Effect of etomidate on hepatic drug metabolism in humans

The authors studied the effect of etomidate on drug metabolism in vivo in humans and in vitro using human liver microsomes. When these liver microsomes were incubated with different concentrations of etomidate, dose-dependent inhibition of ketamine N-demethylation, a cytochrome P-450-dependent enzymatic process, was produced. Cytochrome P-450 binding spectra displayed type II binding with a UV light absorption maximum (lambda max) at a wavelength of 424 nm in the presence of etomidate. In vivo studies were conducted using ketamine and antipyrine as substrates. Evaluation of antipyrine's pharmacokinetic variables after an intravenous infusion of etomidate (0.34 +/- 0.17 mg/kg) revealed an 18% increase in its elimination half-life (P = 0.04). In addition, there were 16% and 11% decreases in the area under the curve (P = 0.05) and in the clearance rate (P = 0.07) for antipyrine, respectively. In patients administered a bolus dose of ketamine during brief outpatient operations, etomidate produced no significant changes in ketamine's pharmacokinetics compared to thiopental. The authors conclude that the etomidate-induced inhibition of hepatic drug metabolism can prolong the elimination of drugs with low hepatic clearance rates (e.g., antipyrine). However, etomidate would not be expected to alter the rate of elimination of high clearance anesthetics and analgesic drugs (e.g., ketamine, fentanyl).     

Aortic Valve Replacement Using Local Myocardial Hypothermia

This material comprises 100 cases of aortic valve replacement. Ninety-one of the valves were replaced with the Björk—Shiley tilting disc valve prosthesis and 9 with the Smeloff—Cutter ball valve. No coronary perfusion was used during surgery. The myocardium was protected by local myocardial hypothermia, achieved by an intracoronary infusion of Bretschneider's solution (+4°C) prior to surgery. A weak and flaccid heart without coronary perfusion cannulas facilitated the surgical procedure. Myocardial function was very good and the course of the patients excellent postoperatively. Seven percent of the patients were lost within one month after operation and late mortality was 13%. A comparison between clinical and haemodynamic findings obtained 2–3 months before and one year after surgery was made in 55 patients. A marked subjective improvement was seen in all but five patients. There was a significant increase of average physical working capacity and regression of ECG-signs of left ventricular hypertrophy and strain as well as of roentgenological heart size. Angina pectoris was present in only three patients postoperatively as compared with 23 before surgery. The improvement of physical working capacity was paralleled by a significant increase of cardiac output during exercise, caused by a rise of stroke volume, heart rate on maximal load tolerated remaining unchanged. Blood pressure reactions during work were normalized in patients with both pre-operative aortic stenosis and aortic insufficiency. A significant postoperative paravalvular leakage was rare in the present material.     

Mitral Valve Reconstruction and Mitral Valve Replacement for Ischemic Mitral Insufficiency

Abstract Background: Patients with ischemic mitral incompetence have a high operative risk whether the valve is repaired or replaced. The advantage of repair over replacement is unclear in this group of patients. Methods: Between April 1986 and December 1994, 232 patients underwent surgery for ischemic mitral valve insufficiency; mitral valve replacement was performed in 98 of them. Operative mortality was 13.3%. The actuarial survival rate after 5 years was 73.3%. The surgical risk in patients whose left ventricular ejection fraction (LVEF) was 10%-30% (operative mortality 50.0%) was higher than in those whose LVEF was greater than 30%. Valve reconstruction was performed in 102 patients. Operative mortality in this patient group was 14.7%. The surgical risk in patients whose LVEF was 30% was higher (operative mortality 42.9%). Results: The total actuarial survival rate of all patients was 64.4% after 5 years. Mortality during follow-up was higher in patients with residual mitral valve insufficiency greater than grade I after mitral valve reconstruction. Twenty-four patients with severly impaired left ventricular function underwent heart transplantation. Operative mortality in this group was 12.5%. Eight patients received left ventricular aneurysmectomy in addition to valve surgery, three of them died early. Conclusions: We conclude that patients with highly impaired left ventricular function and ischemic mitral insufficiency are at too great a risk for either valve reconstruction or replacement. Cardiac transplantation should be considered for this patient group. However, patients with ischemic mitral insufficiency and moderately impaired left ventricular function can undergo valve reconstruction or replacement with an acceptable prognosis. The goal of mitral valve reconstruction should be reducing mitral valve insufficiency to at least grade I. If this is not achieved, the prognosis after repair is worse than after valve replacement, therefore, the surgeon should replace the valve without delay.     

