Thrombogenic side-effects of recombinant factor VIIa after use in coronary artery bypass surgery.

Recombinant activated factor VII (rFVIIa) has been used 'off licence' to successfully treat bleeding and reduce transfusion requirements in complex cardiac surgery. However; concerns over thrombogenic side-effects have limited but not excluded its use in patients undergoing coronary artery bypass surgery (CABG). We present two cases of CABG (one 'on pump' and one 'off pump') which were complicated by intraoperative aortic dissection and severe bleeding. In both cases the bleeding was successfully treated with rFVIIa. However the first case suffered from severe postoperative arrhythmias, myocardial infarction, cardiac arrest and worsening left ventricular dysfunction, suggesting graft patency may have been impaired, whereas the second case remained symptom-free suggesting graft patency was unaffected by the use of rFVIIa. If rFVIIa is needed to treat bleeding during CABG surgery, it may be more appropriate to administer smaller, repeated doses to minimize the risk of thrombosis and early graft failure.

MRL/Mp CD4+,CD25- T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus.

OBJECTIVE: To investigate the hypothesis that loss of suppression mediated by peripheral CD4+,CD25+ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE). METHODS: Mice of the MRL/Mp strain were studied as a polygenic model of SLE. Following immunomagnetic selection, peripheral lymphoid CD25+ and CD25- CD4+ T cells were cultured independently or together in the presence of anti-CD3/CD28 monoclonal antibody-coated beads. Proliferation was assessed by measuring the incorporation of tritiated thymidine. RESULTS: While MRL/Mp CD4+,CD25+ regulatory T cells showed only subtle abnormalities of regulatory function in vitro, syngeneic CD4+,CD25- T cells showed significantly reduced sensitivity to suppression, as determined by crossover experiments in which MRL/Mp CD4+,CD25- T cells were cultured with H-2-matched CBA/Ca CD4+,CD25+ regulatory T cells in the presence of a polyclonal stimulus. CONCLUSION: Our findings highlight a novel defect of peripheral tolerance in SLE. Identification of this defect could open new opportunities for therapeutic intervention.

Reduced cerebral embolic signals in beating heart coronary surgery detected by transcranial Doppler ultrasound.

Cerebral emboli detected by transcranial Doppler imaging were recorded in 20 patients undergoing multiple-vessel coronary artery bypass surgery, either with or without cardiopulmonary bypass, in a prospective unblinded comparative study. Emboli were recorded continuously from the time of pericardial incision until 10 min after the last aortic instrumentation. The numbers of coronary grafts and of aortic clampings were also documented. Patients undergoing revascularization with cardiopulmonary bypass had more emboli (median 79, range 38-876) per case compared with patients having off-pump surgery (median 3, range 0-18). No clinically detectable neurological deficits were seen in either group. Beating heart surgery is associated with fewer emboli than coronary surgery with cardiopulmonary bypass. Further research is necessary to determine whether a smaller number of emboli alters the incidence of neurological deficit after cardiac surgery.

Integrated left anterior small thoracotomy and angioplasty for coronary artery revascularization.

BACKGROUND: The minimal access surgical technique of a left anterior small thoracotomy (LAST) for coronary artery bypass grafting is now well established. This procedure however, does not allow multivessel revascularization. We present our early experience of an integrated approach using LAST and percutaneous transluminal coronary angioplasty (PTCA), either staged or simultaneous. METHODS: Eighteen patients (14 men and 4 women), mean age 63 (range 35-87 years) were treated. Four patients underwent simultaneous LAST and PTCA revascularization. The remaining 14 patients were first treated with the LAST procedure, followed 1-3 days later by angioplasty. Angiographic assessment was carried out before PTCA and at 6 months after. RESULTS: The 14 patients who underwent the staged procedure all had patent left internal mammary artery/left anterior descending coronary artery grafts. Angioplasty was performed on 21 vessels (10 stented) with good early angiographic results. All patients were extubated early, mean intensive care stay was 14.7 + 9.4 hours, mean hospital stay was 5 + 1.5 days. All patients were symptom free at 18 months follow-up. CONCLUSIONS: Staged LAST and angioplasty is a safe and effective approach suitable for patients in whom there are contraindications to the use of extracorporeal circulation. The simultaneous approach is limited by the risk of bleeding associated with the use of anticoagulation when coronary stenting is required.

