Retraction notice to "Haemodynamic effects of the phosphodiesterase inhibitor enoximone in comparison with dobutamine in esmolol-treated cardiac surgery patients" [Br J Anaesth 64 (1990) 611-6].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

Retraction notice to "Influence of hypertonic volume replacement on the microcirculation in cardiac surgery" [Br J Anaesth 67 (1991) 595-602].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

Retraction notice to "Volume replacement with hydroxyethyl starch solution in children" [Br J Anaesth 70 (1993) 661-5].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

Retraction notice to "The role of enoximone in cardiac surgery" [Br J Anaesth 69 (1992) 45-50].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief, Professor Hugh Hemmings, based on the recommendations of Justus-Liebig-University Giessen following an internal review of research conducted by Joachim Boldt at the University. This is further described in 'Further Retractions of Articles by Joachim Boldt', https://doi.org/10.1016/j.bja.2020.02.024.

Comparison of two strategies for the treatment of radiogenic leukopenia using granulocyte colony stimulating factor.

PURPOSE: Radiation-induced leukopenia can cause a delay or discontinuation of radiotherapy. This complication can be overcome with the use of granulocyte colony-stimulating factor (G-CSF). However, an uncertainty exists regarding the mode of application of G-CSF in patients treated with radiotherapy. For this reason, the efficacy of two strategies for the administration of G-CSF in irradiated patients was compared in a prospective randomized clinical study. METHODS AND MATERIALS: Forty-one patients who developed leukopenia (< 2.5 x 10(9) per liter) while undergoing radiotherapy were treated with G-CSF at a daily dose of 5 microg/kg. The first group received single injections of G-CSF as required (n = 21). The second group received G-CSF on at least 3 consecutive days (n = 20). An analysis was made of the changes in leukocyte counts, the number of days on which radiotherapy had to be interrupted, and the side effects of growth-factor treatment. RESULTS: An increase in leukocyte values in the peripheral blood was observed in all patients treated with G-CSF. In the group which received G-CSF when required, two injections (range: 1-8) were administered in most cases. In the second group, most of the patients received three injections (range: 3-9). The average duration of therapy interruptions due to leukopenia was 4.8 days (0-28) in the first therapy arm and 2.5 (0-20) in the second arm. The variance in the duration of therapy interruptions between the two groups was not significant (p = 0.2). Radiotherapy had to be terminated in two patients due to thrombocytopenia but the application of G-CSF did not seem to be a reason of decreasing platelet counts. CONCLUSIONS: Our results reveal that G-CSF is safe and effective in the treatment of radiation-induced leukopenia regardless of the mode of application. Because the calculated difference related to radiation treatment interruptions has no clinical relevance, both approaches examined in our study appear reasonable.

Endotoxemia and cytokine generation in cardiac surgery in relation to flow mode and duration of cardiopulmonary bypass.

We investigated whether pulsatile flow in cardiopulmonary bypass (CPB), which has been shown to improve intestinal perfusion, reduces endotoxin translocation from the gut and, in consequence, decreases cytokine generation. The study population consisted of 48 adult patients who underwent elective CPB surgery. Pulsatile flow was used during aortic cross-clamping in 24 patients and nonpulsatile flow in 24 patients. Plasma endotoxin concentration increased in all patients during CPB. Significantly (P < 0.05) lower peak levels of 8.25 +/- 1.17 (SEM) pg/mL were reached 30 min after CPB in patients with pulsatile flow in contrast to 11.26 +/- 1.42 pg/mL in patients with nonpulsatile flow. The extent of endotoxemia was not related to the duration of CPB. Following the increase of plasma endotoxin, the concentrations of IL-6 and IL-8 increased with delay of approximately 1 h. The peak levels of these cytokines corresponded significantly (P < 0.005 and P < 0.01, respectively) with duration of CPB, but not with flow mode. Thus, in patients with CPB of more than 97 min (median), IL-6 reached a peak of 335.5 +/- 48.87 pg/mL and IL-8 of 64.86 +/- 24.79 pg/mL in contrast to 210.9 +/- 18.45 pg/mL and 21.2 +/- 10.19 pg/mL, respectively, with bypass times of less than 97 min. The degree of endotoxemia in CPB mainly depends on the quality of tissue perfusion. Cytokine generation, however, is not triggered exclusively by endotoxin, but rather by the trauma of CPB and surgery.

Myocardial temperature during cardiac operations: influence on right ventricular function.

