Niels Rahe-Meyer

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patients tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia.

BACKGROUND: The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational thromboelastometry (ROTEM®). In this study, we investigated the effect of fibrinogen concentration and its relative contribution to overall clot strength using ROTEM. METHODS: Blood samples were collected from healthy volunteers. The effects of platelet count on clot strength, determined by maximum clot elasticity (MCE), were evaluated on ROTEM using platelet-rich plasma (PRP) adjusted with autologous plasma to generate a range of platelet counts. PRPs were adjusted to 10 × 103 mm−3, 50 × 103 mm−3, and 100 × 103 mm−3 and spiked with fibrinogen concentrates at 550 and 780 mg/dL. The effect of fibrin polymerization on clot strength, independent of platelet attachment, was analyzed by the cytochalasin D-modified thromboelastometry (FIBTEM®) method. Additional retrospective analysis of clot strength (MCE) in two groups of thrombocytopenic patients was conducted. RESULTS: Clot strength (MCE) decreased at a platelet count below 100 × 103 mm−3, whereas increases in MCE peaked and reached a plateau at platelet counts from 400 × 103 mm−3. Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 × 103 mm−3). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopenic patients. CONCLUSIONS: These in vitro and clinical data indicate that the clot strength increases in a fibrinogen concentration-dependent manner independent of platelet count, when analyzed by ROTEM. The maintenance of fibrinogen concentration is critical in the presence of thrombocytopenia. EXTEM® (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.

Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study

Background Bleeding diathesis after aortic valve operation and ascending aorta replacement (AV–AA) is managed with fresh-frozen plasma (FFP) and platelet concentrates. The aim was to compare haemostatic effects of conventional transfusion management and FIBTEM (thromboelastometry test)-guided fibrinogen concentrate administration. Methods A blood products transfusion algorithm was developed using retrospective data from 42 elective patients (Group A). Two units of platelet concentrate were transfused after cardiopulmonary bypass, followed by 4 u of FFP if bleeding persisted, if platelet count was ≤100×103 µl−1 when removing the aortic clamp, and vice versa if platelet count was >100×103 µl−1. The trigger for each therapy step was ≥60 g blood absorbed from the mediastinal wound area by dry swabs in 5 min. Assignment to two prospective groups was neither randomized nor blinded; Group B (n=5) was treated according to the algorithm, Group C (n=10) received fibrinogen concentrate (Haemocomplettan® P/Riastap, CSL Behring, Marburg, Germany) before the algorithm-based therapy. Results A mean of 5.7 (0.7) g fibrinogen concentrate decreased blood loss to below the transfusion trigger level in all Group C patients. Group C had reduced transfusion [mean 0.7 (range 0–4) u vs 8.5 (5.3) in Group A and 8.2 (2.3) in Group B] and reduced postoperative bleeding [366 (199) ml vs 793 (560) in Group A and 716 (219) in Group B]. Conclusions In this pilot study, FIBTEM-guided fibrinogen concentrate administration was associated with reduced transfusion requirements and 24 h postoperative bleeding in patients undergoing AV–AA.

Thromboelastometry-guided administration of fibrinogen concentrate for the treatment of excessive intraoperative bleeding in thoracoabdominal aortic aneurysm surgery

OBJECTIVE Thoracoabdominal aortic aneurysm operations are associated with extensive blood loss and high requirements for allogeneic blood product transfusion. We assessed the efficacy of intraoperative post-cardiopulmonary bypass administration of fibrinogen concentrate in elective thoracoabdominal aortic aneurysm surgery. METHODS In a retrospective group (group A, n = 12) of patients undergoing elective thoracoabdominal aortic aneurysm surgery, clinically relevant diffuse bleeding after weaning from cardiopulmonary bypass was treated with allogeneic blood products (platelet concentrates, followed by fresh frozen plasma) according to a predetermined algorithm. In a prospective group (group F, n = 6) a first therapy step with fibrinogen concentrate was added to the algorithm. The dose of fibrinogen concentrate was estimated by using thromboelastometric data (ROTEM FIBTEM). Before each step of hemostatic therapy, blood loss in the range of 60 to 250 g per 5 minutes was confirmed. RESULTS In group F, administration of 7.8 +/- 2.7 g of fibrinogen concentrate established hemostasis, completely avoiding intraoperative transfusion of fresh frozen plasma and platelet concentrates. Transfusion of blood products after cardiopulmonary bypass and during the 24 hours after surgical intervention was markedly lower in group F than in group A (2.5 vs 16.4 units; 4/6 patients in group F required no transfusion of blood products), as was 24-hour drainage volume (449 vs 1092 mL). Fibrinogen plasma levels, standard coagulation parameters, and hemoglobin and hematocrit values were comparable between the 2 groups on the first postoperative day. CONCLUSIONS FIBTEM-guided post-cardiopulmonary bypass administration of fibrinogen concentrate resulted in improved intraoperative management of coagulopathic bleeding in thoracoabdominal aortic aneurysm operations and reduced transfusion and 24-hour drainage volume.

Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial.

Background:Fibrinogen is suggested to play an important role in managing major bleeding. However, clinical evidence regarding the effect of fibrinogen concentrate (derived from human plasma) on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative, targeted, first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery. Methods:In this single-center, prospective, placebo-controlled, double-blind study, patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo, administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued, a standardized transfusion protocol was followed. Results:Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication, patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group (median, 2 vs. 13 U; P < 0.001; primary endpoint). Total avoidance of transfusion was achieved in 13 (45%) of 29 patients in the fibrinogen concentrate group, whereas 32 (100%) of 32 patients in the placebo group received transfusion (P < 0.001). There was no observed safety concern with using fibrinogen concentrate during aortic surgery. Conclusions:Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products. Larger multicenter studies are necessary to confirm the role of fibrinogen concentrate in the management of perioperative bleeding in patients with life-threatening coagulopathy.

Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery

Background Normalization of plasma fibrinogen levels may be associated with satisfactory haemostasis and reduced bleeding. The aim of this retrospective study was to assess fibrinogen recovery parameters after administration of fibrinogen concentrate (Haemocomplettan® P) to patients with diffuse bleeding in cardiovascular surgery. Data on transfusion and patient outcomes were also collected. Methods Patient characteristic and clinical data were obtained from patient records. Results of the thromboelastometry (FIBTEM®) and of the standard coagulation tests, including plasma fibrinogen level, measured before surgery, before and after haemostatic therapy, and on the following day, were retrieved from laboratory records. Results Thirty-nine patients receiving fibrinogen concentrate for diffuse bleeding requiring haemostatic therapy after cardiopulmonary bypass were identified. The mean fibrinogen concentrate dose administered was 6.5 g. The mean fibrinogen level increased from 1.9 to 3.6 g litre−1 (mean increment of 0.28 g litre−1 per gram of concentrate administered); maximum clot firmness increased from 10 to 21 mm. The mean fibrinogen increase was 2.29 (sd 0.7) mg dl−1 per mg kg−1 bodyweight of concentrate administered. Thirty-five patients received no transfusion of fresh-frozen plasma (FFP) or platelet concentrate after receiving fibrinogen concentrate; the remaining four patients received platelet concentrate intraoperatively. Eleven patients received platelets, FFP, or both during the first postoperative day. No venous thromboses, arterial ischaemic events, or deaths were registered during hospitalization. Conclusions In this retrospective study, fibrinogen concentrate was effective in increasing plasma fibrinogen level, and contributed to the correction of bleeding after cardiovascular surgery.

Platelet function following trauma. A multiple electrode aggregometry study.

