The effect of tight glycaemic control, during and after cardiac surgery, on patient mortality and morbidity: A systematic review and meta-analysis.

BACKGROUND: Hyperglycaemia is a common occurrence during cardiac surgery, however, there remains some uncertainty surrounding the role of tight glycaemic control (blood glucose <180 mg/dL) during and/or after surgery. The aim of this study was to systematically review the literature to determine the effects of tight versus normal glycaemic control, during and after cardiac surgery, on measures of morbidity and mortality. METHOD: The literature was systematically reviewed, based on pre-determined search criteria, for clinical trials evaluating the effect of tight versus normal glycaemic control during and/or after cardiac surgery. Each paper was reviewed by two, independent reviewers and data extracted for statistical analysis. Data from identified studies was combined using meta-analysis (RevMan5®). The results are presented either as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs). RESULTS: A total of seven randomised controlled trials (RCTs) were identified in the literature, although not all trials could be used in each analysis. Tight glycaemic control reduced the incidence of early mortality (death in ICU) (OR 0.52 [95% CI 0.30, 0.91]); of post-surgical atrial fibrillation (odds ratio (OR 0.76 [95%CI 0.58, 0.99]); the use of epicardial pacing (OR 0.28 [95%CI 0.15, 0.54]); the duration of mechanical ventilation (mean difference (MD) -3.69 [95% CI -3.85, -3.54]) and length of stay in the intensive care unit (ICU) (MD -0.57 [95%CI -0.60, -0.55]) days. Measures of the time spent on mechanical ventilation (I2 94%) and time spent in ICU (I2 99%) both had high degrees of heterogeneity in the data. CONCLUSION: The results from this study suggest that there may be some benefit to tight glycaemic control during and after cardiac surgery. However, due to the limited number of studies available and the significant variability in glucose levels; period of control; and the reporting of outcome measures, further research needs to be done to provide a definitive answer on the benefits of tight glycaemic control for cardiac surgery patients.

A systematic review of brain metabolite changes, measured with 1H magnetic resonance spectroscopy, in healthy aging.

BACKGROUND: (1)H MR spectroscopy (MRS) can identify metabolite abnormalities in age-related, neurological diseases. However, there is little information on how metabolites change with healthy aging. METHODS: We systematically reviewed the literature on MRS, from 1980 to 2006, for studies where healthy young subjects (<60 years) were compared to healthy older subjects (>60 years). We extracted metabolite data reported as "no change", "increase" or "decrease" for each metabolite by brain region and, where data were available, meta-analysed mean metabolite concentrations (mM) for young versus old subjects. RESULTS: Eighteen studies met the inclusion criteria (total n=703 subjects, 284 >60 years old). Most data came from the frontal region, and reported "no change" in older subjects; however, a meta-analysis revealed a decrease in frontal NAA (p=0.05) and increases in parietal choline (p=0.003) and creatine (p<0.001). DISCUSSION: These data suggest that NAA may decrease and choline and creatine increase with age. Therefore, more data are needed from older subjects to characterise age effects better and ratios in older subjects should be interpreted with caution.

The neuronal nitric oxide synthase inhibitor, TRIM, as a neuroprotective agent: effects in models of cerebral ischaemia using histological and magnetic resonance imaging techniques.

Most neuroprotective compounds that appear promising in the pre-clinical phase of testing are subsequently dismissed as relatively ineffective when entered into large-scale clinical trials. Many pre-clinical studies of potential neuroprotective candidates evaluate efficacy in only one or possibly two different models of ischaemia. In this study we examined the effects of 1,2-trifluoromethylphenyl imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor, in three models of cerebral ischaemia (global gerbil, global rat and focal rat). In addition, to follow the progression of the pathology, we also compared traditional histology methods with more advanced magnetic resonance imaging (MRI) as endpoint measures for neurological damage and neuroprotection. TRIM (50 mg/kg i.p.) prevented ischaemia-induced hippocampal damage following global ischaemia in gerbils when administered before or immediately post-occlusion, but failed to protect when administration was delayed until 30 min post-occlusion. Further studies indicated that the compound (administered at 50 mg/kg, i.p., immediately after occlusion) also protected in a rat four-vessel occlusion (4-VO) model using both histological and diffusion-weighted (DW) imaging techniques. In a final study, TRIM (50 mg/kg i.p. 30 min after occlusion) provided a significant reduction in infarct volume at 4 and 24 h as measured using diffusion-weighted (DW) and proton density (PD)-weighted magnetic resonance imaging (MRI). This was confirmed using histological techniques. These studies confirm that nNOS inhibitors may have utility in stroke and provide evidence that combined magnetic resonance and histological methods can provide a powerful method of assessing neuronal damage in rodent models of cerebral ischaemia.