Role of glutamine administration on T-cell derived inflammatory response after cardiopulmonary bypass.

BACKGROUND & AIMS: Cardiac surgery provokes an inflammatory response for which the endothelium, the myocardium, and monocytes/macrophages are primarily responsible. T cells are altered in a different way whereby the pro-inflammatory pathway is suppressed. From the results of experimental studies it was concluded that glutamine (Gln) enhances the production of T-cell cytokines in conditions of Gln deprivation. The aim of this clinical study was to evaluate the role of a perioperative Gln infusion on intracellular inflammatory T-cell cytokine expression in patients undergoing elective cardiac surgery and to evaluate the effects on systemic inflammation, organ dysfunction and ICU length of stay. METHODS: In this prospective, randomized, double-blind study, we included 78 patients (age level older than 70 years, ejection fraction less than 40%, or mitral valve replacement) undergoing elective cardiosurgery with cardiopulmonary bypass. We randomly assigned each subject to receive an infusion with either Gln (0.5 g/kg/day, group A) or an isonitrogenous, isocaloric, isovolemic nutritional solution (group B) or physiological NaCl 0.9% (group C, to eliminate an unspecific nutritional effect). We started the infusion after the induction of anesthesia with 1000 ml/24 h and maintained this state for 3 days. RESULTS: On the first postoperative day plasma Gln levels in group A were significantly increased (958 +/- 331 microM) compared to group B (527 +/- 105 microM) and group C (489 +/- 104 microM), and remained higher until the third postoperative day. At the beginning and after surgery intracellular interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha levels in T cells showed no differences between the groups. Also, no differences could be observed with regard to C-reactive protein, SOFA score, heart and circulation support, postoperative ventilation time, and ICU length of stay. CONCLUSIONS: The elevation of Gln plasma levels as a result of 0.5 g/kg/day perioperative Gln infusion has no influence on the T-cell derived inflammatory response, indicating a sufficient supply of Gln. A Gln supplementation in cardiac surgery patients without a clear Gln deficiency seems not to affect the intracellular inflammatory T-cell cytokine expression.

Perioperative application of L-alanyl-L-glutamine in cardiac surgery: effect on the polarized T cell cytokine expression.

At risk patients undergoing cardiac surgery with cardiopulmonary bypass have increased rates of postoperative infectious morbidity. Postoperatively, after cardiac surgery, an immunosuppression in the form of a polarization of T helper (Th) cells with a decreased Th1 response (IL-2 and IFN-gamma) and an increased Th2 response (IL-4 and IL-10) is recognized. Therapeutic strategies to modulate the immunological response include special key nutrients such as the amino acid glutamine favoring the Th2 response. There is no information available concerning its effect in patients undergoing cardiac surgery. The aim of this clinical study was to evaluate the effects of a perioperative infusion of glutamine on the polarized lymphocyte T cell cytokine expression and on infectious morbidity in cardiac surgery patients at risk of infection. Seventy-eight patients were included in the study undergoing elective cardiac surgery with a lymphopenia less than 1.2 giga/l. One or more of the following criteria had to be met: age older than 70 years, ejection fraction less than 40%, or mitral valve replacement. We randomly assigned patients to receive infusions of either high-dose L-alanyl-L-glutamine dipeptide [0.5 g/(kg day) glutamine] dissolved in an amino acid solution or an isonitrogeneous, isocaloric, isovolemic nutritional solution. An additional group with normal saline served as control to eliminate any nonspecific nutritional effect. We started the infusion after induction of anesthesia with 1,000 ml/24 h and continued it for 3 days. The primary endpoint was intracellular T cell cytokine expression (including the description in tertiles) on the first postoperative day (pod 1). Secondary endpoints were postoperative infection rate, mortality rate, cardiovascular circulation ventilation time, and renal function. A high-dose perioperative glutamine application leading to mean plasma levels of 1,177 microM had only a minor influence on the polarized intracellular T cell cytokine expression. On pod 1 there was a polarization of T cells, i.e., an augmented Th2 response with an increased number of IL-6 and IL-10 producing cells. On the other side the Th1 response with IL-2 and TNF-alpha declined on pods 1 and 2. Only the intracellular IL-2 response in the lower tertile of IL-2 production was improved with glutamine indicating a small influence. We did not observe any effects on the numbers of postoperative infections; on mortality rate; on cardiovascular circulation; on ventilation time or on renal function. The elevation of glutamine plasma levels by a perioperative intravenous infusion of L-alanyl-L-glutamine influenced the intracellular expression of IL-2 in the lower tertile only slightly. However, mean glutamine values in the other groups remained above or close 500 microM, thus suggesting that glutamine supply to the immune cells was still adequate in most patients, and that glutamine deficiency, if it occurred, was marginal. In the event of a severe glutamine deficiency the observed effect on cytokine production could be more pronounced. Furthermore, we could not observe any obvious clinical advantage in this at risk cardiac surgical patient population. A glutamine supplementation for patients undergoing cardiac surgery without a clear glutamine deficiency is not recommended.

