Isolated lung perfusion for the treatment of pulmonary metastatic disease: a review.

Isolated lung perfusion with chemotherapeutic agents is an experimental technique for the treatment of lung metastatic disease from certain solid tumours. The technique had already been developed in the late 1950s but underwent a revival in the early 1980s. By that time, experimental work in large and small animals induced extensive clinical work with different agents such as doxorubicin, tumour necrosis factor, melphalan and cisplatin for which safety profiles and maximal tolerated doses were defined. A review of current work is presented in this article.

Incidence of atrial fibrillation early after cardiac surgery: can choice of the anesthetic regimen influence the incidence?

Occurrence of atrial fibrillation is a common complication after coronary surgery. This study aimed to identify the perioperative factors that are associated with its occurrence with specific attention to the possible influence of the choice of the anesthetic regimen after elective coronary surgery. A retrospective chart analysis was performed in 460 patients who underwent elective coronary artery surgery with cardiopulmonary bypass using the standard institutional anesthetic, surgical and postoperative protocols. The only difference in management was the choice of the primary anesthetic regimen. 110 patients had a total intravenous anesthesia with propofol, 90 patients had a total intravenous anesthesia with midazolam, 150 patients were anesthetized with sevoflurane and 110 patients with desflurane. The primary outcome variable was the incidence of atrial fibrillation within the first 24 postoperative hours. Atrial fibrillation occurred in 64 of the 460 patients included (13.9%). Multiple logistic regression analysis identified increased age (> 70 years), EuroSCORE > 4, prolonged CPB time (> 100 min) and need for prolonged inotropic support (> 6 hours) as the significant independent risk factors for the occurrence of postoperative atrial fibrillation. The incidence of postoperative atrial fibrillation differed among the different anesthetic groups with the lowest incidence in the sevoflurane group (propofol: 17/110; midazolam: 15/90; sevoflurane: 9/150; desflurane: 23/110) (p = 0.004). This finding should be further confirmed in a prospective sufficiently powered multicenter study.

Cerebral oximetry in patients undergoing carotid endarterectomy: preliminary results.

Carotid endarterectomy (CEA) is an appropriate treatment for carotid occlusive disease. The risk of stroke during CEA ranges from 1.1% to 7.5%. Shunting is usually advised when severe ischemia during cross-clamping of the internal carotid artery is suspected. Routine use of an intraluminal shunt may increase the perioperative stroke rate. Popular and well documented methods of neurologic monitoring for ischemia during general anesthesia are electroencephalography (EEG) and transcranial Doppler ultrasonography (TCD) of the middle cerebral artery. The purpose of this prospective study was to compare cerebral oximetry using near infrared spectrophotometry (NIRS) with EEG and TCD. Preliminary data on 14 patients scheduled for elective carotid endarterectomy were included and a literature search was performed to correlate the findings. No postoperative neurologic events occurred. During carotid clamping there was a significant decrease in regional oxygen saturation (rSO2) but there was only a weak correlation with the decrease in mean Doppler flow (R = 0.74; P = 0.02) and no correlation with EEG changes (R = 0.49; P = 0.18). A useful rSO2 cut-off value predictive for cerebral ischemia could not be defined.

Effect of preoperative beta-blockade on perioperative mortality in coronary surgery.

BACKGROUND: Many preoperative factors can influence perioperative mortality in cardiac surgery. Because the perioperative use of beta-blocking agents may reduce perioperative cardiac complications in non-cardiac surgery, we considered the possibility that beta-blocking agents could improve survival in coronary surgery patients. METHODS: In a retrospective study on 1586 patients undergoing coronary bypass surgery, the relative risk of 30-day mortality was determined in relation to preoperative risk factors and medication. Factors included patient characteristics, pre-existing illness, specific cardiovascular risk factors, cardiac status and urgency of surgery. Treatment with beta-blocking agents, calcium antagonists, angiotensin-converting enzyme inhibitors, nitrates, anti-arrhythmic agents, diuretics and antithrombotic agents was taken into account. RESULTS: Sex, age, chronic obstructive pulmonary disease, urgency and the preoperative use of diuretics and chronic beta-blocking therapy were found to be linked to mortality (P<0.05). Backward stepwise regression testing identified age, urgency and beta-blocking therapy as independent factors that could predict mortality. CONCLUSIONS: Increasing age and urgency of surgery are associated with greater mortality, whereas preoperative beta-blocking therapy is associated with less mortality. The characteristics of patients who received chronic beta-blockade did not differ significantly from those of patients who did not. The results suggest that chronic preoperative beta-blocker therapy reduces 30-day mortality in coronary surgery.

Effects of phosphodiesterase III inhibition on length-dependent regulation of myocardial function in coronary surgery patients.

