Cardiovascular surgery without cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II using anticoagulation with recombinant hirudin.
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Biomedical subjects
Publications and source records attributed to F Mertzlufft.
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IMPLICATIONS: Fechtner's syndrome is a rare form of macrothrombocytopenia (potentially associated with other hemostatic deficiencies, e.g., von Willebrand's disease and protein Z deficiency), which can exacerbate the risk of uncontrollable bleeding during surgery. We describe the management of a patient with Fechtner's syndrome involving desmopressin, prednisone, and platelets, which produced safe and effective results during cochlear implant surgery.
UNLABELLED: Recombinant hirudin (r-hirudin) is being used increasingly in patients with heparin-induced thrombocytopenia type II. Renal failure has been demonstrated to prolong the half-life of r-hirudin and to cause bleeding in patients who have undergone cardiopulmonary bypass (CPB). We assessed the ability of different filter systems for modified ultrafiltration to eliminate r-hirudin in vitro using simulated CPB. r-Hirudin concentration was measured (chromogenic laboratory standard plus ecarin clotting time) before and after filtration, and its elimination was calculated using both controlled system flow and arterial inflow (separate pump). Four hemofilters (Renoflow II, Baxter; Arylane H4, Cobe; Ultraflux AV 600, Fresenius; and BCS 110 Plus, Iostra) and two plasmapheresis filter systems (ASAHI Plasmaflow OP, Diamed; and PF 2000 N, Gambro) were assessed (5 filters of each brand = 30 filters) in a closed in vitro CPB system applying conditions usually occurring during CPB. Ten plasmapheresis filters showed a greater ability than 20 hemofilters to eliminate r-hirudin (60%-70% vs 15%-42%) within the shortest time (80 vs 180 s). Among the four hemofilter systems, the Arylane H4 filter provided the most effective (42%) r-hirudin elimination. Elimination of r-hirudin was markedly improved using plasmapheresis systems, compared with hemofilter systems. Our findings may be relevant to patients with impaired renal function, who have been administered r-hirudin during CPB. IMPLICATIONS: Modified ultrafiltration may enhance the elimination of recombinant-hirudin, although plasmapheresis systems provide the most rapid and complete elimination of recombinant-hirudin during simulated cardiopulmonary bypass. The decision to use a specific system will ultimately depend on the prevailing clinical situation and overall health of the patient.
UNLABELLED: We developed a quick and easy method to perform anti-Xa-activity-based whole blood assay and assessed its reliability for online monitoring of unfractionated heparins (UFHs) during cardiopulmonary bypass. Seventy-five microliters of a mixture of 1:3 large- and small-range Heptest reagent were transferred into blank cartridges of the ACT II device. The plastic flags for clot detection and stirring the sample and reagent were inserted and overlaid with 75 microL of Recalmix for recalcification. One-hundred fifty microliters of citrated whole blood were added and measurements performed. In vitro, the linearity of the test over a range of 1-8 IU/mL UFH, as well as the influence of variations in hematocrit (60%, 30%, and 20%), plasma coagulation factors (50%, 30%, and 20%) and platelets (100, 50, and 20 x 10(3)/microL) on the test results were assessed. In vivo measurements performed during cardiopulmonary bypass were compared with the chromogenic assay. The test revealed linearity to concentrations of 6 IU/mL of UFH and was not significantly influenced by the variations in the in vitro set-up despite a prolongation in samples with a hematocrit of 60%. In vivo, the correlation to the chromogenic test was R: = 0.90. The ACT II anti-Xa-UFH assay performed in whole blood was reliable when used over a wide range of conditions that could be encountered clinically. Although the test is useful for point-of-care monitoring, the necessity of individual calibrations and pipetting in the operation room requires further automation before its use in clinical practice. IMPLICATIONS: The ACT II anti-Xa-unfractionated heparin assay allows for reliable monitoring of large concentrations of UFH over a wide range of hematocrit, platelet, and coagulation factor levels. Further evaluation of this point-of-care device is indicated.