Minimal immunoreactive plasma beta-endorphin and decrease of cortisol at standard analgesia or different acupuncture techniques.

BACKGROUND AND OBJECTIVE: Acupuncture has been claimed to be associated with activation of the endogenous antinociceptive system. The analgesic effects of acupuncture have been ascribed to beta-endorphin interacting with opioid receptors. However, firstly, the release of beta-endorphin into the blood has been proven to be induced by stress, i.e. under dysphoric conditions, and, secondly, if released under stress, beta-endorphin has been shown not to be analgesic. Our aim was to test whether beta-endorphin immunoreactive material is released into the cardiovascular compartment during acupuncture comparing the most frequently used types of acupuncture with standard pain treatment under apparently low stress conditions. METHODS: This prospective study included 15 male patients suffering from chronic low back pain. beta-Endorphin immunoreactive material and cortisol were measured in the plasma of patients who underwent, in random order, therapy according to a standard pain treatment, traditional Chinese acupuncture, sham acupuncture, electro acupuncture and electro acupuncture at non-acupuncture points before, at and after the treatment. Statistical analysis was performed using two-way ANOVA with repeated measures. RESULTS: A decrease in plasma cortisol concentration measured over the five treatment protocols was highly significant (P < 0.001). The beta-endorphin immunoreactive material concentrations in plasma were minimal at all times and in all treatment conditions. The influence of treatments by various acupuncture procedures on cortisol and beta-endorphin immunoreactive material plasma concentrations over the three time points was not significantly different. CONCLUSIONS: beta-endorphin immunoreactive material in blood is not released by any type of acupuncture as tested under low stress conditions.

Perioperative changes in cerebral ischemic markers in the cerebrospinal fluid after preoperative nimodipine treatment.

BACKGROUND: Elderly patients with previous organ damage are at risk for minor neurologic deficits after major surgery. Spinal catheter analgesia is used whenever possible in this group and enables regular cerebrospinal fluid (CSF) sampling. Nimodipine, a calcium blocker, may have neuroprotective effects. We examined whether preoperative treatment with nimodipine affects ischemic markers in the CSF during extracranial surgery. METHODS: We performed a prospective, randomized, placebo-controlled, double-blind study in patients (ASA III or IV, 65-85 years) that underwent elective implantation surgery of the hip joint with intrathecal catheter anesthesia. Starting 15 h before surgery, patients received either 30 microg x kg(-1) h(-1) of nimodipine (n = 20) or 0.9% saline solution (placebo, n = 23) as a central venous infusion. The concentrations of neuron-specific enolase, hypoxanthine, creatine-kinase, lactate and pH in the CSF were determined before and immediately after surgery as well as 6 and 24 h after surgery. RESULTS: Before surgery, the baseline CSF pH was normal in all patients. Immediately after surgery it fell significantly to 7.08 +/- 0.29 in the placebo group and non-significantly to 7.27 +/- 0.38 in the treatment group; all values were normalized at 6 and 24 h after surgery in both groups. In the placebo group, lactate levels rose significantly from 1.48 +/- 0.28 mmol l(-1) before surgery to 1.77 +/- 0.27 mmol l(-1) immediately after surgery, and to 2.03 +/- 0.32 mmol l(-1) 24 h after surgery. In the treatment group, lactate concentrations remained stable up to 6 h after surgery (1.55-1.62 mmol l-1), while an increase to 2.10 +/- 0.48 mmol l(-1) was observed 24 h after the operation. Neuron-specific enolase, hypo-xanthine and creatine-kinase showed no change in either group. CONCLUSION: In conclusion, preoperative nimodipine treatment reduced intraoperative CSF acidosis and delayed surgery-related increases in lactate concentration in the CSF by several hours in elderly, comorbid patients at risk for minor postoperative neurologic deficits.

[Variations of pain in the treatment of one classical acupuncture-point versus one point of Yamamoto's new scalp acupuncture]. / Veränderungen der Schmerzempfindung bei der Akupunktur eines klassischen Akupunkturpunktes versus eines Schädelakupunkturpunktes nach Yamamoto - Eine prospektiv randomisierte, placebo-kontrollierte Einfachblindstudie.

INTRODUCTION: In an experimental design the pain reduction effect of acupuncture is studied and compared to the treatment of a classical acupuncture point and a point of the Yamamoto New Scalp Acupuncture (YNSA). METHODS: Experimental pain stimuli (32 per test person) were set in 42 test persons at the upper calcaneus edge and pain reduction was checked intra-individually by using the following variations of treatment: Acupuncture YNSA basis-point D, Acupuncture at the classical point Xiao Chang Shu = Bl 27, Acupuncture at a placebo point of the head, Acupuncture at a placebo point of the gluteal region. RESULTS: Evaluation of the data as well as a statistical investigation using a bi-factoral variance analysis with repeated measurements of 2 respectively 1 factor yielded following results: There are highly significant differences concerning pain reduction through the stimulation of the YNSA basis-point D and the acupuncture at the classical point Bl 27 (p < 0,0007). There are also highly significant differences concerning the verum and the placebo treatment (p < 0,00006). Further hypothesis of controlling the experimental design were tested. CONCLUSIONS: On the whole, the investigation shows that there is a marked difference between the verum and placebo treatment as well as a difference between the acupuncture of the YNSA basis-point D and the classical acupuncture point Xiao Chang Shu (Bl 27) with regard to pain reduction induced by experimental stimuli at the calcaneus. These differences are significant.

