Intravenous and oral prenalterol in congestive heart failure. Effects on systemic and coronary hemodynamics and myocardial catecholamine balance

Systemic and coronary hemodynamic effects of prenalterol, a beta-1 receptor agonist, were determined in patients with chronic congestive heart failure, initially after intravenous administration (10 patients) and then after oral administration (eight patients). Cardiac index increased by 33 percent and 30 percent after intravenous and oral prenalterol, respectively. The increase in stroke volume index and stroke work index and decrease in pulmonary capillary wedge pressure and systemic vascular resistance were not significant. Myocardial oxygen consumption and coronary sinus blood flow increased in the majority of patients, although these changes were not statistically significant. There were no significant changes in transmyocardial norepinephrine or epinephrine balance. The systemic and coronary hemodynamic effects of both intravenous and oral prenalterol were similar. Major side effects included sudden death (two patients) and hypotension and bradycardia (three patients) during oral prenalterol treatment. It is concluded that improved left ventricular function following both intravenous and oral prenalterol may be associated with increased myocardial oxygen consumption, and serious adverse effects may occur during prenalterol therapy.     

Monitoring oxygenation

The most basic goal of anaesthetists and intensivists is to assure that there is an adequate supply of oxygen to the mitochondria throughout the body to maintain aerobic metabolism and cellular function. The determination of adequate oxygenation has historically been monitored by the absence of organ dysfunction because techniques were not available to assess quantitatively the oxygenation of tissues. Over the past 40 years, measurement and monitoring methods have been developed to first quantitate oxygen supply and more recently to continuously asess both invasively and noninvasively the oxygenation of blood and tissue. ¹This article will review the current status of the invasive and noninvasive techniques for monitoring oxygenation.     

Reducing unnecessary cross-matching: a patient-specific blood ordering system is more accurate in predicting who will receive a blood transfusion than the maximum blood ordering system

Most blood transfusions are given in the operating room. Adoption of the Maximum Surgical Blood Ordering Schedule in the 1970s reduced the amount of blood unnecessarily cross-matched, but the national cross-match-to-transfusion ratio remains at approximately two-to-one. We tested the ability of a patient-specific blood ordering system (PSBOS) to more accurately predict potential operative transfusion. All adult patients who had blood cross-matched before surgery (February through June 1999) for elective operative procedures at the University of Michigan Hospital were identified. Complex surgeries were excluded. Surgeons estimated the expected blood loss for their surgeries, and the expected postoperative hematocrit was calculated using the patient's blood volume, the surgeon-defined expected blood loss, and preoperative hematocrit. Lowest tolerated hematocrit was set at 21% except in patients with coronary artery disease or who were ASA physical status III or more (28%). Sensitivity, specificity, positive predictive value, and negative predictive value of the PSBOS were calculated. Our analysis included 178 cases in which blood was cross-matched before surgery, representing 69 different surgeries and 42 surgeons. Only 16% of patients received an intraoperative transfusion. Of the 156 patients that PSBOS predicted would not require an operating room transfusion, 139 were not transfused. Of the 21 patients PSBOS predicted would be transfused, 11 were. The sensitivity of the algorithm as tested was 41%, the specificity 93%, the positive predictive value was 55%, and the negative predictive value was 89%. We conclude that PSBOS, which includes patient and surgeon variables in transfusion prediction, is more accurate than the Maximum Surgical Blood Ordering Schedule, which uses only surgical procedure. IMPLICATIONS: Currently, many units of blood set aside for surgery are never required, resulting in extra work and expense for blood banks. A formula that included patient weight and hematocrit and typical surgery blood loss was used to predict who would require transfusions. We reduced the predicted number of patients who had blood set aside from 178 to 21.     

