Indications for red blood cell transfusion in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Good blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery. METHODS: We did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30-day mortality. FINDINGS: We included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232,806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0.70 (95% CI 0.49-1.02; p=0.060) for cardiac surgical trials and 1.10 (95% CI 0.96-1.27; p=0.16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2.72, 95% CI 2.11-3.49; p<0.0001) and other morbidity, although with substantial heterogeneity and small study effects. INTERPRETATION: Evidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery. FUNDING: None.

Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial.

OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 µg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions.

Non-randomized studies as a source of complementary, sequential or replacement evidence for randomized controlled trials in systematic reviews on the effects of interventions.

The terms applicability, generalizability, external validity and transferability are related, sometimes used interchangeably and have in common that they lack a clear and consistent definition in the classic epidemiological literature. However, all of these terms generally describe one overarching theme: whether or not available research evidence can be directly utilized to answer the healthcare questions at hand, ideally supported by a judgment about the degree of confidence for this utilization. This concept has been called directness. The objectives of this paper were to delineate how non-randomized studies (NRS) inform judgments in relation to directness and the concepts that it encompasses in the context of systematic reviews. We will briefly review what is known and describe the theoretical and practical issues as well as offer guidance to those tackling the challenges of judging directness and using research evidence to answer healthcare questions with evidence from NRS. In particular, we suggest a framework in which authors can use NRS as a complement, sequence or replacement for randomized controlled trials (RCTs) by focusing on judgments about the population, intervention, comparison and outcomes. Authors of systematic reviews will use NRS to complement judgments about the inconsistencies, the rationale and credibility of subgroup analysis, the baseline risk estimates for the determination of absolute benefits and downsides, and the directness of surrogate outcomes. This evidence includes contextual or supplementary evidence. Authors of systematic review and other summaries of the evidence use NRS as sequential evidence to provide evidence when insufficient evidence is available for an outcome from RCTs, but NRS evidence is available (e.g., long-term harms). Use of evidence from NRS may also serve to replace RCT evidence when NRS provide equivalent (or potentially higher) confidence in the evidence (i.e. quality) compared to indirect evidence from RCTs. These judgments will be made in the context of other domains that influence the overall quality of the body of evidence, including the risk of bias, publication bias (i.e. limitations in the detailed study design and execution), inconsistency, imprecision and factors that increase our confidence in effects. This article will support systematic reviewers in their interaction with decision makers, that is, those who use the systematic review to develop guidelines, address health policy makers, and make clinical decisions, by making these judgments transparent. Copyright © 2013 John Wiley & Sons, Ltd.

Warm-blood cardioplegia with low or high magnesium for coronary bypass surgery: a randomised controlled trial.

OBJECTIVE: Magnesium (Mg²âº) is cardioprotective and has been routinely used to supplement cardioplegic solutions during coronary artery bypass graft (CABG) surgery. However, there is no consensus about the Mg²âº concentration that should be used. The aim of this study was to compare the effects of intermittent antegrade warm-blood cardioplegia supplemented with either low- or high-concentration Mg²âº. METHODS: This study was a randomised controlled trial carried out in two cardiac surgery centres, Bristol, UK and Cuneo, Italy. Patients undergoing isolated CABG with cardiopulmonary bypass were eligible. Patients were randomised to receive warm-blood cardioplegia supplemented with 5 or 16 mmol l⁻¹ Mg². The primary outcome was postoperative atrial fibrillation. Secondary outcomes were serum biochemical markers (troponin I, Mg²âº, potassium, lactate and creatinine) and time-to-plegia arrest. Intra-operative and postoperative clinical outcomes were also recorded. RESULTS: Data from two centres for 691 patients (342 low and 349 high Mg²âº) were analysed. Baseline characteristics were similar for both groups. There was no significant difference in the frequency of postoperative atrial fibrillation in the high (32.8%) and low (32.0%) groups (risk ratio 1.03, 95% confidence interval, CI, 0.82-1.28). However, compared with the low group, troponin I release was 28% less (95% CI 55-94%, p=0.02) in the high-Mg²âº group. The 30-day mortality was 0.72% (n = 5); all deaths occurred in the high-Mg²âº group but there was no significant difference between the groups (p=0.06). Frequencies of other major complications were similar in the two groups. CONCLUSIONS: Warm-blood cardioplegia supplemented with 16 mmol l⁻¹ Mg²âº, compared with 5 mmol l⁻¹ Mg²âº, does not reduce the frequency of postoperative atrial fibrillation in patients undergoing CABG but may reduce cardiac injury. (This trial was registered as ISRCTN95530505.).

Community intervention to promote rational treatment of acute respiratory infection in rural Nepal.

OBJECTIVE: To evaluate a community education program about treatment of acute respiratory infection (ARI). METHODS: First, community case definitions for severe and mild ARI were developed. The intervention was then evaluated using a controlled before-and-after design. Household surveys collected data about ARI treatment in 20 clusters, each based around a school and health facility. Treatment indicators included percentages of cases attending health facilities and receiving antibiotics. The intervention consisted of an education program in schools culminating in street theater performances, discussions with mothers after performances and training for community leaders and drug retailers by paramedics. The intervention was conducted in mid-2003. Indicators were measured before the intervention in Nov/Dec 2002 and again in Dec 2003/Jan 2004. RESULTS: Two thousand and seven hundred and nineteen households were surveyed and 3654 under-fives were identified, of whom 377 had severe ARI. After implementing the intervention, health post (HP) attendance rose by 13% in under-fives with severe ARI and fell by 9% in under-fives with mild ARI (test of interaction, P = 0.01). Use of prescribed antibiotics increased in under-fives with severe ARI by 21% but only by 1% in under-fives with mild ARI (test of interaction, P = 0.38). Irrespective of ARI severity, the use of non-prescribed antibiotics dropped by 5% (P = 0.002), and consultation with female community health volunteers (FCHVs)and use of safe home remedies increased by 6.7% (P not estimated) and 5.7% (P = 0.008) respectively. CONCLUSION: The intervention was implemented using local structures and in difficult circumstances, yet had a moderate impact. Thus it has the potential to effect large scale changes in behaviour and merits replication elsewhere.

Challenges to implementing the national programme for information technology (NPfIT): a qualitative study.

OBJECTIVES: To describe the context for implementing the national programme for information technology (NPfIT) in England, actual and perceived barriers, and opportunities to facilitate implementation. DESIGN: Case studies and in depth interviews, with themes identified using a framework developed from grounded theory. SETTING: Four acute NHS trusts in England. PARTICIPANTS: Senior trust managers and clinicians, including chief executives, directors of information technology, medical directors, and directors of nursing. RESULTS: The trusts varied in their circumstances, which may affect their ability to implement the NPfIT. The process of implementation has been suboptimal, leading to reports of low morale by the NHS staff responsible for implementation. The overall timetable is unrealistic, and trusts are uncertain about their implementation schedules. Short term benefits alone are unlikely to persuade NHS staff to adopt the national programme enthusiastically, and some may experience a loss of electronic functionality in the short term. CONCLUSIONS: The sociocultural challenges to implementing the NPfIT are as daunting as the technical and logistical ones. Senior NHS staff feel these have been neglected. We recommend that national programme managers prioritise strategies to improve communication with, and to gain the cooperation of, front line staff.