Renal function during cardiopulmonary bypass: influence of the calcium entry blocker felodipine.

Glomerular filtration and tubular activity are decreased during hypothermic cardiopulmonary bypass (CPB). The role of vasoconstriction to explain these changes is not known. The calcium entry blocking drug felodipine dilates constricted arterioles and reduces renal vascular resistance during noncardiac surgery. The present study was initiated to evaluate the effects of felodipine on renal perfusion and function during hypothermic, low pressure CPB. Twenty-two male patients (aged 61.7 +/- 2.3 y) were included in a prospective, randomized, controlled study. Renal blood flow was measured with thermodilution technique; renal extraction of 51Cr-EDTA and p-aminohippurate (PAH) were used to evaluate glomerular and tubular function. Systemic blood flow during hypothermic CPB was varied experimentally between 1.45 and 2.2 L.min-1.m-2. Felodipine reduced systemic vascular resistance but did not reduce the total renal vascular resistance during CPB. On the contrary, renal vascular resistance was increased at low CPB flow rates. The extraction of PAH (signifying tubular activity) was higher during felodipine infusion (0.74 +/- 0.04 vs 0.64 +/- 0.03 during low CPB flow, and 0.64 +/- 0.03 vs 0.57 +/- 0.05 during high CPB flow), whereas 51Cr-EDTA extraction was not influenced. The mechanism of enhanced PAH extraction may involve reduced regional vasoconstriction in PAH-extracting areas.

Thoracolumbar epidural blockade as adjunct to high dose fentanyl/midazolam anesthesia in coronary surgery: effects of sternotomy.

The present study tests the hypothesis that the changes in myocardial lactate metabolism in the early period of coronary surgery are caused by raised adrenergic activity, and that these are preventable by the addition of thoracolumbar epidural blockade to high dose fentanyl/midazolam anesthesia. Twenty-seven male beta 1-blocked patients undergoing coronary surgery were included in a prospective, controlled, randomized study. High dose fentanyl/midazolam anesthesia alone (control) or supplemented with thoracolumbar epidural blockade (treatment) was used. Measurements were performed before the induction of anesthesia and after sternotomy. After sternotomy adrenaline (A) and noradrenaline (NA) had decreased and were both in the low range, especially in the epidural group (P < 0.01). Arterial pressures decreased in both groups, especially in the epidural group, where coronary perfusion pressure (CPP) decreased from 61 (42-88) to 48 (33-64) mm Hg; Systemic vascular resistance (SVR) decreased with 30% in the epidural group (P < 0.01), but not significantly in the control group. The myocardial fractional extraction of lactate decreased in both groups, from 33 (10-45) to 13 (0-42)% in the control group (P < 0.01), and from 36 (19-43) to 10 (2-20)% in the epidural group. It is concluded that high dose fentanyl/midazolam anesthesia prevents hyperadrenergic activity in the early phase of coronary surgery, but cannot eliminate changes in myocardial lactate metabolism. The addition of the thoracolumbar epidural blockade to high dose fentanyl/midazolam anesthesia offers no obvious benefits in the early phase of coronary surgery.

Renal function during cardiopulmonary bypass: influence of pump flow and systemic blood pressure.

The influence of systemic blood flow (pump flow) and arterial blood pressure on renal function was studied during hypothermic cardiopulmonary bypass (CPB) in 14 male patients where the pump flow rate was varied between 1.45 and 2.20 l.min-1 m-2. Renal blood flow (RBF) was measured in the left renal vein with retrograde thermodilution technique and urinary flow and circulatory variables were measured with an on-line computer set-up. During CPB the RBF comprised 12-13% of the systemic blood flow and was positively related to systemic blood pressure (r = 0.71; P < 0.001) and pump flow rate (r = 0.69; P < 0.001). These findings indicate that the renal autoregulation was not operative during the hypothermic CPB period. According to multiple regression analysis, RBF was primarily determined by the pump flow rate and systemic blood pressure was of secondary importance. Urinary flow increased during hypothermic CPB and became closely related to blood pressure and pump flow. According to multiple regression analysis, urinary flow was primarily determined by systemic blood pressure.

Myocardial metabolism 8 hours after coronary surgery: effects of dopamine.