Pharmacokinetics of antibiotic prophylaxis in major orthopedic surgery and blood-saving techniques.

The pharmacokinetics of cefuroxime, cefotiam, cefamandole, and ampicillin/sulbactam were randomly measured in 40 patients undergoing major orthopedic surgery associated with high blood and volume turnover and intraoperative blood salvage. Serum and bone concentrations and the pharmacokinetics occurring in the context of these procedures were measured. No changes in elimination half-life relative to a normal population occurred with cefuroxime, cefotiam, and ampicillin. Serum and tissue concentrations were slightly lower with cefamandole and sulbactam, but reapplication of the initial dose was required with all antibiotics 4 hours after the first application.

Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-L-glutamine supplementation.

The objective of this study was to determine the effects of diazepam, L-alanyl-L-glutamine (ala-gln) or diazepam combined with ala-gln on polymorphonuclear leukocyte (PMN) free amino acid profiles. In a parallel study the effects on PMN immune functions were also documented for the first time. The incubation of whole blood with diazepam led to significant changes in PMN free glutamine, aspartate, glutamate, ornithine, arginine, citrulline, taurine and methionine as well as branched chain and neutral amino acid concentrations. Ala-gln caused significant increases in PMN glutamine and alanine and asparagine, aspartate, glutamate, ornithine, arginine, serine and glycine profiles. Regarding PMN immune functions, diazepam significantly decreased superoxide anion (O(2)(-)) and hydrogen peroxide production (H(2)O(2)) and myeloperoxidase activity (MPO) while ala-gln significantly increased PMN immune functions. Ala-gln supplemented to diazepam largely reversed the changes in PMN amino acid profiles and PMN immune functions brought about by diazepam. Overall, diazepam or ala-gln lead to significant changes in PMN free amino acids. Important PMN immune functions also seem to be affected. In regards to the results, there is significant relevance to the pharmacological regimens which enhance the supply of diazepam or ala-gln in whole blood suggesting that considerable changes in PMN "labile free amino acid pool" occur. These regimens often follow beneficial nutritional therapy or maleficent pharmacological stress and may be one of the determinants in cell nutrition which influence PMN function. It is partially through its effect on PMN labile free amino acid pool that ala-gln supplemented to diazepam may maintain PMN immune functions in vitro.

Postoperative nausea and vomiting after Faden operation.

OBJECTIVE: The purpose of this study was to evaluate the antiemetic effect of prophylactic dimenhydrinate application prior to Faden operation and to compare the incidence of PONV between bimedial Faden operation (BMF) and horizontal recess-resect procedure (R&R). METHODS: Ninety-nine children (4-10 years) scheduled for BMF were included in this prospective double-blind study. Midazolam (0.5 mg/kg body weight, BW) was administered orally for premedication 30 min before induction of anesthesia. Additionally, children weighing >/=23 kg received either dimenhydrinate suppositories or placebo. The placebo group was compared with 148 children who underwent R&R surgery without antiemetic prophylaxis during the same period. Anesthesia was induced with thiopentone (5-10 mg/kg BW) and vecuronium (0.1 mg/kg BW) bromide and maintained with halothane (1-2 vol%) in N(2)O/O(2) (65/35 vol%). Age, height, weight, and incidence of oculocardiac reflex were documented. PONV was classified into "no vomiting", "vomiting without therapy", and "vomiting requiring rescue medication". In the latter case dimenhydrinate was given again. The chi-square test was used for statistical analysis. RESULTS: Forty-eight patients received placebo, while 51 received dimenhydrinate. No differences between any groups were observed concerning age, height, weight, and incidence of oculocardiac reflex. Compared to R&R surgery, PONV requiring rescue medication occurred significantly more frequently after BMF (45% vs 23% after R&R). PONV after BMF was significantly less severe in the dimenhydrinate group than in the placebo group. The total incidence of PONV after BMF, however, was not significantly reduced. CONCLUSION: The high incidence of PONV after BMF can be explained by the greater invasiveness of BMF than R&R surgery. PONV requiring antiemetic rescue medication can be reduced by preoperative administration of dimenhydrinate suppositories.

Cerebral blood flow velocity during isovolemic hemodilution and subsequent autologous blood retransfusion.