Study of hepatic function matching between Banna minipig inbred and humans

As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig-to-human xenotransplantation due to its clear genetic background and minor interindividual differences. Previous studies of BMI have focused on immunological barriers between BMI and humans. However, a comparison of liver function between donor animals and humans is an essential premise for successful xenotransplantation. In this study, we investigated routine hepatic functions, protein electrophoresis, and drug metabolism to compare capacity of liver synthesis, metabolism, and drainage between BMI and humans. The results showed no significant differences in the concentrations of albumin and globulin synthesized in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI were higher than those in humans, and levels of total bilirubin and direct-reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16 times greater than that by humans, with a mean residual time of antipyrine in BMI, one-tenth of that in human. These findings suggested that BMI livers are similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have stronger functions compared with those of humans. No incompatibility was identified in hepatic function between BMI and humans.     

THIRTY YEARS EXPERIENCE WITH HEART VALVE SURGERY: ISOLATED AORTIC VALVE REPLACEMENT

Background: Thirty years have elapsed since the commencement of open-heart surgery in South Australia. A retrospective study was performed to evaluate mortality and complication rates and to identify factors associated with poor outcomes in all patients who underwent prosthetic aortic valve replacement during this period. Methods: Questionnaires and personal contact have been used to generate a combined database of pre-operative and postoperative information and long-term follow-up on 1322 patients who underwent isolated prosthetic aortic valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital between 1963 and 1992. Results: Complete survival follow-up data were obtained for 94% (1241) of the patients. The Bjork-Shiley valve was used in 668 (875) of the patients, a Starr-Edwards prosthesis in 31% (412). a St Jude prosthesis in 2% (26). and only 0.7% (9) bioprosthetic valves were inserted. The hospital mortality rate for the 30-year period was 2.9%. Progressively older and less fit patients have undergone surgery in recent years. The long-term survival of patients with aortic stenosis and aortic incompetence was not significantly different. Long-term survival was significantly shorter for patients with higher New York Heart Association (NYHA) functional classifications, and for patients in pre-operative atrial fibrillation. Pre-operative dyspnoea was significantly improved following aortic valve replacement. The rates of postoperative haemorrhagic and embolic complications were low by comparison with other published series. Conclusions: Aortic valve replacement can be performed with low hospital mortality and complication rates, and significant symptomatic improvement can be expected. Aortic valve recipients have a favourable prognostic outcome compared with an age- and sex-matched population, and risk factors that determine long-term survival can be identified pre-operatively.     

风湿性瓣膜病合并冠心病的外科治疗

报告１９９１年１月至１９９５年１１月期间１５例风湿性瓣膜病合并冠心病病人瓣膜替换及冠脉桥术（ＣＡＢＧ）的体会。手术均在低温体外循环下进行。其中二尖瓣替换＋ＣＡＢＧ６例，主动脉瓣替换＋ＣＡＢＧ６例、双瓣替换＋ＣＡＢＧ３例，术后死亡３例，其余治愈出院，作者强调了术前明确诊断的重要性，并就冠脉搭桥、心肌保护、主动脉气囊反搏（ＩＡＢＰ）及药物的应用加以讨论。     

Lactate is correlated with the indocyanine green elimination rate in liver resection for cirrhotic patients

