Bernard Stockman

Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration

Background:Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion. In clinical studies, the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period. The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration. Methods:Elective coronary surgery patients were randomly assigned to four different anesthetic protocols (n = 50 each). In a first group, patients received a propofol based intravenous regimen (propofol group). In a second group, propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass (SEVO pre group). In a third group, propofol was replaced by sevoflurane after completion of the coronary anastomoses (SEVO post group). In a fourth group, propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation (SEVO all group). Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively. Results:Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group. Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group. In the SEVO pre and SEVO post groups, stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group. Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group. Conclusion:In patients undergoing coronary artery surgery with cardiopulmonary bypass, the cardioprotective effects of sevoflurane were clinically most apparent when it was administered throughout the operation.

Sevoflurane but not propofol preserves myocardial function in coronary surgery patients

Background Sevoflurane has been shown to protect against myocardial ischemia and reperfusion injury in animals. The present study investigated whether these effects were clinically relevant and would protect left ventricular (LV) function during coronary surgery. Methods Twenty coronary surgery patients were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with sevoflurane. Except for this, anesthetic and surgical management was the same in all patients. A high-fidelity pressure catheter was positioned in the left ventricle and the left atrium. LV response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dtmax. Effects on relaxation were assessed by analysis of the load dependence of myocardial relaxation (R = slope of the relation between time constant &tgr; of isovolumic relaxation and end-systolic pressure). Postoperative concentrations of cardiac troponin I were followed during 36 h. Results Before CPB, leg elevation slightly increased dP/dtmax in the sevoflurane group (5 ± 3%), whereas it remained unchanged in the propofol group (1 ± 6%). After CPB, leg elevation resulted in a decrease in dP/dtmax in the propofol group (−5 ± 4%), whereas the response in the sevoflurane group was comparable to the response before CPB (5 ± 4%). Load dependence of LV pressure fall (R) was similar in both groups before CPB. After CPB, R was increased in the propofol group but not in the sevoflurane group. Troponin I concentrations were significantly lower in the sevoflurane than in the propofol group. Conclusions Sevoflurane preserved LV function after CPB with less evidence of myocardial damage in the first 36 h postoperatively. These data suggest a cardioprotective effect of sevoflurane during coronary artery surgery.

Effects of Propofol, Desflurane, and Sevoflurane on Recovery of Myocardial Function after Coronary Surgery in Elderly High-risk Patients

Background The present study investigated the effects of propofol, desflurane, and sevoflurane on recovery of myocardial function in high-risk coronary surgery patients. High-risk patients were defined as those older than 70 yr with three-vessel disease and an ejection fraction less than 50% with impaired length-dependent regulation of myocardial function. Methods Coronary surgery patients (n = 45) were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with desflurane or sevoflurane. Cardiac function was assessed perioperatively and during 24 h postoperatively using a Swan-Ganz catheter. Perioperatively, a high-fidelity pressure catheter was positioned in the left and right atrium and ventricle. Response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dtmax. Effects on relaxation were assessed by analysis of the load-dependence of myocardial relaxation. Postoperative levels of cardiac troponin I were followed for 36 h. Results After CPB, cardiac index and dP/dtmax were significantly lower in patients under propofol anesthesia. Post-CPB, leg elevation resulted in a significantly greater decrease in dP/dtmax in the propofol group, whereas the responses in the desflurane and sevoflurane groups were comparable with the responses before CPB. After CPB, load dependence of left ventricular pressure drop was significantly higher in the propofol group than in the desflurane and sevoflurane group. Troponin I levels were significantly higher in the propofol group. Conclusions Sevoflurane and desflurane but not propofol preserved left ventricular function after CPB in high-risk coronary surgery patients with less evidence of myocardial damage postoperatively.