PURPOSE: To quantify the influence of hematocrit on cerebral blood flow velocity (CBFV) in healthy volunteers undergoing acute isovolemic hemodilution (HD) with hydroxyethyl starch 10% (HES) and subsequent autologous whole blood retransfusion (RT). METHODS: In 11 volunteers 20 ml x kg(-1) blood was withdrawn over 30 min and simultaneously replaced with HES 10%. Thirty min later, RT was started at a constant rate over 30 min. Recorded parameters included: CBFV pulsatility-index (PI) and resistance-index (RI) of the middle cerebral artery (MCA). Blood pressure (BP), heart rate (HR), hemoglobin (Hb), hematocrit (Hc) peripheral O2-saturation (SpO2), P(ET)CO2, arterial oxygen content (CaO2) and cerebral arterial O2-transport (C(E)-DO2= CaO2 x Vm-MCA) were monitored. RESULTS: An average of 1570 total blood was withdrawn which resulted in a decrease in Hb from 14.5 mg x dl(-1) to 10.3 mg x dl(-1); Hc (and CaO2) decreased from 41.8% (19.8 ml x dl(-1)) to 29.6% (14.2 ml x dl(-1); P < 0.01). Vm-MCA increased from 61.2 cm x sec(-1) to 77.3 cm x sec(-1) (P < 0.01). Following RT, Vm-MCA decreased again, but remained higher than baseline (P < 0.01). PI decreased by 13% following RT (P < 0.05). There were no changes in RI, HR, BP SpO2 and P(ET)CO2. Regression lines could be fitted between Hc and Vm-MCA, Vm-MCA and CaO2, and between Hc and C(E)DO2. CONCLUSIONS: Transcranial Doppler changes in blood flow velocities correlated with the simultaneously recorded systemic Hc and CaO2 values. We found a 2% increase in CBFV for each 1% decrease in Hc and CaO2.

Preoperative microbiologic screening and antibiotic prophylaxis in pulmonary resection operations.

BACKGROUND: Pulmonary resection is associated with considerable risk of infection, so antibiotic prophylaxis has become routine practice in pulmonary operations. We studied two standard flash antibiotic prophylaxis regimens and matched them to preoperatively acquired microorganisms. METHODS: In 120 patients scheduled for elective pulmonary resection, aspirates were taken separately from the left and the right lung using a double-lumen tube. Then the patients received either 1.5 g of sulbactam plus ampicillin (n = 60; group 1) or 2 g of cefazolin (n = 60; group 2) intravenously as a single-shot antibiotic prophylaxis according to a prospective randomized sequence. When bacteria were found in the aspirates, both antibiotics were tested for susceptibility. The patients were monitored for the first 3 postoperative days with regard to bronchopulmonary infections. RESULTS: Fifty-eight pathogens were isolated from the 120 patients. The cultured bacteria did not differ significantly between the two groups. In group 1 all found bacteria were susceptible to the used antibiotic prophylaxis, whereas in group 2 eight of the 25 found bacteria were not susceptible to antibiotic prophylaxis. Postoperatively, group 2 showed significantly more signs of bronchopulmonary infections than the group 1 and subsequently needed additional antibiotics more often. Intensive care unit stay was longer in patients of group 2 and costs were higher for these patients. CONCLUSIONS: Preoperative microbiologic examination could be helpful to evaluate efficacy of the antibiotic prophylaxis regimen. Sulbactam plus ampicillin was significantly more effective than cefazolin.

[Risk factors and frequency of adverse effects after autologous blood donation]. / Risikofaktoren und Häufigkeiten von Nebenwirkungen bei autologen Blutentnahmen.

OBJECTIVE: Autologous blood donation before elective surgery decreases the perioperative risk although donation itself can cause adverse effects. Are there specific donor characteristics, which influence the frequency and severity of adverse effects? METHODS: We investigated in a prospective study 3603 autologous blood donations including registration of patient's age, gender, height, weight, medical record and risk-score by Böcker. The adverse effects were divided into severity groups (SG). The investigation took place in a Department of Anaesthesiology and Intensive Care Medicine in an university hospital. 1041 patients with preoperative autologous blood donation were investigated between January 1995 and April 1997. RESULTS: 7.4% of patients had adverse effects. Hypotension and bradycardia were the most frequent adverse effects. 4.3% of the adverse effects were graded as minimal (SG 1), 2.4% as mild (SG 2) and 0.7% as moderate (SG 3). The rate was higher in young donors (< 25 years). For all other donor characteristics including older age, cardiac or pulmonary diseases and high risk-score no higher donation risk was observed. CONCLUSIONS: Adverse effects during and after autologous blood donation are rare. Predictor for reaction seems to be young age (< 25 years). Referring to donor's characteristics and predonation risk factors it is hardly possible to predict adverse effects. Thus, all autologous blood donors require adequate monitoring by a physician. Under these circumstances the autologous blood donation is a safe procedure even in patients with severe risk factors.

[Reduction of bacterial contamination during mechanical autotransfusion by uv irradiation--initial results]. / Reduktion von bakteriellen Kontaminationen während maschineller Autotransfusion durch UV-Bestrahlung--Erste Ergebnisse.

