Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.     

The ability of the SCORE high-risk model to predict 10-year cardiovascular disease mortality in Norway.

AIMS: To evaluate the predictive accuracy of the Systematic Coronary Risk Evaluation (SCORE) project high-risk function in Norway. METHODS AND RESULTS: We included 57 229 individuals screened in 1985-1992 from two population-based surveys in Norway (age groups 40-49, 50-59, and 60-69 years). The data have been linked to the Norwegian Cause of Death Registry. The SCORE high-risk algorithm for the prediction of 10-year cardiovascular disease (CVD) mortality was applied, and the risk factors entered into the model were age, sex, total cholesterol, systolic blood pressure, and smoking (yes/no). The number of expected events estimated by the SCORE model (E) was compared with the observed numbers (O). The SCORE low-risk algorithm was studied for comparison. In men, the observed number of CVD deaths was 718, compared with 1464 estimated by the SCORE high-risk function (O/E ratios 0.53, 0.53 and 0.45, for age groups 40-49, 50-59 and 60-69, respectively). In women, the observed and expected numbers were 226 and 547. The O/E ratios decreased with age (ratios 0.60, 0.45 and 0.37, respectively), i.e. the overestimation increased with age. The low-risk function predicted reasonably well for men (ratios 0.85, 0.92 and 0.79, respectively), whereas an overestimation was found for women aged 50-59 and 60-69 years (ratios 0.69 and 0.56, respectively). CONCLUSION: The SCORE high-risk model overestimated the number of CVD deaths in Norway. Before implementation in clinical practice, proper adjustments to national levels are required.     

Ultrasonic root-end preparation in apical surgery: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate the potential benefit of an ultrasonic device in apical surgery on the outcome of treatment. STUDY DESIGN: A randomized prospective design was used in a standardized treatment protocol. Patients were allocated to treatment with an ultrasonic device (P-Max Newtron) or treatment with a bur in an otherwise similar protocol. One year after treatment the results were evaluated by 2 oral and maxillofacial surgeons who were blinded for the therapy. RESULTS: Out of a total group of 399 patients who were included in the study, adequate follow-up could be obtained in 290 patients. The overall success rate in the ultrasonic group was 80.5% and in the group treated with a bur 70.9% (P = .056). In molars, the difference in success rate was significant (P = .02). CONCLUSION: The use of an ultrasonic device in apical surgery improved the outcome of treatment. In molars this effect was significant.     

Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs.

Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing.     

Mesenteric vein thrombosis associated with primary cytomegalovirus infection: a case report.

In the past few years several studies have supported an interplay between cytomegalovirus infections and a prothrombotic state. We describe a case of primary cytomegalovirus infection in an immunocompetent adult that was complicated with mesenteric vein thrombosis. Transient protein C deficiency, lupus anticoagulant and activated protein C resistance were found, in combination with a heterozygous prothrombin G20210A mutation. We discuss the possible mechanisms of cytomegalovirus-related venous thrombosis.     

Development of three parallel cytochrome P450 enzyme affinity detection systems coupled on-line to gradient high-performance liquid chromatography.

A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) is connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The three so-called enzyme affinity detection (EAD) systems contained, respectively, liver microsomes from rats induced by beta-naphthoflavone (CYP1A activity), phenobarbital (CYP2B activity), and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate, and organic modifier (isopropyl alcohol, methanol, and acetonitrile) in flow injection analysis mode. Characteristic P450 ligands were used to validate the P450-EAD systems. IC(50) values of the ligands were measured and found to be similar to those obtained with conventional microtiter plate reader assays. Detection limits (n = 3; signal-to-noise ratio = 3) of potent inhibitors ranged from 1 to 3 pmol for CYP1A activity, 4 to 17 pmol for CYP2B activity, and 4 to 15 pmol for CYP3A activity. The three optimized P450-EAD systems were subsequently coupled to gradient HPLC and used to screen compound mixtures for individual ligands. Finally, to increase analysis efficiency, a HRS system was constructed in which all three P450-EAD systems were coupled on-line and in parallel to gradient HPLC. The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s.     

The use of recombinant-activated factor VII in von Willebrand disease: a case series.

Spontaneous and surgery-associated bleeding in patients with von Willebrand disease (vWD) cannot always be controlled with desmopressin or replacement therapy. This paper presents results on the use of recombinant-activated factor VII (rFVIIa) in patients with vWD included in the internet registry Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified from the database and included in this analysis. The bleeding episodes were classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were unspecified in three cases. The median dose of rFVIIa administered was 94 microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27 evaluable patients (85%) and markedly decreased in three patients; the total response rate was 96% (26/27 patients). Response did not correlate with the type of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other replacement therapies were infrequently used, and their use was similar in the 24 h before and after rFVIIa administration. Eighteen patients also received antifibrinolytic treatment, but its impact on response was not recorded. Only one adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as a safe and effective therapy for vWD.