Pieter W. ten Broecke

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.

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.

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.

Assessment of length-dependent regulation of myocardial function in coronary surgery patients using transmitral flow velocity patterns

Background In a subset of coronary surgery patients, a transient increase in cardiac load by leg elevation resulted in a decrease in maximal rate of pressure development (dP/dtmax) and a major increase in end-diastolic pressure (EDP). This impairment of left ventricular (LV) function appeared to be related to a deficient length-dependent regulation of myocardial function. The present study investigated whether analysis of transmitral flow patterns with transesophageal echocardiography constituted a noninvasive method to identify these patients. Methods High-fidelity LV pressure tracings and transmitral flow signals were obtained in 50 coronary surgery patients during an increase in cardiac load by leg elevation. Using linear regression analysis, changes in transmitral E-wave velocity and deceleration time (DT) were related to changes in dP/dtmax and EDP. Results Changes in dP/dtmax with leg elevation were closely related to corresponding changes in E-wave velocity (r = 0.81;P < 0.001) and to changes in DT (r = 0.78;P < 0.001). Similarly, changes in EDP were related to changes in E-wave velocity (r = 0.83;P < 0.001) and to changes in DT (r = 0.84;P < 0.001). The decrease in dP/dtmax and the major increase in EDP in some patients was associated with an increase in E-wave velocity and a decrease in DT, indicating development of a restrictive LV filling pattern. Conclusions Impairment of LV function with leg elevation was associated with the development of a restrictive transmitral filling pattern. Analysis of transmitral flow patterns by means of transesophageal echocardiography therefore allowed noninvasive identification of a subset of coronary surgery patients with impaired length-dependent regulation of LV function.

Effects of nicardipine and urapidil on length-dependent regulation of myocardial function in coronary artery surgery patients

OBJECTIVE To assess effects of a decrease in left ventricular (LV) afterload (pharmacologically induced by nicardipine and urapidil) on myocardial contraction and relaxation, with emphasis on the effects on load dependence of myocardial function. DESIGN Prospective, blinded study. SETTING University hospital. PARTICIPANTS Coronary artery surgery patients. INTERVENTIONS Alterations of systolic load were effected by leg elevation in control conditions and after administration of either nicardipine or urapidil before and after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS High-fidelity LV pressure tracings were obtained at end-expiration while hearts were paced at a fixed rate of 90 beats/min. Hemodynamic effects of leg elevation were compared before and after nicardipine, 7 microg/kg (n = 15), and before and after urapidil, 0.4 mg/kg (n = 15). The effects of leg elevation on parameters of contraction and relaxation were coupled. Both nicardipine and urapidil similarly decreased systolic pressures and peripheral resistance. Nicardipine decreased rate of pressure development (dP/dtmax) and slowed LV pressure fall, whereas load dependence of LV relaxation was not altered. Urapidil did not alter dP/dtmax, rate of LV pressure fall, or load dependence of relaxation. Similar results were observed after cardiopulmonary bypass. CONCLUSIONS The results of the present study indicate that a pharmacologically induced moderate reduction in LV afterload with nicardipine or urapidil did not alter the length-dependent regulation of myocardial function.