Robert Larbuisson

Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery

Background: Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid orreduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion. Methods: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post–cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post–cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population. Results: During the period from the end of cardiopulmonary bypass surgery through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused. Conclusions: Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.

Levels of inflammatory markers in the blood processed by autotransfusion devices during cardiac surgery associated with cardiopulmonary bypass circuit

Intraoperative blood salvage devices allowing a reinfusion of red blood cells (RBCs) after processing of shed blood and stagnant blood in the mediastinal cavity are more and more used to reduce homologous blood requirements in cardiac surgery with cardiopulmonary bypass (CPB). As the proinflammatory activity of the shed blood also contributes to morbidity during CPB, we conducted a prospective study in order to examine the quality of autologous blood before and after processing with five different devices [BRAT2, Sequestra, Compact Advanced, Cell Saver 5 (CS5), Continuous Autologous Transfusion System (CATS)]. All systems resulted in an excellent haemoconcentration, ranging from 53.7% (Compact) to 68.9% (CATS). The concentrations and elimination rates of several inflammatory markers [IL-1β, IL-2, IL-8, TNFα, myeloperoxidase (MPO), elastase] were examined. Except for the Sequestra, an important increase in concentration of IL-1β (between 30% and 220%) has been observed after processing with each device. In contrast, the attenuation rate of IL-6 and TNFα (95%) was optimal for all investigated blood salvages systems. Regarding IL-8, only the CATS and CS5 systems were able to attenuate this biological parameter with an excellent efficacy. The rate of attenuation in MPO and elastase, as markers of leukocyte activation, was higher than 80% for all devices. In conclusion, the different RBC washing systems tested in this study resulted in a significant attenuation of the inflammatory response. Increased levels of IL-1β after processing remained, however, unclear. According to the type of protocol, based on inlet haematocrit, fill and wash speeds, and wash volumes, small variations in reducing the inflammatory response have been observed from one device to another.

Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration

BACKGROUND Cardiopulmonary bypass (CPB) initiates a whole-body inflammatory response where complement and neutrophil activation and cytokine release play an important role. This prospective trial examined the effects of both heparin-coated circuits and aprotinin on the inflammatory processes during CPB, with respect to cytokine release and neutrophil activation. METHODS Two hundred patients undergoing cardiac surgery were randomized in four groups of 50 patients each: heparin-coated circuit with aprotinin (HCO-A) or without aprotinin (HCO) administration, and uncoated circuit with aprotinin (C-A) or without aprotinin administration (C). In groups receiving aprotinin, a high-dose regimen was given. In all groups, high initial doses of heparin were used (3 mg/kg intravenously). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8, and myeloperoxidase and elastase levels were measured in plasma samples taken before, during, and after CPB. RESULTS In all groups, the TNF-alpha, IL-6, and IL-8 levels reached a maximum after protamine administration. After 24 hours, they remained significantly elevated (IL-6 and IL-8) or returned to baseline values (TNF-alpha). A similar pattern was observed with myeloperoxidase and elastase levels. No significant intergroup differences were observed. CONCLUSIONS CPB is associated with cytokine release and neutrophil activation, which are not attenuated by the use of heparin-coated circuits or by the administration of aprotinin. Aprotinin and heparin-coated circuits do not show additive effects.

New approaches and old controversies to postoperative pain control following cardiac surgery