Preoperative Serum Potassium Levels and Perioperative Outcomes in Cardiac Surgery Patients

Context  Although potassium is critical for normal electrophysiology, the association between abnormal preoperative serum potassium level and perioperative adverse events such as arrhythmias has not been examined rigorously. Objective  To determine the prevalence of abnormal preoperative serum potassium levels and whether such abnormal levels are associated with adverse perioperative events. Design and Setting  Prospective, observational, case-control study of data collected from 24 diverse US medical centers in a 2-year period from September 1, 1991, to September 1, 1993. Patients  A total of 2402 patients (mean [SD] age, 65.1 [10.3] years; 24% female) undergoing elective coronary artery bypass grafting who were not enrolled in another protocol. The study population was identified using systematic sampling of every nth patient, in whichn was based on expected total number of procedures at that center during the study period. Main Outcome Measures  Intraoperative and postoperative arrhythmias, the need for cardiopulmonary resuscitation (CPR), cardiac death, and death due to any cause prior to discharge, by preoperative serum potassium level. Results  Perioperative arrhythmias occurred in 1290 (53.7%) of 2402 patients, with 238 patients (10.7%) having intraoperative arrhythmias, 329 (13.7%) having postoperative nonatrial arrhythmias, and 865 (36%) having postoperative atrial flutter or fibrillation. The incidence of adverse outcomes was 3.6% for death, 2.0% for cardiac death, and 3.5% for CPR. Serum potassium level less than 3.5 mmol/L was a predictor of serious perioperative arrhythmia (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.0), intraoperative arrhythmia (OR, 2.0; 95% CI, 1.0-3.6), and postoperative atrial fibrillation/flutter (OR, 1.7; 95% CI, 1.0-2.7), and these relationships were unchanged after adjusting for confounders. The significant univariate association between increased need for CPR and serum potassium level less than 3.3 mmol/L (OR, 3.3; 95% CI, 1.2-9.5) and greater than 5.2 mmol/L (OR, 3.0; 95% CI, 1.1-8.7) became nonsignificant after adjusting for confounders. Conclusions  Perioperative arrhythmia and the need for CPR increased as preoperative serum potassium level decreased below 3.5 mmol/L. Although interventional trials are required to determine whether preoperative intervention mitigates these adverse associations, preoperative repletion is low cost and low risk, and our data suggest that screening and repletion be considered in patients scheduled for cardiac surgery.      

Effect of Propofol With and Without EDTA on Haemodynamics and Calcium and Magnesium Homeostasis During and After Cardiac Surgery

Objective: To determine the effect of the addition of disodium edetate (EDTA) to propofol on haemodynamics, ionised calcium and magnesium serum concentrations, and adverse events during cardiac surgery. Design: Double-blind, randomised, multicenter trial. Setting: Operating room and intensive care unit of 5 academic health centres. Patients: A total of 102 evaluable patients, aged 34 to 85 years, undergoing first-time, elective coronary artery bypass graft surgery. Interventions: Comparison of propofol with EDTA and propofol without EDTA, each in conjunction with the opioid sufentanil, for intraoperative anaesthesia and postoperative sedation. Measurements and Results: There were no significant differences at any time between the two formulations in any clinical chemistry measurements, including ionised calcium, ionised magnesium, total calcium, parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and phosphate. During bypass, the mean concentration of ionised calcium decreased to below the normal range, but the decrease was similar in both groups (propofol with EDTA, 0.98 ± 0.07 mmol/L [N = 51]; propofol, 0.99 ± 0.10 mmol/L [N = 51]; p = NS). Calcium concentration returned to normal after rewarming. Mean ionised magnesium concentrations remained within normal limits in both groups. Similarly, there were no clinically meaningful differences between treatments with respect to haemodynamic variables, efficacy variables, or incidence of adverse events. Conclusions: The inclusion of EDTA in the current formulation of propofol appears to have no significant effects on calcium and magnesium profiles, renal function, haemodynamic variables, or other indicators of safety and efficacy during intraoperative anaesthesia and postoperative sedation in patients undergoing cardiac surgery.     

Catheter ablation of ventricular tachycardia with intracardiac shocks: results in 33 patients

