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ABSTRACT: Although cephalosporins are recommended as primary agents, moxifloxacin may be a suitable second-line antibiotic in cardiac surgery, especially if additional Gram-negative coverage is warranted. Cardiopulmonary bypass (CPB) may alter the pharmacokinetics of drugs in numerous ways. Since no such data exist, the aim of this study was to assess the serum concentrations and pharmacokinetics of moxifloxacin in patients undergoing cardiac surgery with CPB. Fourteen coronary artery bypass graft surgery patients received an intravenous infusion of 400mg moxifloxacin as peri-operative antibiotic prophylaxis. At 15 time points throughout a 24-h period, serum samples were obtained to measure moxifloxacin concentrations using high-performance liquid chromatography. In addition, a non-compartmental pharmacokinetic analysis, i.e. area under the concentration-time curve (AUC), volume of distribution at steady state (VSS), drug clearance (CL), elimination half-life (t1/2) and mean residence time (MRT), was performed in five patients. Apart from a slight transient decrease in moxifloxacin concentration at the onset, CPB did not affect the concentration-time curve. Mean±standard deviation maximum drug concentration (Cmax) (5.12±1.58μg/mL), AUC (36.5±5.40μgh/mL), VSS (2.03±0.30L/kg), CL (11.2±1.91L/h), t1/2 (9.47±0.92h) and MRT (12.9±1.52h) were comparable with historical data for healthy volunteers. We conclude that CPB does not alter the pharmacokinetics of moxifloxacin. No dose adjustments, especially with regard to the CPB circuit and its priming volume, are necessary in cardiac surgical patients.
International journal of antimicrobial agents 03/2013; · 3.03 Impact Factor
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ABSTRACT: In vitro and experimental studies in animals have established the anti-inflammatory effects of moxifloxacin. Cardiopulmonary bypass (CPB) leads to an inflammatory response. The aim of this study was to assess whether the inflammatory cytokine response to CPB is reduced with a perioperative antibiotic prophylaxis, either moxifloxacin or cefuroxime (the standard prophylaxis).
Twenty-eight patients scheduled for elective coronary artery bypass grafting with CPB were randomly assigned to receive either moxifloxacin or cefuroxime as the perioperative antibiotic prophylaxis. Interleukin (IL)-6, -8, -10 and tumour necrosis factor-α (TNF-α) serum concentrations were determined at eight time points before and after CPB.
In both groups, all cytokine concentrations significantly increased after the start of CPB. There were no statistically significant differences between the moxifloxacin and cefuroxime groups at any point; IL-6 concentrations [median (interquartile range)] 240 min after CPB, the primary endpoint, were 364 (192-598) and 465 (325-906) pg/mL (P = 0.323), respectively.
Neither moxifloxacin nor cefuroxime produced significant attenuation of the inflammatory cytokine response to CPB. The reasons why moxifloxacin did not have significant anti-inflammatory effects in this unique clinical situation may be: (i) the inflammatory response to CPB may be different from that of infectious disease states that were used to establish the immunomodulatory effects of moxifloxacin; and (ii) a single intravenous dose, which was used in this investigation, may not lead to high enough plasma and intracellular concentrations.
Journal of Antimicrobial Chemotherapy 01/2012; 67(1):230-3. · 5.07 Impact Factor
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European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 06/2011; 41(2):466; author reply 466-7. · 2.40 Impact Factor
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European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2011; · 2.40 Impact Factor
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ABSTRACT: Although the lysine analogs tranexamic acid (TXA) and aminocaproic acid (EACA) are used widely for antifibrinolytic therapy in cardiac surgery, relatively little research has been performed on their safety profiles, especially in the setting of cardiac surgery. Two antifibrinolytic protocols using either TXA or aminocaproic acid were compared according to postoperative outcome.
A retrospective analysis.
A university-affiliated hospital.
Six hundred four patients undergoing cardiac surgery.
