H. Gombotz

Subcutaneous recombinant human erythropoietin and autologous blood donation before coronary artery bypass surgery

Conventional therapies with recombinant human erythropoietin (rHuEPO) to sustain preoperative autologous blood collection entail high doses of the drug at short intervals. To evaluate the efficacy of a single weekly dose of rHuEPO for autologous blood collection, we randomly assigned 24 male patients scheduled for coronary artery bypass surgery to receive 400 IU/kg rHuEPO subcutaneously once a week or iron only. Patients were examined weekly and a total of up to 4 units of autologous blood were obtained if the hemoglobin level exceeded 12 g/dL. Patients receiving rHuEPO had consistently higher hemoglobin values than those receiving iron only (P < 0.001). Consequently, more autologous red cells were obtained from this group (776 +/- 49 mL vs 682 +/- 91 mL; P < 0.05). One patient receiving rHuEPO and eight in the control group required homologous blood at surgery (P < 0.01). These results suggest that 400 IU/kg rHuEPO administered subcutaneously once a week efficiently stimulates erythropoiesis and compensates the hemoglobin decrease after autologous blood donation.

Open heart surgery in children of Jehovah's witnesses: Extreme hemodilution on cardiopulmonary bypass

SummaryBetween January 1979 and July 1989, 15 children of Jehovahs Witnesses underwent corrective open surgery for congenital heart disease (CHD) on cardiopulmonary bypass (CPB). Ages ranged from 1.5–17 years and body weight from 9.1–63 kg, with five patients weighing less than 15 kg. Eight children were cyanotic, and two of them had had previous thoracic operations.All operations were performed in moderate to deep hypothermia using a modified version of isovolemic hemodilution with bloodless priming technique of extracorporeal circulation. Mean hematocrit levels decreased from 47.3% (36.9–70%) to 34.6% (27.2–49.1%) after hemodilution, and then to 17.9% (10.5–25.6%) during bypass. They increased again to 34.1% (24.4–50%) at the end of the operation and to 33.4% (25.1–40%) on day 12. All intra- and postoperative hematocrit levels were significantly lower (p<0.001). There was one postoperative death, not related to the technique.Our results demonstrate that bloodless cardiac surgery on bypass is feasible in children as shown in this special group of children of Jehovahs Witnesses. Knowing the risks of homologous blood transfusion this technique should be used more extensively in the future.

Preoperative treatment with recombinant human erythropoietin or predeposit of autologous blood in women undergoing primary hip replacement

Background: Controversy exists about the advantages of predeposit of autologous blood (PDAB), and whether more comfortable blood conservation regimens may yield comparable results. To test the hypothesis that preoperative treatment with recombinant human erythropoietin (rHuEPO) with or without acute concomitant normovolaemic haemodilution (ANHD) is as effective as PDAB in reducing allogeneic blood transfusions, we conducted a prospective randomised study in women undergoing primary hip replacement.

Urapidil reduces elevated pulmonary vascular resistance in patients before heart transplantation

BACKGROUND Elevated pulmonary vascular resistance is a major limitation for heart transplantation. Urapidil is a centrally and peripherally acting anti-hypertensive drug, able to decrease elevated pulmonary vascular resistance in patients with either chronic obstructive pulmonary disease or heart failure. Urapidil is available as an oral or intravenous drug. In this study, we evaluated the possible beneficial effects of intravenous urapidil in patients with reversible, elevated pulmonary vascular resistance who were scheduled for heart transplantation. METHODS After approval by the Ethics Committee and written consent, 22 consecutive patients with end-stage heart failure and history of pulmonary vascular resistance >3 Wood units were enrolled into an open, prospective study. Using a (right ventricular ejection fraction) REF-Swan-Ganz catheter, hemodynamics were determined during administration of nitric oxide, and before and after 3 repeated intravenous applications of 10 mg urapidil. The treatment goal was reduction of pulmonary vascular resistance by at least 30%. RESULTS Twenty-two patients were included to obtain complete data for 14 patients. Eight patients were not treated with urapidil: 7 patients had normal pulmonary vascular resistance at baseline, and 1 patient experienced moderate pulmonary edema before the study began. Two patients did not reach the treatment goal. In patients who responded to urapidil, the following hemodynamic changes were observed: decreased pulmonary vascular resistance (-48%), decreased transpulmonary gradient (20.0 to 13.7 mm Hg), decreased mean pulmonary arterial pressure (40 to 31 mm Hg), decreased systemic vascular resistance (-27%), mean arterial pressure (80 to 72 mm Hg), and increased right heart ejection fraction (21% to 27%). Heart rate remained unchanged. CONCLUSIONS Intravenous urapidil lowered elevated pulmonary vascular resistance in patients before heart transplantation. In comparison with other vasodilative drugs, the major benefit of urapidil is its oral formulation.