Maintenance of right heart integrity is frequently neglected during coronary operations. Right ventricular dysfunction sometimes limits the success of the surgical procedure, however. In addition to the use of cardioplegic solutions, myocardial hypothermia during ischemic cardiac arrest seems to be an important factor for guaranteeing right ventricular performance thereafter. This study was designed to measure myocardial temperature in patients with coronary artery disease who have significant stenosis of the right coronary artery in comparison with those who do not have stenosis of the right coronary artery and to evaluate the influence of myocardial temperature on right ventricular hemodynamics after cardiopulmonary bypass. Right ventricular function was assessed by thermodilution technique, which allows measurement of right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume. Right ventricular temperature differed significantly between the two groups, with the lowest value of 15.1 degrees +/- 1.8 degrees C in the group without stenosis of the right coronary artery and a value of 22.2 degrees +/- 2.1 degrees C in the group with stenosis of the right coronary artery. Left ventricular and septal temperatures were without group differences within the investigation period. Right ventricular hemodynamics were impaired only in the group with stenosis of the right coronary artery with a decrease in right ventricular ejection fraction from 44.2% to 34.1% immediately after termination of bypass and an increase in right ventricular end-diastolic volume index (+38%) and right ventricular end-systolic volume index (+70%). Cardiac index decreased only in this group, too (-22.5%). Analysis of covariance revealed a significant correlation only between changes in right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume and the course of right myocardial temperature. It is concluded that right ventricular hypothermia is more difficult to achieve in patients with a diseased right coronary artery. Constant myocardial hypothermia, however, seems to be important in guaranteeing right ventricular function, which easily can be evaluated by the thermodilution technique.

Efficacy of the phosphodiesterase inhibitor enoximone in complicated cardiac surgery.

Acute myocardial dysfunction during cardiac surgery involves various pathophysiologic mechanisms such as reduction in myocardial contractility and an increase in afterload induced by peripheral vasoconstriction. In 30 consecutive patients undergoing coronary artery bypass grafting (CABG) and ten consecutive patients with aortic valve replacement (AVR), in whom therapy with catecholamines was expected to be necessary during and after weaning from cardiopulmonary bypass (CPB) on the basis of a retrospective study ("control" patients), 1.0 mg/kg of the phosphodiesterase (PDE) inhibitor enoximone was administered ten minutes prior to weaning from bypass (enoximone group). In eight CABG and four AVR patients weaning was possible without further pharmacologic support. Significantly less epinephrine was used in enoximone pretreated patients (8.8 +/- 3.0 micrograms/min) than in the control patients (21.4 +/- 4.4 micrograms/kg). The use of additional vasodilators was significantly less pronounced in these patients as well. Seven CABG and four AVR patients in the enoximone group needed additional vasoconstrictors (norepinephrine) to counteract marked, unwanted decrease in peripheral vascular resistance with a decrease in mean arterial pressure (MAP). Hemodynamic monitoring revealed a higher level in heart rate in the control patients with arrhythmia in seven of the CABG patients: MAP, right atrial pressure, cardiac index, and pulmonary capillary wedge pressure were without significant differences between the groups. Pulmonary artery pressure and TSR, however, increased more in the control group, indicating an increase in right and left ventricular afterload. The results of this study demonstrate that patients at risk of circulatory failure during or after weaning from CPB profit from pretreatment with PDE-III inhibitor enoximone due to a reduction in catecholamines and an improvement in hemodynamics.

Comparison of two aprotinin dosage regimens in pediatric patients having cardiac operations. Influence on platelet function and blood loss.

Only a few studies have reported on the effects of aprotinin in pediatric cardiac surgery, and the correct dose is controversial. In a prospective, randomized study, three groups of children weighing less than 20 kg were investigated. In group 1 (n = 14): aprotinin 20,000 U/kg was given after induction of anesthesia, 20,000 U/kg was added to the prime, and another 20,000 U/kg was given every hour of cardiopulmonary bypass (low-dose regimen). In group 2 (n = 14) aprotinin 35,000 U/kg was given after induction followed by an infusion of 10,000 U/kg.min until the end of the operation and 35,000 U/kg was added to the prime (high-dose regimen). In group 3 (n = 14) no aprotinin was used (control). Platelet function was evaluated by aggregometry (maximum platelet aggregation, maximum gradient of platelet aggregation) by means of turbidometric technique (inductors: adenosine diphosphate, collagen, and epinephrine) before and after cardiopulmonary bypass until the first postoperative day. Platelet aggregation was significantly reduced during and after bypass, values ranging from -29% to -54% (maximum aggregation) and -25% to -75% (maximum gradient of aggregation) with regard to baseline values. In the further postoperative course, platelet function recovered and mostly exceeded baseline values on the first postoperative day. Platelet aggregation variables were without any differences among aprotinin-treated and control patients. Blood loss was similar for all three groups and added up to approximately 28 ml/kg until the first postoperative day. The use of packed red cells was also comparable for the three groups, whereas the use of fresh frozen plasma was highest in group 1 (1680 ml until the first postoperative day). We conclude from this study that aprotinin did not improve platelet function and did nor reduce blood loss or the need for homologous blood transfusion in pediatric cardiac surgery, regardless of whether a low-dose or a high-dose regimen was used.

