 mL during surgery and the first 24 h of intensive care unit stay. The primary efficacy outcome is the number of patients with at least one major adverse event (MAE) during 90 postoperative days (all-cause death, acute myocardial injury, acute heart failure or low output syndrome, resternotomy, stroke, major arrhythmia, major bleeding, infection compromising post-procedural rehabilitation, acute kidney injury). Secondary outcomes are total number of MAEs, incidence of major adverse cardiac events (MACE; cardiac death, acute myocardial injury, acute heart failure, arrhythmia), amount of each type of blood product transfused (red blood cells, fresh frozen plasma, platelets), total fluid balance at the end of the intervention period, total measured blood loss, development of acute kidney injury, days alive without mechanical ventilation in 90 days, days alive outside intensive care unit at 90 days, days alive at home at 90 days, and 90-day mortality. DISCUSSION: The findings of this study will provide new evidence regarding efficacy and safety of albumin solution in adult patients undergoing cardiac surgery with CPB. TRIAL REGISTRATION: EudraCT (clinicaltrialsregister.eu) 2015-002556-27 Registered 11 Nov 2016 and ClinicalTrials.gov NCT02560519. Registered 25 Sept 2015.

Relation of Use of Red Blood Cell Transfusion After Acute Coronary Syndrome to Long-Term Mortality.

Registry studies have associated red blood cell (RBC) transfusion with increased in-hospital mortality in patients with acute coronary syndrome (ACS). The impact on long-term mortality after 1-year follow-up remains unknown. Consecutive patients with ACS (n = 2,009) of a prospective Genetic Predisposition of Coronary Artery Disease cohort were followed for a median of 8.6 years (95% confidence interval [CI] 8.59 to 8.69). After discharge, 1,937 (96%) patients survived for over 30 days. Of those survivors, a subgroup of previously transfusion-naïve patients 85/1,937 (4.4%) who had received at least 1 RBC transfusion during hospitalization were compared with 1,278/1,937 patients (66.0%) who had not received any transfusion either during the hospitalization or the entire follow-up. Unadjusted long-term mortality was significantly higher in the patients transfused with RBC compared with their counterparts not transfused with RBC (58.8% vs 20.3%, p <0.001). The results remained significant for hazard ratio (HR) 1.91, 95% CI 1.39 to 2.63, p <0.001, after multivariate Cox proportional hazards model analysis and were similar after 1-year landmark analysis (HR 1.90, 95% CI 1.34 to 2.70, p <0.001). The higher all-cause mortality was largely explained by cancer mortality (15.3% vs 4.1%, p <0.001) and cardiovascular mortality (34.1% vs 12.1%, p <0.001). After 1:1 propensity score matching (n = 65 vs 65), the association of RBC transfusion with worse survival remained significant (HR 2.70, 95% CI 1.48 to 4.95, p = 0.001). Inverse probability weighted Cox analyses turned out similar results (HR 2.07, 95% CI 1.38 to 3.11, p <0.001). In conclusion, the strong association of need for RBC transfusion with increased mortality continued for patients with ACS even after a 1-year follow-up.

[Prophylactic platelet transfusions]. / Trombosyyttisiirrot verenvuotojen ehkäisyssä.

The consumption of platelet products in Finland is exceptionally high. For the most part, platelets are transfused pre-operatively to thrombocytopenic patients in order to prevent hemorrhage. Most of the minor procedures could, however, be conducted even if the patients'platelet levels would be lower than usual. In cardiac surgery, platelets are used because of the hemorrhagic diathesis associated with platelet inhibitors. Platelet inhibitors will, however, also bind to transfused platelets, whereby instead of prophylactic platelet transfusions it would be more sensible to leave the thorax open and not carry out ineffective platelet transfusions until the effect of the inhibitors has run out. We outline the prophylactic use of platelets based on recent international clinical practice guidelines.

Amplatzer Device in Bronchial Stump Fistula after Extrapleural Pneumonectomy.

Endoscopically superimposed Amplatzer (St. Jude Medical, St. Paul, Minnesota, United States) septal occluder plug was successfully used in the treatment of septic right main bronchus fistula having developed after extrapleural pneumonectomy and heated chemotherapy in two patients with malignant pleural mesothelioma. In the first case the method was curative and in the other Amplatzer served as temporary bridging allowing rehabilitation from empyema and sepsis. After 4.5 and 4.2 years both patients are alive with no sign of relapse of mesothelioma or infection.

[Bleeding during operations]. / Verenvuoto leikkauksissa.

Unnecessary use of blood products should be avoided, but excessive caution may on the other hand lead to complications and increase mortality. Attempts to more closely define the indications for use of blood products and reduce perioperative bleeding have over the past five years resulted in an approximately 20% decrease in the consumption of red blood cells. A generally applicable hemoglobin limit for red blood cell transfusions cannot be defined. The guideline often cited in recommendations (80 g/l) is subject to justifiable criticism, whereby a more liberal threshold for transfusion can be favored. Sparing fluid therapy of a surgical patient has been shown to promote recovery and reduce complications.

Indications for early fresh frozen plasma, cryoprecipitate, and platelet transfusion in trauma.

BACKGROUND: Massive blood transfusion can be lifesaving in the treatment of severe trauma. Guidelines for the use of non-RBC blood components in the early phase of trauma resuscitation are largely based on extensions of expert recommendations for general surgery. METHODS: The logic and evidence for the use of plasma, platelets, and cryoprecipitate early in the course of massive transfusion for trauma were reviewed. Large series of consecutive patients were sought. FINDINGS: Resuscitation of the most severely injured and massively hemorrhaging patients usually starts with crystalloid fluids and progresses to uncross-matched RBC. Low blood volume, insensible losses, consumption, and resuscitation with plasma poor RBC concentrates rapidly lead to plasma coagulation factor concentrations of less than 40%. This typically occurs before 10 U of RBC have been transfused. Early initiation of plasma therapy is often delayed by its lack of immediate availability in the trauma center. Platelets usually fall to concentrations of 50-100 x 10(9)/L after 10-20 units of RBC have been given, but platelet concentrations in individual patients are quite variable and can decrease more quickly. Ideal platelet concentrations in trauma patients are not known, but are generally held to be greater than 50 x 10(9)/L. Cryoprecipitate can rapidly increase the concentrations of fibrinogen and von Willebrand's factor, but the advantages of higher than normal concentrations are speculative. CONCLUSIONS: Early use of plasma and platelets at the upper end of recommended doses appears to reduce the incidence of coagulopathy in massively transfused individuals.

Optimizing the use of blood products in trauma care.

Blood transfusion has been used to treat the injured since the US Civil War. Now, it saves the lives of tens of thousands of injured patients each year. However, not everyone who receives blood benefits, and some recipients are injured by the transfusion itself. Effective blood therapy in trauma management requires an integration of information from diverse sources, including data relating to trauma and blood use epidemiology, medical systems management, and clinical care. Issues of current clinical concern in highly developed trauma systems include how to manage massive transfusion events, how to limit blood use and so minimize exposure to transfusion risks, how to integrate new hemorrhage control modalities, and how to deal with blood shortages. Less developed trauma systems are primarily concerned with speeding transport to specialized facilities and assembling trauma center resources. This article reviews the factors that effect blood use in urgent trauma care.