One cohort of 275 consecutive patients received TXA; a second cohort of 329 consecutive patients was treated with EACA. Except for antifibrinolytic therapy, the anesthetic and surgical teams and their protocols remained unchanged.
Besides major outcome criteria, namely postoperative bleeding, the need for allogeneic transfusions, operative revision because of bleeding, postoperative renal dysfunction, neurologic events, heart failure, and in-hospital mortality, the authors specifically sought differences between the groups concerning seizures. The 2 cohorts were comparable over a range of perioperative factors. Postoperative seizures occurred significantly more frequently in TXA patients (7.6% v 3.3%, p = 0.019), whereas EACA patients had a higher incidence of postoperative renal dysfunction (20.0% v 30.1%, p = 0.005). There were no differences in all other measured major outcome factors.
Both lysine analogs are associated with significant side effects, which must be taken into account when performing risk-benefit analyses of their use. Their use should be restricted to patients at high risk for bleeding; routine use on low-risk patients undergoing standard surgeries should face renewed critical reappraisal.
Journal of cardiothoracic and vascular anesthesia 02/2011; 25(1):20-5. · 1.06 Impact Factor
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ABSTRACT: To evaluate the in vitro effects of high concentrations of heparin and its reversal with protamine on routine laboratory parameters as well as on modified thromboelastogram (ROTEM; TEM International, Munich, Germany) and impedance aggregometry (MULTIPLATE; Dynabyte, Munich, Germany).
An observational, nonrandomized in vitro study.
A single-center, university hospital.
Ten healthy volunteers.
Heparinization of whole blood to levels of 2, 4, 6, and 8 IU/mL of heparin and reversal with protamine. For MULTIPLATE measurements, heparin levels up to 20 IU/mL were tested.
The present results show that the prothrombin time (PT) and fibrinogen measurements are altered significantly by heparin concentrations above 2 IU/mL. Protamine reversal also affected coagulation tests except for the fibrinogen. The INTEM test using the ROTEM system was influenced significantly by heparin concentrations of 2 IU/mL or higher, whereas EXTEM measurements remained stable up to 4 IU/mL. The findings for the FIBTEM test were stable up to 6 IU/mL but then declined to values less than 50% of baseline at 8 IU/mL. HEPTEM results remained valid under all concentrations of heparin tested. The effect of protamine on ROTEM was seen mainly in the INTEM and HEPTEM measurements. Heparin concentrations up to a level of 20 U/mL had no effect on MULTIPLATE measurements. Effects of protamine on MULTIPLATE became significant at heparin-to-protamine ratios below 1:1 and were more pronounced for adenosine diphosphate than for thrombin receptor-activated protein testing.
Neither fibrinogen (Clauss) nor derived fibrinogen or FIBTEM testing is valid in the setting of high concentrations of heparin unless antagonized by heparinase. Reversal of heparin with protamine worsens platelet function at all ratios as detected by aggregometry (MULTIPLATE) and thromboelastography (ROTEM), starting at a 1:1 ratio. Therefore, appropriate coagulation testing under cardiopulmonary bypass conditions should be selected carefully according to heparin levels. In particular, fibrinogen values are falsely low at heparin levels of 2 IU/mL and above. Therefore, newer algorithms promoting the correction of fibrinogen levels on cardiopulmonary bypass should be based on appropriate testing.
Journal of cardiothoracic and vascular anesthesia 02/2011; 25(6):981-6. · 1.06 Impact Factor
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ABSTRACT: Tranexamic acid (TXA) and ɛ-aminocaproic acid (EACA) are used for antifibrinolytic therapy in cardiac surgery, although data directly comparing their blood sparing effect and their side effects, especially in paediatric cardiac surgical patients, are still missing.
We analysed perioperative data of 234 paediatric patients weighing less than 20 kg undergoing cardiac surgery. In a 5-month period, all patients (n=114) received TXA (group TXA). During a second 5-month period, all patients (n=120) were treated with EACA (group EACA). Primary outcome was blood loss at 24h postoperatively; secondary outcome criteria were transfusion requirement, rate of revision for bleeding, postoperative complications and in-hospital mortality.