Objective: To evaluate the effect of postoperative pain control in cardiac surgical patients on morbidity, mortality and other outcome measures. Background: New approaches in pain control have been introduced over the past decade. The impact of these interventions, either alone or in combination, on perioperative outcome was evaluated in cardiac surgical patients. Methods: We searched Medline for the period of 1980 to the present using the key terms analgesics, opioid, non‐steroidal anti‐inflammatory drugs, cardiac surgery, regional analgesia, spinal, epidural, fast‐track cardiac anaesthesia, fast‐track cardiac surgery, myocardial ischaemia, myocardial infarction, postoperative care, accelerated care programmes, postoperative complications, and we examined and discussed the articles that were identified to be included in this review. Results: Pain management in cardiac surgery is becoming more important with the establishment of minimally invasive direct coronary artery bypass surgery and fast‐track management of conventional cardiac surgery patients. Advances have been made in this area and encompass specific techniques, such as central neuraxial blockade or selective nerve blocks, and drugs (opioids, sedative‐hypnotics and non‐steroidal anti‐inflammatory drugs). Ideally, these therapies provide not only patient comfort but also mitigate untoward cardiovascular responses, pulmonary responses, and other inflammatory and secondary sympathetic responses. The introduction of these newer approaches to perioperative care has reduced morbidity, but not mortality, in cardiac surgical patients. Conclusions: Understanding perioperative pathophysiology and implementation of care regimes to reduce the stress of cardiac surgery, will continue to accelerate rehabilitation associated with decreased hospitalization and increased satisfaction and safety after discharge. Reorganization of the perioperative team (anaesthesiologists, surgeons, nurses and physical therapists) will be essential to achieve successful fast‐track cardiac surgical programmes. Developments and improvements of multimodal interventions within the context of ‘fast‐track’ cardiac surgery programmes represents the major challenge for the medical professionals working to achieve a ‘pain and risk free’ perioperative course.

SMA circuits reduce platelet consumption and platelet factor release during cardiac surgery

BACKGROUND Platelet count and function are particularly damaged by cardiopulmonary bypass (CPB). This study evaluated the effects of a novel CPB circuit in terms of platelet count and activation, and postoperative need for blood products. METHODS One hundred patients undergoing coronary grafting were randomized in two groups: control group (n = 50) and test group (n = 50, surface modifying additives circuit, SMA group). Blood samples were taken before, during, and after CPB. Postoperative blood loss, number of transfused blood products, and postoperative variables were recorded. RESULTS The platelet count decreased less in the SMA group compared to the control group (end of CPB: respectively, 165 +/- 9 x 10(3)/mm3 vs 137 +/- 8 x 10(3)/mm3; p < 0.01). This was paralleled by a reduction in beta-thromboglobulin plasma levels in the SMA group. There was a trend to decreased blood loss in the SMA group, but the difference was significant only in patients taking aspirin preoperatively (p < 0.05). In the SMA group nearly 50% less fresh frozen plasma and platelet units were administered (p < 0.01). No operative deaths were observed. CONCLUSIONS The use of circuits with surface additives is clinically safe, preserves platelet levels, and attenuates platelet activation. This may lead to a reduced need for blood products.

The use of pre‐operative intrathecal morphine for analgesia following coronary artery bypass surgery

With the emergence of rapid extubation protocols following cardiac surgery, providing adequate analgesia in the early postoperative period is important. This prospective randomised double‐blind study investigated the benefits of pre‐operative intrathecal administration of low dose morphine in patients undergoing coronary artery bypass graft surgery. Postoperative analgesia, pulmonary function, stress response and postoperative recovery profile were assessed. Thirty patients were allocated into two groups, receiving either 500 μg of morphine intrathecally prior to anaesthesia and intravenous patient‐controlled analgesia with morphine postoperatively following tracheal extubation, or only postoperative intravenous patient‐controlled analgesia. In the intrathecal group, the total consumption of intravenous morphine following surgery was significantly reduced by 40% and patients reported lower pain scores at rest, during the first 24 h following extubation. Peak expiratory flow rate was greater and postoperative catecholamine release was significantly lower. Patients in the control group had a higher incidence of reduced respiratory rate following extubation.

Prevention by acebutolol of rhythm disorders following coronary bypass surgery.