Influence of aprotinin on the thrombomodulin/protein C system in pediatric cardiac operations.

Thirty consecutive children scheduled for pediatric cardiac operation with cardiopulmonary bypass were included in the study. Before the operation, the patients were randomly divided into two groups: with aprotinin (n = 15, 30,000 U/kg after induction of anesthesia, 30,000 U/kg added to the prime of the cardiopulmonary bypass or without aprotinin (n = 15). Thrombomodulin, (free) protein S, protein C, and thrombin/antithrombin III complex were measured from arterial blood samples taken after induction of anesthesia (at baseline, before aprotinin) and before, during, and after cardiopulmonary bypass until the first postoperative day. Standard coagulation parameters (antithrombin III, fibrinogen, platelet count, and partial thromboplastin time) were without differences between the groups. Thrombomodulin plasma concentrations were within normal range ( < 40 micrograms/L) and were similar in both groups at baseline. During cardiopulmonary bypass and until 5 hours after cardiopulmonary bypass, however, thrombomodulin plasma levels were significantly lower in the children treated with aprotinin. No further differences were observed on the first postoperative day. Protein C and protein S plasma levels did not differ between the two groups. Thrombin/antithrombin III-complex plasma concentrations increased significantly during cardiopulmonary bypass, however, without showing differences between children with (225 +/- 49 micrograms/L) and without (149 +/- 31 micrograms/L) aprotinin treatment. Blood loss and the need for homologous blood and blood products did not differ significantly between the two groups. We concluded that administration of aprotinin resulted in reduced thrombomodulin plasma levels in pediatric patients undergoing cardiac operation without altering protein C/protein S plasma concentration. The exact role of aprotinin in endothelium-derived coagulation should be further studied.

Perioperative management of pulmonary hypertension after heart transplantation in childhood.

BACKGROUND: Pulmonary hypertension is responsible for a substantial part of perioperative and postoperative mortality and morbidity after cardiac transplantation. Treatment of right ventricular failure after increased pulmonary vascular resistance is difficult especially in infants and children. Therefore we started a preventive therapy of pulmonary hypertension after cardiac transplantation to avoid right ventricular failure and compared the results with a group of patients with conventional therapy. METHODS: Group 1 (n = 13), with transplantation from 1988 to 1991, was treated with vasodilators when symptoms of right ventricular failure developed. Group 2 (n = 19) had preventive treatment with prostaglandin E1 (PGE1), the phosphodiesterase-III inhibitor enoximone, and alkalinazation starting during weaning from cardiopulmonary bypass. RESULTS: Six patients in group 1 died; four of them as the result of right ventricular failure in the immediate postoperative course despite aggressive treatment. In group 2 there were three deaths as the results of rejection (2) and infection (1). None of these patients developed right ventricular failure (p = 0.02). Cold ischemic time, extracorporeal circulation time, and waiting time before transplantation were significantly longer in group 2. Side effects of this preventive therapy were not observed. CONCLUSIONS: We conclude that prophylactic therapy of pulmonary hypertension with vasodilators in infants and children after heart transplantation is safe and effective in preventing right ventricular failure in the postoperative course.

Heparin management during cardiac surgery with respect to various blood-conservation techniques.

BACKGROUND: Various methods to reduce blood consumption are used in cardiac surgery. This study was designed to investigate the influence of various blood-conservation techniques on heparin plasma levels and coagulation variables in the perioperative period. METHODS: Anticoagulation was achieved by application of 300 units/kg bovine heparin before cardiopulmonary bypass (CPB). Ninety patients undergoing coronary bypass surgery were randomly divided into six groups according to different blood-conservation methods: group 1, blood during and after CPB was concentrated by a cell saver (CS); group 2, blood was concentrated by means of a hemofiltration device (HF); group 3, acute normovolemic hemodilution (ANH) was performed in combination with the CS technique (ANH-CS); group 4, ANH was carried out in combination with an HF during CPB (ANH-HF); group 5, acute plasmapheresis (APP) was performed and a CS was used during CPB (APP-CS); and group 6, APP was used in combination with an HF device (APP-HF). RESULTS: Heparin plasma concentration during CPB did not differ significantly among the six groups, ranging from 1.60 to 2.03 units/ml. Antagonization with protamine sulfate after termination of bypass in a 1:1 ratio decreased heparin concentration almost to baseline values. Fibrinogen concentration and antithrombin-III level were lowest in the CS group but were not decreased critically during the entire investigation period. Activated clotting time differed widely among the patients (range 383 to 807 seconds) and showed no significant correlation to heparin plasma levels. Partial thromboplastin time was higher than 300 seconds during the entire period of CPB, also indicating sufficient anticoagulation. Blood loss until day 1 after surgery was significantly most pronounced in the CS group and least in the APP-HF group. CONCLUSIONS: The blood conservation techniques used in this study were safe with regard to sufficient anticoagulation during CPB. No insufficient antagonization with protamine could be observed in the postbypass period.

