Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial ...infarction and death without inducing hemodynamic instability.
We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.
Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval CI, 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients 47.6% vs. 1854 patients 37.1%; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% 16 patients vs. 0.1% 5 patients; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).
Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery.
To determine whether ...preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery.
Prospective cohort study.
16 hospitals in 9 countries.
10 402 patients aged 45 years or older having inpatient noncardiac surgery.
All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery.
In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index RCRI) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL incidence, 0.3%, 100 to less than 200 pg/mL incidence, 0.7%, 200 to less than 1500 pg/mL incidence, 1.4%, and 1500 pg/mL or greater incidence, 4.0%).
External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings.
Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI.
Canadian Institutes of Health Research.
Background
Blood products are a lifesaving but limited resource, particularly in resource‐limited settings. Evidence‐based transfusion criteria tailored to local hospitals have shown great promise in ...reducing costs, minimising shortages, and ameliorating the morbidity and mortality associated with liberal blood product usage. We implemented the “Saving Blood, Saving Lives” project to: promote responsible blood product use and reduce blood product ordering inefficiencies and expenditure.
Methods
A comprehensive change management programme, preceded by 3 months of clinical department consultation and training, was implemented. A new evidence‐based protocol for blood product utilisation was developed, together with an accountability form. This form was used in monthly audit meetings to refine policies, identify new problems, improve communication, and to drive hospital staff accountability and training. The primary measure of the programme's success was the change in the number of red cell concentrate units ordered.
Results
Project implementation required minimal time and no additional budget or staff. Annual red cell concentrate usage reduced from 7211 units in year one to 4077 units in year 5 (p < 0.001). Similar reductions were seen in freeze‐dried plasma and platelet usage, as well as administrative costs. Total project saving, adjusted to baseline admission numbers, amounted to over R46 million ($2.5 million).
Conclusions
As a change management programme centred the “Saving Blood, Saving Lives” project, was able to significantly reduce blood product‐related administration and expenditure by implementing evidence‐based transfusion criteria. The programme is simple, replicable and cost effective, making it ideally suited for use in resource‐constrained environments.
Abstract
OBJECTIVES
We carried out a pilot randomized controlled study to determine the feasibility of a large trial evaluating the impact of colchicine versus placebo on postoperative atrial ...fibrillation or atrial flutter (POAF) among patients undergoing lung resection surgery.
METHODS
Patients ≥55 years of age undergoing lung resection surgery were randomly assigned to receive colchicine 0.6 mg or placebo starting a few hours before surgery. Postoperatively, patients received colchicine 0.6 mg or placebo twice daily for an additional 9 days. Our feasibility outcomes included the period of time required to recruit 100 patients, the completeness of follow-up and compliance with the study drug. The primary efficacy outcome was POAF within 30 days of randomization.
RESULTS
One hundred patients were randomized (49 to colchicine and 51 to placebo) over a period of 12 months at 2 centres in Canada. All patients completed the 30-day follow-up. The mean staff time required to recruit and to follow-up each patient was 165 min. In all, 71% of patients completed the study drug course without interruption. Patient refusal to continuing taking the study drug was the main reason for permanent drug discontinuation. New POAF occurred in 5 (10.2%) patients in the colchicine group and 7 (13.7%) patients in the placebo group (adjusted hazard ratio 0.69, 95% confidence interval 0.20–2.34).
CONCLUSIONS
These results show the feasibility of a trial evaluating Colchicine for the prevention of perioperative Atrial Fibrillation in patients undergoing lung resection surgery. This pilot study will serve as the foundation for the large multicentre COP-AF trial.
A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of ...these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture.
Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization.
Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26-1.39).
These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial.
ClinicalTrials.gov, no. NCT01344343.
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