Myocardial substrate metabolism is abnormal in the early period after cardiac surgery. Myocardial uptake of substrates remains restricted 6 hours postoperatively and cannot match the demand during periods of increased energy requirements. We investigated the relationship between myocardial oxidative rate and substrate uptake in 22 men c. 8 hours after coronary surgery. Myocardial energy demand was raised experimentally by infusing dopamine. The influence of selective beta 1-blockade was analyzed. The uptake of free fatty acids dominated (34.74 +/- 8.83 mmol/min*10(-3) and sufficed to explain the oxygen consumption in basal postoperative conditions (0.468 +/- 0.051 mumol/min) and during amplified energy requirements (0.881 +/- 0.117, r = 0.71). Although the capacity to adjust substrate uptake to energy requirements thus was regained, the uptake of glucose and of lactate (6.14 +/- 13.13 and 2.29 +/- 20.31 mmol/min*10(3) respectively) was marginal, which may be important for ischaemic tolerance. Metoprolol influenced oxygen consumption during amplified adrenergic activity, but did not markedly affect substrates.

Calculation of renal extraction during high diuresis and low renal plasma flow conditions.

The renal fractional extraction (Ex) is a parameter describing the ability of the kidneys to remove a substance x from the circulating plasma. Ex is calculated often as the ratio between the arteriovenous concentration difference and the arterial concentration. This method simplifies the calculations but it is associated with an underestimation of Ex. In the study described here, a theoretical analysis of the error is made, with a graphical presentation of its magnitude in different diuresis/renal plasma flow (RPF) ratios and at different levels of Ex. The error was analysed also in a clinical situation where the renal extraction of PAH (EPAH) and EDTA (EEDTA) were determined in six patients during different stages of cardiac surgery. The underestimation of EPAH was seldom more than 4%, while EEDTA was underestimated often with more than 20%. It is concluded that the simplified formula is accurate when calculating the renal extraction for substances like PAH, with a normally high extraction, even if the diuresis/RPF ratio is high. For substances with low extractions, e.g. filtration markers, in some clinical and experimental situations it is necessary to take the renal plasma flows into consideration or to arrange for low urine production to avoid significant errors.

Absent diastolic cerebral blood flow velocity after circulatory arrest but not after low flow in infants.

It is controversial whether profound hypothermia (15 degrees C) provides adequate cerebral protection during a limited period of total circulatory arrest during pediatric cardiac surgery. In the present study, transcranial Doppler echography was used to monitor the blood flow velocity (BFV) pattern in the middle cerebral artery (MCA). The purpose of the study was to investigate the influence of a period of circulatory arrest on MCA BFV, as judged from the reperfusion flow velocity pattern. The MCA BFV was studied in 22 small children undergoing profound hypothermic cardiac operations after induction of anesthesia. Twelve of the children had a period of profound hypothermic circulatory arrest (15 to 74 minutes; arrest group). Circulation was maintained in the remaining 10 children (nonarrest group). Time-averaged MCA BFV was decreased and diastolic BFV was absent immediately after cardiopulmonary bypass in 10 of 12 children in the arrest group. In contrast, only 1 of 10 patients in the nonarrest group (p < 0.05) showed this pattern. Diastolic BFV normalized 54 to 328 minutes after the arrest in the arrest group. Circulatory arrest during profound hypothermia is followed by a period of low cerebral perfusion, whereby time-averaged MCA BFV is decreased and MCA BFV is absent during diastole. We speculate that this can be explained by an increase in intracranial pressure after brain edema.

Acute renal failure after coronary surgery--a study of incidence and risk factors in 2009 consecutive patients.

To obtain a model for the prediction of acute renal failure (ARF) after coronary surgery, 2009 consecutive patients were investigated. ARF was defined as a peak postoperative serum creatinine value exceeding the preoperative value by 50% or more or a need for dialysis. A postoperative increase in serum creatinine of less than 50% was associated with an early mortality (< or = 30 days postop.) of 0.4%. Sixteen per cent of the patients increased their serum creatinine by more than 50% and in this group there was a mortality of 1.3%. Twenty-five patients (1.2%) required postoperative haemodialysis because of ARF and of these 11 (44%) died early, whereas another 7 patients with chronic renal failure, requiring both pre- and postoperative haemodialysis, all survived. Peak postoperative serum creatinine and changes from the preoperative value were analyzed and related to clinical variables. Multivariate analysis indicated that high preoperative serum creatinine, high age and postoperative haemodynamic instability were the most important risk factors for developing renal failure. A logistic model including these risk factors versus the probability of developing ARF is presented.

Myocardial uptake and release of lactate after high dose neurolept endotracheal intubation in coronary surgery.