Does platelet size correlate with function in patients undergoing cardiac surgery?

OBJECTIVE: Platelet dysfunction secondary to cardiopulmonary bypass (CPB) is one of the major reasons for nonsurgical post-operative bleeding in cardiac surgery. Whether platelet size is an indicator for platelet function was investigated in patients undergoing coronary artery bypass grafting. DESIGN: Prospective study. SETTING: Intra-operative, cardiac surgery operations. PATIENTS: 80 consecutive patients undergoing coronary artery bypass grafting. Excluding criteria were pre-operative coagulation disorders and medication with anticoagulants within the last 10 days before the operation day. MEASUREMENTS AND RESULTS: Platelet function was assessed by aggregometry using a turbidimetric method (inductors: ADP 2.0 mumol/l, collagen 4 micrograms/l, epinephrine 25 mumol/l). Mean platelet volume (MPV) was measured by an electrical conductivity method. Measurements were carried out before, during, and after CPB until the 1st post-operative day on intensive care unit (ICU). Platelet size decreased significantly during CPB (max. -25% after weaning from bypass) and returned to baseline values on the 1st post-operative day. Platelet count (ranging from 93 - 304 x 10(9)/l) did not correlate significantly with MPV or aggregation variables. Maximum aggregation and maximum gradient of aggregation induced by ADP and collagen were significantly decreased by CPB with the most pronounced reduction at the end of CPB (ranging from -25% to -45%). Analyses of co-variance revealed a significant correlation between changes in MPV and changes in aggregation variables (ADP, collagen). CONCLUSIONS: Platelet volume is easy to measure even in the operation room or in ICU and may indicate abnormalities in platelet function in the post-bypass period of cardiac surgery patients.

Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?

BACKGROUND: The differences between hypothermic and normothermic cardiopulmonary bypass (CPB) on platelet function and endothelial-related coagulation (eg, the thrombomodulin/protein C/protein S system) should be investigated. METHODS: According to a randomized sequence, 30 patients undergoing aortocoronary bypass grafting underwent either hypothermic (rectal temperature, 27 degrees C to 28 degrees C, n = 15) or normothermic CPB (rectal temperature, more than 35 degrees C, n = 15). Arterial blood samples were taken after induction of anesthesia (baseline values), before, during, and immediately after CPB, 5 hours after CPB, and on the morning of the first postoperative day. Circulating thrombomodulin, (free) protein S, protein C, and thrombin/antithrombin III complex were measured from these samples. Platelet function was assessed by aggregometry (turbidometric technique) induced by adenosine diphosphate (2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L). RESULTS: Hypothermic patients showed a significantly higher blood loss and need for homologous blood than the normothermic patients. Thrombomodulin plasma level increased more in the hypothermic (from 28 +/- 5 ng/mL to 60 +/- 10 ng/mL) than in the normothermic group (from 28 +/- 7 ng/mL to 41 ng/mL); p < 0.05). Both protein C and (free) protein S were reduced significantly in the hypothermic (protein C, from 88% +/- 25% to 60% +/- 11%; protein S, from 71% +/- 10% to 40% +/- 8%) than in the normothermic patients. Platelet aggregation was significantly more decreased in the hypothermic (adenosine diphosphate, maximum decrease by -43% relative to baseline) than in the normothermic patients (adenosine diphosphate, maximum decrease by -22% relative to baseline). In the hypothermic CPB group, platelet aggregation had recovered incompletely, whereas in the normothermic patients platelet aggregation even slightly exceeded baseline values. CONCLUSIONS: Hypothermic CPB resulted in more pronounced alterations of platelet aggregation and endothelial-related coagulation than normothermic CPB. Plasma levels of soluble thrombomodulin were more increased in hypothermic than in normothermic CPB indicating more extensive endothelial damage or activation associated with hypothermic CPB.

