Does heparin rebound lead to postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass?

BACKGROUND: Heparin rebound is a common observed phenomenon after cardiac surgery with CPB and is associated with increased postoperative blood loss. However, the administration of extra protamine may lead to increased blood loss as well. Therefore, we want to investigate the relation between heparin rebound and postoperative blood loss and the necessity to provide extra protamine to reverse heparin rebound. METHODS: We searched PubMed, Cochrane, EMBASE, Google Scholar and Web of Science to review the question: "Does heparin rebound lead to postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass." Combination of search words were framed within four major categories: heparin rebound, blood loss, cardiac surgery and cardiopulmonary bypass. All studies that met our question were included. Quality assessment was performed using the Cochrane risk of bias (RoB2) tool for randomized controlled trials and the risk of bias in non-randomized studies of intervention (ROBINS-I) for non-randomised trials. RESULTS: 4 randomized and 17 non-randomized studies were included. The mean incidence of heparin rebound was 40%. The postoperative heparin levels, due to heparin rebound, were often below or equal to 0.2 IU/mL. We could not demonstrate an association between heparin rebound and postoperative blood loss or transfusion requirements. However the quality of evidence was poor due to a broad variety of definitions of heparin rebound, measured by various coagulation tests and studies with small sample sizes. CONCLUSION: The influence of heparin rebound on postoperative bleeding seems to be negligible, but might get significant in conjunction with incomplete heparin reversal or other coagulopathies. For that reason, it might be useful to get a picture of the entire coagulation spectrum after cardiac surgery, as can be done by the use of a viscoelastic test in conjunction with an aggregometry test.

Does Intraoperative Fibrinogen Affect Blood Loss or Transfusion Practice After Aortic Arch Surgery: A Prematurely Ended Randomized Trial.

Cardiovascular surgery is often complicated by significant bleeding due to perioperative coagulopathy. The effectiveness of treatment with fibrinogen concentrate to reduce the perioperative blood transfusion rate after thoracic aortic replacement surgery in prior studies has shown conflicting results. Therefore, we conducted a double-blind randomized controlled trial to investigate if a single dose of intraoperative fibrinogen administration reduced blood loss and allogeneic transfusion rate after elective surgery for thoracic arch aneurysm with deep hypothermic circulatory arrest. Twenty patients were randomized to fibrinogen concentrate (N = 10) or placebo (N = 10). The recruitment of study patients was prematurely ended due to a low inclusion rate. Perioperative transfusion, 5-minute bleeding mass after study medication and postoperative blood loss were not different between the groups with fibrinogen concentrate or placebo. Due to small volumes of postoperative blood loss and premature study termination, a beneficial effect of fibrinogen concentrate on the number of blood transfusions could not be established. However, treatment with fibrinogen efficiently restored fibrinogen levels and clot strength to preoperative values with a more effective preserved postoperative thrombin generation capacity. This result might serve as a pilot for further multicenter studies to assess the prospective significance of automated and standardized thrombin generation as a routine assay for monitoring perioperative coagulopathy and its impact on short- and long-term operative results.

External Validation of the ACTA-PORT Transfusion Risk Score in Older Cardiac Surgery Patients at Risk of Frailty.

OBJECTIVES: Accurate preoperative transfusion risk stratification may serve to better manage older patients undergoing cardiac surgery. Therefore, the aim of the present study was to externally validate the existing Association of Cardiothoracic Anesthetists perioperative risk of blood transfusion (ACTA-PORT) score in a population ≥70 years of age scheduled for cardiac surgery. Furthermore, the study authors investigated the additional prognostic value of individual frailty variables to this transfusion risk score. DESIGN: A retrospective analysis. SETTING: At a tertiary-care hospital. PARTICIPANTS: Five hundred seven patients aged ≥70 years undergoing elective cardiac surgery from July 2015 to August 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the administration of a perioperative blood transfusion. Frailty domains were assessed in a preanesthesia geriatric assessment, and a priori selection of biomarkers derived from blood was determined. The original ACTA-PORT score resulted in a c-statistic of 0.78 (95% confidence interval 0.74-0.82), with moderate calibration in predicting perioperative allogeneic transfusion in older patients undergoing cardiac surgery. Model updating, using the closed testing procedure, resulted in model revision with a higher discriminatory performance (c-statistic of 0.83, 95% confidence interval 0.79-0.86) and corrected calibration slope. Iron deficiency, impaired nutritional status, and physical impairment were associated with perioperative transfusions. The addition of individual frailty variables to the updated ACTA-PORT model did not result in improved predictive performance. CONCLUSIONS: External validation of the original ACTA-PORT score showed good discrimination and moderate calibration in older patients at risk of frailty undergoing cardiac surgery. Updating the original ACTA-PORT improved the predictive performance. Careful evaluation of additional frailty domains did not add prognostic value to the ACTA-PORT score.