OBJECTIVE: To investigate the effects of UV-radiation of autologous blood on bacteria and red blood cells when using intraoperative sampling of autologous blood using a cell separator--an established method for reducing the need for donor blood during surgery--which is reported to have a bacterial contamination rate of 5-75%, due mainly to coagulase-negative staphylococci (CNS). METHODS: Cell-separator blood was diluted to a haematocrit level permitting transmission of 1% of the UV-radiation used in this study (lambda 254 nm, coat thickness 1 mm). CNS samples were irradiated for 2, 4, 10, 20 and 30 seconds. Free haemoglobin and methaemoglobin levels were measured, and erythrocytes examined microscopically at the end of the procedure. RESULTS: Blood samples had to be diluted to a haematocrit of 1% to permit transmission of 1% of the UV light. The optimal irradiation duration was 4 seconds, when bacteria were completely eliminated. Longer irradiation durations were associated with increasing levels of free haemoglobin and methaemoglobin, the levels of which at 4 seconds exposure were 12.5 mg/L and 15.5%, respectively. CONCLUSIONS: It is possible to prevent CNS contamination of cell-separator blood by irradiation with UV light. Prior to clinical application, however, the method will need to be modified to minimize side effects and increase its decontamination efficacy.

[Effects of various feeding regimens in multiple trauma patients on septic complications and immune parameters]. / Auswirkungen verschiedener Ernährungsregime bei polytraumatisierten Patienten auf septische Komplikationen und Immunparameter.

OBJECTIVE: The aim of this study was to investigate the incidence of septic complications, the immunological changes by the course of lymphocyte subsets and metabolic parameters on polytraumatised patients when given nutritional support in form of early enteral and total parenteral nutrition. Furthermore, we looked for differences between a standard enteral diet and a diet supplemented with arginine, omega-3-fatty acids, nucleotide, and selenium. METHODS: 30 polytraumatised patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II)-Score > 10 points, who received nutritional support for a minimum of 7 days, were randomised to a "supplemented enteral group" (group 1), an "enteral standard group" (group 2), or a "parenteral group" (group 3). In the first both groups there were early enteral feeding. The patients of group 3 were fed isonitrogenous and isocaloric to group 2. Leucocytes, lymphocytes, CD3(+)-, CD4(+)-, CD3+HLA-DR(+)-, CD8(+)-, CD19(+)-subsets, natural killer-cells (CD56+) and metabolic parameters were measured on days 1, 3, 5, 7. RESULTS: Septic complications occurred in 2 patients in group 1, in 1 patient in group 2 and in 4 patients in group 3. The total number of lymphocytes had an increase on day 7 in group 1 (1420/microliter) and group 2 (1620/microliter) and were higher compared with group 3 (1044/microliter). On day 7 T-cells (CD3+) were 1107/microliter in group 1, 1014/microliter in group 2 and 770/microliter in group 3, T-helper-cells (CD4+) rose on day 7 higher in the enteral fed groups (group 1:746/microliter, group 2:719/microliter) than in group 3 (570/microliter). No significant differences between the groups were seen by CD3+HLA-DR(+)-cells, T-suppressor-cells (CD8+), B-cells (CD19+) and natural killer-cells (CD56). CONCLUSION: Early enteral nutrition seems to stabilise the immunosuppression of polytraumatised patients in an earlier phase. There is a consolidation of the lymphocyte counts, and of T(CD3+)- and T-helper-cells (CD4+). This could be the immunological correlate for the number of septic complications in the enteral fed groups. Therefore polytraumatised patients should be fed rather early enteral than parenteral when possible. In the initial phase after the trauma the way of nutritional support has more importance on the immune system as nutritional contents. So, in this form of studying, there is no advantage of immunonutrition.

The influence of acute preoperative plasmapheresis on coagulation tests, fibrinolysis, blood loss and transfusion requirements in cardiac surgery.

OBJECTIVE: Withdrawal of autologous plasma and reinfusion after cardiopulmonary bypass (CPB) offers the opportunity of improving patients' haemostasis and reducing homologous blood consumption in cardiac surgery. The influence of acute, preoperative plasmapheresis (APP) on coagulation tests, fibrinolysis, blood loss and transfusion requirements was investigated in elective aortocoronary bypass patients. METHODS: Forty patients were randomized to a control or pheresis group. The pheresis group had platelet-rich plasmapheresis (PRP-group, n = 20) performed before incision and the platelet-rich plasma (PRP) was returned after CPB. The control group (n = 20) was managed without pheresis. All patients had serial coagulation studies, including prothrombin split products (F1/F2), fibrinopeptide A (FPA), protein C (PC), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), haemoglobin and platelet counts determined intra- and postoperatively. Chest tube drainage and transfusion requirements were recorded. RESULTS: APP had no negative effects on the quality of PRP. The platelet count of the withdrawn autologous plasma was 239 +/- 33 x 10(9)/l. From the end of the operation (after retransfusion of autologous plasma) until the first postoperative day platelet counts were significant higher in the PRP-group (P > 0.05). Plasma concentrations of modified antithrombin III (ATM), F1/F2 and FPA increased (166-290% from baseline) and PC- and TM-antigen decreased (11-49% from baseline) to a different extent for both groups throughout CPB. t-PA-activity increased intraoperatively peaking at the end of CPB (PRP-group: 4.8 +/- 0.8 IU/ml, control-group: 8.1 +/- 2.3 IU/ml)(P > 0.05). With onset of CPB PAI-1 levels decreased and were further reduced after CPB in control patients in comparison to PRP-patients (P < 0.05). FPB beta 15-42 occurred in peak concentrations after neutralisation of heparin by protamine. Only PRP-patients showed baseline values of coagulation and fibrinolytic parameters on the next morning (P < 0.05). Total postoperative blood loss during the first 24 h was 503 +/- 251 ml (PRP-group) and 937 +/- 349 ml in the control-group (P < 0.05). None of the PRP-patients received allogeneic blood, whereas five control-patients received 11 units of packed red cells (P < 0.05). CONCLUSIONS: The findings suggest that in elective cardiac surgery heparin cannot prevent generation of both thrombin and fibrin, born throughout CPB and postoperatively. The use of PRP withdrawn immediately preoperatively is an attractive technique to reduce allogeneic blood usage and preoperative blood loss, especially in patients in whom withdrawal of autologous whole blood cannot be performed.