Effect of dopexamine hydrochloride on renal vascular resistance index and haemodynamic responses following coronary artery bypass graft surgery.

A randomized double-blind study was carried out on 20 patients after coronary artery bypass surgery to investigate the effects of graded doses of dopexamine hydrochloride or placebo on systemic haemodynamic responses and renal vascular resistance index (RVRI) measured using Doppler ultrasound. Pre-operatively, all patients had good left ventricular function and normal renal function. Eleven were allocated randomly to receive incremental infusions of dopexamine 0.5, 1, 2, and 4 micrograms kg-1 min-1 for 40 min each, and nine received corresponding infusions of placebo. One patient was withdrawn from the dopexamine group because of tachycardia. In the remaining 19, heart rate (HR) and cardiac index (CI) were significantly (P < 0.05) increased from base-line with dopexamine: the HR values with dopexamine differed significantly from those with placebo at the 2 and 4 micrograms kg-1 min-1 dose and at 4 micrograms kg-1 min-1 for CI. Systemic vascular resistance index (SVRI) fell significantly in both groups: the reduction was significantly greater with dopexamine 4 micrograms kg-1 min-1 than with the corresponding infusion of placebo. RVRI increased and urine output decreased significantly during the infusions in both groups, but with no significant difference between groups. There were no changes in systemic arterial pressures, pulmonary artery occlusion pressures, stroke volume index or left ventricular stroke work index. Where changes from base-line occurred in either group, they had not returned to base-line within 40 min of stopping the infusions (except perhaps for CI in the dopexamine group). Dopexamine appears to offer no particular protection to the renal vascular bed.

A study of the combined haemodynamic effects of dobutamine and enoximone in patients taking beta adrenoceptor antagonists.

We conducted a randomized, double-blind investigation to determine whether enoximone affects the actions of dobutamine in patients taking beta adrenoceptor antagonists. We studied sixteen patients with good ventricular function after coronary artery bypass operations. All patients were taking a beta adrenoceptor antagonist. The patients received a standardized intravenous anaesthetic, which was maintained throughout the investigation. They received a masked infusion, containing either normal saline or enoximone. Haemodynamic data were recorded before, during, and after an infusion of dobutamine, which was given at three different rates. Patients receiving enoximone had a greater cardiac output, a higher heart rate and a lower systemic vascular resistance than patients receiving saline. They also required an average of 1500 ml more intravenous colloid in the immediate postoperative period to achieve haemodynamic stability. Dobutamine produced a consistent, significant peripheral vasoconstriction, but no inotropic or chronotropic effect. There was no significant difference in this effect between the two groups, and it was not influenced by concurrent therapy with enoximone. The alpha adrenergic action of dobutamine prevented us from using high enough rates of infusion to explore any interaction between the inotropic actions of dobutamine and enoximone.

Comparison of i.v. and intra-tracheal administration of adrenaline.

Adrenaline is the single most important therapeutic agent used in advanced cardiac life support (ACLS). Ideally it should be given into a large central vein but the European Resuscitation Council, the American Heart Association and the Resuscitation Council (U.K.) advise that adrenaline may be given into the trachea if i.v. access is not available. We have studied the effects of intra-tracheal and i.v. adrenaline in 16 patients undergoing mechanical ventilation. Log dose-response curves were constructed for systolic arterial pressure and heart rate responses. Intra-tracheal doses of adrenaline up to 10 micrograms kg-1, approximately one-third of that recommended for resuscitation, had no effect on arterial pressure or heart rate, whereas adrenaline 0.1 microgram kg-1 i.v. produced a mean increase in systolic pressure of 24 mm Hg. The intra-tracheal doses recommended for resuscitation (2-3 mg) are likely to be ineffective and consideration should be given to abandoning the tracheal route for adrenaline in ACLS.