All descriptive and intra-operative parameters were well comparable. There was no evidence for a difference in blood loss at 24h postoperatively (TXA 21 ml kg(-1) (14-38) (median (interquartile range)) vs EACA 29 ml kg(-1) (14-40), p=0.242), rate of re-operation for bleeding (TXA 9.6% vs EACA 8.3%, p=0.725) and transfusion of blood products. The incidence of postoperative complications such as seizures (TXA 3.5% vs EACA 0.8%, p=0.203) and other neurological complications (TXA 2.6% vs EACA 1.7%, p=0.677), renal injury (TXA 9.6% vs EACA 13.3%, p=0.378), renal failure (TXA 1.8% vs EACA 4.2%, p=0.447), low cardiac output syndrome (TXA 12.3% vs EACA 10.8%, p=0.729), and vascular thrombosis (TXA 4.4% vs EACA 5.0%, p=0.824), as well as the in-hospital mortality (TXA 2.6% vs EACA 3.3%, p>0.999) did not show any statistically significant difference.
TXA and EACA are well comparable in their effect on perioperative blood loss as well as in major clinical outcome criteria. Although the fourfold risk for seizures using TXA was not significant, we currently use EACA in paediatric cardiac surgery.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 11/2010; 39(6):892-7. · 2.40 Impact Factor
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ABSTRACT: A shortage of blood products is predicted for the near future in many countries all over the world. Preoperative autologous blood donation (PABD) in cardiac surgery is considered an option to reduce the need of allogeneic blood products. We analysed a 1-year period of our institutional database according to the safety and efficiency of our autologous blood donation programme.
All patients who donated autologous blood prior to cardiac surgery were matched to a non-donor according to age, body weight, body mass index, sex, haemoglobin concentration, EuroSCORE, antifibrinolytic therapy and risk for bleeding. We analysed the occurrence of adverse effects during donation in all donors as well as the main perioperative data, haemoglobin levels and the need for allogeneic blood transfusion in all patients.
There were no major cardiac events such as myocardial infarction, worsened cardiac insufficiency or death in the donor group during the PABD process. A total of 216 patients could be matched. Exposure to allogeneic blood products was significantly reduced in the donor group (packed red cells 70 patients (pts) vs 118 pts (p<0.001), fresh frozen plasma 26 pts vs 54 pts (p=0.001), platelets 10 pts vs 22 pts (p=ns)). There were no reports of transfusion-related side effects. Further, there was no difference in haemoglobin concentrations at postoperative day 1 and at discharge.
In this large matched-pair analysis without the need for risk stratification, PABD reduces the need for allogeneic blood products in adult cardiac surgery. In a carefully selected cohort, PABD is a safe and efficient alternative to allogeneic transfusion.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2010; 37(6):1396-401. · 2.40 Impact Factor
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ABSTRACT: Our aim was to investigate postoperative complications and mortality after administration of aprotinin compared to tranexamic acid in an unselected, consecutive cohort.
Perioperative data from consecutive cardiac surgery patients were prospectively collected between September 2005 and June 2006 in a university-affiliated clinic (n = 1188). During the first 5 mo, 596 patients received aprotinin (Group A); in the next 5 mo, 592 patients were treated with tranexamic acid (Group T). Except for antifibrinolytic therapy, the anesthetic and surgical protocols remained unchanged.