BACKGROUND: Phosphodiesterase III inhibitors increase myocardial contractility and decrease left ventricular (LV) afterload. We studied whether these effects altered LV response to an increase in cardiac load and affected length-dependent regulation of myocardial function. METHODS: Before the start of cardiopulmonary bypass, a high-fidelity pressure catheter was positioned in the left ventricle and the left atrium in 10 coronary surgery patients. LV response to an increased cardiac load, caused by leg elevation, was assessed during baseline conditions and after administration of milrinone at a dose of 20 micrograms kg-1 over 15 min. Effects on contraction were measured by changes in maximal rate of pressure development (dP/dtmax). Effects on relaxation were assessed by analysis of changes in maximum rate of pressure decrease and by analysis of the load dependency of myocardial relaxation (R = slope of the relation between the time constant of isovolumic relaxation and end systolic pressure). RESULTS: Milrinone increased dP/dtmax but measures of relaxation were unaltered. Leg elevation had more effect on measures of contraction and relaxation after milrinone than at baseline. The relationship between R and changes in dP/dtmax shifted downwards and to the right with milrinone, whereas the relationship between R and changes in end diastolic pressure (EDP) shifted downwards and to the left. CONCLUSIONS: This suggests that milrinone improved contraction, reduced the load dependency of LV pressure decrease, and reduced the change in EDP after leg elevation.

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 tau 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 tau 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.

The effects of the pericardium on length-dependent regulation of left ventricular function in coronary artery surgery patients.

OBJECTIVE: To analyze the effects of the pericardium on the length-dependent regulation of myocardial function in coronary artery surgery patients. DESIGN: Prospective. SETTING: University hospital. PARTICIPANTS: Patients scheduled for elective coronary artery surgery. INTERVENTIONS: In 10 patients, a combined micromanometer transducer conductance catheter was inserted into the left ventricle for measurement of left ventricular pressures and volumes. MEASUREMENTS AND MAIN RESULTS: Consecutive data were obtained during a progressive increase in left ventricular pressures and volumes obtained by leg elevation in closed chest-closed pericardium and open chest-open pericardium conditions. Pericardiotomy did not alter baseline left ventricular hemodynamics. The effects of leg elevation were different, however. In closed chest-closed pericardium conditions, stroke volume and stroke work remained unchanged, whereas these parameters increased in open chest-open pericardium conditions. This increase was related to the increase in end-diastolic volume that was observed in open chest-open pericardium conditions and not in closed chest-closed pericardium conditions. CONCLUSIONS: In coronary artery surgery patients, pericardiotomy does not alter baseline left ventricular function. When cardiac load is increased by leg elevation, however, use of the Frank-Starling mechanism is enhanced in open chest-open pericardium conditions.

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.

Length-dependent regulation of left ventricular function in coronary surgery patients.

BACKGROUND: Load-dependent impairment of left ventricular (LV) function was observed after leg elevation in a subgroup of coronary surgery patients. The present study investigated underlying mechanisms by comparing hemodynamic effects of an increase in LV systolic pressures with leg elevation to effects of a similar increase in systolic pressures with phenylephrine. METHODS: The study was performed in patients undergoing elective coronary surgery prior to cardiopulmonary bypass. High-fidelity LV pressure tracings (n = 25) and conductance LV volume data (n = 10) were obtained consecutively during leg elevation and after phenylephrine administration (5 microg/kg). RESULTS: Leg elevation resulted in a homogeneous increase in end-diastolic volume. The change in stroke volume (SV), stroke work (SW) and dP/dtmax was variable, with an increase in some patients but no change or a decrease in other patients. For a matched increase in systolic pressures, phenylephrine increased SW and dP/dtmax in all patients with no change in SV. Load dependence of relaxation (slope R of the tau-end-systolic pressure relation) was inversely related for changes in SV, SW, and dP/dtmax with leg elevation but not with phenylephrine. CONCLUSIONS: The different effects of leg elevation and phenylephrine suggest that the observed decrease in SV, SW, and dP/dtmax with leg elevation in some patients could not be attributed to an impaired contractile response to increased systolic LV pressures. Instead, load-dependent impairment of LV function after leg elevation appeared related to a deficient length-dependent regulation of myocardial function.

Contraction-relaxation coupling and impaired left ventricular performance in coronary surgery patients.

