Jean S. Bussières

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].).

High Tidal Volumes in Mechanically Ventilated Patients Increase Organ Dysfunction after Cardiac Surgery

Background: High tidal volumes in patients with acute respiratory distress syndrome and acute lung injury lead to ventilator-induced lung injury and increased mortality. We evaluated the impact of tidal volumes on cardiac surgery outcomes. Methods: We examined prospectively recorded data from 3,434 consecutive adult patients who underwent cardiac surgery. Three groups of patients were defined based on the tidal volume delivered on arrival at the intensive care unit: (1) low: below 10, (2) traditional: 10–12, and (3) high: more than 12 ml/kg of predicted body weight. We assessed risk factors for three types of organ failure (prolonged mechanical ventilation, hemodynamic instability, and renal failure) and a prolonged stay in the intensive care unit. Results: The mean tidal volume/actual weight was 9.2 ml/kg, and the tidal volume/predicted body weight was 11.5 ml/kg. Low, traditional, and high tidal volumes were used in 724 (21.1%), 1567 (45.6%), and 1,143 patients (33.3%), respectively. Independent risks factors for high tidal volumes were body mass index of 30 or more (odds ratio [OR] 6.25; CI: 5.26–7.42; P < 0.001) and female sex (OR 4.33; CI: 3.64–5.15; P < 0.001). In the multivariate analysis, high and traditional tidal volumes were independent risk factors for organ failure, multiple organ failure, and prolonged stay in the intensive care unit. Organ failures were associated with increased intensive care unit stay, hospital mortality, and long-term mortality. Conclusion: Tidal volumes of more than 10 ml/kg are risk factors for organ failure and prolonged intensive care unit stay after cardiac surgery. Women and obese patients are particularly at risk of being ventilated with injurious tidal volumes.

Perioperative cardiorespiratory complications in adults with mediastinal mass: Incidence and risk factors

BackgroundPatients with a mediastinal mass are at risk for cardiorespiratory complications in the perioperative period. The authors’ objectives were to evaluate the incidence of life-threatening intraoperative cardiorespiratory and postoperative respiratory complications in adult patients and to study the usefulness of clinical signs and symptoms, radiologic evaluation, and pulmonary function tests in the determination of the perioperative risk. MethodsThe authors reviewed the investigation and treatment of adult patients presenting with anterior or middle mediastinal masses for surgery under anesthesia between January 1994 and July 2000. ResultsNinety-eight patients underwent 105 anesthetic cases. The incidences of intraoperative cardiorespiratory and postoperative respiratory complications were 4 in 105 and 11 in 105, respectively. No collapse of the airways occurred during anesthesia. However, a high incidence of early postoperative life-threatening respiratory complications was observed (7 in 105). In a multivariate logistic regression analysis model, perioperative complications were predicted by the occurrence of cardiorespiratory signs and symptoms at the initial presentation (odds ratio [OR], 6.2) and the presence of combined obstructive and restrictive patterns (mixed pulmonary syndrome) on pulmonary function tests (OR, 3.9). Intraoperative complications were associated with pericardial effusion on computed tomography scan (OR, 19.8). Postoperative respiratory complications were related to tracheal compression of more than 50% on preoperative computed tomography scan evaluation (OR, 7.4) and mixed pulmonary syndrome on pulmonary function tests (OR, 15.1). ConclusionObstruction of the airway in an adult with a mediastinal mass is a rare event in the intraoperative period. Nevertheless, caution should be observed for the occurrence of early postoperative life-threatening respiratory complications. Patient at high risk of perioperative complications can be identified by the occurrence of cardiopulmonary signs and symptoms at presentation, combined obstructive and restrictive pattern on pulmonary function tests, and computed tomography scan findings (tracheal compression > 50%, pericardial effusion, or both).

Influences of spinal anesthesia on exercise tolerance in patients with chronic obstructive pulmonary disease.

RATIONALE Lower limb muscle dysfunction contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We hypothesized that signaling from lower limb muscle group III/IV sensory afferents to the central motor command could be involved in premature cycling exercise termination in COPD. OBJECTIVES To evaluate the effects of spinal anesthesia, which presumably inhibited central feedback from the lower limb muscle group III/IV sensory afferents on exercise tolerance and cardiorespiratory response during constant work-rate cycling exercise in patients with COPD. METHODS In a crossover and double-blind randomized design, eight patients with COPD (FEV(1), 67 ± 8% predicted) completed a constant work-rate cycling exercise after sham (NaCl, interspinous L(3)-L(4)) or active (fentanyl 25 μg, intrathecal L(3)-L(4)) spinal anesthesia. MEASUREMENTS AND MAIN RESULTS When compared with placebo, endurance time was significantly prolonged after spinal anesthesia with fentanyl (639 ± 87 s vs. 423 ± 38 s [mean ± SEM]; P = 0.01). Ventilation and respiratory rate were reduced at isotime points under the fentanyl condition, whereas ventilatory efficiency and dead space ventilation were improved. Patients exhibited less dynamic hyperinflation at isotime points with spinal anesthesia. Consequently, the rise in dyspnea was significantly flatter during the fentanyl condition than with placebo. CONCLUSIONS Spinal anesthesia enhanced cycling exercise tolerance in patients with COPD, mostly by reducing ventilatory response and dyspnea during exercise; these effects were possibly mediated through the inhibition of group III/IV lower limb sensory muscle afferents.