Association of Plasma Fibrinogen and Thromboelastography With Blood Loss in Complex Cardiac Surgery.

Postoperative coagulopathic bleeding is common in cardiac surgery and is associated with increased morbidity and mortality. Ideally, real-time information on in-vivo coagulation should be available. However, up to now it is unclear which perioperative coagulation parameters can be used best to accurately identify patients at increased risk of bleeding. The present study analyzed the associations of perioperative fibrinogen concentrations and whole blood viscoelastic tests with postoperative bleeding in 89 patients undergoing combined cardiac surgery procedures. Postoperative bleeding was recorded until 24 hours after surgery. Regression analyses were performed to establish associations between blood loss and coagulation parameters after cardiopulmonary bypass including a prediction model with known confounding factors for bleeding. Coagulation tests show large changes over the perioperative course with the strongest coagulopathic deviations from baseline after cardiopulmonary bypass. After adjustment for multiple confounders, viscoelastic clot strength instead of fibrinogen concentration showed a similar performance for 24 hour blood loss and a better performance for 6 hour blood loss. This makes intraoperative viscoelastic testing a useful tool to strengthen early clinical decision-making with the potential to reduce perioperative blood transfusions.

Blood loss after coronary artery bypass by aspirin responsiveness assessed with preoperative VerifyNow aspirin testing.

BACKGROUND: Aspirin is important for preventing thrombotic events but also increases bleeding complications. Minimizing bleeding while preventing thrombotic events remains challenging in patients undergoing coronary artery bypass grafting (CABG). Establishing the patient's preoperative aspirin response could distinguish patients at risk for perioperative blood loss. OBJECTIVE: Aim was to compare 12-h blood loss after CABG between aspirin-sensitive and aspirin-resistant patients. PATIENTS/METHODS: The primary analysis of this substudy of the POPular CABG trial (NCT02352402) included patients that used aspirin monotherapy preoperatively. A preoperative platelet function test by the VerifyNow aspirin assay was performed before CABG and patients were classified as aspirin-sensitive or aspirin-resistant based on an aspirin reaction units cutoff value of 550. The primary end point was 12-hour blood loss after CABG. The secondary end point was, among others, clinical bleeding events after CABG. RESULTS: A total of 128 patients were included in the primary analysis. Of these, 116 patients were aspirin sensitive and 12 were aspirin resistant. Mean blood loss 12 hours after CABG was 555 ± 278 mL in aspirin-sensitive patients and 406±110 mL in aspirin-resistant patients (P = .04). All bleeding events (n = 15; 11.7%) occurred in aspirin-sensitive patients. CONCLUSIONS: In patients who are on aspirin preoperatively, aspirin sensitivity was associated with 12-hour blood loss after CABG, suggesting that preoperative VerifyNow aspirin testing could identify patients undergoing CABG at high risk for perioperative bleeding.

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

Intra-operative red blood cell transfusion and mortality after cardiac surgery.

BACKGROUND: Anemia in cardiac surgery patients has been associated with poor outcomes. Transfusion of red blood cells during surgery is common practice for perioperative anemia, but may come with risks. Little is known about the association between intra-operative transfusion and mortality in patients undergoing cardiac surgery. METHODS: Single centre historical cohort study in 2933 adult patients undergoing coronary surgery with or without aortic valve replacement from June 2011 until September 2014. To estimate the odds ratio for mortality in patients receiving intra-operative transfusion, a propensity score based logistic regression analysis was performed. RESULTS: Intra-operative transfusion was associated with a more than three-fold increased risk of 30-day mortality. Patients in the highest quartile of probability of transfusion were older (age 75 vs 66; P <  0.001), had a higher EuroSCORE (6 vs 3; P <  0.001), had lower preoperative hemoglobin levels (7.6 vs 8.9 mmol/l; P < 0.001), had combined surgery more often (CABG + AVR in 33.4% of cases vs 6.6% (P < 0.001) and a longer duration of surgery (224 vs 188 min; P < 0.001). The association between intra-operative transfusion and mortality persisted after adjustment for these risk factors (adjusted OR 2.6; P = 0.007). CONCLUSIONS: Intra-operative transfusion of red blood cells was found to be associated with increased mortality in adults undergoing coronary surgery. Preoperative patient optimization may improve perioperative outcomes by reducing the likelihood of requiring transfusion and thus its associated risk.

Perioperative point of care platelet function testing and postoperative blood loss in high-risk cardiac surgery patients.