BACKGROUND: The authors assessed the heparin management test in vitro in volunteers and in vivo during cardiopulmonary bypass. METHODS: In vitro, the heparin management test was analyzed for heparin levels between 0 and 6 IU/ml using variations in hematocrit, platelets, procoagulants, and storage time. The in vivostudies consisted of two groups: In group I (cardiopulmonary bypass </= 90 min, n = 40), anticoagulation was performed according to the activated clotting time (with or without aprotinin); in group II (cardiopulmonary bypass >/= 180 min, with aprotinin) included use (n = 10) and nonuse of coumadin (n = 10) and anticoagulation according to the automated heparin dose-response assay. Tests were performed in duplicate (whole blood, two heparin management test analyzers) and compared with anti-Xa activity (plasma). RESULTS: In vitro, the results of the heparin management test (n = 1,070) correlated well with heparin concentration (r2 = 0.98). Dilution and storage time did not affect the heparin management test; a hematocrit of 60% and reduced procoagulants (10%) prolonged clotting time. In vivo, the correlation (heparin management test vs. anti-Xa) was strong in group I (r2 = 0.97 [with aprotinin] and 0.96 [without aprotinin]; n = 960) and group II without coumadin (r2 = 0.89, n = 516). In group II with coumadin, the overall correlation was r2 = 0.87 and 0.79 (n = 484), although the range varied widely (0.57-0.94, between-analyzer differences 0-47%). CONCLUSIONS: The results of the heparin management test were influenced by hematocrit, plasma coagulation factors, and the heparin level, but not by use of aprotinin. The heparin management test provided reliable values in vitro in group I, and in group II without coumadin but was less reliable in group II with coumadin.
OBJECTIVE: To explore the possible use of recombinant hirudin (r-hirudin) as an alternative to heparin for anticoagulation during cardiovascular surgery. DESIGN: Retrospective analysis. SETTING: Two university hospitals. PARTICIPANTS: Fifty-seven patients with heparin-induced thrombocytopenia type II (HIT II) in whom r-hirudin was used during cardiovascular surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The r-hirudin concentration was monitored on-line, at the point of the patient's care using the ecarin clotting time and maintained in the range of 3 to 4 microg/mL. The r-hirudin elimination at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. The duration of CPB was 63 to 246 minutes. The r-hirudin requirement per minute of CPB was 0.016 to 0.035 microg/kg/min, and the 24-hour blood drainage was 50 to 2,200 mL. Of the 57 patients, 54 fully recovered, including 9 patients who did not require any allogenic products. Four patients, all with impaired renal function, showed prolonged r-hirudin elimination and excessive bleeding and required surgical reexploration. Three patients died as a result of complications unrelated to the perioperative management. CONCLUSION: This study provides evidence that r-hirudin can be used safely and effectively for routine anticoagulation during CPB in patients diagnosed with HIT II. Almost 95% of the patients in whom it was used were discharged uneventfully. Patients with perioperative renal failure, however, showed increased bleeding.
OBJECTIVE: To assess the reliability of the TAS/ecarin clotting time (ECT) for on-line monitoring of r-hirudin in cardiovascular surgery with and without cardiopulmonary bypass (CPB). DESIGN: Samples were spiked with r-hirudin (0 to 5 microg/mL) and calibration curves constructed. Reproducibility was evaluated by measurement of the sample five times at each concentration. The influence of variations in hematocrit, plasma factors, and platelet count on the test results was examined. Samples were obtained from patients during cardiovascular surgery with CPB (n = 8), without CPB (n = 3), and from volunteers (n = 5) and compared with the laboratory reference tests. All tests were performed in duplicate. SETTING: Deutsches Herzzentrum Berlin. PARTICIPANTS: Five healthy volunteers and 11 patients undergoing cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The TAS/ECT showed linearity and reliability to an r-hirudin concentration of 5 microg/mL and was not influenced (p < 0.005) by the varying conditions of the in vitro setup. The correlation to the laboratory method was 0.74 for the CPB group and 0.87 for the non-CPB group. CONCLUSIONS: The TAS/ECT is a reliable assay for monitoring r-hirudin at the point of care. With this information, the use of r-hirudin during surgery or angioplasty should become more effective and safer.
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OBJECTIVE: A variety of influences reduce the validity of the measured oxygen partial pressure (paO(2)). Most errors occur when obtaining the blood sample and preparing it for analysis. Unfortunately, there is great controversy concerning the relevance and extent of these pre-analytic errors. Apart from this, the exact estimation of influencing factors under hyperoxic conditions has been neglected. Therefore, the objective of this study was to assess pre-analytic measuring errors for paO(2) under the condition of hyperoxia as completely as possible and to work out solutions to eliminate these errors. METHODS: paO(2) analysis was performed on more than 2000 blood samples. Errors analyzed were the technique of sample taking (direct puncture or from an indwelling catheter), aspirated air bubbles (0.05-0.35 ml), time and temperature of sample storage, and the material, size and manufacturer of the analyzing syringe. RESULTS: The paO(2) was on average 41 mmHg lower in samples taken from the indwelling catheter than by direct puncture. An air bubble size of 0.1-0.25 ml caused a decrease of 17-41 mmHg. Storage time of 2 min accounted for an paO(2) reduction of 6-67 mmHg depending on the type of syringe used. Glass syringes turned out to be more accurate than plastic syringes. The best results were obtained not from commercial "blood gas syringes" but from a simple plastic injection syringe. For all pre-analytic errors correction factors were established. CONCLUSION: All pre-analytic errors investigated caused a significant paO(2) decrease. Even an ideal procedure (almost no air bubble, short storage on ice) contributes a significant error. Only the appropriate correction factors as calculated from this study for routine use lead to the correct results. If they are not taken into account the paO(2) values will be falsely low, potentially leading to misinterpretation and misjudgement of a patient's condition.
