Micael Appelblad

Clinical effects of the heparin coated surface in cardiopulmonary bypass

OBJECTIVE In a randomised study of 120 patients, undergoing primary operation for coronary heart decease, two groups were investigated as regards to the effects of heparin coated cardiopulmonary bypass on brain function parameters and general clinical outcome. The study group (n = 56) was perfused using an extra-corporeal circuit treated with covalent bonded heparin; the control group (n = 59) used an identical set-up without heparin treatment. Systemic heparin doses were calculated to achieve ACT levels of 250 and 500 s, respectively. Postoperative course was evaluated by examining a set of clinically relevant parameters including a detailed registry of postoperative deviations. Brain function was assessed by the biochemical marker S-100 and tests of memory performance. RESULTS There were several signs of reduced operative trauma in the study group. Hospital stay was reduced by nearly 1 day (P < 0.05). Time on postoperative ventilatory support was approximately 4 h shorter (P = 0.009). Chest drain blood loss was decreased both at 8 (P = 0.01) and 24 h (P = 0.007) postoperatively. Body temperature was lower after surgery and especially on days 2 (P = 0.03) and 3 (P = 0.01). Perioperative creatinine elevation was significantly reduced (P = 0.03). Neurological deviations were fewer (P = 0.01). Brain function assessment revealed reduced plasma levels of S-100 both at termination of cardiopulmonary bypass (P = 0.008) and 7 h later (P = 0.04). However, no remediation of memory impairment could be demonstrated. CONCLUSIONS Cardiopulmonary bypass with covalent bonded heparin attached to the extra-corporeal circuit in combination with a reduced systemic heparin dose seems to reduce safely and effectively the operative stress to the patient. There were also signs of improved cerebral protection.

Use of heparin-bonded circuits in cardiopulmonary bypass improves clinical outcome.

Objective : The use of heparin-coated surfaces in cardiopulmonary bypass has been shown to decrease the inflammatory response imposed by the contact between blood and artificial surfaces. One would expect this reaction to improve clinical outcome. However, this has been difficult to verify. This investigation is based on an aggregation of two randomized studies from our institution and highlights possible effects of heparin coating on a number of clinically oriented parameters. Design : Departmental analysis of patients subjected to coronary artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was employed using either the Carmeda or Duraflo heparin coatings compared with a control. The systemic heparin dose was reduced in the heparin-coated groups (ACT > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating related to clinical outcome were studied. Results : The use of heparin-coated circuits reduced the mean length of stay in hospital from 7.8 - 2.5 to 7.3 - 1.8 days ( p = 0.040) and postoperative ventilation time from 9.7 - 9.2 to 8.2 - 8.5 h ( p = 0.018), blood loss 8 h post surgery from 676 - 385 to 540 - 245 ml ( p = 0.001), individual perioperative change of haemoglobin loss ( p = 0.001), leukocyte count ( p = 0.000) and creatinine elevation ( p = 0.000), proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% ( p = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% ( p = 0.006), postoperative deviations from the normal postoperative course 47.2 vs 36.7% ( p = 0.035), neurological deviations 9.4 vs 3.9% ( p = 0.021) and atrial fibrillation 26.4 vs 18.0% ( p = 0.041). No effects were found with respect to perioperative platelet count, postoperative fever reaction and 5-year survival. Conclusion : Based on several indicators, the use of heparin coating in cardiopulmonary bypass is associated with improved clinical results.

Neurological and general outcome in low-risk coronary artery bypass patients using heparin coated circuits

OBJECTIVE The clinical significance of heparin coating in cardiopulmonary bypass has previously been investigated. However, few studies have addressed the possible influence on brain function and memory disturbances. METHODS Three hundred low-risk patients exposed to coronary bypass surgery were randomised into three groups according to type of heparin coating: Carmeda Bioactive Surface, Baxter Duraflo II and a control group. Outcome was determined from a number of clinically oriented parameters, including a detailed registry of postoperative deviations from the normal postoperative course. Brain damage was assessed through S100 release and memory tests, including a questionnaire follow-up. RESULTS Clinical outcome was similar for all groups. Blood loss (Duraflo only), transfusion requirements and postoperative creatinine elevation were reduced in the heparin-coated groups. A lower incidence of atrial fibrillation was noted in the Duraflo group. Heparin coating did not uniformly attenuate the release of S100 or the degree of memory impairment. CONCLUSIONS Cardiopulmonary bypass (CPB) with heparin coating and a reduced dose of heparin seems to be safe. Clinical outcome and neurological injury seem not to be associated with type of heparin coating used for CPB. However, blood loss and transfusion requirements may be reduced.