The pre- and intraoperative variables were comparable between the treatment groups. Postoperatively, a significantly higher incidence of seizures was found in Group T (4.6% vs 1.2%, P < 0.001). This difference was also significant in the primary valve surgery and the high risk surgery subgroups (7.9% vs 1.2%, P = 0.003; 7.3% vs 2.4%, P = 0.035, respectively). Persistent atrial fibrillation (7.9% vs 2.3%, P = 0.020) and renal failure (9.7% vs 1.7%, P = 0.002) were also more common in Group T, in the primary valve surgery subgroup. On the contrary, among primary coronary artery bypass surgery patients, there were more acute myocardial infarctions and renal dysfunction in Group A (5.8% vs 2.0%, P = 0.027; 22.5% vs 15.2%, P = 0.036, respectively). The 1-yr mortality was significantly higher after aprotinin treatment in the high risk surgery group (17.7% vs 9.8%, P = 0.034).
Both antifibrinolytic drugs bear the risk of adverse outcome depending on the type of cardiac surgery. Administration of aprotinin should be avoided in coronary artery bypass graft and high risk patients, whereas administration of tranexamic acid is not recommended in valve surgery.
Anesthesia and analgesia 12/2008; 107(6):1783-90. · 3.08 Impact Factor
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Journal of Cardiothoracic and Vascular Anesthesia 03/2007; 21(1):162-4. · 1.64 Impact Factor
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Canadian Journal of Anaesthesia 03/2006; 53(2):208-9. · 2.35 Impact Factor
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ABSTRACT: For a microdialytic trapping method we systematically investigated changes in concentrations of 2,5-dihydroxy-benzoic acid (2,5-DHBA) and 2,3-dihydroxy-benzoic acid (2,3-DHBA) in freshly prepared solutions of salicylic acid (SA). The solvent was 0.9% saline exposed to different atmospheric concentrations of oxygen (0, 21, and 100%). The solutions were treated by freezing-thawing and an ultrasonic bath in presence and absence of aluminium foil. Without aluminium the concentrations of 2,5-DHBA and 2,3-DHBA kept constant over an observed period of 160 min on different levels from below 20 ng/ml to about 100 ng/ml. In presence of aluminium the concentrations increased to maximum 307 ng/ml after 160 min. Ultrasonic irradiation amplified this effect to maximum 341 ng/ml. HPLC/ECD processing and quantitative analysis of dihydroxy-benzoic acids (DHBAs) in microdialysis may be artificially influenced by varying oxygen environment and metal catalysis.
Journal of Chromatography B 03/2006; 831(1-2):320-3. · 2.89 Impact Factor
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ABSTRACT: IMPLICATIONS: The fluoride inhibition of mivacurium hydrolysis by pseudocholinesterase increases in hypothermia, but it will very rarely occur in clinical practice because it requires rather large fluoride concentrations (>50 micromol/L) and very low temperatures (<28 degrees C).
Anesthesia & Analgesia 08/2002; 95(2):397-9, table of contents. · 3.29 Impact Factor
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ABSTRACT: Volatile anesthetics are frequently used during cardiopulmonary bypass (CPB) to maintain anesthesia. Uptake and elimination of the volatile agent are dependent on the composition of the oxygenator. This study was designed to evaluate whether the in vivo uptake and elimination of isoflurane differs between microporous membrane oxygenators containing a conventional polypropylene (PPL) membrane and oxygenators with a new poly-(4-methyl-1-pentene) (PMP) membrane measuring isoflurane concentrations in blood.
Twenty-four patients undergoing elective coronary bypass surgery with the aid of CPB were randomly allocated to one of four groups, using either one of two different PPL-membrane oxygenators for CPB or one of two different PMP-membrane oxygenators. During hypothermic CPB, 1% isoflurane in an oxygen-air mixture was added to the oxygenator gas inflow line (gas flow, 3 l/min) for 15 min. Isoflurane concentration was measured in blood and in exhaust gas at the outflow port of the oxygenator. Between-group comparisons were performed for the area under the curve (AUC) during uptake and elimination of the isoflurane blood concentrations, the maximum isoflurane blood concentration (C(max)), and the exhausted isoflurane concentration (F(E)).
