Alizapride and ondansetron for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic gynaecological surgery: A double-blind, randomised, placebo-controlled noninferiority study.

BACKGROUND: Postoperative nausea and vomiting (PONV) can be prevented. Alizapride is an established antiemetic that may be effective in this role. OBJECTIVE: Our primary objective was to test the hypothesis that alizapride is noninferior to ondansetron for the prophylaxis of PONV. DESIGN: A randomised, placebo-controlled, double-blinded noninferiority study. SETTING: University hospitals of Leuven, Belgium, from November 2008 to July 2011. PATIENTS: A total of 523 patients undergoing laparoscopic gynaecological surgery were included in the study. Reasons for exclusion were American Society of Anesthesiologists (ASA) greater than 2, hypersensitivity to the study medication, pregnancy, mental disorders, psychiatric illness or consumption of antiemetic drugs within 24 h before initiation of the study. INTERVENTION: Patients received either alizapride 100 mg, ondansetron 4 mg or placebo intravenously 30 min before the end of surgery. MAIN OUTCOME MEASURES: The main outcome measures included the incidences of postoperative nausea (PON) and postoperative vomiting (POV) during the stay in the postanaesthetic care unit (PACU), with noninferiority testing for alizapride versus ondansetron. The region of noninferiority was defined as a relative difference in incidence of 25%. Secondary outcome was the incidence of PONV in the PACU and after 24 h. RESULTS: In the alizapride group, 32% of the patients experienced PON during the PACU stay, compared with 28% in the ondansetron group [relative risk 1.13, 90% confidence interval (CI) 0.87 to 1.46], exceeding the predefined margin of noninferiority. With respect to the incidences of POV during the PACU stay, 12.8% of the patients randomised to receive alizapride experienced POV, compared with 7.7% of who received ondansetron (relative risk 1.67, 90% CI 1.00 to 2.87). The incidences of PON and POV in the placebo group during the PACU stay were 34.2 and 9.8%, respectively. The 24-h incidences of PONV were lower than expected in this high-risk group of patients and were similar at 39.3, 36.8 and 31.5% in the placebo, alizapride and ondansetron groups, respectively (χ², P = 0.36). Patients treated with ondansetron required significantly less rescue medication than placebo-treated patients (P = 0.035). Due to the lower than expected incidences of PONV in this study, the power to conclude any noninferiority of alizapride was reduced to only 41%. CONCLUSION: We found no evidence to support the noninferiority of alizapride 100 mg when compared with ondansetron 4 mg for the intraoperative prophylaxis of PONV. However, the lower than expected incidences of PONV reduced the power of this study to conclude noninferiority or confirm significant beneficial effects for either antiemetic for PON and POV during the PACU stay. TRIAL REGISTRATION: Eudra CT 2008-004789-20.

A safety and efficacy evaluation of hemoglobin-based oxygen carrier HBOC-201 in a randomized, multicenter red blood cell controlled trial in noncardiac surgery patients.

BACKGROUND: We present the results of a previously unpublished hemoglobin-based oxygen carrier (HBOC) study conducted in 1998-1999. METHODS: In a multicenter, randomized, single-blind, comparative study of HBOC-201 versus allogeneic red blood cell (RBC) transfusions, no-cardiac surgery patients received HBOC-201 to a maximum of 7 units (n = 83) or RBCs (n = 77). Patients could be switched to RBCs for safety or any other reason. The efficacy end points were elimination and/or reduction of allogeneic RBC transfusions for 28 days. RESULTS: The proportion of patients in the HBOC-201 group that avoided RBC transfusion was 0.427 (95% confidence interval, 0.321-0.533). Subjects in the HBOC-201 group received on average 3.2 units of RBCs versus 4.4 units in the control arm (P = 0.004). Seventy-nine (95.2%) subjects in the HBOC-201 group and 72 (93.5%) in the RBC group experienced adverse events (AEs), judged to be associated with study treatment in 59 (71.1%) and 18 (23.4%) subjects, respectively. Thirty-day mortality, 5 (6.0%) vs 4 (5.2%) patients (P = 1.00), incidence of serious AEs, 24 (28.9%) vs 20 (26.0%) (P = 0.73), or time to intensive care unit (log-rank P = 0.15) or hospital discharge (log-rank P = 0.53) were similar for the HBOC-201 and RBC groups, respectively. CONCLUSIONS: Up to 7 units of HBOC-201 infused over the course of 6 days resulted in RBC transfusion avoidance in 43% of patients. There were no notable differences in mortality and serious AEs incidence. The use of HBOC-201 was associated with a notable excess of nonserious AEs.

Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery.

OBJECTIVES: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. DESIGN: A prospective randomized clinical trial. SETTING: University hospital. PARTICIPANTS: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. INTERVENTIONS: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. MEASUREMENTS AND MAIN RESULTS: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor alpha; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (p = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. CONCLUSIONS: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery.

OPCAB versus early mortality and morbidity: an issue between clinical relevance and statistical significance.

OBJECTIVE: To evaluate the impact of OPCAB on major postoperative events in a large consecutive cohort of patients, covering the complete spectrum of risk. METHODS: A consecutive series of 3333 CABG patients operated in a single institution (Jan/97-Jan/03) is analyzed after a complete (98%) midterm reengineering towards off-pump surgery (Oct/99). Patients in cardiogenic shock are excluded. The on- (N=1593) or off-pump (N=1740) datasets are comparable for most demographic and non-cardiac variability. The studied events are early mortality, early stroke, early infarct, early dialysis and hospital stay. Three methods adjust for possible patient selection: similar datasets, forced inclusion of a saturated OPCAB propensity score and finally multivariate correction. RESULTS: Non-risk adjusted. The 3-month survival was 96.7+/-0.4% (OPCAB) and 95.9+/-0.5% (ECC) (P=0.2). The 8-day freedom from stroke was 99.4+/-0.2% (OPCAB) and 98.5+/-0.3% (ECC) (P=0.004). The prevalence of dialysis was 1.67% in OPCAB and 2.27% in ECC (P=0.2). The 8-day freedom from infarct was 98.4+/-0.2% (OPCAB) and 98.3+/-0.2% (ECC) (P=0.7). The freedom from hospital discharge day 15 was 17.6+/-0.9% (OPCAB) and 18.4+/-0.8% (ECC) (P=0.001). Propensity score corrected and adjusted for event-related variability. The survival effect remained non-significant (P=0.3), also for patients with a EuroSCORE>8 (P=0.9). The stroke effect became non-significant (P=0.2), but stayed significant for patients with severe internal carotid artery stenosis (P=0.02). The dialysis-effect remained non-significant (P=0.6), also for patients with an elevated creatinine (P=0.7). The early infarct-effect remained non-significant (P=0.8), also for the female patients (P=0.8). The hospital discharge was significantly influenced by the OPCAB approach for the total group (P=0.02) as well as for the patients with EuroSCORE>8 (P=0.01). CONCLUSIONS: The observed 20% reduction of mortality, 60% reduction of stroke and 20% reduction of dialysis were partly neutralized by the adjusting methods and demand, at least, larger datasets to obtain statistical significance. Subdatasets with fewer patients but higher risk identified risk-reducing effects for stroke. Hospital stay was shortened by the OPCAB approach. The interactions between risk, number of patients and the risk-reducing effect are the cornerstones of evidence generation for the OPCAB approach. These results were obtained through a very strict reengineering and cannot be extended to all OPCAB programs.

Effect of sutureless implantation of the Perceval S aortic valve bioprosthesis on intraoperative and early postoperative outcomes.