To evaluate the relationship between the hemodynamic and ECG variables used in routine surveillance of coronary surgery and myocardial lactate metabolism, 23 middle-aged, male, beta 1-blocked patients about to undergo coronary surgery were monitored before and after endotracheal intubation with high dose (30 micrograms/kg) fentanyl-midazolam anesthesia. The induction of anesthesia was followed by a mean arterial pressure decrease (from 98 +/- 4 to 76 +/- 3 mm Hg) and heart rate increase (from 53 +/- 3 to 66 +/- 2 beats/min). After intubation the hemodynamic variables were stable except for a further, transient increase in heart rate (to 69 +/- 2 beats/min). The myocardial uptake of lactate decreased after intubation, from 48 +/- 5 mumol/min to a lowest level of 24 +/- 3 mumol/min. A lactate release was exhibited in 7/23 patients (30%). No ST-segment changes were observed. The correlation between the myocardial lactate uptake/release and hemodynamic or ECG variables was unimpressive or non-existent (r < or = 0.20). Thus, a reduced uptake and even a release of lactate occurred irrespective of the ST-segment, heart rate, or systemic or pulmonary artery pressures. In conclusion, endotracheal intubation in patients with coronary disease was consistently (17/23 patients) followed by a reduced myocardial uptake of lactate, in spite of high dose neurolept anesthesia and beta 1-blockade. This metabolic event was not consistently related to hemodynamic changes.

High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy.

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. Negative inotropic effects may outweigh the expected benefit, however. Against this background hemodynamic and metabolic effects of early postoperative infusion with the beta 1-selective agent metoprolol were studied in 22 patients after coronary operations. During basal postoperative conditions, intravenous metoprolol reduced cardiac index and stroke volume index compared with control patients, while other variables were unaffected. During the higher adrenergic level of a dopamine infusion (7 micrograms/kg per minute), the heart rate, rate pressure product, and myocardial oxygen uptake were attenuated in proportion to the plasma level of metoprolol. Intravenous beta 1-blockade did not affect the cardiac output or stroke volume responses to dopamine (the cardiac output was still, however, 19% lower than in control patients). A release of myocardial creatinine kinase isoenzyme myocardial band was observed during dopamine infusion, suggesting that myocardial ischemia was induced. The release was not influenced by metoprolol, but it correlated with heart rate (r = 0.60; p < 0.01). It is concluded that infusion of metoprolol early after coronary operations depresses myocardial contractility with some 19%, which was without clinical significance in straightforward patients; the increased myocardial metabolic demand during a period of increased adrenergic stress was attenuated by metoprolol. This may be of importance for myocardial recovery.

Influence of beta 1-blockade on myocardial substrates early after a coronary operation.

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. This study was undertaken to find out if early postoperative high-dose infusion of the selective beta 1-blocking agent metoprolol tartrate has additional effects on metabolic variables related to myocardial energy supply/demand balance compared with those obtained with a late preoperative oral dose. The study included 21 male patients undergoing coronary bypass grafting. All patients received an oral dose of metoprolol before the operation. After the operation, patients were randomized to a control group or a group receiving intravenous infusion of metoprolol. Myocardial uptake of oxygen and substrates was determined before and during atrial pacing. Metoprolol reduced arterial concentrations of free fatty acids, reduced myocardial uptake of free fatty acids, and enhanced myocardial uptake of lactate. During paced tachycardia, the metoprolol concentration correlated negatively with myocardial uptake of free fatty acids (r = -0.80; p < 0.001) and positively with myocardial uptake of lactate (r = 0.53; p < 0.05). It is concluded that postoperative infusion of metoprolol induces myocardial metabolic changes compatible with an improved energy supply/demand balance.

Transcranial Doppler-estimated versus thermodilution-estimated cerebral blood flow during cardiac operations. Influence of temperature and arterial carbon dioxide tension.

