Sven-Erik Ricksten

Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease

The effect of cardiac sympathetic blockade by high thoracic epidural anesthesia (TEA) (T1-T6, bupivacaine) on the luminal diameter of normal and diseased portions of epicardial coronary arteries was determined by quantitative coronary angiography in patients (n = 27) with severe coronary artery disease (CAD). In a separate group of patients (n = 9) with severe CAD, the effects of TEA on coronary arterioles (resistance vessels) were studied, by measuring total and regional myocardial blood flow and metabolism with the retrograde coronary sinus thermodilution technique. At the stenotic segments, TEA induced an increase in luminal diameter from 1.34 +/- 0.11 to 1.56 +/- 0.13 mm (P less than 0.002), but did not change the diameter of the nonstenotic segments (3.07 +/- 0.13 to 2.99 +/- 0.13 mm). In the second group of patients, TEA induced no changes in coronary perfusion pressure, total or regional myocardial blood flow, coronary venous oxygen content, coronary blood flow distribution, regional myocardial oxygen consumption, or lactate extraction or uptake. Two patients had chest pain in the control situation and had regional myocardial lactate production that was attenuated by TEA. We conclude that TEA may increase the diameter of stenotic epicardial coronary artery segments in patients with CAD without causing a dilation of coronary arterioles. These effects may be beneficial when high TEA is used to treat severe ischemic chest pain in patients at rest.

Thoracic Epidural Anesthesia Improves Global and Regional Left Ventricular Function During Stress-induced Myocardial Ischemia in Patients With Coronary Artery Disease

The aim of the present investigation was to study the effects of high thoracic epidural anesthesia (TEA), including the cardiac sympathetic segments, on ischemic ST-segment changes and left ventricular global and regional wall motion abnormalities. Ten patients with a two- or three-vessel coronary artery disease, all treated with the β-adrenergic blocker metoprolol because of severe stable angina pectoris, performed two identical exercise stress tests, the first without TEA (control exercise) and the second with TEA (TEA exercise). Before each stress test, intravenous metoprolol was given to achieve maximal or near maximal β-adrenoceptor blockade. Systolic and diastolic arterial pressures (radial artery cannula), heart rate, and rate-pressure product, as well as global and regional ejection fractions, using equilibrium radionuclide angiography in the left anterior oblique projection, were measured at rest and during maximal exercise. ST-segment analysis (V3 or V5) was performed, and the regional wall motion score was calculated at control exercise and TEA exercise. Intravenous metoprolol or intravenous metoprolol plus TEA at rest did not cause any significant changes of any of the variables. During TEA exercise, systolic arterial pressure, diastolic arterial pressure, and rate-pressure product, but not heart rate, were significantly lower compared to control exercise. The global and anterolateral ejection fractions were significantly higher (52.8% versus 46.5% and 53.2% versus 46.0%, respectively, P < 0.05), and the regional wall motion score was significantly lower (8.8 versus 11.8, P < 0.01) during TEA exercise than during control exercise. ST-segment depression was significantly lower during TEA exercise (−1.03 versus −1.84 mV, P < 0.01). It is concluded that cardiac sympathetic blockade with TEA, in patients with coronary artery disease, improves ischemia-induced left ventricular global and regional wall motion abnormalities at a certain physical stress, associated with less pronounced ST-segment depression.

Thoracic epidural anesthesia and central hemodynamics in patients with unstable angina pectoris.

The effects of high thoracic epidural anesthesia (TEA) on central hemodynamics as measured by pulmonary arterial catheterization were studied in nine patients with severe coronary artery disease and unstable angina pectoris. The patients were also treated with a combination of betablockers, calcium antagonists, and nitrates, as well as salicylates, low-dose heparin, and nitroglycerin infusion for >24 hr. Management of pain with high TEA was started with the bolus epidural injection of 4.3 ± 0.2 mL bupivacaine (5 mg/mL), which induced a sympathetic blockade from Th1–8. During ischemic chest pain, pulmonary artery and pulmonary capillary wedge pressures were significantly increased. TEA, while relieving the chest pain, significantly decreased systolic arterial blood pressure, heart rate, and pulmonary artery and pulmonary capillary wedge pressures, without any significant changes in coronary perfusion pressure, cardiac output, stroke volume, and systemic or pulmonary vascular resistances. In some patients, ST-segment depression was less pronounced during TEA. Thus, during ischemic chest pain, TEA has beneficial effects on the major determinants of myocardial oxygen consumption, without jeopardizing coronary perfusion pressure. TEA may therefore favorably alter the oxygen supply/demand ratio within ischemic myocardial areas.