Acute hearing loss following non-otologic surgery and general anesthesia is a rare occurrence. Deafness following anesthesia has more commonly been associated with spinal anesthesia or cardiopulmonary bypass surgical procedures. We present a case with unilateral cochlear dysfunction and sensorineural hearing loss after inguinal hernia operation. The literature is reviewed and the mechanisms causing hearing loss during anesthesia are discussed.
Gamma-hydroxybutyrate (GHB) may well be developed as an alternative for optional sedation during spinal anaesthesia. As in the case of propofol (PRO), GHB has good sedative properties associated with cardiovascular and respiratory stability. When used as a narcotic agent, recovery times are variable (e.g. > 30 min); in contrast, sedative dosages, as used in intensive care patients (e.g. 10-20 mg kg-1 h-1), result in adequate clinical recovery. The goal of the present study was to compare the clinical properties of GHB and PRO after continuous administration during spinal anaesthesia (SPA). Thirty patients (ASA I and II) received either GHB (n = 15) or PRO (n = 15) at random. Patients refusing sedation (n = 15) received 0.9% saline (control). At eight defined time points, haemodynamic (BP, HR), respiratory (RR, RMV, PaO2, SpO2, PETO2, PETCO2, VO2, VCO2) and endocrinological parameters (plasma concentrations of noradrenaline and adrenaline) as well as the clinical side-effects were assessed simultaneously. With both sedatives, the desired level of sedation was achieved. Recovery times ranged between 1.7 +/- 0.9 min with PRO and 6.1 +/- 4.9 min with GHB. GHB provided stable haemodynamic conditions without clinically relevant respiratory depression. In contrast, PRO caused a decrease in mean arterial pressure (MAP) of 15%, whereas respiratory minute volume was decreased by 53% (with periods of apnoea, SpO2 < 90%). VO2 and VCO2 correlated with respiratory minute volume (GHB, PRO, control). Plasma noradrenaline and adrenaline concentrations remained nearly constant in the GHB and control groups and declined during sedation with PRO. Both GHB and PRO are suitable for optional sedation during spinal anaesthesia. Control and recovery are acceptable for clinical purposes. It seems that GHB and PRO have similar haemodynamic, respiratory and endocrinological characteristics. Therefore, GHB may serve as an alternative for the established management of continuous sedation during SPA with PRO.
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BACKGROUND: The generation of iron-dependent toxic oxygen radicals during the initial resuscitation from hemorrhagic shock was shown to be a relevant factor for the initiation of the inflammatory cascade. Therefore, this experimental study was designed to evaluate the effects of a deferoxamine-conjugated hydroxyethyl-starch solution (HES-DFO) on oxygen radical induced injury and microcirculatory alterations in the rat liver compared with resuscitation with regular hydroxyethyl-starch, lactated Ringer's solution (RL), or a gelatin-based solution. METHODS: After hemorrhage and random assignment to 1 hour of blood-free resuscitation with the aforementioned solutions, hepatic microcirculation and leukocyte adhesion characteristics were assessed by intravital fluorescence microscopy in anesthetized rats. Oxygen radical activity was estimated by determination of glutathione levels in liver homogenate and determination of thiobarbituric acid-reactive substances in plasma as markers of lipid peroxidation. RESULTS: Resuscitation by HES-DFO resulted in restoration of hemodynamic parameters compared with gelatin-based solution and HES. The hepatic microcirculation was severely altered 1 hour after resuscitation from shock in all groups indicated by sinusoidal narrowing and reduced sinusoidal blood flow. HES-DFO, however, attenuated leukocyte adhesion and improved velocity index in sinusoids as well as sinusoidal perfusion. The shock-associated generation of oxygen radicals during resuscitation was prevented by HES-DFO as indicated by restored glutathione and reduced thiobarbituric acid-reactive substances. CONCLUSION: The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.