The ability of the noninvasive continuous transcranial Doppler technique to reflect changes in cerebral blood flow during cardiac operations was evaluated in seven adults. Middle cerebral artery blood flow velocity changes were compared with simultaneous thermodilution measurements of venous blood flow in the ipsilateral internal jugular vein during 11 preset stages of the procedure. Cerebral blood flow was varied by changes in arterial carbon dioxide tension and temperature. High-dose fentanyl-droperidol anesthesia and alpha-stat pH management were employed. To facilitate comparisons between the two methods, the individual awake values of middle cerebral artery flow velocity (45.1 +/- 3.3 cm/sec, mean +/- standard error of the mean) and jugular venous blood flow (382 +/- 37 ml/min) were normalized (100%). Cerebral metabolic rate for oxygen was calculated as the product of jugular arteriovenous oxygen content difference and middle cerebral artery flow velocity or jugular venous blood flow, respectively. The individual correlations between the two flow estimates varied between 0.76 and 0.87 (median 0.83), and the correlation of the combined data from all seven patients was 0.77 (p less than 0.0001). Variations in arterial carbon dioxide tension induced significant changes in the two flow estimates both during normothermia before cardiopulmonary bypass and at deep hypothermia (20 degrees C) during cardiopulmonary bypass. The significant arterial carbon dioxide tension changes had no significant effects either on Doppler- or thermodilution-estimated cerebral metabolic rate for oxygen. Deep hypothermia (20 degrees C) reduced Doppler- and thermodilution-estimated cerebral metabolic rate for oxygen to 22.0% +/- 3.9% and 20.6% +/- 6.9% of the awake levels, respectively. The study supports the validity of using middle cerebral arterial flow velocity changes as an estimate of changes in volume flow through the brain during cardiac operations.

Continuous vectorcardiography in cardiac surgery: natural course of vector changes and relationship to myocardial oxygen uptake.

Continuous vectorcardiography was registered before and during the first 18 hours after cardiac surgery in 53 patients. QRS vector changes (QRS-VD) occurred during the operation, but no further changes were observed postoperatively. The ST vector (ST-VM) increased during the operation, and a further slight increase occurred postoperatively. Perioperative myocardial infarction occurred in three patients. Their ST-VM was higher than the average in patients without myocardial infarction, while QRS-VD did not differ from the average pattern. Twelve other patients were studied in pacemaker-induced moderate tachycardia. QRS-VD increased in proportion to heart-rate changes (rs median = 0.93, p less than 0.01). QRS-VD also correlated with myocardial oxygen uptake (rs median = 0.62, p less than 0.05). The ST-VM responses were not uniform. The data suggest that vectorcardiogram variables can provide information related to myocardial energy metabolism.

Myocardial recovery after cardiac surgery: a study of hemodynamic performance and electrophysiology during the first 18 postoperative hours.

Hemodynamic and vectorcardiographic variables were monitored in 23 patients with acquired heart disease, before and during the first 18 postoperative hours of cardiac surgery. The hemodynamic pattern directly after surgery was characterized by left ventricular depression and increased heart rate. Thus, stroke volume index had decreased from the preoperative 29 +/- 1 to 24 +/- 1 mL/beat/m2, and heart rate had increased from 61 +/- 2 to 94 +/- 4 beats/min. During the following hours a gradual normalization of stroke volume occurred, leading to a cardiac index that was adequate after 8 to 10 hours, judging from the mixed venous oxygen saturation (68% +/- 1%). Fourteen patients had an uneventful postoperative course, with no signs of acute myocardial infarction, and did not require inotropic support. These patients had small but consistent vectorcardiographic changes; the QRS vector difference increased moderately, and the ST vector magnitude also increased. No correlation was found between hemodynamic and vectorcardiographic variables, nor between timing of hemodynamic recovery and vectorcardiographic changes. Patients with a perioperative myocardial infarction had a vectorcardiographic pattern that was compatible with acute myocardial infarction. These patients had markedly elevated ST vector magnitude and QRS vector difference values, which were discernible during the first postoperative hours. The present data suggest that the timing of metabolic and electrophysiological recovery of the heart differ, and a computerized vectorcardiographic system may be of value in the early detection of perioperative myocardial infarction.

An evaluation of the perioperative efficacy of selective beta 1-blockade in coronary surgery. Studies with a late preoperative dose of metoprolol.

The plasma concentration of metoprolol was measured hourly following an oral dose on two consecutive days--the day before, and the day of, coronary surgery. No significant difference was found between the two sampling days, though there was a tendency to lower concentrations during and after extracorporeal circulation. After a median dose of 50 mg the peak concentration (reached on average after 1.5 h) was 545 +/- 70 nmol/l on the first day and 388 +/- 57 on the day of surgery. The respective elimination rates from plasma, expressed as half-life, were 3.4 +/- 0.21 and 3.5 +/- 0.19 hours (NS). On the day of surgery the heart rate rose during the second half of the observation period, peaking above 130 beats/min. Heart rate was inversely correlated to metoprolol concentration in plasma with coefficient -0.68 before induction of anesthesia and -0.77 two hours after termination of extracorporeal circulation. The perioperative efficacy of beta-blockade following a late preoperative oral dose of the agent thus appeared to be reduced and inadequate.