Anton Klingler

Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration.

BACKGROUND:To explore whether disturbed fibrin polymerization is the main problem underlying dilutional coagulopathy and can be reversed by fibrinogen administration, we conducted a prospective study using modified thrombelastography (ROTEM®). METHODS:Sixty-six orthopedic patients randomly received modified gelatin solution, hydroxyethyl starch 130/0.4, or exclusively Ringer lactate solution. ROTEM® analysis was performed, concentrations of coagulation factors and markers of thrombin generation were measured. Fibrinogen concentrate (Hemocomplettan®) was administered (30 mg/kg) when thrombelastographically measured fibrinogen polymerization was critically decreased. RESULTS:The α angle, clot firmness, and fibrinogen polymerization (median [min to max]) significantly decreased in the patients receiving hydroxyethyl starch (area under the curve minus baseline (−5 [−9 to −2]), followed by gelatin solution (−3 [−8 to 0]), with the least reductions seen for Ringer lactate solution (−2 [− 4 to 1]) (colloids versus Ringer lactate P < 0.0001). Thirteen patients in the colloid groups but none in the Ringer lactate group needed fibrinogen concentrate to maintain borderline clot firmness. Activity of FVII, FVIII, FIX, and von Willebrand ristocetin activity decreased significantly with colloids. Thrombelastographically measured coagulation time, molecular markers of thrombin generation, and activity of all other coagulation factors were comparable in all groups. CONCLUSION:Disturbance of fibrinogen/fibrin polymerization is the primary problem triggering dilutional coagulopathy during major orthopedic surgery. The magnitude of clot firmness reduction is determined by the type of fluid used, with hydroxyethyl starch showing the most pronounced effects. These undesirable effects of intravascular volume therapy can be reversed by increasing fibrinogen concentration by administering fibrinogen concentrate, even during continuing blood loss and intravascular volume replacement.

Risk for postoperative infection after transfusion of white blood cell-filtered allogeneic or autologous blood components in orthopedic patients undergoing primary arthroplasty.

BACKGROUND:  This study was designed to obtain data on the incidence of postoperative infection in patients undergoing elective orthopedic surgery and receiving white blood cell (WBC)‐filtered blood components prepared according to current standards.

The Effect of Fibrinogen Substitution on Reversal of Dilutional Coagulopathy: An In Vitro Model

Colloids and crystalloids are usually administered as treatment for hypovolemia in severely injured patients. However, dilution of clotting factors and platelets together with impaired fibrinogen polymerization are associated with fluid therapy and may aggravate hemorrhage, thus worsening final outcome of these patients. We investigated, in an in vitro model, whether the addition of fibrinogen to diluted blood samples can reverse dilutional coagulopathy. Blood from 5 healthy male volunteers was diluted by 60% using lactated Ringers solution, 4% modified gelatin solution, or 6% hydroxyethyl starch 130/0.4, as well as the combination of lactated Ringers solution with either of the 2 colloid solutions. Thereafter, aliquots of diluted blood samples were incubated with 3 different concentrations of fibrinogen (0.75, 1.5, and 3.0 mg/mL). Measurements were performed by modified thrombelastography (ROTEM®; Pentapharm, Munich, Germany). After 60% dilution, clotting times increased, whereas clot firmness and fibrin polymerization decreased significantly. After administration of fibrinogen, clotting times decreased and clot firmness, as well as fibrin polymerization, increased in all diluted blood samples. The effect of in vitro fibrinogen substitution on ROTEM® variables was dependent on the fibrinogen dosage and the type of solution used to dilute the blood samples.

The effect of the combined administration of colloids and lactated Ringer's solution on the coagulation system: an in vitro study using thrombelastograph coagulation analysis (ROTEG.

Gelatin solutions are often given in clinical practice once the maximal dose of a median-weight hydroxyethyl starch (HES) has been reached. Colloids are usually combined with lactated Ringer’s solution (RL). Whether the combined administration of colloids and/or crystalloids affects blood coagulation is not known. We diluted blood by 20%, 40%, and 60% with RL, gelatin (Gelofusin®), 6% HES 130/0.4 (Voluven®), and 6% HES 200/0.5 (Iso-Hes®), as well as with combinations of these solutions at a ratio of 1:1 (gelatin/RL, 6% HES 130/0.4:RL, 6% HES 200/0.5:RL, 6% HES 130/0.4:gelatin, 6% HES 200/0.5:gelatin). Thereafter, blood was analyzed by using modified thrombelastograph® coagulation analysis (ROTEG®) and clotting time, clot formation time, and maximal clot firmness were determined. RL had the least effect on hemostasis. Gelatin administered alone impaired the coagulation system significantly less than each median-weight HES administered alone. We conclude that gelatin combined with 6% HES 200/0.5 or 6% HES 130/0.4 decreases hemostasis <6% HES 200/0.5 or 6% HES 130/0.4 administered alone.