The influence of hemorrhage on organ perfusion during deliberate hypotension in rats.

There is general concern that major blood loss during deliberate hypotension could produce severe organ ischemia, but documentation of the magnitude of this response remains obscure. To examine this response, we studied 43 male Sprague-Dawley rats that were divided into seven groups: the control animals received 1 MAC (1.4%) isoflurane only; the hypotensive animals received a 1.4% isoflurane baseline anesthetic and were then rendered hypotensive by either increasing the isoflurane concentration (dISO), or by adding sodium nitroprusside (SNP), or 2-chloroadenosine (2AD) to the baseline anesthetic, decreasing the MAP to 51 mmHg; hemorrhaged animals had hypotension produced in the same manner as for the hypotensive animals, but additionally were bled 20% of estimated blood volume during deliberate hypotension produced with either deep isoflurane (dISOH), sodium nitroprusside (SNPH), or 2-chloroadenosine (2ADH). After a 25-min period of hypotension, or hypotension plus hemorrhage, cardiac output and blood flow to brain, heart, gastrointestinal tract, kidney, and liver were measured with 141Ce-labelled 15-microns microspheres. Hypotension was associated with decreased blood flow to the kidneys in all groups and to the liver in the 2AD group and an increased blood flow to the heart in the SNP and 2AD groups. Hemorrhage decreased blood flow during deliberate hypotension to the brain and the gastrointestinal tract in the dISOH and 2ADH groups and to the liver in the dISOH group. Our results suggest that hemorrhage during deliberate hypotension with dISO or isoflurane plus 2AD may be associated with compromised organ blood flow, whereas blood flow to vital organs is maintained after 20% hemorrhage during isoflurane and superimposed SNP-induced hypotension.

Total i.v. anaesthesia with propofol and alfentanil for coronary artery bypass grafting.

The haemodynamic effects of total i.v. anaesthesia with a combination of propofol and alfentanil infusions were studied in eight patients with good left ventricular function undergoing coronary artery bypass surgery. Haemodynamic indices were measured before anaesthesia and at specified intervals before cardiopulmonary bypass. The technique resulted in haemodynamic changes comparable to those reported with opioid-based anaesthesia for coronary artery surgery, and has potential advantages.

Metoclopramide and renal vascular resistance.

We have studied the effect of i.v. metoclopramide on renal vascular resistance in nine healthy volunteers. Peak systolic and end-diastolic frequencies were measured using duplex Doppler ultrasound of a renal interlobar artery, before and after the administration of i.v. metoclopramide 10 mg, and the resistance index derived. There was no significant change in mean arterial pressure or resistance index following metoclopramide.

Preoxygenation in the elderly: a comparison of the four-maximal-breath and three-minute techniques.

To compare the effectiveness of two routinely used methods of preoxygenation in protecting against hypoxia in the elderly, the arterial O2 saturation was measured using an oximeter. Twenty-four elderly patients (greater than or equal to 65 yr) presenting for elective orthopedic surgery were randomly allocated to receive either 3-min or four-maximal-breaths of 100% O2 via a Bain circuit. After preoxygenation, anesthesia was induced, tracheal intubation performed with patients kept apneic, and the endotracheal tube left open to air. The arterial O2 saturation was measured before preoxygenation and continually recorded during desaturation. Although attaining similar arterial O2 saturation values after preoxygenation, patients in the four-maximal-breath group had significantly shorter times (P less than 0.0001) to all levels of desaturation. We suggest that preoxygenation with 3-min breathing of 100% O2 offers more protection against hypoxia due to prolonged apnea after induction of anesthesia in the elderly than does four maximal breaths of 100% O2.

Automatic arterial pressure regulation using isoflurane: comparison with manual control.

