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.     

Gallbladder sensitivity to cholecystokinin in coeliac disease. Correlation of gallbladder contraction with plasma cholecystokinin-like immunoreactivity during infusion of cerulein.

The present study was undertaken to determine whether alterations in the gallbladder sensitivity to cholecystokinin (CCK), apart from a reduced endogenous CCK secretion, contribute to the abnormally decreased postprandial gallbladder contraction in patients with coeliac disease. Gallbladder emptying, measured by cholescintigraphy, and plasma CCK levels, measured by radioimmunoassay, were studied during infusion of graded doses of the CCK analog cerulein in six coeliac patients with subtotal villous atrophy, six coeliac patients on a gluten-free diet with normal villous architecture, and nine control subjects. Both in the patients and in the controls infusion of stepwise increasing doses of cerulein, in the range of 1-16 ng.kg-1.h-1, induced dose-related changes in plasma CCK-like immunoreactivity (CCK-LI) (r = 0.99; p less than 0.001) and gallbladder emptying (r greater than 0.97; p less than 0.01-p less than 0.001). Plasma CCK-LI and gallbladder responses were not significantly different among untreated coeliac patients, treated coeliac patients, and controls. Gallbladder sensitivity to cerulein in untreated and treated coeliac patients was not significantly different from that in controls. It is concluded that the abnormally decreased gallbladder contraction in coeliac patients is the result of a reduced endogenous CCK secretion and not of a lack of end-organ responsiveness to CCK.     

The HemoCue®, a point of care B-hemoglobin photometer, measures hemoglobin concentrations accurately when mixedin vitro with canine plasma and three hemoglobin-based oxygen carriers (HBOC)

PURPOSE: Accuracy of measurement of low hemoglobin concentrations using the HemoCue, a B-hemoglobin photometer (HemoCue AB, Angelholm, Sweden) may exhibit significant variability. Infusion of hemoglobin-based oxygen carriers (HBOC) results in low concentrations of plasma hemoglobin. Our study assessed B-hemoglobin photometer measurement accuracy of three HBOC: (hemoglobin glutamer-200 (bovine; Oxyglobin, Biopure Corp., Cambridge, MA, USA); hemoglobin glutamer-250 (bovine; Hemopure, Biopure Corp, Cambridge, MA, USA), and hemoglobin-raffimer, (human; Hemolink, Hemosol, Inc., Toronto, Ontario, Canada). METHODS: In the laboratory, 45 split canine plasma samples were mixed with hemoglobin glutamer-200 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 samples were mixed with hemoglobin glutamer-250 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 with hemoglobin-raffimer (12.5, 25.0, 50.0 g x L(-1) concentrations), and measured. Plasma samples without HBOC served as control. Hemoglobin concentration was determined by a laboratory analyzer (Coulter Corporation, Hiafeah, FL, USA) and B-hemoglobin photometer (HemoCue, Angelholm, Sweden). Two independent technicians performed blinded sample measurements and randomly tested each sample five times. Results were analyzed according to Bland and Altman analysis. RESULTS: B-hemoglobin photometer demonstrated high repeatability for all three HBOCs. Repeatability coefficients were 0.37 g x L(-1) and 0.48 g x L(-1) for hemoglobin glutamer-200, 0.39 g x L(-1) and 0.4 g x L(-1) for hemoglobin glutamer-250 and 1.07 g x L(-1) and 0.85 g x L(-1) for hemoglobin-raffimer. An acceptable agreement was found between the B-hemoglobin photometer and the laboratory analyzer for all three HBOCs tested. CONCLUSION: The B-hemoglobin photometer accurately determined the concentration of three HBOC solutions dissolved in canine plasma.     

Xanthogranulomatous pyelonephritis: Comparison of extent using computed tomography and magnetic resonance imaging in one case

In a case of diffuse xanthogranulomatous pyelonephritis, computed tomography (CT) and magnetic resonance (MR) were used. The MR proved to be more precise in the preoperative evaluation of inflammatory extension to the spleen and into the abdominal wall. The CT was more accurate in excluding spread to the colon.     