Risk factors for anastomotic leakage after resection for rectal cancer

BACKGROUND Controversy still exists concerning the impact of patient and tumor characteristics on anastomotic dehiscence after resection for rectal cancer. METHODS Between January 1986 and July 2006, 472 patients underwent curative rectal resection. Patient and tumor characteristics, details of treatment, and postoperative results were recorded prospectively. Univariate and multivariate analysis were applied to identify risk factors for anastomotic leakage. RESULTS In our patients, the anastomotic leak rate was 10.4% (49 of 472 patients), and mortality was 2.2% (1 of 49 patients). In univariate analysis, tumor diameter and absence of a protective stoma were associated with increased anastomotic leak rate, whereas American Society of Anesthesiologists (ASA) score and tumor localization showed borderline significance. In multivariate analysis, tumor diameter, tumor localization, and absence of a protective stoma were significantly associated with anastomotic leakage. CONCLUSIONS Patients with large and low lying rectal tumors are at high risk for anastomotic leakage. A protective stoma significantly decreases the rate of clinical leaks and subsequent reoperation after low anterior resection.

Point-of-care whole blood impedance aggregometry versus classical light transmission aggregometry for detecting aspirin and clopidogrel: the results of a pilot study.

BACKGROUND:We determined whether whole blood impedance aggregometry using the Multiplate® detects the effects of antiplatelet drugs as reliably as does classical light transmission aggregometry (LTA) or the platelet function analyzer PFA-100®. METHODS:Multiplate (M) assays, measuring changes in electrical resistance as aggregation units over time (AU*min), and LTA assays induced by collagen (COL), adenosine diphosphate (ADP) or arachidonic acid (AA) and PFA-100 testing, using epinephrine (PFA100-EPI) or ADP (PFA100-ADP) cartridges, were performed simultaneously using arterial blood samples obtained before induction of anesthesia in 70 consecutive patients scheduled for elective coronary artery bypass grafting. Patients in group A (n = 48) served as controls, patients in group B (n = 11) received aspirin 100 mg/d and those in group C (n = 11) aspirin 100 mg/d and clopidogrel 75 mg/d until the day before surgery. RESULTS:In controls the median (1st, 3rd quartiles) change in impedance AU*min for M-COL (374 [231–469]) was significantly greater than in patients receiving aspirin (164 [86–211], P = 0.0009) or receiving aspirin and clopidogrel (118 [101–244], P = 0.004). M-ADP values in controls were 258 (158–389), in patients receiving aspirin 261 (159–393), and in patients receiving aspirin and clopidogrel 88 (48–231, P = 0.054). M-AA values were significantly lower in patients receiving aspirin alone (45 [28–60], P = 0.0004) or aspirin and clopidogrel (44 [26–221], P = 0.008) than in controls (200 [86–345]). The areas under the receiver operating characteristic curves indicating the ability to discriminate patients taking aspirin from those not taking aspirin were comparable for COL and AA assays using whole blood impedance aggregometry or classical LTA (M-COL 0.84 [P = 0.001], LTA-COL 0.85 [P = < .001], M-AA 0.84 [P = < .001] and LTA-AA 0.87 [P = < .001]), but only 0.74 for PFA-100-EPI (P = 0.03). Similarly, for discrimination of patients not taking antiplatelet drugs from patients taking clopidogrel and aspirin the areas under the receiver operating characteristic curve were also comparable for both aggregometry methods M-COL 0.77 (P = 0.006), LTA-COL 0.78 (P = 0.004), M-ADP 0.74 (P = 0.015), LTA-ADP 0.73 (P = 0.018). CONCLUSION:Results achieved with the bedside Multiplate assays were not different than those obtained with classical aggregometry for detecting the effects of aspirin and clopidogrel in preoperative patients scheduled for elective cardiac surgery.

Blunted erythropoietic response to anemia in multiply traumatized patients.

ObjectivesTo assess the relations between anemia, serum erythropoietin (EPO), iron status, and inflammatory mediators in multiply traumatized patients. DesignProspective observational study. SettingIntensive care unit. PatientsTwenty-three patients suffering from severe trauma (injury severity score ≥30). InterventionsNone. Measurements and Main Results Blood samples were collected within 12 hrs after the accident (day 1) and in the morning on days 2, 4, 6, and 9 to determine blood cell status, serum EPO, tumor necrosis factor-&agr; (TNF-&agr;), soluble tumor necrosis factor-receptor I (sTNF-rI), interleukin-1 receptor antagonist (IL1-ra), interleukin-6 (IL-6), neopterin, and iron status, respectively. Hemoglobin concentration was low at admission (mean, 10.0 g/dL; range, 6.8–12.9 g/dL) and did not increase during the observation time. Serum EPO concentration was 49.8 U/L (mean value) on day 1 and did not show significant increases thereafter. No correlation was found between EPO and hemoglobin concentrations. TNF-&agr; remained within the normal range. sTNF-rI was high at admission and increased further. IL1-ra was above the normal range. IL-6 was very high at admission and did not decrease thereafter. The initial neopterin concentration was normal, but increased until day 9. Serum iron was significantly decreased on day 2 posttrauma and remained low during the study. Serum ferritin increased steadily from day 2, reaching its maximum on day 9. In contrast, concentrations of transferrin were low from admission onward. ConclusionsMultiply traumatized patients exhibit an inadequate EPO response to low hemoglobin concentrations. Thus, anemia in severe trauma is the result of a complex network of bleeding, blunted EPO response to low hemoglobin concentrations, inflammatory mediators, and a hypoferremic state.