[Is the elimination of osteosarcoma cells with intraoperative "mesh autotransfusion" and leukocyte depletion filters possible?]. / Ist die Elimination von Osteosarkomzellen durch "maschinelle Autotransfusion" und Leukozyten-Depletionsfilter möglich?

UNLABELLED: Intraoperative autotransfusion is contraindicated in cancer surgery because of the possible risk of systemic tumor spread. The aim of the present study was to investigate whether a cell saver in combination with a white blood cell depletion filter can remove osteosarcoma cells. METHODS: A defined number of osteosarcoma cells from an established cell line were added to red cell concentrates and Ringer solution. The tumor cell concentration was 1000/ ml in the first five experiments, 7111/ml in test no. 6, 1667/ml in test no. 7 and 167/ml in test no. 8. Following thorough mixing, each unit was processed separately by a cell saver (DIDECO BT 795/P) in its normal operation mode to produce a red cell concentrate. This red cell concentrate was filtered using a leukocyte depletion filter (PALL BPF 4). Samples were taken before and after processing with the autotransfuser and after filtration with the white cell depletion filter. Cytospin specimens from all samples were examined for osteosarcoma cells by three different methods (Papanicolaou stain, Vimentin antibodies, DNA analysis). RESULTS: After processing with the autotransfuser, tumor cells were identified in the red cell concentrate. No osteosarcoma cells were evident after the combined use of cell saver and leukocyte depletion filter. CONCLUSION: The sole use of the autotransfuser DIDECO BT 795/P during osteosarcoma surgery is not recommended because of the potential danger of retransfusion of malignant cells. In combination with the leukocyte depletion filter PALL BPF 4, no osteosarcoma cells were identified in the red cell concentrate. Since the adhesiveness of tumor cells from established cell lines may be different from that of tumor cells in the intraoperative salvaged blood, further studies with blood from the surgical field are necessary to determine the efficacy of white cell depletion filters to eliminate osteosarcoma cells.

The effect of the anticoagulation regimen on endothelial-related coagulation in cardiac surgery patients.

Heparin is still the most commonly used anticoagulant in cardiac surgery necessitating cardiopulmonary bypass. In recent years, endothelial-related coagulation (e.g. thrombomodulin/protein C-system) has enlarged our knowledge of the regulation of haemostasis. In a controlled randomised study, the influence of different regimens of anticoagulation on the thrombomodulin/protein C-system was studied. Sixty patients undergoing elective coronary artery bypass grafting were randomly allocated into four groups (n = 15) to receive: 300 IU.kg-1 of heparin before bypass; 600 IU.kg-1 of heparin; 300 IU.kg-1 of heparin as bolus followed by a continuous infusion of 10 000 IU.h-1 until the end of bypass; or 600 IU.kg-1 of heparin plus 'high dose' aprotinin (2 million IU of aprotinin before bypass, 500 000 IU.h-1 until the end of the operation and 2 million IU added to the bypass pump prime). Grouping was blinded for the surgeon and the anaesthetist. Plasma concentrations of thrombomodulin, protein C and (free) protein S as well as thrombin/antithrombin III were measured by enzyme-linked-immunosorbent assays after induction of anaesthesia, during and after bypass, at the end of surgery, 5 h after bypass, and on the first postoperative day. Activated clotting time was significantly longer during bypass in group 2 (566 (60)s) and group 4 (655 (59)s), whereas standard coagulation parameters showed no differences between the four groups. Blood loss and use of homologous blood and blood products were highest in groups 2 and 3. Thrombomodulin plasma levels were similar (and normal) at baseline (< 40 ng.l-1), decreased during bypass and reached baseline values postoperatively without showing significant group differences. Protein C did not show any differences among the groups within the investigation period. 'Free' protein S plasma levels were most reduced in group 1 (from 68 (8)% to 48 (9)% after bypass). Thrombin/antithrombin III plasma concentrations increased most in groups 1 (to 69 (14) micrograms.l-1 after bypass) and 2 (to 48 (7) micrograms.l-1 after bypass), whereas they remained significantly lower in groups 3 and 4. The thrombomodulin/protein C-system was not significantly influenced by the regimen of anticoagulation. Administration of 'high-dose' heparin was associated with the highest blood loss, which could not be related to endothelial-associated coagulation.

