Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study.

BACKGROUND: Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium-induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. METHODS: In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. RESULTS: After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124±9.6, 143±163, 151±207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109±13.8, 124±0.6, and 135±14.1 sec. Times to TOF ratio 0.9 were 114±75 and 186±105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. CONCLUSION: Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade.

Ultrasound identification of nerve cords in the infraclavicular fossa: a clinical study.

BACKGROUND: This study aimed to analyze nerve trunk anatomy in the infraclavicular fossa and to correlate these data with the most common anthropometric parameters. METHODS: A Mylab 30 Gold (Esaote) and the linear transducer LA523 (7.5 MHz frequency) were used. The probe was oriented according to a parasagittal plane, parallel to the lateral chest wall and immediately medial to the coracoid process underneath the clavicle. Measurements included the distance between the artery and the cutaneous surface (mm) and the apical corner of the ultrasound image (mm), the number of identified nervous cords and their position related to the axillary artery, and the position and number of axillary veins. Sex, age, height, weight, body mass index (BMI), biceps girth, and breast size were recorded. Statistical analysis included calculation of linear Pearson correlation coefficient and Student's t test. RESULTS: Two hundred and two consecutive patients were enrolled. The position of the three cords was highly variable around the artery. In a small but significant percentage of patients (8.9%), the medial and the lateral cords were located together at the top of the artery. The visibility of the trunks and the distance between the upper part of the artery and the apical corner of the ultrasound image correlated with anthropometric characteristics. The vein position with respect to the artery and nerves was markedly variable. CONCLUSION: Sono-anatomic study of the infraclavicular region adds important data that is useful when conducting nerve blocks to improve safety and likelihood of success.

Effects of type 5-phosphodiesterase inhibition on energy metabolism and mitochondrial biogenesis in human adipose tissue ex vivo.

OBJECTIVE: An excess of adipose tissue (AT) in obese individuals is linked to increased cardiovascular risk and mitochondria have been shown to be defective in the muscle and AT of patients with metabolic disorders such as obesity and Type 2 diabetes. Nitric oxide (NO) generated by endothelial NO synthase (eNOS) plays a role in mitochondrial biogenesis through cyclic-GMP (cGMP). AT harbors the whole molecular signaling pathway of NO, together with type 5-phosphodiesterase (PDE- 5), the main cGMP catabolising enzyme. AIM: Our aim was to evaluate the effect of the modulation of NO pathway, through PDE-5 inhibition, on energy metabolism and mitochondria biogenesis in human omental AT. METHODS AND MEASUREMENTS: Cultured human omental AT was stimulated with PDE-5 inhibitor, vardenafil, at different concentration for 24 and 72 h. Analysis of the expression of both key-regulator genes of adipocyte metabolism and mitochondria-biogenesis markers was performed. RESULTS: We found an increased gene expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), adiponectin, and proliferator- activated receptor gamma coactivator-1 α (PGC-1α) after a 24-h stimulation with vardenafil at the lowest concentration employed compared to controls (p<0.05). After 72 h of stimulation, a significant increase of mitochondrial DNA was found compared to control samples (p<0.05). CONCLUSION: Our data suggest that PDE-5 inhibition could have an impact on mitochondrial content of human AT suggesting a positive effect on energy metabolism and adding new elements in the comprehension of AT pathophysiology.

Mitral valve endocarditis in a severe burn patient.

The authors describe the case of a 40-year-old female with severe burns (85% of total body surface area including the thorax) caused by thermal injury who presented mitral valve endocarditis during intensive care unit stay. Bacterial endocarditis represents a rare cause of fatal septicemia complicating thermal injury. The authors focus on diagnosis and on timing of surgical treatment.

Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization.

Insulin-like factor 3 (INSL3) plays a crucial role in testicular descent. Genetic ablation of Insl3 or its G protein-coupled receptor, leucine-rich repeat-containing G-protein-coupled receptor (Lgr8), causes cryptorchidism in mice. Mutation analyses of INSL3 in humans showed an association with cryptorchidism but led to non-conclusive data about a causative role. In this study, we explored the hypothesis that mutations in INSL3 may be associated with the signs of testicular dysgenesis syndrome (TDS). We screened for mutations in INSL3 gene in 967 subjects with a history of maldescended testes and/or infertility and/or testicular cancer and in 450 controls. Furthermore, we carried out in vitro functional analysis of three novel mutations by analysis of INSL3-dependent cAMP increase in cells expressing LGR8. We found six INSL3 mutations in 18 of 967 patients (1.9%) and no mutations in controls. Prevalence of mutations was similar in the different groups of patients (cryptorchidism and/or infertility and/testicular cancer). Three mutations were novel findings (R4H, W69R, and R72K); however, their analysis showed normal cAMP increase after the activation of LGR8 receptor. In conclusion, we found a significant association of INSL3 gene mutations in men presenting one or more signs of TDS syndrome. However, a causative role for some of these mutations is not clearly supported by functional analyses. Although a role for mutations of INSL3 and LGR8 genes in cryptorchidism is reasonable, additional studies are needed to establish an association between the disruption of INSL3 pathway and higher risk of infertility or testicular cancer.