OBJECTIVE: Prolonged aortic crossclamping can increase mortality and morbidity after aortic valve replacement in elderly and high-risk patients. Sutureless implantation of the prosthesis has the potential to shorten aortic crossclamp time. METHODS: The Perceval S valve (Sorin Biomedica Cardio Srl, Sallugia, Italy), a sutureless implantable aortic bioprosthesis, was used in 32 patients (median age, 78 years; median logistic euroSCORE, 9.99) requiring aortic valve replacement with or without concomitant coronary artery bypass grafting. Hemodynamic parameters and clinical outcome were obtained at discharge, at 6 months, and up to 1 year postoperatively. RESULTS: Aortic crossclamp time needed for aortic valve replacement was 18 ± 6 minutes. Hemodynamics at discharge showed good function of all Perceval S valves with low transvalvular pressure gradients (mean, 12 ± 5 mm Hg and peak, 23 ± 9 mm Hg) and low incidence of paravalvular or valvular leakage. Operative mortality was 0%. Follow-up at 1 year showed 3 non-valve-related deaths. Survivors showed good clinical outcome and stable hemodynamic function of the valve prosthesis, except for 1 patient in whom endocarditis developed. Despite a moderate decrease in platelet counts persisting up to 12 months, freedom of bleeding and thromboembolic events was 100%. CONCLUSIONS: It is possible to implant a well-functioning sutureless stent-mounted valve in the aortic position in less than 20 minutes of aortic crossclamping. This is associated with excellent early clinical and hemodynamic outcome in high-risk patients. Moderate changes in hematologic parameters persisted but were not related to clinical events.

Performance analysis of interactive multimodal CME retraining on attitude toward and application of OPCAB.

OBJECTIVE: The transfer of tacit and codified knowledge on a surgical technique is studied in a consecutive cohort of teams participating in interactive multimodal continuing medical education (CME) retraining in off-pump coronary artery bypass (OPCAB). METHODS: Fifty teams of 1.3 +/- 0.5 surgeons and 1.1 +/- 1.9 anesthetists visited 2.2 +/- 0.7 days. Variables describe the pre-visit cardiac activity and OPCAB attitude, complexity score (10 frequently cited complexity criteria), application, and conversion rate. The multimodal approach to knowledge transfer included interactive discussions (commitment; resistances; levers and process of change; methods; outcome; resource optimization), active participation in 3.8 +/- 1.3 unselected cases (anchor-stitch, enucleation techniques), low-fidelity bench model (shunt placement, anastomotic technique), and CD-ROM. Exit end points included OPCAB attitude and complexity score. Late end points (3 months) included OPCAB attitude, complexity score, and application rate. RESULTS: OPCAB was considered, upon exit, beneficial for all patients by 90% of the teams (versus 29 % pre-visit), but by only 62 % of the teams at 3 months. The complexity score downgraded at exit from 3.6 +/- 2 (pre-visit) to 1.2 +/- 1 (P <.001) but increased again at 3 months to 1.6 +/- 1 (P =.001 versus pre-visit and P =.001 versus exit). The 3-month OPCAB rate of the surgeons was 49% +/- 32% versus 23% +/- 28% pre-visit (P <.0001). This was influenced by the pre-visit OPCAB rate and education, as well as by the post-visit changes in complexity scores and attitude. The conversion rate toward cardiopulmonary bypass improved from 3.5% +/- 5% (pre-visit) to 1.3% +/- 3% (3 months, P =.006). CONCLUSIONS: The multimodal OPCAB re-training resulted in a substantial increase of the application, concomitant with a decrease in conversion. The positive impact on attitude and complexity score, at exit, was somewhat reduced in the following clinical confrontation.

Cardiac output monitoring using a brachial arterial catheter during off-pump coronary artery bypass grafting.

OBJECTIVE: To investigate the accuracy of cardiac output measurements by transpulmonary thermodilution and pulse contour analysis using a brachial arterial catheter. STUDY DESIGN: Criterion standard study. SETTING: University hospital, single institution. POPULATION: Twenty-three adult patients undergoing off-pump coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured with a thermistor-tipped brachial arterial catheter using pulse contour analysis (COpc) and transpulmonary thermodilution (COba), which serves to calibrate COpc in the system tested. Both methods were compared separately with standard pulmonary artery thermodilution (COpa). COba was closely correlated with COpa (r = 0.93, p < 0.001). Bland-Altman analysis showed a bias of 0.91 L/min with limits of agreement of +/-0.98 L/min. COpc was also closely correlated (r = 0.80, p < 0.001) with COpa and was found to have a bias of 1.08 L/min with limits of agreement of +/-1.50 L/min. During the surgical procedure, changes in COpa from baseline were closely correlated with changes in COba (r = 0.90, p < 0.01) and COpc (r = 0.81, p < 0.01). CONCLUSIONS: The brachial arterial access allows a reliable assessment of cardiac output by transpulmonary thermodilution and pulse contour analysis in patients undergoing off-pump coronary artery bypass grafting.