The role of lactate in liver ischemia-reperfusion injury in cirrhosis has not been clarified. Fifty patients with hepatocellular carcinoma who underwent partial liver resection under Pringle's maneuver were included in this study. We performed the indocyanine green clearance test before the operation and three times during the surgery to calculate its elimination rate. Blood lactate and base excess were measured at the corresponding times. Systolic and diastolic systemic arterial pressure, heart rate, cardiac index, and esophageal temperature were monitored. Aminotransferase levels were recorded the day before the operation, 1 h after the operation, and on the first and third postoperative days. We calculated the increase or decrease in lactate levels during the preischemic, ischemic, and postischemic phases, and examined the correlation between these results and the changes in indocyanine green elimination rate and some clinical factors. The lactate levels increased before reperfusion and began to decrease after reperfusion. The lactate increase and decrease during the ischemic and postischemic phases correlated with the change in indocyanine green elimination rate (P < 0.0001 and P = 0.02 for the respective phases). The lactate increase during the preischemic phase correlated with the duration of the preischemic phase (P < 0.0001). In cirrhotic patients who undergo liver resection with Pringle's maneuver and who do not show postoperative liver failure, the blood lactate profile might be a reliable indicator of liver metabolic capacity during surgery. IMPLICATIONS: In cirrhotic patients who underwent liver resection with Pringle's maneuver, the lactate increase and decrease during the ischemic and postischemic phases correlated with the change in the indocyanine green elimination rate. The blood lactate profile might be a reliable indicator of liver metabolic capacity during surgery.     

Mitral valve surgery in infants and children

The pre-operative findings and surgical results of forty-three patients under thirteen years of age undergoing mitral valve surgery, are presented. Eight underwent surgery for mitral stenosis. Four had open mitral valvotomy with a satisfactory result, one developed severe regurgitation which required mitral valve replacement. Two had primary valve replacement and two had excision of a mitral subvalvar diaphragm. Thirty five children underwent surgery for mitral regurgitation. Twelve had a mitral annuloplasty. Two of these developed further regurgitation which required mitral valve replacement. Twenty one children had primary mitral valve replacement. The results and choice of valve replacement are discussed.     

Aortic valve replacement in a patient with liver cirrhosis and coagulopathy

Open heart surgery in patients with end-stage liver disease is accompanied by various complications. Coagulopathy resulting from liver failure tends to cause uncontrollable hemorrhage. Severe aortic insufficiency has moderate to severe risk for liver transplantation. It can lead to heart failure, liver congestion, and finally rejection of the transplanted liver. Aortic valve replacement in patients diagnosed as having cirrhosis has a significant risk of mortality because of the above-mentioned complications. We present a patient with liver cirrhosis and severe aortic insufficiency who had thrombocytopenia and severe coagulopathy. Aortic valve replacement was performed successfully using cardiopulmonary bypass before the liver transplantation. Hemostasis management was done effectively perioperation. The postoperative course was uneventful, and the patient was discharged after 10 days. Liver transplantation was performed successfully 2 months later.     

Ten years' experience in heart valve replacement with artificial prostheses: immediate and long-term results in 1812 cases.

A ten year follow up of 1,812 patients who underwent heart valve replacement with artificial prothesis between October 1963 and December 1973 is reported. Hospital mortality was 8.5% for aortic valve replacement; 13.6% for mitral valve replacement and 19.3% for multiple valve replacement. Late mortality was 13.3% for aortic valve replacement; 25.7% for mitral valve replacement and 25.9% for multiple valve replacement. The survival rate of the different groups of patients were actuarially determined. The survival rates following replacement of the aortic valves was 81% after 9 years. The main late complications are embolism and valve leakage. All surviving patients show a clinical improvement, particularly in the groups of isolated aortic a mitral valve replacement. The heart size reduction after operation has been measured. This is more evident 6 months after surgery: the average reduction was 23% after aortic valve replacement and 20% after mitral valve replacement.     

