Systemic anticoagulant effect of low-dose subcutaneous unfractionated heparin as determined using thrombelastography.

In an observational study using heparinase-modified thrombelastography, we investigated the percentage of elective cardiothoracic surgical patients receiving low-dose unfractionated heparin (5000 IU 12 hourly subcutaneously) who had a demonstrable systemic heparin effect. Blood samples were obtained at induction from 40 adult elective cardiothoracic surgical patients who had received 5000 IU unfractionated heparin subcutaneously within six hours. Simultaneous kaolin and heparinase-modified thrombelastographies were run on all samples. Fourteen patients (35%; 95% CI: 20 to 50%) had a demonstrable heparin effect (defined as a kaolin thrombelastography R time >25% longer than the heparinase-modified control). Their mean +/- SD kaolin thrombelastography R time was 13.6 +/- 5.9 minutes (normal range 4 to 8 minutes) vs. 7.1 +/- 2.0 minutes for the heparinase-modified controls. In 10 patients the thrombelastography R times were >50% longer and in four patients >100% longer than their respective heparinase-modified controls. In a post hoc analysis, there was little correlation between the extent of the prolongation and patient age (r = 0.02), weight (r = -0.31), preoperative creatinine (r = -0.17), or time since administration of heparin (r = 0.14). These results indicate that about one third of patients who have received low-dose unfractionated heparin subcutaneously within six hours have a demonstrable heparin effect. The potential for this effect should be considered if central neural blockade is planned.

The effect of excess protamine on thrombelastography in vitro.

The aim of the current study was to assess the direct effect of protamine on conventional thrombelastography in vitro. Protamine was added to blood samples collected from 25 adult cardiac surgical patients prior to the induction of anaesthesia and after separation from cardiopulmonary bypass. The final protamine concentrations were 0 (control), 0.05 mg/ml, 0.1 mg/ml and 0.2 mg/ml (i.e. sufficient to reverse heparin 0, 5, 10 and 20 IU/ml respectively, assuming a 1:1 reversal ratio). In the pre-induction samples, protamine was associated with increases in r time and reductions in maximum amplitude (P<0.01). After bypass, the control samples demonstrated a heparin effect as expected, which was corrected by the addition of protamine 0.05 mg/ml. However, the higher concentrations of protamine were again associated with increases in r time and reductions in maximum amplitude (P<0.01). The results indicate that protamine has a direct anticoagulant effect on conventional thrombelastography in vitro. This effect occurs whether protamine is present alone, or whether protamine is present in excess after neutralization of heparin. Unless this effect is taken into account, excess protamine may confound the interpretation of conventional thrombelastography in cardiac surgical patients.

The relationship between oxygenator exhaust P(CO2) and arterial P(CO2) during hypothermic cardiopulmonary bypass.

During cardiopulmonary bypass the partial pressure of carbon dioxide in oxygenator arterial blood (P(a)CO2) can be estimated from the partial pressure of gas exhausting from the oxygenator (P(E)CO2). Our hypothesis is that P(E)CO2 may be used to estimate P(a)CO2 with limits of agreement within 7 mmHg above and below the bias. (This is the reported relationship between arterial and end-tidal carbon dioxide during positive pressure ventilation in supine patients.) During hypothermic (28-32 degrees C) cardiopulmonary bypass using a Terumo Capiox SX membrane oxygenator, 80 oxygenator arterial blood samples were collected from 32 patients during cooling, stable hypothermia, and rewarming as per our usual clinical care. The P(a)CO2 of oxygenator arterial blood at actual patient blood temperature was estimated by temperature correction of the oxygenator arterial blood sample measured in the laboratory at 37 degrees C. P(E)CO2 was measured by connecting a capnograph end-to-side to the oxygenator exhaust outlet. We used an alpha-stat approach to cardiopulmonary bypass management. The mean difference between P(E)CO2 and P(a)CO2 was 0.6 mmHg, with limits of agreement (+/-2 SD) between -5 to +6 mmHg. P(E)CO2 tended to underestimate P(a)CO2 at low arterial temperatures, and overestimate at high arterial temperatures. We have demonstrated that P(E)CO2 can be used to estimate P(a)CO2 during hypothermic cardiopulmonary bypass using a Terumo Capiox SX oxygenator with a degree of accuracy similar to that associated with the use of end-tidal carbon dioxide measurement during positive pressure ventilation in anaesthetized, supine patients.

Drug therapy before coronary artery surgery: nitrates are independent predictors of mortality and beta-adrenergic blockers predict survival.

UNLABELLED: We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed. IMPLICATIONS: We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy.

Risk prediction in coronary artery surgery: a comparison of four risk scores.

OBJECTIVE: To determine which of four proposed risk scores best predicts immediate outcome of cardiac surgery. DESIGN: Observational cohort study. SETTING: Sir Charles Gairdner Hospital (a university teaching hospital), Perth, Western Australia, 18 March 1993 to 5 March 1996. SUBJECTS: 927 consecutive patients undergoing surgery for coronary artery disease. OUTCOME MEASURES: Patient risk scores (by methods of Parsonnet et al., Higgins et al., Tremblay et al. and Tu et al.); in-hospital mortality; postoperative hospital stay > 14 days; receiver operating characteristic (ROC) curves comparing sensitivity and specificity in predicting adverse outcomes for each risk score. RESULTS: In-hospital mortality rate was 3.5% and mean postoperative hospital stay was 10.7 days. The four scores had similar predictive abilities, with mean areas under the ROC curves (95% confidence intervals) for mortality and postoperative stay > 14 days, respectively: 0.70 (0.62-0.78) and 0.70 (0.65-0.75) for the Parsonnet score; 0.68 (0.59-0.77) and 0.70 (0.64-0.75) for the Higgins score; 0.68 (0.59-0.77) and 0.67 (0.62-0.73) for the Tremblay score; and 0.68 (0.60-0.76) and 0.69 (0.64-0.75) for the Tu score. CONCLUSION: Any of the scores may be used to estimate perioperative risk and to compare outcome between coronary surgery units, but none has sufficient specificity and sensitivity to identify specific individuals who will experience an adverse outcome. Further development of risk assessment is needed before adverse outcome can be accurately predicted in cardiac surgical patients.