[Mechanical autologous transfusion in orthopedic surgery in children. Is the use of mechanical autologous transfusion possible even in pediatric orthopedic surgical procedures?]. / Maschinelle Autologe Transfusion (MAT) während orthopädischer Eingriffe bei Kindern. Ist der Einsatz der Maschinellen Autotransfusion auch bei kinderchirurgischen Eingriffen möglich?

The use of autotransfusion devices is an established method of reducing the need for homologous transfusions in surgery [3, 11, 13], but technical factors still contraindicate the washing and concentration of blood volumes smaller than 300 ml. Therefore, haemoconcentration of small volumes of salvaged blood, as usually found in paediatric surgery, is considered to be a complicated and questionable practice [5]. Whereas these amounts of blood loss are easily tolerated by adults, they may necessitate homologous transfusions in paediatric surgery. In a prospective study, we investigated whether a simple technical modification in the processing of salvaged blood could facilitate the use of autotransfusion devices, especially in children. PATIENTS AND METHODS. Intraoperative blood salvage was performed in children 6 months to 10 years old undergoing surgery for hip dysplasia. Autotransfusion (Dideco STAT) was started when the blood loss was estimated to be more than 20% of the total blood volume (TBV). As a reference, we used a formula based on body weight [10]: for children up to the age of 6 years 80 ml/kg blood volume and for children up to 10 years 75 ml/kg. The total volume of salvaged fluid including blood, anticoagulant solution, and surgical irrigation was collected in a reservoir and transferred to the autotransfusion set, after which the reservoir was rinsed with 500 ml 0.9% saline solution in order to save the remaining blood. After processing, the blood was stored in the retransfusion bag. By adding the same volume of plasma expander (6% hydroxyethyl starch [HES], molecular weight 450,000), spontaneous sedimentation of the washed autologous erythrocytes (RBCs) for 10-15 min led to a concentrate of RBCs. After 10 mu filtration, the RBC suspension was retransfused (Figs. 1-3). RESULTS. Within 12 months, autotransfusion was performed during 6 out of 15 surgical procedures according to the method described above. The calculated blood loss averaged 25.6% of TBV, of which 21.4% (= 272 ml) could be processed by the autotransfusion device (Table 3). The mean values of 2.6 g/dl haemoglobin (Hb) and 6.8% haematocrit (HCt) in the salvaged blood increased to 9.4 g/dl and 27.3% in the processed RBC concentrates. After adding 6% HES solution, spontaneous sedimentation of the RBCs led to values of Hb 22.1 g/dl and HCt 59.8%. An average of 59.5 ml (22-99 ml) sedimented RBCs was retransfused to the patients, including 11.6 ml 6% HES solution (Table 4). In this manner, the need for homologous transfusions could be avoided in these patients both during and after surgery. CONCLUSIONS. This study shows that the use of blood salvaging in paediatric surgery is indicated under certain conditions. With the aid of the simple modification described above, we solved the main problem in paediatric autotransfusion by concentrating RBC suspensions with low Hb and Hct values after using the autotransfusion device.

Does aprotinin influence endothelial-associated coagulation in cardiac surgery?

Aprotinin has been reported to reduce bleeding in cardiac surgery patients. Its mechanisms of action on coagulation have not been fully elucidated. In a prospectively randomized study of 40 patients undergoing elective aortocoronary bypass grafting, the influence of high-dose aprotinin (2 million IU of aprotinin before CPB, 500,000 IU/h until the end of operation, 2 million IU added to the prime) (N = 20) on endothelial-related coagulation was compared to a nontreated control group (N = 20). Thrombomodulin (TM), protein C and (free) protein S as well as thrombin/antithrombin-III (TAT) plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) before the aprotinin infusion, before cardiopulmonary bypass (CPB), during CPB and after CPB, at the end of surgery, 5 hours after CPB, and on the first postoperative day. All standard coagulation parameters (AT-III and fibrinogen plasma levels, platelet count, partial thromboplastin time) did not differ between the two groups. At baseline, TM plasma levels were within the normal range (< 40 ng/mL) and similar in both groups. During CPB, TM plasma concentrations decreased similarly in both groups (aprotinin: 18 +/- 6 ng/mL, control: 17 +/- 7 ng/mL) followed by a comparable increase in the postbypass period until the first postoperative day (aprotinin: 60 +/- 10 ng/mL, control: 53 +/- 11 ng/mL). Protein C and (free) protein S plasma levels also showed no differences between the two groups. On the first postoperative day, baseline values for protein C and protein S had not yet been reached.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effectiveness of oral versus parenteral iron substitution in autologous blood donors]. / Wirkung oraler versus parenteraler Eisensubstitution bei Eigenblutspendern.