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Recently, transportable capnographs fulfilling the practical demands of emergency medicine have become commercially available (NPB-75, sidestream, Nellcor Puritan Bennett; and Tidal Wave, mainstream, Novametrix). A prerequisite for their use is an accuracy as required for clinical purposes (i.e., pCO2 +/- 2 mmHg). Additionally, environmental conditions in emergency medicine (e.g., changes in ambient temperature) should not have a significant impact on accuracy. The objective of this investigation was to analyse the accuracy of the two capnographs. The accuracy of the pCO2 measurement was evaluated under the following conditions: (1) measurement with three gas mixtures of defined concentrations (gas A: 5% CO2, 95% O2; gas B: 5% CO2, 20% O2, 75% N2; gas C: 10% CO2, 90% N2) related to STPD conditions (STPD = Standard Temperature and Pressure, Dry); and (2) exposure to changes in temperature (from +22 degrees C to -20 degrees C, and from -20 degrees C to +22 degrees C) applying the aforementioned 3 gas mixtures (STPD); and (3) in 20 patients manually ventilated with pure oxygen following endotracheal intubation (i.e., BTPS conditions = body temperature and pressure, saturated). Adequacy of the results was compared to the alveolar gas monitor AGM 1304 (Bruel & Kjaer, Copenhagen, Denmark; sidestream) which served as the reference method (providing an accuracy for the alveolar carbon dioxide partial pressure (pACO2) of +/- 1 mmHg). In the 3 dry gas mixtures, mean inaccuracy proved to be +4.5 +/- 4.1, +2.8 +/- 3.7, and +2.2 +/- 7.0 mmHg (gas A, gas B, gas C; STPD) with the Nellcor sidestream device. Using the Novametrix mainstream capnograph the results were found as follows: (1) -1.1 +/- 0.6, +2.9 +/- 0.6, and +5.6 +/- 2.3 mmHg (oxygen compensation enabled); and (2) +0.2 +/- 1.6, +2.2 +/- 0.6, and +3.2 +/- 4.2 mmHg (oxygen compensation disabled). After changing the environmental temperature (-20 degrees C / +22 degrees C), the resulting deviations (gases A-C, STPD) found with the Nellcor device averaged -12 +/- 4% and +15 +/- 3% (Nellcor); with the Novametrix mainstream device the deviations averaged -1 +/- 2% and +1 +/- 1%, and -2 +/- 1% and +1 +/- 1% (oxygen compensation enabled/disabled). Mean inaccuracy of the pCO2 measurement during ventilation of patients with pure oxygen (BTPS) was found to average -0.9 +/- 0.9 (Nellcor), and either +3.9 +/- 0.8 or +2.1 +/- 0.7 mmHg with the Novametrix (oxygen compensation enabled/disabled). Under BTPS conditions, both devices showed an acceptable deviation of the measurement accuracy up to a maximum of +/- 2 mmHg. The higher deviations of the "NPB-75" (Nellcor Puritan Bennett, sidestream) when using dry gas mixtures (STPD) may be explained by the automatic water vapour correction. Under the conditions of low and changing ambient temperature (-20 degrees C, +22 degrees C), only the "Tidal Wave" (Novametrix; mainstream) remained uninfluenced, whereas deviations of -12% and +15% were found with the "NPB-75".
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UNLABELLED: The introduction of biosensor technology for near bedside measurement of plasma lactate concentrations has been a promising step for critical care profiling. However, methodological drawbacks and relevant inaccuracy have been reported. With the advent of a new biosensor (Chiron Diagnostics) and a revised NOVA Biomedical device, accuracy was expected to be improved. The goal of the present investigation was to evaluate the accuracy of both methods. METHODS: Two devices (System 860, Chiron Diagnostics; StatProfile 9, NOVA Biomedical) were simultaneously analysed using 9 biosensors in both fresh frozen plasma and citrated whole blood. The results were compared with an established photometric method (Lactat PAP, Analyticon). Measurements were performed as duplicates (n = 1120) before and after the addition of 1 molar sodium lactate solution (2-24 mmol/L). For the estimation of between-day precision commercially available aqueous and serum-based quality controls were analysed daily over a period of 60 days. RESULTS: Reproducibility in blood was 2.6 +/- 2.8% (Chiron), 4.1 +/- 4.0% (NOVA) and 1.5 +/- 2.1% (Analyticon), in plasma respectively 2.1 +/- 2.4%, 2.1 +/- 2.9% and 1.0 +/- 1.1%. Mean inaccuracy in plasma presented to be -0.2 +/- 16.4% (plasma) and +7.2 +/- 13.1% (blood) for Chiron, +9.4 +/- 18.4% and +18.7 +/- 16.7% for NOVA, and -37.8 +/- 18.2% and -27.5 +/- 17.6% for Analyticon. Calculated between-day-precision (variation coefficients mean values) was 11.5 +/- 4.9% (Chiron) and 14.0 +/- 5.9% (NOVA). CONCLUSION: Although accuracy of lactate concentrations obtained with biosensor technology has improved (mean 0-18%), the variability of the results still poses a problem (mean 13-18%). Therefore, from the methodological point of view, interpretation of a single lactate value requires caution when applying to the critically ill, particularly with view to threshold values, and should be considered vis-à-vis other options.