THIRTY YEARS EXPERIENCE WITH HEART VALVE SURGERY: ISOLATED MITRAL VALVE REPLACEMENT

Background : Thirty years have elapsed since the commencement of open-heart surgery in South Australia. A retrospective study was performed to evaluate mortality and complication rates and to identify factors associated with poor outcomes in all patients who underwent prosthetic mitral valve replacement during this period. Methods : Questionnaires and personal contact have been used to generate a combined database of pre-operative and postoperative information and long-term follow-up on 938 patients who underwent isolated prosthetic mitral valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital between 1963 and 1993. Results : Complete survival follow-up data were obtained for 92% (865) of the patients. The Starr-Edwards valve was used in 95% (891) of the patients, a Bjork-Shiley prosthesis in 2.5% (23) of the patients, and only 24 (2.5%) other valves were inserted. The hospital mortality rate for the 30-year period was 4.7%. The mean age of the patients who underwent surgery was greater in each of the three successive decades. A long-term survival advantage was observed for patients with mitral stenosis, however, survival was significantly shorter for patients with higher New York Heart Association (NYHA) functional classifications and for patients in pre-operative atrial fibrillation. Pre-operative dyspnoea was significantly improved following mitral valve replacement. The rates of postoperative haemorrhagic and embolic complications were low by comparison with other published series. Conclusion : Mitral valve recipients do not regain a normalized life expectancy, but risk factors that determine long-term survival can be identified pre-operatively to aid appropriate patient selection.     

Estimation of functional liver reserve in patients before cardiac surgery using antipyrine plasma clearance test

BACKGROUND: Hyperbilirubinemia is not uncommon and is sometimes fatal after valvular surgery. One important cause of it is a poor functional liver reserve, however, conventional tests reflect hepatic blood flow and do not offer precise evaluation of the pure functional liver reserve. Antipyrine has particular pharmacological properties, and its plasma clearance represents quantitatively the functional capacity of the liver. In this study, we measured antipyrine plasma clearance in cardiac surgical patients and evaluated the feasibility of using this parameter as a predictor of the risk of postoperative hyperbilirubinemia. METHODS: The plasma clearance of antipyrine was measured preoperatively in 40 cardiac patients undergoing mitral and/or tricuspid valvular surgery and its relations with hemodynamics or postoperative course were studied. RESULTS: Antipyrine clearance in preoperative patients was 0.365+/-0.175 (mean +/- SD) ml/min/kg, lower than the normal range (0.405+/-0.04 ml/min/kg), and showed no correlation with cardiac index, while the plasma disappearance rate of indocyanine green depended on the cardiac index. The maximum postoperative total bilirubin level showed significant correlation with antipyrine clearance (r=-0.699); this correlation coefficient was greater than that with indocyanine green (-0.477). The correlation was more prominent in patients with cardiac dysfunction. Furthermore, antipyrine clearance showed significant predictability of the duration of ICU stay. CONCLUSIONS: Antipyrine clearance provides a precise estimate of functional liver reserve which is independent of hemodynamics and predicts the risk of postoperative hyperbilirubinemia in preoperative cardiac patients.     

心脏瓣膜置换同期双极射频消融的围术期护理体会

目的探讨心脏瓣膜病合并房颤的患者,在行瓣膜置换的同时联合进行双极射频消融术时,在围术期各阶段所采取的护理措施。方法我科从2012年6月至2013年4月对80例风湿性心脏瓣膜病合并房颤的患者,实施了心脏瓣膜置换联合双极射频消融术,其中二尖瓣置换＋双极射频消融术17例,二尖瓣置换＋三尖瓣成形术＋双极射频消融术31例,主动脉瓣置换＋二尖瓣置换＋双极射频消融术9例,主动脉瓣置换十二尖瓣置换＋三尖瓣成形术＋双极射频消融术23例。结果本组共11例患者出现心律失常,其中7例为室上速,4例口服可达龙后心率维持在100~／min左右,3例经静脉泵入后心率维持在100～120~／min,上述患者出院时心率基本正常,嘱患者出院后继续口服可达龙;另有4例出现窦性心动过缓,心率50～60次／min,经过停用可达龙,1例心率恢复正常,2例给予异丙肾上腺素0．01—0．05斗∥（kg·min）微量泵泵入,2～7d后心率恢复正常,1例使用心表临时起搏器,2周后顺利停用,恢复正常心率。所有患者均康复出院,出院时维持窦性心律。出院后随访3—12个月,均维持窦性心律,未见心脑血管意外等并发症。结论心脏瓣膜病合并房颤的患者,在行瓣膜置换的同时联合进行双极射频消融术,具有安全、疗效显著、远期复发率低等优点。在围术期各阶段采取正确、有针对性的护理措施,有利于促进患者更快的恢复,并有效防止远期并发症的发生。     