The in vitro effects of fibrinogen concentrate, factor XIII and fresh frozen plasma on impaired clot formation after 60% dilution.

BACKGROUND:Previous investigations have shown that increasing fibrinogen concentration improves dilution-dependent impairment of clot formation. We conducted an in vitro study to explore whether substitution with fibrin-stabilizing factor XIII (FXIII) combined with fibrinogen promotes further improvement of clot formation, and whether fibrinogen administration as concentrate or fresh frozen plasma (FFP) results in comparable effects. METHODS:Blood from six healthy donors was diluted by 60% using lactated Ringer’s solution. Aliquots of diluted blood samples were incubated with two different doses of fibrinogen concentrate, FXIII concentrate, the combination of both, or with two different doses of FFP. Using thrombelastometry (ROTEM®) blood samples were analyzed at baseline (undiluted), after dilution and after supplementation. Variables were analyzed for changes from baseline, and effects of fibrinogen concentrate alone or combined with FXIII were compared with effects observed with corresponding FFP doses. RESULTS:After 60% in vitro dilution of blood all ROTEM parameters and global coagulation tests changed significantly. Among the substitutes tested FXIII alone had no effect, the combination with fibrinogen improved coagulation time, &agr; angle and fibrinogen/fibrin polymerization significantly more than did small-dose fibrinogen alone. After substituting fibrinogen, median values of all ROTEM variables were within the normal range, thereby showing dose dependency but also significant differences (P = 0.027) from corresponding FFP doses (EXTEM MCF FFP small dose [38 (35, 40.3) mm)], which enabled only coagulation time to be shortened to baseline levels. CONCLUSIONS:Supplementation of fibrinogen restored all ROTEM parameters after dilution. This effect was partially enhanced by adding FXIII and was significantly stronger than for FFP substitution.

Antifactor Xa activity in intensive care patients receiving thromboembolic prophylaxis with standard doses of enoxaparin

BACKGROUND Low-molecular-weight heparins (LMWHs) have become increasingly used to prevent thromboembolic complications in intensive care patients. Unlike in medical and surgical patients, no data on the anticoagulant effectiveness of standard LMWH dosages exist in intensive care patients. Therefore, we prospectively investigated antifactor Xa (aFXa) levels after subcutaneous administration of 40 mg of enoxaparin in 89 intensive care patients over a 24-h period. METHODS AFXa levels were measured before, 4, 12 and 24 h after subcutaneous administration of enoxaparin. Laboratory parameters including prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen as well as platelet count were collected at same intervals. Demographics included age, sex, height, weight, body mass index, admission diagnosis, a thromboembolic risk score and a modified Goris multiple organ dysfunction score. RESULTS At 4, 12 and 24 h, 56.5%, 39.3% and 12.6% of the study patients were within recommended antithrombotic aFXa levels (0.1-0.3 U ml(-1)). Presence of multiple organ dysfunction as well as high body weight were significantly correlated with low aFXa levels. CONCLUSION European standard dosages of 40 mg of enoxaparin once daily proved to be ineffective in achieving recommended antithrombotic aFXa levels in intensive care patients. This was most pronounced in patients with high body weight and presence of multiple organ dysfunction.

Respiratory symptoms in patients with gastroesophageal reflux disease following medical therapy and following antireflux surgery.

BACKGROUND It is not known whether antireflux surgery is more effective than medical therapy to control respiratory symptoms (RS) in gastroesophageal reflux disease (GERD). METHODS In 21 GERD patients with RS, reflux was assessed by endoscopy, manometry, and pH monitoring. Patients had proton pump inhibitor therapy and cisapride for 6 months. After GERD relapsed following withdrawal of medical therapy, 7 patients with normal esophageal peristalsis had a laparoscopic Nissen fundoplication and 14 with impaired peristalsis a Toupet fundoplication. Respiratory symptoms were scored prior to treatment, at 6 months following medical therapy, and at 6 months after surgery. RESULTS Heartburn and esophagitis were effectively treated by medical and surgical therapy. Only surgery improved regurgitation. Respiratory symptoms improved in 18 patients (85.7%) following surgery and in only 3 patients (14.3%) following medical therapy (P <0.05). Esophageal peristalsis improved following the Toupet fundoplication. CONCLUSION Medical therapy fails to control reflux since it does not inhibit regurgitation. Surgery controls reflux and improves esophageal peristalsis, which contributes to its superiority over medical therapy in the treatment of RS associated with GERD.