Hitoshi Shimura

Application of Akaike information criterion to evaluate warfarin dosing algorithm

INTRODUCTION Several factors responsible for inter-individual differences in response to warfarin have been confirmed; however, unidentified factors appear to remain. The purpose of this study was to examine a simple method to evaluate whether optional variables are appropriate as factors to improve dosing algorithms. MATERIALS AND METHODS All patients were Japanese. Genotyping of selected genes was conducted, and other information was obtained from medical record. Dosing algorithms were constructed by multivariate linear regression analyses and were evaluated by the Akaike Information Criterion (AIC). RESULTS AND CONCLUSIONS Multivariate analysis showed that white blood-cell count (WBC), concomitant use of allopurinol, and CYP4F2 genotype are apparently involved in warfarin dose variation, in addition to well-known factors, such as age and VKORC1 genotype. We evaluated the adequacy of these variables as factors to improve the dosing algorithm using the AIC. Addition of WBC, allopurinol administration and CYP4F2 genotype to the basal algorithm resulted in decreased AIC, suggesting that these factor candidates may contribute to improving the prediction of warfarin maintenance dose. This study is the first to evaluate the warfarin dosing algorithm by AIC. To further improve the dosing algorithm, AIC may be a simple and useful tool to evaluate both the model itself and factors to be incorporated into the algorithm.

The effect of preoperative aspirin administration on postoperative level of von Willebrand factor in off-pump coronary artery bypass surgery

The effect of preoperative administration of aspirin on endothelial function in the patients undergoing off-pump coronary artery bypass (OPCAB) surgery is still unclear. Fifty consecutive patients undergoing OPCAB between May 2006 and May 2007 were equally divided into two groups — one without preoperative aspirin (group A; the first 25 patients) and the other with preoperative aspirin (group B; the next 25 patients). We investigated the degree of postoperative endothelial dysfunction by measuring the von Willebrand factor activity, which is a possible indicator of endothelial damage. The level of von Willebrand factor was not different between groups before surgery (group A 166% ± 53% vs group B 181% ± 62%; P = 0.39). Immediately after surgery it was significantly higher than before surgery in group A (231% ± 79%; rate of increase 1.24 ± 0.58), but not in group B (183% ± 77%; rate of increase 1.03 ± 0.55) (P < 0.02). The level was still significantly higher in group A than in group B on postoperative day 1 (group A 294 ± 66 vs 254 ± 51; P = 0.03), but there was no difference between groups on postoperative day 6. Although the frequency of blood transfusion was higher in group B, there was no difference in the amount of intraoperative bleeding between the groups. Preoperative use of aspirin before OPCAB could suppress the postoperative increase in von Willebrand factor, a possible indicator of endothelial damage, only in the early postoperative phase.

Pitfalls of skeletonized internal thoracic artery: comparison of graft kinking between skeletonized and pedicled grafts based on postoperative angiography findings.

Abstract  Background and aim of the study: Skeletonization of the internal thoracic artery (ITA) has several advantages: sequential bypass grafting can be easily performed, and a graft of increased length can make the distal coronary artery accessible. However, kinking of the grafts has been observed on postoperative angiograms in a few cases. We investigated whether there were significant differences in the frequency of graft kinking and stenosis degree at the kink site between pedicled and skeletonized grafts. Methods: Postoperative angiography was performed for all cases. In pedicled (n = 65) and skeletonized (n = 129) groups, the results of postoperative graft angiography were analyzed to investigate the presence of graft kinking and stenosis degree at the kink site. Results: Kinking was observed in 4 (5.9%) and 9 (3.9%) arteries in the pedicled and skeletonized groups, respectively (p = 0.341). The stenosis degree at the kink site (mean ± SD) was significantly higher in the skeletonized group (47.2 ± 16.8%) than in the pedicled group (23.5 ± 13.7%), (p = 0.032). In four patients in whom early postoperative angiography showed a kink with more than 50% stenosis, late‐term angiography was performed. All four cases showed regression of the stenosis degree at the kink site. Conclusions: When the ITA had a kink, the stenosis degree at the kink site was significantly higher in the skeletonized group than in the pedicled group. Late angiography often reveals regression of stenosis at the kink site. Immediate intervention need not always be performed if the patient has no angina caused by a stenotic lesion at the kink site.

Surgical Treatment for Chronic Pulmonary Thromboembolism Under Cardiopulmonary Bypass with Selective Cerebral Perfusion

Abstract The median sternotomy approach for the treatment of chronic pulmonary thromboembolism was recently improved by Daily, Jamieson, and coworkers who adopted it for use under cardiopulmonary bypass with intermittent circulatory arrest; however, we have sometimes found that the circulatory arrest time was too short to complete thromboendarterectomy. Therefore, we attempted to perform a selective cerebral perfusion technique to extend the endarterectomy time. Although we noted slight back-bleeding from the bronchial arteries, we were able to extend the endarterectomy time without causing any postoperative delirium. We conclude that the median sternotomy approach using cardiopulmonary bypass with selective cerebral perfusion may be the best option for extending the thromboendarterectomy time.

Heparin-Induced Thrombocytopenia After Coronary Artery Bypass Grafting with Cardiopulmonary Bypass: Report of a Case

A 79-year-old man was transferred to our hospital with severe chest pain and a suspected diagnosis of acute myocardial infarction. Emergency cardiac catheterization showed triple-vessel coronary artery disease, and we performed coronary artery bypass grafting under cardiopulmonary bypass (CPB). Continuous hemodiafiltration was started for acute renal failure postoperatively, and heparin was given as an anticoagulanting agent. By 9 days after the initiation of heparin therapy, his platelet count had fallen and a deep vein thrombosis had formed in his left leg. We suspected heparin-induced thrombocytopenia (HIT), and immediately discontinued the heparin, implementing danaparoid (Orgaran) instead, following which the platelet count recovered. Heparin-induced thrombocytopenia, which causes thrombosis, is a serious side effect of heparin therapy and few cases of HIT associated with CPB surgery have been reported in Japan.