Catheter electrical ablation of ventricular tachycardia (VT) was attempted in 33 patients who had recurrent unimorphic VT refractory to 3.7 +/- 1.2 (mean +/- SD) antiarrhythmic drugs. Their mean age was 56 +/- 14 years. Twenty-two patients had coronary artery disease, six had other types of heart disease, and five had no structural heart disease. The mean left ventricular ejection fraction was 0.34 +/- 0.17. Thirty patients had only one documented morphologic type of spontaneous VT, whereas three patients had more than one. One to four shocks of 100 to 300 J each were delivered to the endocardial exit site of VT, as identified by endocardial activation mapping and pace-mapping. In each patient endocardial activation at the exit site of VT preceded the onset of the QRS complex (mean activation time -50 +/- 30 msec). Pace-mapping was possible in 26 patients, and in all but two patients the QRS complexes during VT and during pacing at the exit site of VT were very similar in at least 10 of 12 electrocardiographic leads. In 29 patients, shocks were delivered between an endocardial electrode (cathode) and a patch electrode on the chest wall (anode). Seven patients (including three who first received shocks using an external anode) whose VT originated in the septum received transseptal shocks between two electrodes positioned on either side of the septum. The procedure was successful in 15 patients (45%), who had no recurrence of VT either on no antiarrhythmic therapy or on the same regimen that was ineffective before ablation, over a follow-up period of 15.5 +/- 10 months (range 5 to 35). The ablation attempt was unsuccessful in 18 patients (55%). There were no significant differences in clinical and electrophysiologic variables between patients with and without a successful outcome. Seven nonfatal complications occurred in six patients: sustained nonclinical VT immediately after the shock, ventricular fibrillation on days 5 and 6 after ablation, neurologic deficits (n = 2), atrioventricular block (n = 2), and brachial artery thrombosis. In conclusion, catheter electrical ablation of VT has modest efficacy and is relatively safe in a selected group of patients who have predominantly one configuration of unimorphic VT.     

Hemodynamic alterations and regional myocardial blood flow during supraceliac aortic occlusion in dogs with a critical coronary stenosis

The hemodynamic consequences and myocardial blood flow alterations associated with cross-clamping of the thoracic aorta were studied during pentobarbital (control), halothane (1 MAC), and isoflurane (1 MAC) anesthesia in dogs with a critical stenosis of the left circumflex coronary artery. Aortic clamping at the level of the diaphragm resulted in significant and equivalent increases in mean aortic pressure and left atrial pressure during the control clamp, halothane clamp, and isoflurane clamp periods. Likewise, aortic clamping resulted in a significant and equivalent decrease in cardiac output during control-clamp, halothane clamp, and isoflurane clamp. Myocardial contractility as assessed by dP/dt was depressed during halothane and isoflurane anesthesia when compared with control, but no further change in contractility was associated with aortic clamping. No significant alterations in regional or transmural myocardial blood flow were found with halothane or isoflurane anesthesia, or with aortic clamping during halothane or isoflurane anesthesia. It is concluded that there are significant hemodynamic consequences associated with aortic clamping, that neither halothane nor isoflurane anesthesia alters these consequences when compared with pentobarbital anesthesia alone, and that the deterioration in myocardial function observed during aortic clamping with halothane and isoflurane anesthesia cannot be attributed to any maldistribution of myocardial blood flow.     

Induction of IgM, IgA and IgE Antibodies in Colorectal Cancer Patients Vaccinated with a Recombinant CEA Protein

Purpose

Previous clinical studies have indicated that natural IgM antibodies have the ability to induce apoptosis of tumor cells but IgE and IgA may also mediate tumor cell killing (in addition to IgG). The aim of the study was to analyse induction of IgM, IgA and IgE antibodies in patients vaccinated with the tumor associated antigen CEA.

Methods

Twenty-four resected CRC patients without macroscopic disease were immunized seven times with CEA?±?GM-CSF. Four different dose schedules were used over a 12-month period. IgM, IgA and IgE antibody responses against recombinant CEA were determined by ELISA. Patients were monitored immunologically for 36 months and clinically for 147 months.

Results

GM-CSF significantly augmented the anti-CEA response for all three antibody classes. Low dose of CEA tended to induce a higher IgM, IgA or IgE anti-CEA antibody response than higher. Anti-CEA IgA antibodies could lyse CEA positive tumor cells in antibody dependent cellular cytotoxicity (ADCC) as well as in complement dependent cytotoxicity (CDC). A significant correlation between survival and high IgA anti-CEA titers was noted (p?=?0.02) irrespective of GM-CSF treatment.

Conclusions

The observation that IgA anti-CEA antibodies were cytotoxic and associated with improved survival might indicate that also these antibodies may exert a clinical anti-tumor effect.