Charles MacAdams

A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery

BACKGROUND Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences. METHODS In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days. RESULTS The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22). CONCLUSIONS Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).

Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Surgery

Background— This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk. Methods and Results— At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (P<0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and >15 red blood cell units transfused before therapy. Conclusions— In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.

Anaesthesia for coronary artery bypass surgery supplemented with subarachnoid bupivacaine and morphine: a report of 18 cases

We report our experience, with general anaesthesia (GA) supplemented with subarachnoid bupivacaine and morphine for coronary artery bypass surgery (CABG) in 18 patients. Fifteen patients were male, and mean age was 62 yr. Anaesthesia (GA) was induced with alfentanil 97 ± 22 μg · kg− 1 and midazolam 0.04 ± 0.02 mg · kg− 1 supplemented with a muscle relaxant, and maintained with isoflurane (0.25–0.5%) in oxygen throughout surgery. Spinal anaesthesia (SA) was then performed at a lumber level using hyperbaric bupivacaine (23–30 mg) and/ or lidocaine (150 mg) with morphine (0.5–1 mg). Pooled data showed the following haemodynamic results (P < 0.05). Induction of GA produced a decrease in mean arterial pressure (MAP). Addition of SA produced a decrease in heart rate. Heart rate and MAP did not change with sternotomy. Phenylephrine support of arterial blood pressure was used at some time during operation in 17 patients. Supplementation of GA was minimal. Patients received 2.7 ± 0.7 coronary grafts. Operating room time was 3.9 ± 0.6 hr. Postoperative analgesic requirements were minimal, and in half of the patients tracheal extubation occurred on the day of surgery. Complications included one myocardial infarction, one resternotomy, a metabolic encephalopathy in a dialysis- dependent patient, and one case of herpes labialis. No patient recalled intraoperative events. Combined GA with SA may be an effective technique for CABG surgery. Further study of the cardiovascular, neurological and metabolic effects of the technique is required.RésuméNous rapportons notre expérience avec l’anesthésie générale (AG) associée à une rachianesthésie (RA) à la bupivacaïne et à la morphine réalisée chez 18 opérés pour pontages coronaires. Quinze des patients sont des hommes et l’âge moyen est de 62 ans. L’anesthésie générale est induite avec de l’alfentanil 97 ± 22 μg · kg− 1, du midazolam 0,04 ± 0,02 mg · kg− 1 et un myorelaxant, et maintenue avec de l’isoflurane (0,25–0,5%) en oxygène. Après l’induction, une rachianesthésie lombaire est alors exécutée avec de la bupivacaïne hyperbare (23–30 mg) avec ou sans lidocaïne (150 mg) et avec de la morphine (0,5–1 mg). Les données groupées révèlent les résultats hémodynamiques suivants (P < 0,05). L’induction de l’AG provoque une baisse de la pression artérielle moyenne (PAM). L’addition de la RA produit un ralentissement de la fréquence cardiaque (FC). La sternotomie ne modifie ni la FC ni la PAM. A un moment ou un autre de l’intervention, la pression artérielle a dû être soutenue chez 17 patients avec de la phényléphrine. Le besoin d’AG supplémentaire est minime. Les pontages aortocoronariens totalisent 2,7 ± 0,7 par patient. La durée moyenne des interventions est de 3,9 ± 0,6 h. Les besoins d’analgésie postopératoires sont minimes et la moitié des patients sont extubés le jour de la chirurgie. Les complications comprennent: un infarctus du myocarde, une reprise de sternotomie, une encéphalopathie métabolique et un herpès labial. Aucun des patients ne s’est remémoré d’événements peropératoires. L’AG combinée à la RA pourrait s’avérer une technique efficace pour la chirurgie de revascularisation myocardique. Des études plus poussées au regard des répercussions cardiov-asculaires, neurologiques et métaboliques s’imposent.

Somatosensory Evoked Potential Monitoring During Cardiac Surgery: An Examination of Brachial Plexus Dysfunction

OBJECTIVE To observe the effects of the Favoloro and sternal retractors on the ulnar and median nerve somatosensory evoked potentials (SSEPs) and to identify any relationship with postoperative brachial plexus injury. DESIGN Prospective study. SETTING University hospital. PARTICIPANTS Twenty cardiac patients. INTERVENTIONS SSEPs were studied in patients undergoing cardiac surgery using normothermic cardiopulmonary bypass. Evoked potentials were obtained from bilateral median and ulnar nerves. MEASUREMENTS The incidence of nerve-specific SSEP changes and their temporal relationship to retractor usage were determined. The overall incidence of SSEP changes was 75%. There were no differences (p > 0.05) between the group showing changes (n = 15) and the group with no changes (n = 5) with respect to age, body surface area, weight, cross-clamp or cardiopulmonary bypass times. There also were no differences (p > 0.05) between the frequencies of left- and right-sided changes, or in nerve-specific SSEP changes. Seventy-four percent of SSEP changes correlated with retractor usage. No SSEP changes were associated with the Favoloro retractor. Significant SSEP depression, assessed by either percentage reduction in amplitude or persistent amplitude reduction, occurred in the absence of postoperative neurological deficits. There were no detected postoperative brachial plexus injuries. CONCLUSIONS SSEP changes correlate with the use of the sternal retractor but not the Favoloro retractor. It was not possible to replicate the results of previous investigators in predicting postoperative neurological deficits based on the SSEP changes, and therefore the routine application of SSEP as a monitor cannot be recommended on the basis on these data.

Anesthesia supplemented with subarachnoid bupivacaine and morphine for coronary artery bypass surgery in a child with Kawasaki disease.

AWASAKI disease is a major cause of acquired heart disease in children in North America. I Twenty percent of untreated children develop cardiovascular sequelae of coronary artery aneurysms and stenoses. In one percent of cases, giant coronary artery aneurysms or occlusions may occur, and coronary artery bypass surgery (CABG) may be required. 2 Although surgically more difficult to perform, internal mammary artery grafts provide better long-term patency than saphenous vein grafts in children. 3 Postoperatively, avoidance of unnecessary controlled ventilation and excellent control of pain are priorities in children undergoing cardiac surgery. Use of spinal opioids in cardiac surgery has been reported in adults and children. 4,5 The authors have reported anesthesia for CABG in adults supplemented with subarachnoid bupwacaine and morphine. 6 Waldron reported on the anesthetic implications of Kawasakl disease, but there are no reports in the hterature on anesthetic management for CABG for Kawasaki disease in children. 7 Therefore, the case of a 10-year-old boy who underwent CABG using bilateral internal mammary artery grafts under general anesthesia supplemented with subarachnold bupivacaine and morphine is reported.

Regulatory decisions pertaining to aprotinin may be putting patients at risk

The antifibrinolytic agent aprotinin, a naturally occurring serine protease inhibitor, was removed from the worldwide market in October 2007.[1][1] Aprotinin and two other antifibrinolytic agents (the lysine analogues tranexamic acid and aminocaproic acid) had been used in cardiac surgery to