Showing papers by "Niels Rahe-Meyer published in 2009"

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

Abstract: 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 concentrat

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

Abstract: Complex cardiac surgery is frequently accompanied by excessive perioperative bleeding because of coagulation system impairment, inadequate surgical haemostasis, or both.1 Bleeding increases the risk of re-exploration, allogeneic blood transfusion, or perioperative myocardial infarction, and consequently, associated morbidity and mortality.2 Aortic valve operation and ascending aorta replacement (AV–AA) typically involves hypothermia, prolonged cardiopulmonary bypass (CPB), and large graft anastomoses, and is associated with an increased risk of intra- and postoperative blood loss and high transfusion rates.3,4 Conventional haemostatic therapy consists of transfusion of allogeneic blood products that include fresh-frozen plasma (FFP), platelet concentrate, and cryoprecipitate. However, although the use of these products was developed empirically, their haemostatic efficacy has not been evaluated thoroughly in the surgical setting.5,6 Haemocomplettan® P (brand name in Europe)/Riastap (brand name in USA) (CSL Behring, Marburg, Germany) is a highly purified, lyophilized, virus-inactivated fibrinogen concentrate obtained from human plasma that can be rapidly reconstituted without the need for thawing and cross-matching, which are necessary for FFP and cryoprecipitate. The administration of fibrinogen concentrate was originally reserved for replacement therapy in congenital fibrinogen deficiency, and in the USA, Riastap is only approved for this indication. In the meantime, European reports on haemostatic therapy with Haemocomplettan® P in acquired perioperative deficiency of fibrinogen have been published.7–11 Acquired fibrinogen deficiency occurring during and after CPB is associated with increased bleeding after cardiac surgery.12,13 However, the haemostatic efficacy of fibrinogen concentrate in correcting such deficiency in complex cardiac surgery has not been investigated to date. To reduce blood component transfusion in cardiac surgery, point-of-care methods such as thrombelastography/thromboelastometry have been applied in algorithms supporting bleeding management in relation to blood clotting quality.14–16 Thromboelastometry (ROTEM®; Pentapharm GmbH, Munich, Germany) assesses the viscoelasticity of whole blood. One of the ROTEM® tests, the FIBTEM test, provides prompt information on the clot strength specifically attributed to fibrin/fibrinogen using cytochalasin-D-induced inactivation of platelets in vitro.17 This test may be used to guide the administration of fibrinogen concentrate for prompt haemostatic therapy.9–11 We hypothesized that postoperative haemostasis could be improved by increasing plasma fibrinogen concentrations, since bleeding complications were observed to be lower in patients with high perioperative fibrinogen concentrations.12,13 The primary aim of this pilot study was to evaluate whether FIBTEM-guided intraoperative fibrinogen repletion was able to reduce the use of allogeneic blood products and postoperative bleeding in patients undergoing AV–AA.

Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model

Abstract: Background Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted whole blood above which the rate of clot formation approaches normal. Methods Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50–300 mg dl −1 and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls. Results Coagulation parameters and platelets were reduced by 74–85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl −1 . Adding tissue plasminogen activator, 0.15 μg ml −1 , led to a decrease of clot firmness and lysis time. Conclusions The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl −1 as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.

Platelet concentrates transfusion in cardiac surgery and platelet function assessment by multiple electrode aggregometry.

Abstract: Background: Platelet dysfunction contributes to the pathophysiology of bleeding complications during and after cardiac surgery. In most surgical institutions, no peri-operative point-of-care monitoring of platelet function is used. We evaluated the usefulness of the Multiplate® platelet function analyser based on impedance aggregometry for identifying groups of patients at a high risk of transfusion of platelet concentrates (PC). Methods: Platelet function parameters were determined in 60 patients before and after routine cardiac surgery. Impedance aggregometry measurements were performed on Multiplate® using ADP (ADPtest), collagen (COLtest) and thrombin receptor activating peptide (TRAPtest) as platelet activators. The correlations between the aggregometry results and the transfusion of PC were calculated. The results of the aggregation tests were also divided into tertiles and the differences in PC transfusion between the low and the high tertile were assessed. Results: Low aggregometry delimited groups of patients with significantly higher PC transfusion. In the receiver operating characteristic curve, low pre-operative aggregation in the ADPtest identified patients with high total transfusion of PC (area under the curve 0.74, P=0.001), while the ADPtest performed at the end of the operation identified patients with high PC transfusion on the intensive care unit (ICU) (area under the curve 0.76, P=0.002). Conclusions: Near-patient platelet aggregation may allow the identification of patients with enhanced risk of PC transfusion, both pre-operatively and upon arrival on the ICU.

Multicentric comparison of single portion reagents and liquid reagents for thromboelastometry.