Platelets play a central role in coagulation. Currently, information on platelet function following trauma is limited. We performed a retrospective analysis of patients admitted to the emergency room (ER) at the AUVA Trauma Centre, Salzburg, after sustaining traumatic injury. Immediately after admission to the ER, blood was drawn for blood cell counts, standard coagulation tests, and platelet function testing. Platelet function was assessed by multiplate electrode aggregometry (MEA) using adenosine diphosphate (ADPtest), collagen (COLtest) and thrombin receptor activating peptide-6 (TRAPtest) as activators. The thromboelastometric platelet component, measuring the contribution of platelets to the elasticity of the whole-blood clot, was assessed using the ROTEM device. The study included 163 patients, 79.7% were male, and the median age was 43 years. The median injury severity score was 18. Twenty patients (12.3%) died. Median platelet count was significantly lower among non-survivors than survivors (181,000/μl vs. 212,000/μl; p=0.01). Although platelet function defects were relatively minor, significant differences between survivors and non-survivors were observed in the ADPtest (94 vs. 79 U; p=0.0019), TRAPtest (136 vs. 115 U; p<0.0001), and platelet component (134 vs.103 MCEEXTEM - MCEFIBTEM; p=0.0012). Aggregometry values below the normal range for ADPtest and TRAPtest were significantly more frequent in non-survivors than in survivors (p=0.0017 and p=0.0002, respectively). Minor decreases in platelet function upon admission to the ER were a sign of coagulopathy accompanying increased mortality in patients with trauma. Further studies are warranted to confirm these results and investigate the role of platelet function in trauma haemostatic management.

Perioperative Coagulation Management and Control of Platelet Transfusion by Point-of-Care Platelet Function Analysis

About one third of all blood components transfused intraoperatively is used in cardiac surgery, whereas mortality of cardiosurgical patients correlates nearly linear with the number of transfused units of packed red blood cells. Acquired platelet function disorders play a major role in perioperative bleeding in cardiac surgery. Therefore, the use of point-of-care-suitable platelet function analyzers seems to be reasonable in this field. Methods: Platelet function analyzer PFA-100®, rotational thrombelastometry (ROTEM®), and multiple platelet function analyzer (Multiplate®) are in principle applicable for point-of-care testing. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. Results: Perioperative use of platelet function analyzers is helpful in prediction of blood loss in cardiac surgery. Perioperative usage of blood components and their respective costs can be reduced by an appropriate coagulation management. Conclusion: Algorithms for perioperative coagulation management based on point-of-care testing permit a fast diagnostic and goal-directed therapy of coagulation and functional platelet disorders. The possibility to reduce the mortality of patients and the overall cost for hospital stay is subject of further studies.

Comparison of inhaled iloprost and nitric oxide in patients with pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective randomized trial.

OBJECTIVE The objective of this study was to compare the efficacy of inhaled iloprost and nitric oxide (iNO) in reducing pulmonary hypertension (PHT) during cardiac surgery immediately after weaning from cardiopulmonary bypass (CPB). DESIGN A prospective randomized study. SETTING A single-center university hospital. PARTICIPANTS Forty-six patients with PHT (mean pulmonary artery pressure (mPAP) > or = 26 mmHg preoperatively at rest, after anesthesia induction, and at the end of CPB) scheduled to undergo cardiac surgery were enrolled. INTERVENTIONS Patients were randomly allocated to receive iloprost (group A, n = 23) or iNO (group B, n = 23) during weaning from CPB. MEASUREMENTS AND MAIN RESULTS Heart rate, mean arterial pressure, central venous pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, and left atrial pressure were recorded continuously. Iloprost and iNO were administered immediately after the end of CPB before heparin reversal. Both substances caused significant reductions in mean PAP (mPAP) and pulmonary vascular resistance (PVR) and significant increases in cardiac output 30 minutes after administration (p < 0.0001). However, in a direct comparison, iloprost caused significantly greater reductions in PVR (p = 0.013) and mPAP (p = 0.0006) and a significantly greater increase in cardiac output (p = 0.002) compared with iNO. CONCLUSIONS PHT after weaning from CPB was significantly reduced by the selective pulmonary vasodilators iNO and iloprost. However, in a direct comparison of the 2 substances, iloprost was found to be significantly more effective.

A comparison of fibrinogen measurement methods with fibrin clot elasticity assessed by thromboelastometry, before and after administration of fibrinogen concentrate in cardiac surgery patients

BACKGROUND: Fibrinogen concentrate administration can be guided by measuring fibrinogen concentration or quality of the fibrin‐based clot. This study compared different fibrinogen concentration measurement methods with maximum clot firmness (MCF) of the fibrin clot, assessed by thromboelastometry (FIBTEM), in 33 cardiovascular surgery patients receiving fibrinogen concentrate for hemostatic therapy.