Choice of Primary Anesthetic Regimen Can Influence Intensive Care Unit Length of Stay after Coronary Surgery with Cardiopulmonary Bypass

Background:Volatile anesthetics protect the myocardium during coronary surgery. This study hypothesized that the use of a volatile agent in the anesthetic regimen would be associated with a shorter intensive care unit (ICU) and hospital length of stay (LOS), compared with a total intravenous anesthetic regimen. Methods:Elective coronary surgery patients were randomly assigned to receive propofol (n = 80), midazolam (n = 80), sevoflurane (n = 80), or desflurane (n = 80) as part of a remifentanil-based anesthetic regimen. Multiple logistic regression analysis was used to identify the independent variables associated with a prolonged ICU LOS. Results:Patient characteristics were similar in all groups. ICU and hospital LOS were lower in the sevoflurane and desflurane groups (P < 0.01). The number of patients who needed a prolonged ICU stay (> 48 h) was also significantly lower (propofol: n = 31; midazolam: n = 34; sevoflurane: n = 10; desflurane: n = 15; P < 0.01). Occurrence of atrial fibrillation, a postoperative troponin I concentration greater than 4 ng/ml, and the need for prolonged inotropic support (> 12 h) were identified as the significant risk factors for prolonged ICU LOS. Postoperative troponin I concentrations and need for prolonged inotropic support were lower in the sevoflurane and desflurane group (P < 0.01). Postoperative cardiac function was also better preserved with the volatile anesthetics. The incidence of other postoperative complications was similar in all groups. Conclusions:The use of sevoflurane and desflurane resulted in a shorter ICU and hospital LOS. This seemed to be related to a better preservation of early postoperative myocardial function.

Cardioprotective properties of sevoflurane in patients undergoing aortic valve replacement with cardiopulmonary bypass.

In coronary surgery patients the use of a volatile anesthetic regimen with sevoflurane was associated with a better recovery of myocardial function and less postoperative release of troponin I. In the present study we investigated whether these cardioprotective properties were also apparent in the cardiac surgical setting of aortic valve replacement (AVR) surgery for the correction of aortic stenosis. Thirty AVR surgery patients were randomly assigned to receive either target-controlled infusion of propofol or inhaled anesthesia with sevoflurane. Cardiac function was assessed perioperatively using a pulmonary artery catheter. Perioperatively, a high-fidelity pressure catheter was positioned in the left ventricle. Postoperative concentrations of cardiac troponin I were followed for 48 h. After cardiopulmonary bypass (CPB), stroke volume and dP/dtmax were significantly higher in the patients with sevoflurane. Post-CPB, the effects of an increase in cardiac load on dP/dtmax were similar to pre-CPB in the sevoflurane group (1.0 % ± 5.4% post-CPB versus 1.3% ± 8.6% pre-CPB) but more depressed in the propofol group (−8.2% ± 4.4% post-CPB versus 0.1% ± 4.9% pre-CPB). The rate of relaxation was significantly slower post-CPB in the propofol group. Postoperative levels of troponin I were significantly lower in the sevoflurane group. Our data indicate that the use of a volatile anesthetic regimen in AVR surgery was associated with better preservation of myocardial function and a reduced postoperative release of troponin I.

Is EuroSCORE useful in the prediction of extended intensive care unit stay after cardiac surgery