Thoracic Epidural Anesthesia During Coronary Artery Bypass Surgery: Effects on Cardiac Sympathetic Activity, Myocardial Blood Flow and Metabolism, and Central Hemodynamics

The effects of high thoracic epidural anesthesia (TEA) on cardiac sympathetic nerve activity, myocardial blood flow and metabolism, and central hemodynamics were studied in 20 patients undergoing coronary artery bypass grafting (CABG). In 10 of the patients, TEA (T1-5 block) was used as an adjunct to a standardized fentanyl-nitrous oxide anesthesia. Hemodynamic measurements and blood sampling were performed after induction of anesthesia but prior to skin incision and after sternotomy. Assessment of total and cardiac sympathetic activity was performed by means of the norepinephrine kinetic approach. Prior to surgery, mean arterial pressure (MAP), great cardiac vein flow (GCVF), and regional myocardial oxygen consumption (Reg-MVO2) were lower in the TEA group compared to the control group. During sternotomy there was a pronounced increase in cardiac norepinephrine spillover, MAP, systemic vascular resistance index (SVRI), pulmonary capillary wedge pressure (PCWP), GCVF, and Reg-MVO2 in the control group. These changes were clearly attenuated in the TEA group. None of the patients in the TEA group had metabolic (lactate) or electrocardiographic signs of myocardial ischemia. Three patients in the control group had indices of myocardial ischemia prior to and/or during surgery. We conclude that TEA attenuates the surgically mediated sympathetic stress response to sternotomy, thereby preventing the increase in myocardial oxygen demand in the pre-bypass period without jeopardizing myocardial perfusion.

The Additive Pulmonary Vasodilatory Effects of Inhaled Prostacyclin and Inhaled Milrinone in Postcardiac Surgical Patients with Pulmonary Hypertension

Selective pulmonary vasodilation is an advantageous therapeutic strategy for cardiac surgical patients with increased pulmonary vascular resistance (PVR) and right ventricular failure. We hypothesized that milrinone, an adenosine-3′,5′-cyclic monophosphate (cAMP)-selective phosphodiesterase enzyme (PDE) inhibitor may, when nebulized and inhaled, cause selective pulmonary vasodilation and potentiate the vasodilation by inhaled prostacyclin (iPGI2). Consequently, we investigated the hemodynamic effects of inhaled milrinone or the combination iPGI2 + inhaled milrinone in cardiac surgical patients with postoperative mean pulmonary arterial pressure (MPAP) >25 mm Hg and PVR >200 dynes · s−1 · cm−5. During mechanical ventilation and using a conventional nebulizing system, 9 patients inhaled incremental concentrations of milrinone (0.25, 0.5 and 1 mg/mL) in subsequent 10-min periods (Study Part 1). In the same manner, 11 patients received iPGI2 (10 &mgr;g/mL) followed by the combination of iPGI2 (10 &mgr;g/mL) and inhaled milrinone (1 mg/mL) (Study Part 2). Inhaled milrinone reduced PVR with a maximal effect (−20%, P < 0.001) at the largest concentration. As compared with iPGI2 alone, iPGI2 + inhaled milrinone caused a further and prolonged reduction of PVR (−8%, P < 0.05) and increased stroke volume (+5%, P < 0.05). Systemic vascular resistance or mean arterial pressure was not affected by inhalation of either drug(s). The authors conclude that inhalation of the cAMP-selective PDE-inhibitor milrinone selectively dilates the pulmonary vasculature without systemic effects in cardiac surgical patients with pulmonary hypertension. Furthermore, inhaled milrinone appears to potentiate and prolong the pulmonary selective vasodilatory effect of iPGI2. Inhaled milrinone alone or combined with iPGI2 may be an important therapeutic option in the treatment of patients with pulmonary hypertension and right ventricular failure.

Thoracic epidural versus intravenous patient-controlled analgesia after cardiac surgery : A randomized controlled trial on length of hospital stay and patient-perceived quality of recovery