Increased hepatic microsomal activity after halothane anaesthesia in children

The effect of anaesthesia and surgery on microsomal enzyme activity was studied in 19 children aged 4-9 years, scheduled for tonsillectomy. The children were randomly allocated to either halothane or ketamine anaesthesia. Antipyrine clearance was measured before and 4 days after surgery by a salivary one-sample technique. Statistically significant (p less than 0.001) increases in antipyrine clearance was found in children who received halothane anaesthesia. The antipyrine clearance was increased by a mean of 26% 4 days after surgery, compared with a pre-operative control measurement. No significant change in antipyrine clearance was observed in children who received ketamine anaesthesia. There was also a significant difference in antipyrine clearance changes after surgery between the two groups (p less than 0.05). Halothane has enzyme-inducing properties after a single exposure in children, while a single dose of ketamine does not.     

慢性肾功能不全病人行体外循环心脏直视手术围术期处理

探讨慢性肾功能不全病人行体外循环心内直视手术的危险性。方法：１９９３年３月到１９９７年６月间对术前诊断为氮质血症期１８例,肾功能不全代偿期４例,尿毒平期１例共２３现人,在心脏手术围术期均给予积极治疗。结果术后早期肾功能指标较术前差,围术期腹透４例,血透１例治疗后,肾功能指标有所改善。２０例昨出院３例死亡。结论术前肾功能不全病人绝大多数可以安全地渡过肾功能衰竭关,达到改善症状及提高生活质量的目的。     

Improved early results after heart valve surgery over the last decade

Objectives: This study was undertaken to investigate time trends in early mortality, morbidity and clinical characteristics of patients undergoing heart valve surgery over the last decade. Methods: A regional, prospectively collected, study comprising all patients (2327) undergoing valve surgery in a defined geographical area from January 1990 to December 1999 was conducted. Data were collected from 1746 patients submitted to aortic valve replacement (AVR), 432 to mitral valve replacement (MVR), 78 to double valve replacement (DVR) and 71 to mitral valve repairs. Logistic regression was used to identify risk factors for early mortality. Time trends of early mortality, morbidity and clinical characteristics were analysed. Results: The total early mortality rate was 5.9%; for AVR it was 4.8%, MVR 9%, DVR 14% and mitral valve repair 1.4%. The risk factor profiles for early mortality were similar in all groups of valve interventions, with shock, age over 70 years and advanced NYHA class as the strongest risk factors. There was a decrease in early mortality over the period which remained after correction for risk factors. The proportion of patients over 70 years of age and of patients with diabetes increased, whereas other risk factors were not altered during the study period. Conclusion: It is confirmed that early risks for death after heart valve surgery have decreased. This improvement was consistent after adjustment for risk factors.     