OBJECTIVE Risk stratification allows preoperative assessment of cardiac surgical risk faced by individual patients and permits retrospective analysis of postoperative complications in the intensive care unit (ICU). The aim of this single-center study was to investigate the prediction of extended ICU stay after cardiac surgery using both the additive and logistic model of the European System for Cardiac Operative Risk Evaluation (EuroSCORE). METHODS A retrospective observational study was conducted. We collected clinical data of 1562 consecutive patients undergoing cardiac surgery over a 2-year period at the Antwerp University Hospital, Belgium. EuroSCORE values of all patients were obtained. The outcome measure was the duration of ICU stay in days. The predictive performance of EuroSCORE was analyzed by the discriminatory power of a receiver operating characteristic (ROC) curve. Each EuroSCORE value was used as a theoretical cut-off point to predict duration of ICU stay. Three subsequent ICU stays were defined as prolonged: more than 2, 5 and 7 days. ROC curves were constructed for both the additive and logistic model. RESULTS Patients had a median ICU stay of 2 days and a mean ICU stay of 5.5 days. Median additive EuroSCORE was 5 (range, 0-22) and logistic EuroSCORE was 3.94% (range, 0.00-87.00). In the additive EuroSCORE model, a predictive value of 0.76 for an ICU stay of >7 days, 0.72 for >5 days and 0.67 for >2 days was found. The logistic EuroSCORE model yielded an area under the ROC curve of 0.77, 0.75 and 0.68 for each ICU length of stay, respectively. CONCLUSIONS In our patient database, prolonged length of stay in the ICU correlated positively with EuroSCORE. The logistic model was more discriminatory than the additive in tracing extended ICU stay. The overall predictive performance of EuroSCORE is acceptable and most likely based on the presence of variables that are risk factors for both mortality and extended ICU stay. Hence, EuroSCORE is a useful predicting tool and provides both surgeons and intensivists with a good estimate of patient risk in terms of ICU stay.

Effects of Desflurane and Sevoflurane on Length-dependent Regulation of Myocardial Function in Coronary Surgery Patients

Background Desflurane and sevoflurane have negative inotropic effects. The current study investigated whether these effects resulted in an altered left ventricular response to increased cardiac load and affected length-dependent regulation of myocardial function. Length-dependent regulation of myocardial function refers to the ability of the heart to improve its performance when preload is increased. Methods A high-fidelity pressure catheter was positioned in the left ventricle and left atrium in 20 coronary surgery patients with a preoperative ejection fraction greater than 40%. Studies were performed before the initiation of cardiopulmonary bypass. Left ventricular response to increased cardiac load, obtained by leg elevation, was assessed during control conditions and during increasing concentrations of desflurane (2, 4, and 6% end tidal; n = 10) or sevoflurane (1, 2, and 3% end tidal; n = 10). Effects on contraction were evaluated by analysis of changes in maximal rate of pressure development. Effects on relaxation were assessed by analysis of changes in minimum rate of pressure development and by analysis of the load dependence of myocardial relaxation (R = slope of the relation between time constant &tgr; of isovolumic relaxation and end-systolic pressure). Peak left atrial–left ventricular pressure gradients were analyzed during early left ventricular filling. Results With both desflurane and sevoflurane, maximal and minimum rates of pressure development decreased while &tgr; increased. Peak left atrial–left ventricular pressure gradients remained unchanged. The hemodynamic effects of leg elevation were similar at the different concentrations. Changes in parameters of contraction and relaxation during leg elevation were coupled and were not altered by desflurane or sevoflurane. Conclusions Despite their negative inotropic and lusitropic effects, neither desflurane nor sevoflurane adversely affect length-dependent regulation of left ventricular function. In the conditions of our study, the ability of the left ventricular to respond to increased cardiac load is not altered by the use of desflurane or sevoflurane.

Long-term survival of a phase I clinical trial of isolated lung perfusion with melphalan for resectable lung metastases

