Synergistic effect of the association between lidocaine and magnesium sulfate on peri-operative pain after mastectomy: A randomised, double-blind trial.

BACKGROUND: Recently, the use of venous adjuvants, such as lidocaine and magnesium sulfate, has been gaining ground in multimodal analgesia. However, no study has evaluated the impact a combination of the two drugs. OBJECTIVES: To evaluate the efficacy of venous adjuvants in reducing opioid consumption and pain scores after mastectomy. DESIGN: Randomised, double-blind, parallel-group, noninferiority clinical trial with a 1 : 1 : 1 : 1 allocation ratio. SETTING: Hospital de Base do Distrito Federal, Brasilia, Federal District, Brazil from November 2014 to December 2017. PATIENTS: One-hundred and ninety-eight patients were electively scheduled for mastectomy. Seventy-eight were excluded. INTERVENTIONS: Intra-operative infusions of remifentanil (0.1 µg kg min), lidocaine (3 mg kg h), magnesium sulfate (50 mg kg + 15 mg kg h) or lidocaine with magnesium sulfate were used. All patients received standard general anaesthesia. MAIN OUTCOME MEASURES: Peri-operative opioid consumption and pain scores. RESULTS: The patients who received both lidocaine and magnesium sulfate group (n=30) consumed less alfentanil during surgery (P < 0.001) and less dipyrone (P < 0.001) and morphine (P < 0.001) in the postoperative period. Only two patients (6.7%) in the lidocaine and magnesium sulfate group needed morphine (P < 0.001). These requirements were significantly lower when compared with patients who received remifentanil (n=30; 76.6%) and magnesium sulfate (n=30; 70%; odds ratio 46.0, 95% confidence interval 8.69 to 243.25, P < 0.001, and odds ratio 32.66, 95% confidence interval 6.37 to 167.27, P < 0.001, respectively). The patients of the lidocaine and magnesium sulfate group had lower pain scores in the first 24 h postoperatively using the numerical rating scale and verbal rating scale at discharge from the postanaesthesia care unit (P < 0.001), after 12 h (P < 0.001) and after 24 h (P < 0.001) when compared with the other three groups. CONCLUSION: Our findings suggest a synergistic effect of the use of both lidocaine and magnesium in peri-operative pain. This may be another potential strategy in the multimodal analgesia regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02309879.

Adverse outcome has a U-shaped relation with acute phase change in insulin sensitivity after ST-Elevation Myocardial Infarction.

BACKGROUND: Although stress hyperglycemia after myocardial infarction (MI) is consistently associated with increased mortality, recent studies suggest that the addition of upstream markers of glucose metabolism may improve risk identification. Hence, our aim was to evaluate the association between insulin sensitivity changes during MI hospitalization and outcomes. METHODS: A prospective cohort of 331 consecutive ST-Elevation MI (STEMI) patients without insulin provision therapy was used for the analyses. Blood samples were collected upon admission (D1) and after 5days (D5) of the inciting event. We measured blood glucose and insulin to estimate insulin sensitivity using the updated Homeostasis Model Assessment (HOMA2S). Patients were assessed for intra-hospital death and major adverse cardiac events (MACE) during follow-up. RESULTS: HOMA2S was 62%±52% on D1 and 86%±57% on D5 (p<0.001). Total follow-up was a median of 2 (0.9-2.8) years and found a U-shaped relation between the change in HOMA2S from D1 to D5 (ΔHOMA2S) and major adverse cardiac events (MACE) (p=0.017). Fully adjusted cox-regression models showed that patients from T1 and T3 were about 2.5 times more prone to suffer from MACE than those in T2. Net Reclassification Index adding ΔHOMA2S as a categorical variable dichotomized as T2 and T1 or T3 to a model of GRACE risk score with glucose D1 yielded a better predictive model (0.184 [95% CI 0.124-0.264]; p=0.032). CONCLUSION: A U-shaped curve describes the relation between insulin sensitivity change and MACE during acute phase STEMI and, thus indicating that acute dysglycemia must be appreciated in light of a time spectrum and insulin levels.

Adiponectin concentration data improve the estimation of atherosclerotic risk in normal and in overweight subjects.