Background:Perioperative thoracic epidural analgesia reduces stress response and pain scores and may improve outcome after cardiac surgery. This prospective, randomized trial was designed to compare the effectiveness of patient-controlled thoracic epidural analgesia with patient-controlled analgesia with intravenous morphine on postoperative hospital length of stay and patients’ perception of their quality of recovery after cardiac surgery. Methods:One hundred thirteen patients undergoing elective cardiac surgery were randomly assigned to receive either combined thoracic epidural analgesia and general anesthesia followed by patient-controlled thoracic epidural analgesia or general anesthesia followed by to patient-controlled analgesia with intravenous morphine. Postoperative length of stay, time to eligibility for hospital discharge, pain and sedation scores, degree of ambulation, lung volumes, and organ morbidities were evaluated. A validated quality of recovery score was used to measure postoperative health status. Results:Length of stay and time to eligibility for hospital discharge were similar between the groups. Study groups differed neither in postoperative global quality of recovery score nor in five dimensions of quality of recovery score. Time to extubation was shorter (P < 0.001) and consumption of anesthetics was lower in the patient-controlled thoracic epidural analgesia group. Pain relief, degree of sedation, ambulation, and lung volumes were similar between the study groups. There was a trend for lower incidences of pneumonia (P = 0.085) and confusion (P = 0.10) in the patient-controlled thoracic epidural analgesia group, whereas cardiac, renal, and neurologic outcomes were similar between the groups. Conclusions:In elective cardiac surgery, thoracic epidural analgesia combined with general anesthesia followed by patient-controlled thoracic epidural analgesia offers no major advantage with respect to hospital length of stay, quality of recovery, or morbidity when compared with general anesthesia alone followed by to patient-controlled analgesia with intravenous morphine.

Anti-Ischemic and Anti-Anginal Effects of Thoracic Epidural Anesthesia Versus Those of Conventional Medical Therapy in the Treatment of Severe Refractory Unstable Angina Pectoris

BACKGROUND Cardiac sympathetic blockade by thoracic epidural anesthesia (TEA) dilates stenotic coronary arteries and has been used to control pain in patients with unstable angina. The aim of the present study was to evaluate the potential anti-ischemic effects of cardiac sympathetic blockade by TEA in severe, refractory, unstable angina. METHODS AND RESULTS Forty patients with unstable angina refractory to standard anti-anginal therapy were randomized to receive either continuous epidural infusion of bupivacaine (TEA, Th1 to Th5) or to standard anti-anginal therapy including beta-blockers, calcium antagonists, aspirin, heparin, and nitroglycerin infusion (control group). The primary end points were number of anginal attacks and severity of myocardial ischemia assessed by 48-hour ambulatory Holter monitoring. The incidence of myocardial ischemia was lower in the TEA group (22% versus 61%; P<.05). The number of ischemic episodes per patient was 1.0+/-0.6 in the TEA group and 3.6+/-0.9 in the control group (P<.05). The episode duration per patient was 4.1+/-2.5 minutes and 19.7+/-6.2 minutes in the TEA and the control groups, respectively (P<.05). The mean area-under-the-ST-time-curve was 6.8+/-4.3 and 32.2+/-14.3 (mm-min) in the TEA and the control groups, respectively (P<.05). Fifteen anginal attacks were recorded in the control group and one attack in the TEA group (0.83+/-0.21 versus 0.06+/-0.06/patient, respectively, P<.01). CONCLUSIONS The anti-ischemic and anti-anginal effects of continuous TEA are superior to those of conventional therapy in the treatment of refractory unstable angina.

Effects of thoracic epidural anaesthesia on central haemodynamics compared to cardiac beta adrenoceptor blockade in conscious rats with acute myocardial infarction

The study aimed to compare the effects of thoracic epidural anaesthesia (TEA) with those of the beta‐adrenoceptor blocker, metoprolol, on central haemodynamics in conscious rats with acute myocardial infarction. During methohexital anaesthesia, appropriate vascular catheters were inserted, a thoracic epidural catheter was implanted and the left coronary artery was ligated. A recovery period of 1–2 h elapsed after termination of surgery and anaesthesia. Experiments were performed on four separate groups of animals (A‐D). In Group A (n= 10) mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) were measured, and stroke volume (SV) and systemic vascular resistance (SVR) were calculated before and 10–15 min after the induction of TEA (bupivacaine 5 mg · ml‐1). In Group B (n=6) left ventricular end‐diastolic pressure (LVEDP) and maximal dP/dt were recorded as in Group A. In Group C (n = 10) central haemodynamics were measured 10 min after i.v. metoprolol (0.5 mg · kg‐1) and again 10–15 min after the addition of TEA. In Group D (n=6) LVEDP and max dP/dt were measured as in Group C. The reduction in CO, SV, HR and max dP/dt was of the same magnitude with TEA and metoprolol. TEA lowered MAP by 17%, while metoprolol did not change MAP. Metoprolol caused an increase in LVEDP from 20.8 ± 1.8 to 27.5 ± 2.7 mmHg (2.8 ± 0.2 to 3.7 ± 0.4 kPa) (P < 0.01), while TEA induced a decrease in LVEDP from 24.2 ± 1.4 to 17.8 ± 1.6 mmHg (3.2 ± 0.2 to 2.4 ± 0.2 kPa) (P < 0.05). SVR increased 27% with metoprolol but was not affected by TEA. Induction of TEA during maximal beta blockade did not cause any further changes in CO, HR, max dP/dt or SV. In this situation, however, MAP and SVR decreased significantly by 23% and 19%, respectively, and LVEDP decreased from 27.5 ± 2.7 to 20.2 ± 2.3 mmHg (3.7 ± 0.4 to 2.7 ± 0.3 kPa) (P < 0.01). Compared to metoprolol, TEA may have more favourable effects on central haemodynamics during acute myocardial infarction, as, in striking contrast to metoprolol, TEA decreased indices of wall tension and outflow impedance of the left ventricle.