Postoperative coagulopathic bleeding is common in cardiac surgery and associated with increased morbidity and mortality. Platelet function is affected by multiple factors, including patient and procedural characteristics. Point-of-care (POC) multiple electrode aggregometry (MEA) can rapidly detect and quantify platelet dysfunction and could contribute to optimal patient blood management. In patients undergoing CABG and heart valve surgery platelet function was assessed using POC MEA at four different perioperative timepoints in response to stimulation with four specific receptor agonists (ADP, AA, COL, TRAP). Postoperative bleeding was recorded during 24 h after surgery. Regression analyses were performed to establish associations between perioperative platelet function and postoperative blood loss. Ninety-nine patients were included in the study. Fifty-nine patients (60%) were on antiplatelet therapy (APT) at time of surgery. ADP- and AA-induced platelet aggregation declined during CPB and after decannulation from CPB, with a maximum decrease of 55% for ADP (35 vs. 77 AU at baseline; P < 0.001) and 78% for ASPI (14 vs. 64 AU at baseline; P < 0.001). A linear relationship was present between ADP-induced platelet aggregometry at baseline and postoperative blood loss (r = -0.249; P = 0.015). In aspirin users, the maximum decline in platelet function between baseline and CPB decannulation was related to postoperative blood loss (r = 0.308; P = 0.037). In multivariate analysis, a reduced ADP platelet function prior to surgery remained associated with postoperative blood loss (r = -0.239; P = 0.012). Reduced ADP-induced platelet aggregation at baseline is associated with increased postoperative blood loss in high-risk cardiac surgery patients.

Acidosis induced by carbon dioxide insufflation decreases heparin potency: a risk factor for thrombus formation.

BACKGROUND: Since the introduction of CO2 insufflation during open heart surgery in our hospital, we incidentally observed thrombus formation in the dissected heart, in the pericardium and in the cardiotomy reservoir of the cardiopulmonary bypass system. Furthermore, we measured very high levels of pCO2, causing severe acidosis, in stagnant blood in the pericardium and cardiotomy reservoir. OBJECTIVES: In this in vitro study, we assessed the influence of acidosis and hypothermia on heparin potency and thrombin formation. METHODS: We assessed heparin potency in function of pH (pH 5.0-7.4) and temperature (24-37°C) by comparing the activated partial thromboplastin time in platelet-poor plasma between samples with and without unfractionated heparin. We measured thrombin formation in platelet-poor plasma by means of fluorescent, calibrated, automated thrombography in function of pH (pH 5.0-7.4) and temperature (24-37°C). The parameters of interest were the endogenous thrombin potential and the peak amount of thrombin generation. RESULTS: The major finding of this study is the significant decrease in the efficiency of unfractionated heparin in delaying thrombus formation at acidotic (pH 5.0-7.0) conditions (p=0.034-0.05). Furthermore, we found that thrombin formation is significantly increased at hypothermic (24-34°C) conditions (p=<0.001-0.01). CONCLUSIONS: Based on the results of our in-vitro study, we conclude that acidosis may lead to a decreased heparin potency. Acidosis, as induced by CO2 insufflation, may predispose patients to incidental thrombus formation in stagnant blood in the open thorax and in the cardiotomy reservoir. Hypothermia might further increase this risk. Therefore, we recommend reconsidering the potential advantages and disadvantages of using CO2 insufflation during cardiopulmonary bypass.

Anterior resection of rectal cancer without bowel preparation and diverting stoma.

PURPOSE: Since the introduction of total mesorectal excision (TME) as the standard operation technique for rectal cancer, anastomotic leakage percentages of up to 18% have been reported. To prevent such leakage, the use of mechanical bowel preparation and also the construction of a diverting ileostoma or colostomy have been standard procedures for years. In our institute, however, all patients undergoing colorectal surgery are operated upon without these measures. The present study was undertaken to investigate the results of this strategy in terms of the occurrence of postoperative anastomotic leakage. METHODS: All patients who underwent an elective (low) anterior resection between January 1996 and December 2001 (n = 144) entered the study. The clinical and pathological records of these patients were reviewed retrospectively. The exclusion criteria were patients with fixed rectal carcinoma who received preoperative radiotherapy and/or a stoma only at operation, emergency operations, abdominoperoneal resections, and Hartmann's procedures. RESULTS: Anastomotic leakage occurred in 7 out of 144 patients (4.9%). There was a trend toward a higher leakage frequency in men, in patients with a distal anastomosis, in patients with a stapled anastomosis, and in patients with a T3-T4 tumor or with positive lymph nodes. None of these factors, however, had a significant prognostic value based on a univariate or multivariate analysis. Those who died after leakage tended to be older than those who did not (P < 0.05). CONCLUSION: A (low) anterior resection can be performed safely without mechanical bowel preparation or a diverting stoma, and results in an anastomotic leakage percentage of less than 5%. Appropriate selection of patients may be important, but none of the investigated patient- or tumor-related factors could be identified as decisive.