BACKGROUND: The combinations of adipokines and body mass parameters to estimate carotid atherosclerotic disease have not been completely delineated. OBJECTIVE: To test the combinations of well-established, easily accessible body mass indices and circulating biomarkers to identify increased carotid intima-media thickness (cIMT) in a primary prevention setting. DESIGN AND PATIENTS: In a cross-sectional analysis of 339 asymptomatic individuals with no history of cardiovascular events, inflammatory and insulin sensitivity biomarkers as well as adipokine levels were measured and combined with body mass parameters to evaluate the best marker for increased cIMT. RESULTS: As isolated parameters, body mass index (BMI) and adiponectin best identified abnormal cIMT (P = .04). Adiponectin levels were also linked to the relationship between BMI and cIMT (ß = 0.0371; P = .01). Twenty-nine individuals with increased cIMT were missed by BMI alone but detected by combining BMI and adiponectin measurements. When compared with BMI alone, the combination of adiponectin plus BMI improved the c-statistic (0.549-0.567) and the integrated discrimination improvement index (0.01725; P = .021). Segregation of individuals by the combined use of BMI + adiponectin is associated with significant differences in insulin sensitivity, glomerular filtration rate, systemic inflammatory activity, dyslipidaemia and cIMT. CONCLUSIONS: Combining plasma adiponectin measurements and BMI improves estimation of cIMT as compared to anthropometric parameters.

TCF7L2 polymorphism is associated with low nitric oxide release, endothelial dysfunction and enhanced inflammatory response after myocardial infarction.

BACKGOUND: The favorable effects of insulin during myocardial infarction (MI) remain unclear due to the divergence between mechanistic studies and clinical trials of exogenous insulin administration. The rs7903146 polymorphism of the transcription factor 7-like 2 (TCF7L2) gene is associated with attenuated insulin secretion. METHODS: In non-diabetic patients with ST-elevation MI (STEMI), using such a model of genetically determined down-regulation of endogenous insulin secretion we investigated the change in plasma insulin, C-peptide, interleukin-2 (IL-2), C-reactive protein (CRP), and nitric oxide (NOx) levels between admission (D1) and the fifth day after MI (D5). Coronary angiography and flow-mediated dilation (FMD) were performed at admission and 30 days after MI, respectively. Homeostasis Model Assessment estimated insulin secretion (HOMA2%ß) and insulin sensitivity (HOMA2%S). RESULTS: Although glycemia did not differ between genotypes, carriers of the T-allele had lower HOMA2%ß and higher HOMA2%S at both D1 and D5. As compared with non-carriers, T-allele carriers had higher plasma IL-2 and CRP at D5, higher intracoronary thrombus grade, lower FMD and NOx change between D1 and D5 and higher 30-day mortality. CONCLUSION: In non-diabetic STEMI patients, the rs7903146 TCF7L2 gene polymorphism is associated with lower insulin secretion, worse endothelial function, higher coronary thrombotic burden, and higher short-term mortality. GENERAL SIGNIFICANCE: During the acute phase of MI, a lower capacity of insulin secretion may influence clinical outcome.

Multivariate optimization of a GC-MS method for determination of sixteen priority polycyclic aromatic hydrocarbons in environmental samples.

This paper describes the development and optimization, by using multivariate analysis, of a GC-MS-SIM method for evaluation of the 16 polyaromatic hydrocarbons considered as priority pollutants in atmospheric particulate material by the US EPA. In order to assure an adequate separation in the shortest analysis time, a multivariate design was used to set the conditions of the oven temperature program. The optimization process was carried out using factorial fractional design and Box-Behnken design. The following factors were evaluated: initial temperature, temperature rate #1, intermediary temperature, temperature rate #2, and final temperature. The optimized conditions were set at: 70 degrees C (2 min) --> 200 degrees C (30 degrees C/min, 5 min) --> 300 degrees C (5 degrees C/min, 1.67 min). Moreover, we have also optimized the injector temperature as 310 degrees C and sampling time as 0.8 min. The total analysis time was 33 min. Validation of GC-MS-SIM yielded satisfactory results for repetitivity of the detector response and retention times, and linearity of calibration curves. LOD were established as 0.13-0.34 ng/mL (peak area) and 0.18-0.72 ng/mL (peak height). The method has been shown to be appropriate for the analysis of samples of atmospheric particulate material and/or other environmental matrices.