Quality assurance in clinical perfusion

OBJECTIVE To investigate the properties and usefulness of prospective routine registration of incidents related to cardiopulmonary bypass and its clinical significance as a quality assurance instrument. METHODS Incidents or deviations from the normal course observed during cardiopulmonary bypass procedures were registered in a computer database. Each incident was classified according to 14 pre-defined categories. The cause of each incident was evaluated, as well as patient outcome. Incidents leading to permanent or temporary injury were denoted accidents. The general- and category-related incidence rate was calculated for the observation period 1989-1997 encompassing 6918 cardiopulmonary bypass procedures. RESULTS The general incidence rate varied between 4.5-7.6% per year during the registration period. Most incidents (57%) occurred during established, or start of, cardiopulmonary bypass, whereas the remaining proportion of incidents were detected either before (27%) or when terminating (16%). The most common category of incidents was oxygenator failure (1.6%), followed by mechanical (1.4%) and surgical (1.2%) incidents. Accidents and fatal outcomes occurred in 0.03% of the cases. CONCLUSIONS Routine registration of incidents yields a clinically attractive instrument of controlling safety aspects and quality measures in cardiopulmonary bypass. The observed incidence rates are somewhat higher than previously reported, probably primarily related to the methodology implemented in this study.

Fat reduction in pericardial suction blood by spontaneous density separation: an experimental model on human liquid fat versus soya oil

Pericardial suction blood (PSB) contains mediastinal liquid wound fat with an embolic potential to cause brain damage after cardiopulmonary bypass (CPB). The aims were to measure how fat separates spontaneously from blood by density and how temperature and fat surface adhesion affect the results under experimental conditions. Human liquid fat was heat-extracted from retrieved pericardial fat tissue of coronary artery bypass graft (CABG) patients ( n =10). Human fat or soya oil, 5% and 10%, respectively, were mixed with postoperatively shed mediastinal blood ( n =20). The mixture was loaded into a temperature-controlled (37°C, 20°C, 10°C) vertical separation column. At 1, 2.5, 5 and 10 minutes, the blood was collected in five fractions, representing layers of density separation, followed by centrifugation. Human fat solidified at 8°C. Soya oil remained liquid below 0°C. Soya oil separated fast in water, but was slower in blood. At 10 minutes and 37°C 73±6% of added soya oil was found in the top 20% fraction. Human fat at 37°C behaved similarly to soya oil, with 58-2% separation at 10 minutes. However, at lower temperatures the density separation became less efficient ( p <0.001), whereas human fat more effectively adhered to the walls of the column, which added to the removal. In total, 66%-78% of the human fat was removed, depending on temperature. In conclusion, fat in PSB can be reduced by simple density separation and surface adhesion while it is temporarily retained from the CPB circuit.

Measurement of the activated clotting time during cardiopulmonary bypass: differences between Hemotec ACT and Hemochron Jr apparatus.

Background: Measurement of the activated clotting time (ACT) represents a standard method for coagulatory assessments. The test employs specific agents to trigger the coagulation process. The present study aimed to compare kaolin (Hemotec®) versus a combination of silica, kaolin and phospholipid (Hemochron® Jr) ACTs. Methods: Hemotec® and Hemochron® Jr ACT monitors were compared by simultaneous measurement of paired arterial blood samples (n-114) with respect to precision and bias during clinical conditions of cardio-pulmonary bypass (CPB). The influence of haemodilution on the ACT was tested in an ex-vivo model. Results: The precision of Hemotec® and Hemochron®Jr ACT measurements attained 21±2.6 s versus 27.0±2.6 s(p= 0.126) during CPB and 2.5±2.2 s versus 9.4±6.9 s (p= 0.000) after protamine administration, respectively. The Hemochron® Jr monitor was associated with a bias of −102±13.7 s compared to the Hemotec® ACT monitor (p= 0.000) during CPB and −6.9±2.9 s after protamine (p= 0.025). Linear regression analysis of ACT readings between monitors reached r- 0.526 (p= 0.000). Hemochron® Jr ACT values correlated with the erythrocyte volume fraction r- 0.379 (p= 0.000). Ex-vivo data indicated that the Hemotec® ACT monitor was associated with relatively higher ACT readings after haemodilution. Conclusion: The ACT is not a standardized measure. Test results are strongly associated with the specific compounds used to initiate the coagulation process.

Reversal of heparin after cardiac surgery: protamine titration using a statistical model.