Acute renal failure is NOT an "acute renal success"--a clinical study on the renal oxygen supply/demand relationship in acute kidney injury.

Objectives:Acute kidney injury occurs frequently after cardiac or major vascular surgery and is believed to be predominantly a consequence of impaired renal oxygenation. However, in patients with acute kidney injury, data on renal oxygen consumption (RVO2), renal blood flow, glomerular filtration, and renal oxygenation, i.e., the renal oxygen supply/demand relationship, are lacking and current views on renal oxygenation in the clinical situation of acute kidney injury are presumptive and largely based on experimental studies. Design:Prospective, two-group comparative study. Setting:Cardiothoracic intensive care unit of a tertiary center. Patients:Postcardiac surgery patients with (n = 12) and without (n = 37) acute kidney injury were compared with respect to renal blood flow, glomerular filtration, RVO2, and renal oxygenation. Interventions:None Measurements and Main Results:Data on systemic hemodynamics (pulmonary artery catheter) and renal variables were obtained during two 30-min periods. Renal blood flow was measured using two independent techniques: the renal vein thermodilution technique and the infusion clearance of paraaminohippuric acid, corrected for renal extraction of paraaminohippuric acid. The filtration fraction was measured by the renal extraction of 51Cr-EDTA and the renal sodium resorption was measured as the difference between filtered and excreted sodium. Renal oxygenation was estimated from the renal oxygen extraction. Cardiac index and mean arterial pressure did not differ between the two groups. In the acute kidney injury group, glomerular filtration (−57%), renal blood flow (−40%), filtration fraction (−26%), and sodium resorption (−59%) were lower, renal vascular resistance (52%) and renal oxygen extraction (68%) were higher, whereas there was no difference in renal oxygen consumption between groups. Renal oxygen consumption for one unit of reabsorbed sodium was 2.4 times higher in acute kidney injury. Conclusions:Renal oxygenation is severely impaired in acute kidney injury after cardiac surgery, despite the decrease in glomerular filtration and tubular workload. This was caused by a combination of renal vasoconstriction and tubular sodium resorption at a high oxygen demand.

Effects of Levosimendan on Left Ventricular Relaxation and Early Filling at Maintained Preload and Afterload Conditions After Aortic Valve Replacement for Aortic Stenosis

Background— We determined the effects of levosimendan, a calcium sensitizer, on left ventricular (LV) diastolic function in patients with LV hypertrophy. Methods and Results— In this prospective, randomized, blinded study, 23 patients received either levosimendan (0.1 and 0.2 &mgr;g · kg−1 · min−1; n=12) or placebo (n=11) after aortic valve replacement for aortic stenosis. The effects on LV performance, dimensions, filling patterns, and isovolumic relaxation time, as well as systemic hemodynamics, were assessed by pulmonary artery thermodilution catheterization and transesophageal 2-dimensional Doppler echocardiography. To circumvent the confounding effects of the levosimendan-induced hemodynamic changes on Doppler echocardiographic indexes of LV early relaxation, heart rate and mean arterial and central venous pressures were kept constant during levosimendan/placebo infusion by atrial pacing, vasopressor, and colloid infusions. In the levosimendan group, dose-dependent increases in cardiac output (28%; P<0.001) and stroke volume (26%; P<0.001) and a decrease in systemic vascular resistance (−22%; P<0.001) were observed. There was a trend for an increase in LV ejection fraction (12%; P=0.058) with levosimendan. There were no significant differences in systolic, diastolic arterial, or LV filling pressures or LV end-diastolic area between the 2 groups. Isovolumic relaxation time decreased (−23%; P<0.001), as did the deceleration slope of early diastolic filling (−45%; P<0.01), whereas peak early diastolic filling velocity (16%, P<0.01) and peak late diastolic filling velocity (15%; P<0.001) increased after levosimendan compared with placebo. Conclusion— Levosimendan, in addition to its inotropic effects, exerts a direct positive lusitropic effect in patients with LV hypertrophy as it shortens isovolumic relaxation time and improves LV filling.