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 effect of coffee on blood lipids and blood pressure. Results from a Norwegian cross-sectional study, men and women, 40-42 years

The association between boiled and filter coffee consumption and levels of cholesterol, triglycerides and blood pressure was studied, including 14168 men and 14859 women. A total of 94% drank coffee, 55% of the men and 48% of the women drank more than 4 cups per day. The type of coffee consumed varied between the counties, from 11 to 49% boiled and 49 to 87% filter coffee. Serum cholesterol increased linearly with increasing coffee consumption, and most strongly for boiled coffee. Controlling for other variables gave, for boiled coffee, an 8% increase for men and 10% for women. For filter coffee drinkers the coffee dose-cholesterol association remained significant only for women. Triglycerides showed a negative association with coffee, significant after adjustment for other variables. This effect was stronger for filter than for boiled coffee in both sexes. For men and women drinking 1 cup of coffee or more, a significant negative association between both systolic and diastolic blood pressure and number of cups of filter coffee was found. The influence of high consumption of different coffee-types on death rate from coronary heart disease is discussed.     

Seat belt use among drinking drivers in Minnesota.

OBJECTIVES. Among the reasons cited for recent declines in alcohol-related traffic fatalities is the enactment of seat belt use laws by most states. It is suspected that drinking drivers are less likely to comply with such laws, although evidence on the relationship between belt use and drinking by drivers is sparse and conflicting. The purpose of this study was to examine the relationship of drinking to driver seat belt use. METHODS. Observational, self-report, and chemical breath test data were collected on nighttime drivers in 16 Minnesota communities during September, 1990. RESULTS. Drivers with an illegal blood alcohol concentration (> or = 100 mg/dL) were substantially less likely to be wearing a seat belt (odds ratio [OR] = 2.17). Belt use was also more common among females (OR = 2.02) and before midnight (OR = 1.47). Males who had been drinking were less likely to be belted. Belt use was related to drinking before, but not after, midnight. Belt use was not related to drinking status among college graduates, but it was strongly related to drinking status among those with less education. CONCLUSIONS. The present findings provide further argument for rapid implementation of passive countermeasures (airbags) and for development of creative, carefully focused interventions to target high-risk populations.     

High-dose epirubicin in chemotherapy refractory non-seminomatous germ cell cancer: a phase II study. EORTC Genito-Urinary Tract Cancer Co-operative Group. EORTC Early Clinical Trials Group.

Eighteen patients with progressive disseminated, platinum-resistant germ cell tumors were treated with epirubicin 135 mg/m2, every 3 weeks. One patient had stable disease, 17 developed progression. Myelosuppression was dose-limiting. One patient died of neutropenic septicemia. High-dose epirubicin is not active against platinum-resistant germ cell cancer.     

Incompatibility of contrast agents with intravascular medications. Work in progress

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.     

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.     

Cranial nerve dysfunction in metastatic cancer of the prostate

We report 11 patients with cranial nerve dysfunction due to bone metastases from advanced prostatic cancer. Diplopia, speech disturbances, tongue deviation and headache were the typical clinical symptoms. X-ray and/or computed tomography of the base of the skull demonstrated bone destruction (and the surrounding soft tissue tumour) in 8 cases. In 1 patient the bone destruction was visualised only by bone scan. In 2 cases no bone destruction could be demonstrated in spite of the clinical findings. In 9 of the 10 evaluable patients the clinical symptoms improved after high voltage radiotherapy and high dose corticosteroid treatment. Cranial nerve dysfunction is a late complication of hormone-resistant prostatic cancer. The symptoms are usually due to bone destruction at the base of the skull. Radiotherapy combined with corticosteroid treatment is an excellent palliative measure if started immediately after the onset of symptoms.