OBJECTIVE To establish a statistical model for determination of protamine dose in conjunction with cardiopulmonary bypass. DESIGN Prospective. SETTING University hospital. PARTICIPANTS Ninety consecutive cardiac surgical patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A series of clinically oriented variables were introduced into a statistical model for projection of the protamine dose after cardiopulmonary bypass. The following significant predictors were identified using multivariable regression analysis: The patients body surface area, the administered dose of heparin, heparin clearance, and the preoperative platelet count. The statistical model projected the protamine dose within 3±23 mg of the point-of-care test used as reference. CONCLUSION Protamine dosing based on statistical modeling represents an alternative to point-of-care tests.

The relative safety of an oxygenator.

Analysis of prospectively registered incidents related to cardiopulmonary bypass (CPB) was initiated to establish the incident rate for 10 different oxygenator brands employed over a seven-year period in 5000 clinical perfusions. A general safety index (SI) was defined as the number of recorded incidents in a given series of oxygenators divided by its total number and multiplied by 100. Specific SI was calculated for each of the following categories: high-pressure drop, debris, gas exchange, leakage, material failure and oxygenator change-out. An SI of 0.2 was arbitrarily set as a reference and an acceptable safety level. An estimate of the relative risk for a particular oxygenator brand was compared with the reference by calculating the odd’s ratio with a 95% confidence interval. The mean SI was determined to be 1.6, ranging from 0 for the Maxima CBAS and the Cobe CML to 2.92 for the Safe oxygenator. The dominating specific type of incident was HPD with an SI of 0.81 followed by debris, SI = 0.71. A systematic analysis of adverse events in CPB may be used to evaluate and to set standards, a method already employed in the pharmaceutical industry. Our results indicate that oxygenator safety margins may vary between different brands.

Disturbances in Oxygen Balance During Cardiopulmonary Bypass : A Risk Factor for Postoperative Delirium

OBJECTIVE The aim of this study was to determine risk factors for postoperative delirium after cardiac surgery, specifically associated with the conduct of cardiopulmonary bypass (CPB). DESIGN Prospective observational study. SETTING Heart Centre, University Hospital. PARTICIPANTS The study included 142 patients aged 70 years and older scheduled for elective cardiac surgery with CPB. INTERVENTIONS Risk factor analysis comprised information collected from the hospital clinical and CPB dedicated databases in addition to the medical chart. Delirium was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criterion using the Mini Mental State Examination and the Organic Brain Syndrome scale. MEASUREMENTS AND MAIN RESULTS Assessments of delirium diagnosis were executed preoperatively and on the following first and fourth postoperative days. Delirium occurred in 55% (78/142) of the patients. Patients with delirium were identified with significantly higher body weight and body surface area preoperatively, accompanied with longer CPB time, higher positive fluid balance per CPB, and lower systemic pump flow related to body surface area. Furthermore, the duration of the mixed venous oxygen saturation (SvO2) below 75% was significantly longer during CPB. The result from the multivariable logistic regression analysis included the duration of SvO2 below 75%, fluid balance per CPB and patient age as independent risk factors for postoperative delirium. CONCLUSIONS The influence of the SvO2 level during CPB, fluid balance, and patient age should be recognized as risk factors for postoperative delirium after cardiac surgery in patients 70 years and older.

Reporting of perfusion-related incidents: pitfalls and limitations

Safety and risk-containment associated with cardiopulmonary bypass (CPB) procedures have always been a prime concern, ever since the introduction of CPB in cardiac surgery, more than half a century ago. Contrary to the old days, due to the immense worldwide expansion of cardiac surgery, current practice is highly standardized with few associated risks. Albeit this tremendous advance, the overall development of extracorporeal technology has not reached a level that guarantees total safety or ways to prevent every unforeseen event. If such a situation ever will occur is difficult to say, nevertheless, it should be our ultimate goal. In a recent study, the Institute of Medicine found that as many as 98 000 Americans die from preventable medical errors. Nowhere are patient safety issues more critical than in the anaesthesia, surgery and critical care environments. One typical activity is the use of CPB. Its associated specific risks are, however, poorly defined. Our knowledge of adverse events related to CPB is, at present, limited to a number of surveys, the oldest dating over 20 years back in time. 10 These studies are also constrained by representing only a selection of hospitals, without any obvious connections to safety standards in general set by hospital or national regulations. The risks associated with CPB at a specific hospital or unit are, for these reasons, literally not known. To fill this gap, it is essential to establish a widespread use of reliable monitoring systems to collect CPB-sensitive safety information. However, the process of collecting critical incident data during CPB is associated with a number of pitfalls and limitations, which need to be looked into in more detail. Historical glimpses of safety assessment in cardiopulmonary bypass