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.

Stopping vs. Continuing Aspirin before Coronary Artery Surgery

BACKGROUND Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. METHODS We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P=0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P=0.08). CONCLUSIONS Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery

Background Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. Methods In a trial with a 2‐by‐2 factorial design, we randomly assigned patients who were scheduled to undergo coronary‐artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Results Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fishers exact test). Conclusions Among patients undergoing coronary‐artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.)

New landmarks improve the positioning of the left Broncho-Cath double-lumen tube-comparison with the classic technique.

PurposeTo compare a new technique (NT) for positioning the left modified Broncho-Cath™ double-lumen tube (LM-DLT) by fibreoptic bronchoscopy (FOB) to the classic technique (CT).MethodsSixty-one adult patients undergoing elective thoracic surgery with LM-DLT were randomly assigned to the NT orto the CT group. For the NT, the endoscopist confirms the left mainstem endobronchial intubation. The proximal edge of the blue bronchial cuff should not be visualized at the carina. Then, through the left bronchial lumen, by transparency across the wall of the tube, the position of the tube is adjusted so that the carina lies midway between the black radiopaque line and the top of the bronchial cuff. After this, the orifice of the left upper lobe (LUL) bronchus should be clearly seen. For the CT, the endoscopist uses the technique described by Benumof and Slinger. After lateral positioning of the patient, the LM-DLT was repositioned if the top of the endobronchial cuff was above the carina or when the LUL bronchus was obstructed.ResultsThe incidence of proximal repositioning was significantly less in the NT compared to the CT (16%vs 43%, P=0.007).ConclusionUsing this new technique, the LM-DLT is inserted deeper in the left mainstem bronchus. This new landmark augments the range of movement that can be tolerated without requiring repositioning of the LM-DLT, This NT to position and to assess LM-DLT, by transparency across the wall of the tube with FOB, is better adapted to the LM-DLT and its recent modifications.RésuméObjectifComparer une nouvelle technique (NT) de positionnement du tube double-lumière Broncho-Cath™ gauche modifié (TDL-GM), à l’aide de la fibroscopie, à la technique classique (TC).MéthodesSoixante et un patients adultes devant subir une chirurgie thoracique programmée avec un TDL-GM ont été randomisés aux groupes NT ou TC. Suivant la NT, l’endoscopiste confirme l’intubation de la bronche souche gauche et le sommet du ballonnet ne doit pas être visualisé juste sous la carène. Par la lumière bronchique, par transparence au travers de la paroi du tube, on ajuste celui-ci pour que la carène se situe à mi-chemin entre la ligne noire radio-opaque et le sommet du ballonnet bronchique. On s’assure également que la bronche lobaire supérieure gauche (LSG) est libre. Suivant la TC, l’endoscopiste utilise la technique décrite par Benumof et Slinger. Après le positionnement en décubitus latéral, le TDL-GM est repositionné lorsque le sommet du ballonnet fait hernie au dessus de la carène ou si la bronche LSG est obstruée.RésultatsLes repositionnements proximaux sont significativement moins fréquents en utilisant la NT comparativement à la TC (16%vs 43%,P = 0,007).ConclusionLorsqu’on utilise la NT, la partie endobronchique du TDL-GM est insérée plus profondément dans la bronche souche gauche avec de nouveaux points de repère et augmente par conséquent la marge de mouvement qui peut être tolérée sans nécessiter un repositionnement du TDL-GM. Cette NT de positionnement et de vérification, par transparence au travers de la paroi du tube, est mieux adaptée aux modifications récentes du TDL-GM.

The combination of inhaled nitric oxide and pulmonary artery balloon inflation improves oxygenation during whole-lung lavage.

We present a case in which the use of inhaled nitric oxide associated with temporary partial unilateral pulmonary artery occlusion further improved oxygenation during whole-lung lavage. This is the first case in the literature describing the simultaneous use of these two modalities.

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