OBJECTIVE: Is intravenous iron therapy as efficient as oral iron supplementation in patients undergoing autologous blood donation? DESIGN: Prospective, randomized study. PATIENTS AND SETTING: 30 male and 30 female patients, separated into two groups were examined prior to total hip replacement. INTERVENTIONS: Patients of group O were given 6 x 50 mg Fe2+ aspartate/day orally, and patients of group P were given 0.75 mg/kg BW complex-bound Fe3+ once a week by infusion. In both groups therapy was started two weeks prior to the first donation. The substitution was continued the following six weeks until surgery. Hemoglobin, ferritin plasma concentrations and reticulocytes were monitored. The appearance of unwanted side effects was studied by questionnaire. RESULTS: Hb decreased significantly in both groups. A difference was seen in the reticulocyte count and in the ferritin levels. Here we found a significant increase in group P compared with group O. 40% of the patients who took the iron orally complained about unwanted side effects such as obstipation and diarrhoea, whereas none of the patients of the parenteral group had any complaints. CONCLUSIONS: Stimulation of the erythropoiesis appeared to be more efficient with intravenous iron therapy than with oral iron supplementation. The oral dose has in about 40% unwanted side effects. For this reason a parenteral iron therapy can be considered, but one must be aware that in some cases dangerous anaphylactic reactions could appear.

[The effect of different autotransfusion procedures on the antibiotic picture. A study on cephalosporin cefamandole]. / Der Einfluss unterschiedlicher Autotransfusionsverfahren auf Antibiotikaspiegel. Studie zum Cephalosporin Cefamandol.

Infection after open heart surgery is a serious complication since eradication of infection in these cases is difficult even with appropriate antibiotic therapy. In the attempt to avoid this problem, prophylactic administration of antibiotics is common. Their relative safety and their broad spectrum of activity make cephalosporin antibiotics popular choices for prophylaxis prior to and during operations, including cardiovascular procedures. METHODS. Preoperative antibiotic prophylaxis with 2 g cefamandole was performed in a prospective randomized study including 62 male patients divided into three groups. All patients gave informed consent, and the study was approved by the ethics committee of the hospital. Patients in group 1 (n = 21) and group 2 (n = 21) underwent aortocoronary bypass (ACVB) with extracorporeal circulation (ECC), while patients in group 3 (n = 20) had carotid surgery. Anaesthesia, coronary-bypass procedures and infusion regime were standardized. The flow rate during ECC was maintained at 2.41/min/m2 and the rectal temperature between 33 degrees and 34 degrees C. Arterial and urine specimens for the determination of plasma and urine levels of cefamandole were taken at definite times. Autologous blood salvage during operation was performed with haemofiltration techniques (HF) in group 1 (HF 80, Fresenius, Bad Homburg, Germany) and with cell separation techniques (CS) in group 2 (Hemonetics III, Hemonetics). Plasma and urine cefamandole levels were measured by high-pressure liquid chromatography (HPLC). RESULTS. After administration of 2 g cefamandole mean peak levels of 404.6 +/- 141.7 micrograms/ml were seen. Because of haemodilution at the beginning of extracorporeal circulation, group 1 and 2 showed much lower cefamandole plasma levels, 22.1 +/- 11.6 micrograms/ml and 24.3 +/- 14.4 micrograms/ml, than group 3 (after the same time course), with 47.4 +/- 19.1 micrograms/ml. For all patients in group 1 and 2 prebypass time (70.3 +/- 22.4 min) and the duration of the ECC (72.3 +/- 17.7 min) were comparable. There was a significant correlation between prebypass time and cefamandole plasma levels at the beginning of extracorporeal circulation (P < 0.001). No correlation could be seen for the plasma concentration after discontinuation of the extracorporeal circulation and the duration of extracorporeal circulation. The volume of autologous red packed cells and the enclosed amount of cefamandole showed a significant difference (P < 0.001) between group 1 (1120.0 +/- 296.8 ml, 27.5 +/- 17.1 mg) and group 2 (734.3 +/- 186.6 ml, 2.9 +/- 3.2 mg). The plasma cefamandole level after transfusion of autologous blood displayed a significant correlation (p < 0.01) with cefamandole concentration in the autologous red packed cells. Transfusion of the autologous blood produced no significant increase in plasma cefamandole levels. With an operation time of more than 2.5 h during ECC the cefamandole plasma level decreased below the necessary minimal inhibitory concentration (MIC90), particularly for gram-negative bacteria. CONCLUSION. Additional administration of 1 g cefamandole shortly before the beginning of cardiopulmonary bypass is recommended, particularly for surgical procedures with ECC of more than 2.5 h. Adjustment of drug dosage prior to or during surgery may be required to optimize therapy, but before this can be achieved precisely, more information on drug disposition during the operative procedures is needed.