Seventy-one patients submitted routinely to coronary artery bypass surgery were randomized into 2 groups. Group A (32 patients) received 24 hr after initiation of surgery an intravenous perfusion of 100 mg of acebutolol given over 24 hr (22 cases) or 600 mg administered orally (10 cases). On subsequent days, they received 1200 mg of acebutolol/day orally. Group B (39 patients) was used as control. The groups were comparable in terms of age, sex, severity of coronary disease, preoperative therapy, duration of extracorporeal circulation, aortic clamping time, and immediate postoperative haemodynamic findings. No patient received digitalis. During hospital stay (10 days), 1 group A patient (3%) and 13 group B patients (33%; P less than 0.001) developed a sustained episode of atrial arrhythmia (fibrillation, flutter or atrial ectopic tachycardia). The majority of these rhythm disorders developed between days 2 and 4. On Holter monitoring on days 7-10, malignant ventricular extrasystoles (grades IV and V of Lowns classification) were more frequent in group B (65.2%) than in group A (19.3%; P less than 0.001). Haemodynamic measurements taken at rest performed in 27 patients on days 7-10 (16 patients of group A; 11 of group B). No difference was observed between the two groups. Acebutolol is a safe and efficacious drug for the prevention of arrhythmias following coronary surgery.

The value of serum CK-MB and myoglobin measurements for assessing perioperative myocardial infarction after cardiac surgery

In 41 patients who underwent coronary bypass surgery, creatine kinase (CK)-MB mass concentration was repeatedly measured in serum during and after the intervention using a new two-site immunoenzymetric assay (IEMA). Serum CK-MB activity was determined with the use of four different techniques: immunoinhibition, immunoinhibition-immunoprecipitation, column chromatography and electrophoresis. Myoglobin (Mb) was also measured in each specimen by radioimmunoassay. In the 33 patients who followed a completely uneventful postoperative course, the cumulated CK-MB release was, on the average, 12.2-fold less than after acute myocardial infarction. The CK-MB peak concentrations using the IEMA were 33 +/- 3 micrograms/l (X +/- SEM) and occurred 6.4 +/- 0.5 h after the intervention was started; CK-MB levels had decreased to 2.9 +/- 0.4 micrograms/l at the end of the first postoperative day. The evolution of the CK-MB concentration was parallel to that of the enzyme activity. The serum Mb maximum concentrations (518 +/- 39 micrograms/l) were reached after 3.3 +/- 0.1 h. The other eight patients developed perioperative myocardial infarction (PMI); in this group, the cumulated CK-MB release was higher, and the serum CK-MB postoperative curves were of three different types. The patients with delayed CK-MB peaks (type I pattern) or sustained elevations (type III) of this isoenzyme also showed increased serum Mb levels at the end of the first postoperative day. The PMI patients with early (10 h) CK-MB elevations (type II) did not demonstrate abnormal serum Mb levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Assistance for Hemodynamic Evaluation

As early as in the 1950’s, physicians and computer scientists recognized that computers could be of assistance in clinical decision making. Since this time a variety of informatic techniques have been applied, accounting for thousands of references in the clinical and computer literature [1]. Arguments for such a line of research are numerous: optimum acquisition of data collected from diverse sources, quickness and reliability of reasoning processes, accuracy of the clinical diagnosis, comparison and dialogue with computer, cost efficiency of test and therapy [2]. Additionally, two other fundamental contributions are to be expected: improvement of our understanding of the structure of medical knowledge and understanding of the clinical decision making process. Physicians should be convinced that this research is mostly their task; limiting factor is not today’s computer technology but both the specific knowledge acquisition and medical acceptability [2]. Knowledge representation needs formalization of the medical reasoning processes as well as methodological and semantic consensus. Acceptability implies that it be interactive, user friendly and that its performance has been fully evaluated.

Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass: frequency, time course and risk factors.

Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (&agr;1-protease inhibitor, &agr;2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and &agr;1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT ≥40 ng/mL, amylase ≥42 IU/mL, and pancreatic isoamylase ≥20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, &agr;1-protease inhibitor, and &agr;2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.