Efficacy of Elective Intra-aortic Balloon Pump Therapy for High-Risk Off-Pump Coronary Artery Bypass: A Prospective Comparative Study

OBJECTIVE This study evaluated the usefulness of elective intra-aortic balloon pumping (IABP) in high-risk off-pump coronary artery bypass grafting (OPCAB). MATERIALS AND METHODS From October 2002 through September 2006, total of 143 patients were operated with OPCAB. These patients were divided into two groups and clinical outcomes were compared: Group E (N = 30): Elective IABP group and Group C (N = 113): Control group, OPCAB without IABP. The criteria of elective application of IABP were severe stenosis of left main coronary artery (LMCA) or left ventricular dysfunction with an ejection fraction of less than 35%. RESULTS No significant difference was noted in the duration of ICU stay (Group E: 1.13 ± 0.43 days; Group C: 1.18 ± 0.60 days, p = 0.710), the number of patients on a respirator for 24 hours or longer after surgery (Group E: 10.0%; Group C: 5.3%, p = 0.397), hospital mortality (Group E: 0%; Group C: 0%), or the frequency of postoperative major complications between two groups. CONCLUSIONS The outcomes of OPCAB using elective IABP in high-risk patients, such as those with severe LMCA stenosis or left ventricular dysfunction, were similar to those of OPCAB in low-risk patients, suggesting the usefulness of elective IABP in OPCAB.

A Successful Case of Pulmonary Thromboendarterectomy for Chronic Thromboembolic Pulmonary Hypertension with a Thrombus in the Right Ventricle

Chronic thromboembolism is a frequent cause of progressive hypertension and carries a poor prognosis. Medical treatment is not effective and surgery provides the only potential for a cure at present. We herein report a successful case of thromboendarterectomy treated via a median sternotomy with intermittent circulatory arrest. A 43-year-old man was admitted to our hospital complaining of progressive dyspnea, edema of the lower extremities, and a fever with an unknown origin. A subsequent definitive evaluation showed him to be suffering from surgically accessible chronic thromboembolic pulmonary hypertension with a thrombus in the right ventricle. He underwent a pulmonary thromboen-darterectomy and thrombectomy via a median sternotomy with intermittent circulatory arrest on November 24, 1994. Postoperatively he showed a marked improvement in his hemodynamic status and blood gas analysis. He has also returned to work with no trouble. Deep vein thrombosis appeared to be the pathogenesis of this case, but we could not find the origin of his unknown fever. He is currently being controlled by treatment with methylprednisolone as before.

Is it safe to initiate selective cerebral perfusion with normothermia

Abstract  Objective: Preceding selective cerebral perfusion (P‐SCP) is a method whereby SCP and systemic perfusion start simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization due to detachment of atherosclerotic material from the aorta, caused by the “sandblasting” effect of high‐velocity jets of blood exiting the aortic cannula. However, neither the safety of SCP at normothermia nor the influence of extended SCP time has been sufficiently clarified. To clarify the safety of P‐SCP, the comparison study of P‐SCP and conventional SCP (C‐SCP) was performed retrospectively. Methods: Fifty‐seven patients (C‐SCP group: 29 patients; P‐SCP: 28 patients) underwent surgery between 1992 and 2002. Results: Nine (15.8%) in‐hospital death occurred; 4 in the C‐SCP group (13.8%) and 5 in the P‐SCP group (17.9%) (NS). The SCP time was 136.6 ± 68.5 minutes in the C‐SCP group and 195.8 ± 30.7 minutes in the P‐SCP group (p < 0.05). One patient in each group exhibited postoperative neurological dysfunction. Conclusion: It may be little dangerous to initiate the SCP with normothermia. P‐SCP may be useful in cases in which there is pedunculated atherosclerotic material, or mural thrombus in the ascending and arch aorta.

Steal phenomenon with kinked graft caused a loss of viability in a dialysis patient.

Abstract  A 74‐year‐old man with chronic renal failure under hemodialysis via the left upper extremity underwent an off‐pump coronary artery bypass (OPCAB). The left internal thoracic artery (LITA), which was harvested in a skeletonized manner, was anastomosed to the left anterior descending artery (LAD). Postoperatively, he complained of chest pain only during dialysis. Angiography revealed a kinking in the LITA. However, myocardial scintigraphy revealed no ischemia. One year after OPCAB, left ventriculography revealed akinesis and myocardial scintigraphy revealed no viability in the anterior wall. This suggested that the viability was lost due to graft kinking and steal phenomenon during hemodialysis. If the length of the skeletonized ITA graft is redundant, kinking of the graft rarely occurs after the chest is closed. We also suggest that to avoid the kinking of the ITA graft, fibrin glue should be used to paste the ITA graft running in a gentle curve.

Evaluation of cerebral pathologic changes and long-term behavioral disorder after deep hypothermic circulatory arrest in dogs

The purpose of this study is to evaluate the extent of brain damage following deep hypothermic circulatory arrest (DHCA), using behavior and pathological findings. The dogs underwent 60, 90 or 120 min of DHCA. After 72 h or 6 months, their cerebrum pathological findings were examined. No neurological deficit was found in any of the dogs. After 72 h, hippocampus cells (CA1) were TUNEL positive in 120-min-DHCA dogs. This study demonstrates that 90-min-DHCA-dogs can survive healthily over 6 months, and apoptotic cell death occurs in canine hippocampus following 120 min of DHCA at 15 degrees C.