BACKGROUND: Dependence of left ventricular (LV) relaxation on cardiac systolic load is a function of myocardial contractility. The authors hypothesized that, if a tight coupling would exist between LV contraction and relaxation, the changes in relaxation rate with an increase in cardiac systolic load would be related to the changes in LV contraction. METHODS: Coronary surgery patients (n = 120) with preoperative ejection fraction >40% were included. High-fidelity LV pressure tracings (n = 120) and transgastric transesophageal echocardiographic data (n = 40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on contraction were evaluated by analysis of changes in dP/dt(max) and stroke area. Effects on relaxation were assessed by analysis of R (slope of the relation between tau and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearson's coefficient r. RESULTS: Baseline LV end-diastolic pressure was 10+/-3 mm Hg (mean +/- SD). During leg raising, systolic LV pressure increased from 93+/-9 to 107+/-11 mm Hg. The change in dP/dt(max) was variable and ranged from -181 to +254 mm Hg/s. A similar variability was observed with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in dP/dt(max) and in stroke area were closely related to individual R values (r = 0.87, P<0.001; and r = 0.81, P<0.001, respectively) and to corresponding changes in LV end-diastolic pressure (r = 0.81, P< 0.001; and r = 0.74, P<0.001, respectively). CONCLUSIONS: A tight coupling was observed between contraction and relaxation. Leg raising identified patients who developed a load-dependent impairment of LV performance and increased load dependence of LV relaxation.

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.

Effects of calcium on left ventricular function early after cardiopulmonary bypass.

OBJECTIVES: Evaluation of the effects of intravenous CaCl2 on systolic and diastolic function early after separation from cardiopulmonary bypass (CPB) DESIGN: Prospective study SETTING: University hospital PARTICIPANTS: Twenty patients scheduled for elective coronary artery surgery INTERVENTIONS: Left ventricular (LV) pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the LV were simultaneously recorded on videotape. Measurements were obtained before the start of CPB, 10 minutes after termination of CPB, after intravenous administration of CaCl2, 5 mg/kg, and 10 minutes later. MEASUREMENTS AND MAIN RESULTS: Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relation. CaCl2 increased Ees from 2.62 +/- 0.46 to 5.58 +/- 0.61 (mean +/- SD), but induced diastolic dysfunction with an increase in Kc from 0.011 +/- 0.006 to 0.019 +/- 0.007. These changes were transient and had disappeared within 10 minutes after administration of CaCl2. CONCLUSIONS: CaCl2 early after CPB transiently improved systolic function at the expense of an increase in ventricular stiffness, suggesting temporary diastolic dysfunction.

Effects of lidoflazine on left ventricular function in patients.

OBJECTIVE: The present study evaluated the effects of the nucleoside transport inhibitor, lidoflazine, at a dose of 1 mg/kg, on left ventricular function. DESIGN: Patients were randomly assigned to receive either lidoflazine or saline in a double-blind manner. SETTING: A university hospital. PARTICIPANTS: The study was performed in 32 patients scheduled for elective coronary artery bypass surgery. INTERVENTIONS: Left ventricular pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relationship. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relationship. Cardiac function was assessed at baseline and after administration of either lidoflazine (group A [n = 16]) or placebo (group B [n = 16]). Data were compared using two-factor analysis of variance. MEASUREMENTS AND MAIN RESULTS: At baseline, diastolic and systolic function were comparable in both groups. Lidoflazine increased Kc from 0.079 +/- 0.015 to 0.125 +/- 0.017 mmHg/mL and decreased Ees from 2.481 +/- 0.213 to 1.217 +/- 0.211 mmHg/mL (p = 0.009 and p = 0.004, respectively). None of these changes occurred when placebo was administered. CONCLUSIONS: Administration of lidoflazine before the start of cardiopulmonary bypass impaired left ventricular systolic function but also increased diastolic stiffness.

Epidural sufentanil for postoperative patient-controlled analgesia (PCA) with or without background infusion: a double-blind comparison.

To evaluate the usefulness of a concurrent infusion in patient-controlled epidural analgesia (PCEA), 40 patients scheduled for elective cesarean section under a combined spinal-epidural technique were assigned randomly in a double-blind fashion to receive sufentanil by PCEA with a concomitant infusion of either sufentanil or saline. The sufentanil 24-h consumption was significantly (P < 0.001) higher in those patients receiving the opioid-containing infusion (212.7 +/- 9.5 vs 128.4 +/- 10.8 micrograms, SEM). The number of additional demands and the quality of sleep did not differ between the two groups. The degree of sedation was significantly less pronounced in patients treated with incremental sufentanil doses only. The visual analog scale (VAS) pain scores at rest were identical in both groups except at 6 h (2.5 +/- 0.4 vs 3.7 +/- 0.3, in favor of the patients treated with the sufentanil background infusion). We conclude that, except for a lower pain score during the initial hours, a background infusion in PCEA with sufentanil does not offer major advantages in terms of sleep quality or sufentanil consumption. Side effects may be more pronounced owing to increased drug administration.