On-pump beating heart versus hypothermic arrested heart valve replacement surgery

BACKGROUND: Comparison of neurological parameters in patients undergoing prosthetic heart valve replacement with two operating techniques-either cardioplegic arrest of the heart under hypothermic cardiopulmonary bypass (CPB) or the heart beating on normothermic bypass, with or without cross-clamping the aorta, without cardioplegic arrest. methods: Fifty valvular surgery patients were randomly assigned into three groups. Sixteen patients underwent beating heart valve replacement with normothermic bypass without cross-clamping the aorta, 17 patients underwent the same procedure with cross-clamping the aorta and retrograde coronary sinus perfusion, and the remaining 17 patients had conventional surgery with hypothermic bypass and cardioplegic arrest. RESULTS: Two-channel electroencephalography (EEG) was recorded to assess changes in cerebral cortical synaptic activity and 95% spectral edge frequency values were recorded continuously. Bispectral monitoring was used to measure the depth of anesthesia. Blood flow rates in middle cerebral artery (MCA) were measured by transcranial Doppler (TCD). Reduction in spectral edge frequency (>50%) or bispectral index (BIS) (<20) or transcranial Doppler flow velocity (>50%) was detected in four patients in Group 1, five patients in Group 2, and three patients in Group 3. BIS or EEG values never reached zero, which indicates isoelectric silence during surgery. Gross neurological examinations were normal in all patients postoperatively. CONCLUSION: There is no difference regarding neurological monitoring results between on-pump beating heart and hypothermic arrested heart valve replacement surgery. Also no significant difference was encountered among the groups regarding the clinical outcomes.     

3-dimensional printing for the diagnosis of left ventricular outflow tract obstruction after mitral valve replacement

The objective of this study was to evaluate the use of the generation of 3D models and 3D prints of complex cases for physicians at the example of an intricate left ventricular outflow tract obstruction (LVOTO). LVOTO is a known complication of mitral valve surgery. A 38-year-old female patient with increasing dyspnoea after mitral valve replacement was referred to our centre. Echocardiography showed a strut of the bioprosthetic heart valve protruding into the left ventricular outflow tract. However, the diagnosis of a LVOTO was difficult based on echocardiography alone. Therefore, we fabricated a physical model of the left ventricular outflow tract, the mitral valve, the aortic valve and the left ventricle. With this physical model in hand, we were able to visualize the LVOTO and to discuss potential therapeutic options. Moreover, we were able to plan the subsequent redo surgery in detail using the model. This case shows the benefit of 3D printing technologies for surgeons and patients, not only for analysis, but also during the decision-making and pre-operative planning process.     

Mitral valve replacement in children

Rheumatic fever leading to advanced valvular heart disease, in adults and children, is still frequently seen in developing countries. In the period 1981-87, 1137 patients underwent open heart surgery for either repair (489 patients), or replacement (639 patients) of defective cardiac valves. The experience with 75 children who underwent mitral valve replacement among this group is reviewed. The aetiology of mitral valve disease was rheumatic in 71, and infective endocarditis in four; 85% of the children were in NYHA functional class III, and 15% in class IV. Seven children had intra-operative findings of rheumatic activity. Pure mitral regurgitation was seen in 41, while mixed mitral valve disease was observed in 34 children. Twenty-seven children underwent mitral valve replacement with Ionescu-Shiley bovine pericardial valves, and 48 with mechanical Bi-leaflet valves. The operative mortality was 9.3%, and the actuarial survival rate, calculated by the Cutler and Ederers method, was 87% at 5 years.     

Effects of mitral valve replacement on ventilation, volumes, diffusing capacity and regional perfusion of lungs in patients with mitral valve disease

The effects of mitral valve replacement on ventilation, lung volumes, diffusing capacity and regional perfusion of the lungs were studied in eight patients with long-standing mitral valve disease. Eight patients of the same age with coronary artery disease who underwent coronary bypass operation were tested as controls. Preoperatively, the patients with mitral valve disease had significantly higher perfusion of the upper lung fields and the ratio of residual volume to total lung capacity than the control patients. Vital capacity, forced expiratory volume in one second and maximal expiratory flow at 50% of vital capacity were lower in comparison with the control group. Seven days after open heart surgery the values of all the parameters mentioned above had decreased significantly from the preoperative levels in both groups. Three months post-operatively, the values returned to preoperative levels. The abnormal overperfusion of the upper lung fields and other derangements in the ventilatory pattern did not subside even though cardiac haemodynamics were corrected by mitral valve replacement.