Abstract: Thromboelastometry ROTEM (Pentapharm, Munich, Germany) is a viscoelastic method of whole blood clotting assessment with applications in perioperative hemostasis and hematology. The different tests available for the investigation of distinct coagulation aspects are performed with combinations of liquid reagents. The use of liquid reagents for the ROTEM measurement requires several pipetting steps, which complicates their application in clinical routine even though pipetting is performed semiautomatically. New single portion reagents (SPR) containing in one vial all lyophilized reagents necessary for each test have been recently developed. SPR require only addition of blood into the single-use reagent vial in a unique pipetting step in order to mix reagents with the blood sample. Our study compared SPR and standard liquid reagents (Pentapharm) in 21 blood samples from normal subjects and 46 samples from patients in three study centers. Following ROTEM tests were performed: EXTEM (extrinsically activated TEM), INTEM (intrinsically activated TEM), FIBTEM (fibrin-based TEM), APTEM (aprotinin-controlled TEM) and HEPTEM (heparin-insensitive TEM). In the second part of the study, the stability of SPR at 37 degrees C was also assessed on 23 blood samples in one center. Very good correlation was found between SPR and liquid reagents for all clotting parameters (correlation coefficient between 0.85-0.99). The SPR reagents showed excellent stability against thermic stress and the measurements were easier to perform than with the conventional liquid reagents system.

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

Abstract: 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� 10 3 ml 21 when removing the aortic clamp, and vice versa if platelet count was .100� 10 3 ml 21 . 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 w 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. Br J Anaesth 2009; 102: 785–92

Bicarbonate-buffered ultrafiltration during pediatric cardiac surgery prevents electrolyte and acid-base balance disturbances.

Abstract: Pediatric cardiopulmonary bypass is still a challenge because of electrolyte disturbances and inflammation. Many investigations deal with different types of hemofiltration to reduce these potentially harmful side effects. We tested the hypothesis of whether bicarbonate-buffered hemofiltration of the priming solution minimizes electrolyte and acid-base disturbances during the initiation of cardiopulmonary bypass and whether bicarbonatebuffered hemofiltration performed during cardiopulmonary bypass could reduce cytokine levels. Twenty children younger than 2 years of age (mean age 166 ± 191 days; mean weight 6.42 ± 3.22 kg) scheduled for pediatric cardiac surgery with cardiopulmonary bypass were enrolled in this prospective clinical study. Cardiopulmonary bypass circuits were primed with a bicarbonatebuffered hemofiltration solution, gelatin and 1 unit of packed red blood cells. The priming was hemofiltered using an ultrahemofilter until approximately 1000 mL of ultrafiltrate was restored with the buffered solution. Further hemofiltration was performed throughout the whole bypass time, especially during rewarming. Blood gas analyses and inflammatory mediators were monitored during the operation. Blood gas analysis results after initiation of cardiopulmonary bypass and throughout the entire study remained within the physiologic ranges. Even potassium decreased from 4.0 ± 0.3 to 3.4 ± 0.4 mmol.l �1 after initiation of cardiopulmonary bypass. Plasma levels of tumor necrosis factor alpha decreased significantly (47 ± 44 vs. 24 ± 21 pg.mL �1 ) whereas complement factor C3a (5.0 ± 2.9 vs. 16.8 ± 6.6 ng.mL �1 ) and interleukin-6 (7.3 ± 15.2 vs. 110 ± 173 pg.mL �1 ) increased despite hemofiltration. In conclusion, this study shows that bicarbonate-buffered ultrafiltration is an efficient, simple and safe method for performing hemofiltration, both of the priming solution and during the entire bypass time. The use of a physiological restitution solution prevents electrolyte and acid-base balance disturbances. The elimination of inflammatory mediators seems to be as effective as other ultrafiltration methods. Perfusion (2009) 24, 19–25.

Comparison of breathing tube connectors during invasive bronchial procedures.

Abstract: Summary Bronchoscopy and bronchial suctioning during intra-operative artificial ventilation often causes leakage from the ventilation circuit with a decrease in ventilatory parameters and possible workplace contamination with anaesthetic gases. Different connectors have been developed to reduce gas leakage. We evaluated the following connectors : VBM 2 mm, 3 mm and 5 mm, Bodai Suction-Safe, Bodai Bronch-Safe and Bodai Trach-Safe, as well as the BE 105-7, BE 105-8 and SH 7-45. Invasive bronchial instruments (catheters, bronchoscopes and bronchial blockers) with 1.67–7.33 mm diameter were used. Pressure-controlled ventilation was performed on a test lung using a ventilator. Sevoflurane concentration in the room was measured 0.2 and 1.5 m from the connector using a photo-acoustic infrared-spectroscope. The VBM connectors caused the least gas leak and ensured stability of ventilation parameters even at peak pressures when combined with smaller instruments. With instruments > 6 mm, BE 105-7, BE 105-8 and SH 7-45 connectors performed best. The Bodai connectors showed a reduced ability to prevent leakage and to keep ventilatory parameters stable. All connectors, excluding the Bodai Trach-Safe, prevented exposure to anaesthetic gases beyond the current safety recommendations when combined with the fitting instruments. The connectors showed different ranges of tightness, equivalent to different ranges of compatibility with the instruments used.