Intraoperative heart rate reduction - alinidine versus metoprolol

In a double‐blind randomized protocol the effectiveness of the specific bradycardic agent alinidine (0.6 mg.kg‐1 i.v.) was compared to that of the betablocker metoprolol (0.035 mg.kg‐1 i.v.). Twenty‐four coronary artery disease patients undergoing a bypass procedure with an intraoperative heart rate increase of more than 20% were included. Patients with a concomitant intraoperative mean arterial pressure increase of more than 30% or with an intraoperative wedge pressure higher than 15 mmHg (2.0 kPa) were excluded. After application of alinidine and metoprolol, heart rate decreased significantly (P<0.01) in the alinidine group from 88 ± 19 beats per min to 72 ± 13 and in the metoprolol group from 82 ± 16 to 72 ± 12. Baseline values were not obtained. Compared to the hemodynamic changes in the metropolol group, the alterations of pulmonary capillary wedge pressure (P<0.05) (P<0.05), stroke volume index (SVI) (P<0.05), left ventricular stroke work index (LVSWI) (P<0.01) and right ventricular stroke work index (RVSWI) (P<0.05) in the alinidine group were statistically significantly different. PCWP remained unchanged after alinidine and increased in the metoprolol group (1.4 ± 0.4 to 1.6 ± 0.4 kPa). In the alinidine group LVSWI (43.1 ± 15 to 49.2 ± 18g‐m.m‐2), RVSWI (5.1 ± 4 to 6.6 ± 3 g‐m.m‐2) and SVI (37.2 ± 12.2 to 42.5 ± 12.8 ml.m‐2) increased. In the metoprolol group LVSWI (44.2 ± 8 to 40.6 ± 9 g‐m.m‐2) and RVSWI (5.5 ± 3 to 5.3 ± 2 g‐m.m‐2) decreased slightly, whereas SVI was unchanged. Based on the hemodynamic data alinidine seems to be a less cardiodepressive agent than metoprolol in phases of predominant sinus tachycardia. This drug may be especially advantageous for patients with suspected or documented ischemic heart disease, those who do not tolerate betablockers well and patients who require a greater heart rate reduction than can be obtained with betablockers.

First clinical experience with the rapid-, short-acting amiodarone derivative E 047/1 after cardiac surgery

BACKGROUND AND OBJECTIVE Amiodarone is very effective against a variety of dysrhythmias but has poor pharmacodynamic properties and many undesired side-effects. Its short- and rapid-acting derivative E 047/1 may circumvent some of these drawbacks. It is easier to titrate while retaining the high efficacy of amiodarone and may have acceptable influences on haemodynamics and cardiac conduction in patients who develop serious, destabilizing ventricular tachydysrhythmias after cardiac surgery. METHODS Testing E 047/1 was performed prospectively in two consecutive phase II open, clinical studies. Out of 504 patients scheduled for surgery using cardiopulmonary bypass for coronary artery grafting and/or valve repair, 35 developed serious, haemodynamically destabilizing ventricular dysrhythmias (Lown 2-Lown 4b) after surgery and were treated with a 1 mg kg(-1) (pilot study, n = 15) or randomized to a 2 or 3 mg kg(-1) bolus of E 047/1, followed by a 1 mg kg(-1) h(-1) continuous infusion for 2 h (n = 10 in each group). Dysrhythmias, PQ, QTc intervals and haemodynamics using the thermodilution technique were evaluated for up to 24 h after drug initiation. RESULTS At the time of final inclusion the patients had between 6 and 12 (or more) ventricular ectopics per minute. Within the first 2-3 min of application in the pilot trial E 047/1 induced a decrease of ventricular dysrhythmias to between 0 and 4 per min, a decrease that held for the duration of treatment. The area under the curve decreased from 434 (322, 855; median, quartiles) to 114 (9, 477, P < 0.01) events per hour. In the randomized trial, E 047/1 administered in either dose rapidly reduced ventricular dysrhythmias at least as effectively as in the pilot trial 565 (478, 701) to 33 (8, 238, P < 0.05) after a 2 mg bolus; 482 (339, 482) to 95 (13, 540, P < 0.01) events per hour after a 3 mg bolus. Approximately 4-6 h after drug termination, dysrhythmias reappeared in the majority of patients. In only three patients did the incidence of dysrhythmias return to inclusion criteria levels. In contrast to the pilot trial, in the randomized trial there was a slight increase of mean pulmonary artery pressure, central venous pressure and pulmonary arterial wedge pressure and a slight decrease of LCWI in both groups. E 047/1 did not cause QTc prolongation. CONCLUSIONS E 047/1 appears to be a safe alternative to amiodarone in the perioperative setting of cardiac surgery when serious, destabilizing dysrhythmias occur.

Comparison of alinidine and esmolol in the treatment of intraoperative sinus tachycardia

The hemodynamic effects of esmolol (1 mg/kg loading dose followed by an infusion of 150 μ g/kg/min) were compared with those of the specific bradycardia agent alinidine (0.6 mg/kg as a bolus). Twenty-four patients with good ventricular function undergoing coronary artery bypass graft operations with an intraoperative heart rate increase of more than 20% were included. After esmolol or alinidine, a similar 20% decrease in heart rate was found, but the baseline values were not reached. Compared with the hemodynamic changes in the esmolol group, the alterations of pulmonary capillary wedge pressure (PCWP) ( P P P P 2 ) and LVSWI (58.8 ± 16 to 34.1 ± 13 g · m/m 2 ) were found in the esmolol group, when compared with the alinidine group (CI: 3.7 ± 0.9 to 3.3 ± 1.1 L/min/m 2 ; LVSWI: 56.8 ± 13 to 47.7 ± 20 g · m/m 2 ). SVI remained unchanged after alinidine (47.8 ± 15 to 47.8 ± 17 mL/m 2 ), but decreased in the esmolol-treated patients (47.6 ± 6 to 39.4 ± 17 mL/m 2 ). Based on these hemodynamic data, alinidine seems to possess fewer negative hemodynamic side effects than esmolol. In patients with a sinus tachycardia and concomitant hypertension, esmolol seems to be more advantageous.

Transoesophageal echocardiography during removal of a caval filter in a patient at high risk of massive pulmonary thromboembolism

A new type of vena caval filler was to be removed from a woman who had a high risk of massive pulmonary thromboembolism because of extensive thrombus in the iliac vein incorporating the filter. The removal was performed under general anaesthesia in the cardiac operating theatre using transoesophageal echocardiography to monitor the right heart and the pulmonary artery during the critical phase of removal. The manoeuvre succeeded with only insignificant embolisation occurring, and that was identified by transoesophageal echocardiography.