OBJECTIVE Surgical resection of lung metastases is a widely accepted procedure but 5-year survival rates remain low and vary between 20% and 50%. Isolated lung perfusion (ILuP) is an experimental technique to deliver a high dose of chemotherapy to the lung, without systemic toxicity. Long-term survival of ILuP has not been reported yet and was determined in a phase I clinical trial. METHODS From May 2001 to December 2004, a phase I clinical trial was conducted to define the maximum tolerated dose (MTD) of ILuP with melphalan. Twenty-nine procedures were performed in 23 patients. The primary tumour was colorectal in 10 patients, renal in eight, sarcoma in four and salivary gland in one. Toxicity results were previously reported and the MTD of melphalan was determined at 45 mg when given at 37°C. Follow-up was updated and long-term survival is reported. RESULTS Follow-up was complete, except for one patient who was lost to follow-up after 8 months. After a median follow-up of 62 months, 6 out of 23 patients were alive and free of recurrent disease. One patient died after a subsequent operation. Sixteen patients developed recurrent disease, of whom 11 died. Nine patients had intrathoracic recurrent disease only, one intra- and extrathoracic recurrences each and five extrathoracic only. In one patient, the location of recurrence was not known. Overall- and disease-free 5-year survival rates were 54.8 ± 10.6% and 27.5 ± 9.5%, respectively with an overall median survival time (MST) of 84 months (95% confidence interval (CI): 41-128) and disease-free MST of 19 months (95% CI: 4-34). Lung function and diffusion capacity initially dropped 1 month after perfusion, slightly improving afterwards. Radiographic follow-up with chest computed tomography showed no long-term toxicity from ILuP. CONCLUSION ILuP can be applied without major long-term pulmonary toxicity. Five-year survival rate, overall and disease-free MST in this phase I clinical trial are promising. This is another incentive to perform further studies with ILuP.

Isolated lung perfusion and related techniques for the treatment of pulmonary metastases

Surgical resection is a widely accepted treatment for pulmonary metastases on the condition that a complete resection can be obtained. However, many patients will develop recurrent disease in the thorax despite the use of systemic chemotherapy, dosage of which is limited because of systemic toxicity. Similar to the basic principles of isolated limb and liver perfusion, isolated lung perfusion is an attractive and promising surgical technique for the delivery of high-dose chemotherapy with minimal systemic toxicity. The use of biological response modifiers, like tumour necrosis factor, is also feasible. Other related methods of delivering high-dose locoregional chemotherapy include embolic trapping (chemo-embolisation) and pulmonary artery infusion without control of the venous effluent. Isolated lung perfusion has proven to be highly effective in experimental models of pulmonary metastases with a clear survival advantage. Lung levels of cytostatic drugs are significantly higher after isolated lung perfusion compared to intravenous therapy without systemic exposure. Phase I human studies have shown that isolated lung perfusion is technically feasible with low morbidity and without compromising the patients pulmonary function. Further clinical studies are necessary to determine its definitive effect on local recurrence, long-term toxicity, pulmonary function and survival.

Fractional Flow Reserve–Guided Revascularization in Patients With Aortic Stenosis

Fractional flow reserve (FFR) has never been investigated in patients with aortic stenosis (AS). From 2002 to 2010, we identified 106 patients with AS and coronary artery disease with at least one intermediate lesion treated according to FFR guidance. We matched 212 contemporary control patients with AS in which revascularization was decided on angiography only. More patients in the FFR-guided group underwent percutaneous coronary intervention (24% vs 13%; p = 0.019), whereas there was a trend toward less coronary artery bypass grafting (CABG) performed. After FFR, the number of diseased vessels was downgraded within the FFR-guided group (from 1.85 ± 0.97 to 1.48 ± 1; p <0.01) and compared with the angio-guided group (1.48 ± 1 vs 1.8 ± 0.97; p <0.01). Less aortic valve replacement was reported in the FFR-guided group (46% vs 57%; p = 0.056). In patients who underwent CABG, less venous conduits (0.5 ± 0.69 vs 0.73 ± 0.76; p = 0.05) and anastomoses (0.61 ± 0.85 vs 0.94 ± 1; p = 0.032) were necessary in the FFR-guided group. Up to 5 years, we found no difference in major adverse cardiac events (38% vs 39%; p = 0.98), overall death (32% vs 31%; p = 0.68), nonfatal myocardial infarction (2% vs 2%; p = 0.79), and revascularization (8% vs 7%; p = 0.76) between the 2 groups. In conclusion, FFR guidance impacts the management of selected patients with moderate or severe AS and coronary artery disease by resulting into deferral of aortic valve replacement, more patients treated with percutaneous coronary intervention, and in patients treated with CABG, into less venous grafts and anastomoses without increasing adverse event rates up to 5 years.