A self-tuning, closed-loop controller, based on the algorithm of Clarke and Gawthrop, was used to regulate the inspired concentration of isoflurane to reduce arterial pressure electively in 33 patients undergoing ENT surgery. The patients were allocated randomly to one of four groups and received differing doses of fentanyl and labetalol to vary the range of sensitivities to the hypotensive action of isoflurane. The performance of the controller was evaluated at two target arterial pressures (AP), by its response to simulated changes in AP and by a comparison with a further group of eight patients with manual control of AP. The controller's undershoot of AP (range 2.8 +/- 0.5-4.5 +/- 1.3 mm Hg) and % time spent within +/- 5 mm Hg of the target AP (range 83 +/- 3.4-89 +/- 2.2%) were acceptable and equalled the manual performance figures (range 3.3 +/- 0.8 mm Hg; 90 +/- 5%). The regulation of induced hypotension in all four groups was rapid, accurate, stable and reproducible.

Determination of agmatine, arginine, citrulline and ornithine by reversed-phase liquid chromatography using automated pre-column derivatization with o-phthalaldehyde.

A method is presented for the pre-column derivatization of agmatine, arginine, citrulline or ornithine with o-phthalaldehyde-2-mercaptoethanol, and subsequent separation of the derivatives by reversed-phase liquid chromatography. Fluorescent response is linear from 10 to 150 pmol of injected analyte and detection limits range from 28 to 100 fmol. Response factors relative to the internal standard, homocysteic acid, were 1.16 (agmatine and arginine), 1.03 (citrulline) and 0.34 (ornithine). The applicability of the method to the measurement of arginase, arginine deaminase, arginine decarboxylase and other enzyme activities in bacterial extracts was examined.

Haemodynamic effects of a prolonged infusion of propofol as a supplement to nitrous oxide anaesthesia. Studies in association with peripheral arterial surgery.

The haemodynamic effects of propofol at two infusion rates (54-65 and 108-130 micrograms kg-1 min-1) have been studied during peripheral arterial surgery in eight elderly patients premedicated with morphine sulphate 0.15 mg kg-1. The haemodynamic response to laryngoscopy and intubation was partially suppressed: neither arterial pressure nor heart rate exceeded awake values. During stable anaesthesia at the lower infusion rate before surgery, systolic (SAP) and diastolic (DAP) arterial pressures were significantly decreased from awake values (SAP: -47%; DAP: -46%) as a result of decreases in cardiac output (-32%) and systemic vascular resistance (SVR) (-9%). During surgery, with either spontaneous (SV) or intermittent positive pressure (IPPV) ventilation, both infusion rates were associated with decreases in arterial pressures when compared with the awake state. Cardiac output was decreased (SV: -35%, IPPV: -36%) and SVR increased (SV: +22%, IPPV: +45%) at the lower infusion rate; similar changes were observed during the faster infusion rate.

Dose requirements of propofol by infusion during nitrous oxide anaesthesia in man. II: Patients premedicated with lorazepam.

The infusion rate of propofol required to supplement 67% nitrous oxide in oxygen to maintain surgical anaesthesia was determined in 72 patients premedicated with lorazepam. Following an induction dose of propofol 2 mg kg-1, groups of eight patients received an infusion of propofol varying from 60 to 200 micrograms kg-1 min-1. Probit analysis was used to determine the ED50 (130 micrograms kg-1 min-1; 95% confidence limits: 106-167 micrograms kg-1 min-1) and ED95 (348 micrograms kg-1 min-1; 95% confidence limits: 233-1296 micrograms kg-1 min-1) for propofol infusion. Whole blood propofol concentrations at the time of surgical incision correlated strongly with the infusion rate, giving an EC50 value of 2.5 micrograms ml-1, and an EC95 value of 5.92 micrograms ml-1. There was no significant correlation between the rate of infusion of propofol, or the total propofol dose, and the times to response to command, or to recall of birthdate.