The uptake of isoflurane, expressed as AUC of isoflurane blood concentration and a function of F(E), was significantly reduced in PMP oxygenators compared to PPL oxygenators (P < 0.01). C(max) was between 8.5 and 13 times lower in the PMP-membrane oxygenator groups compared to the conventional PPL-membrane oxygenator groups (P < 0.01).
The uptake of isoflurane into blood via PMP oxygenators during CPB is severely limited. This should be taken into consideration in cases using such devices.
Anesthesiology 07/2002; 97(1):133-8. · 5.36 Impact Factor
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ABSTRACT: Background: Volatile anesthetics are frequently used during cardiopulmonary bypass (CPB) to maintain anesthesia. Uptake and elimination of the volatile agent are dependent on the composition of the oxygenator. This study was designed to evaluate whether the in vivo uptake and elimination of isoflurane differs between microporous membrane oxygenators containing a conventional polypropylene (PPL) membrane and oxygenators with a new poly-(4-methyl-1-pentene) (PMP) membrane measuring isoflurane concentrations in blood.
Anesthesiology 06/2002; 97(1):133-138. · 5.36 Impact Factor
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ABSTRACT: Exposure to pollutants, in particular polychlorinated biphenyls (PCB), was established at a school built in 1966. Because of a statistically conspicuous increased frequency of breast cancer observed in the teachers of the school this study was performed to ascertain whether the teachers in the polluted school have an increased level of micronucleated cells (MN) or sister chromatid exchanges (SCE) as an expression of a raised cytogenetic risk. Teachers in a directly adjacent school served as one control group and those from a school about 30 km away as a second one. Each teacher had to answer a questionnaire and after venous blood samples had been taken, the number of MN and SCE in peripheral lymphocytes were determined. For the teachers in the polluted school, in addition, the length of stay in the building during the last month and year was recorded. Thereby no correlation with the number of MN and SCE was proven. In comparison with the two control groups, neither the number of MN nor SCE was increased in the teachers of the polluted school. Even if their predictive value for cancer risk assessment is disputed, MN and SCE have a high rating as standard procedures in the proof of an exposure to genotoxic agents. This study thus does not provide any evidence that, for the teachers in the polluted school, a relevant exposure to genotoxic agents exists.
International Journal of Hygiene and Environmental Health 11/2000; · 3.81 Impact Factor
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ABSTRACT: Objective: Recently, the safety of aprotinin administration during open-heart surgery has been debated. The aim of the study was to compare the blood sparing effect and the side effects of aprotinin and tranexamic acid in paediatric cardiac surgery patients. Methods: Perioperative data of 199 consecutive patients weighing less than 20 kg undergoing open-heart cardiac surgery were prospectively collected between September 2005 and June 2006. During the first 5 months, 85 patients received aprotinin (group A); in the next 5 months, 114 patients were treated with tranexamic acid (group T). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained unchanged. Postoperative complications and in-hospital and 1-year mortality were considered as outcome parameters. Results: The descriptive parameters and the intraoperative parameters were well comparable in the two groups. The blood loss was significantly lower in group A compared to group T at 6 h [55 (35–82.5) vs 70 (45–100) ml, p = 0.031], but not at 12 and 24 h after operation. The incidence [9 (11%) vs 25 (22%), p = 0.035] and the amount of red blood cell transfusion during the first 24 h after surgery were also significantly lower in group A (0.1 ± 0.4 vs 0.3 ± 0.6 unit, p = 0.036). There were significantly less rethoracotomies in group A [2 (2.4%) vs 11 (9.6%), p = 0.039]. We found no difference in the incidence of the postoperative complications and in-hospital and 1-year mortality. There was a tendency for a higher incidence of seizures in group T [4 (3.5%) vs 0 (0%), p = 0.14]. Conclusions: Aprotinin administration bears no additional risks compared to tranexamic acid and it has a stronger blood sparing effect in paediatric cardiac surgery. There were fewer rethoracotomies and less postoperative red blood cell transfusion in patients who received aprotinin.
European Journal of Cardio-Thoracic Surgery.