Aprotinin in pediatric cardiac operations: platelet function, blood loss, and use of homologous blood.

Excessive hemorrhage secondary to cardiopulmonary bypass may be encountered after pediatric cardiac operations. Platelet dysfunction appears to be especially responsible for this problem. The proteinase inhibitor aprotinin is suggested to possess platelet preservation properties and reduce blood loss in this situation. The effects of aprotinin (25,000 U/kg after induction of anesthesia, 25,000 U/kg added to the prime, 25,000 U/kg every hour of cardiopulmonary bypass) on platelet function were randomly studied in 12 children with a weight of less than 10 kg (group 2) and 12 children weighing more than 10 kg (group 4), who were compared with two groups of children without aprotinin (group 1, < 10 kg; group 3, > 10 kg). Twelve children undergoing major vessel operations without cardiopulmonary bypass and aprotinin served as a control. Platelet function was assessed using aggregometry (turbidometric technique with adenosine diphosphate, 2.0 mumol/L; collagen, 4 micrograms/mL; epinephrine, 25 mumol/L; NaCl [control]). Platelet function was not altered in the control patients within the entire investigation period. Maximum aggregation in the small children was already lower at baseline in comparison with that of the children > 10 kg. Cardiopulmonary bypass was followed by a significant reduction in platelet aggregation in all groups. Treatment with aprotinin did not improve platelet function (maximum aggregation and maximum gradient of aggregation) in any group. On the first postoperative day, maximum aggregation in the small children exceeded baseline values, whereas in both groups of children > 10 kg baseline values had almost been established. Postoperative blood loss was not reduced by treatment with aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet function in cardiac surgery: influence of temperature and aprotinin.

Hypothermic cardiopulmonary bypass (CPB) has been associated with both coagulation defects and hemorrhage. The influence of temperature on platelet function and the benefits of aprotinin in this situation were studied in 60 patients undergoing elective aortocoronary bypass grafting. The patients were randomly divided into four groups (15 patients per group): group 1, normothermic CPB (nasopharyngeal temperature > 34 degrees C); group 2, normothermic bypass and administration of high-dose aprotinin (2 million IU before CPB, 500,000 IU/h until the end of the operation, and 2 million IU added to the prime); group 3, hypothermic CPB (nasopharyngeal temperature < 28 degrees C); and group 4, hypothermic CPB and aprotinin. Platelet function was evaluated by aggregometry (turbidimetric technique), and aggregation was induced by adenosine diphosphate (1 and 2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L) before, during, and after CPB into the first postoperative day. Starting from comparable baseline values, maximum platelet aggregation and maximum gradient of platelet aggregation were significantly most reduced after CPB in group 3 (hypothermic CPB without aprotinin) (ranging from -30% to -53% relative to baseline values). In comparison with the other groups, platelet function in this group also recovered less quickly in the later post-bypass period. Hypothermic CPB with aprotinin resulted in less-altered platelet function than hypothermic CPB without aprotinin. Platelet aggregation in aprotinin-treated patients was comparable overall with that in patients undergoing normothermic CPB. On the first postoperative day, aggregation variables had returned to or exceeded baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

RETRACTED: Acute preoperative plasmapheresis and established blood conservation techniques.

Plasmapheresis performed weeks before an operation producing autologous plasma has proved to be of benefit in elective operations. First experiences in acute plasmapheresis, which is performed immediately before the operation, have been reported recently. When acute plasmapheresis is used in cardiac operations, however, it must be viewed in connection with other techniques for reducing blood consumption such as the Cell Saver (CS) and ultrafiltration devices. In 60 patients undergoing elective aortocoronary bypass grafting, acute plasmapheresis was performed, producing either platelet-poor plasma or platelet-rich plasma, in combination with either the Cell Saver or hemofiltration. Fluid balance during cardiopulmonary bypass was significantly lower in the hemofiltration patients. Postoperatively, none of these patients received donor blood, whereas 4 patients of the Cell-Saver groups needed packed red blood cells. AT-III, fibrinogen, the number of platelets, albumin, total protein, and colloid osmotic pressure were less compromised when hemofiltration was used in combination with acute plasmapheresis in contrast to combination with the Cell-Saver technique. Plasma hemoglobin was without differences during the investigation period, and polymorphonuclear elastase was less increased when platelet-rich plasma was produced preoperatively. On the first postoperative day, most of the differences between the groups had already disappeared. We conclude that when acute plasmapheresis is used in cardiac operations, discarding of plasma by the Cell Saver should be avoided and ultrafiltration devices should replace centrifugation techniques for blood conservation.