Independent component analysis and clustering improve signal-to-noise ratio for statistical analysis of event-related potentials

OBJECTIVE: To evaluate the effectiveness of a new method of using Independent Component Analysis (ICA) and k-means clustering to increase the signal-to-noise ratio of Event-Related Potential (ERP) measurements while permitting standard statistical comparisons to be made despite the inter-subject variations characteristic of ICA. METHODS: Per-subject ICA results were used to create a channel pool, with unequal weights, that could be applied consistently across subjects. Signals derived from this and other pooling schemes, and from unpooled electrodes, were subjected to identical statistical analysis of the N170 own-face effect in a Joe/No Joe face recognition paradigm wherein participants monitored for a target face (Joe) presented amongst other unfamiliar faces and their own face. Results between the Joe, unfamiliar face and own face conditions were compared using Cohen's d statistic (square root of signal-to-noise ratio) to measure effect size. RESULTS: When the own-face condition was compared to the Joe and unfamiliar-face conditions, the channel map method increased effect size by a factor ranging from 1.2 to 2.2. These results stand in contrast to previous findings, where conventional pooling schemes failed to reveal an N170 effect to the own-face stimulus (Tanaka JW, Curran T, Porterfield A, Collins D. The activation of pre-existing and acquired face representations: the N250 ERP as an index of face familiarity. J Cogn Neurosci 2006;18:1488-97). Consistent with conventional pooling schemes, the channel map approach showed no reliable differences between the Joe and Unfamiliar face conditions, yielding a decrease in effect size ranging from 0.13 to 0.75. CONCLUSIONS: By increasing the signal-to-noise ratio in the measured waveforms, the channel pool method demonstrated an enhanced sensitivity to the neurophysiological response to own-face relative to other faces. SIGNIFICANCE: By overcoming the characteristic inter-subject variations of ICA, this work allows classic ERP analysis methods to exploit the improved signal-to-noise ratio obtainable with ICA.     

Distribution of drugs over whole blood: II. The transport function of whole blood for phenytoin

Phenytoin (DPH) partition between the three main blood compartments, i.e., plasma proteins, erythrocytes, and plasma water, was studied at various concentrations in vitro and in vivo. In vitro, the partition ratio of DPH in a system of erythrocytes in plasma water was 4.5 at concentrations between 0.8 and 100.8 micrograms DPH/ml. In vitro in whole blood (hence, in the presence of plasma proteins), this ratio was approximately 3.9. At 38 degrees C, blank erythrocytes were already in equilibrium with DPH-spiked plasma 3 min after contact, whereas at 20 degrees C, equilibration took 10 minutes or more. By adding blank ultrafiltrate to blood containing DPH, DPH concentrations of blood compartments shifted. It appeared that with the added blank ultrafiltrate, DPH was delivered overproportionally from erythrocytes and less from the protein fraction. In vivo, the elimination half-life of DPH in erythrocytes was 21.4 h and in plasma proteins 67.9 h. These results are similar to those obtained with valproate. It is concluded that erythrocytes have a low affinity for DPH. Their high-capacity transport system, having a "last-come-first-go" mechanism, plays a quantitatively important role in the transport of DPH.     

A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization

Urinary follicle stimulating hormone (FSH) is being used forthe treatment of human infertility. Recently, FSH manufacturedby means of recombinant DNA technology with a much higher purity(>99%) has become available. A prospective, randomized, assessor-blind,multicentre (n = 18) study was conducted in infertile womenundergoing in-vitro fertilization comparing recombinant FSH(Org 32489, Puregon®) and urinary FSH (Metrodin®). Eligiblesubjects were randomized (recombinant versus urinary FSH = 3:2)and pretreated with buserelin for pituitary suppression. FSHwas given until three or more follicles with a diameter of atleast 17 mm were seen. After oocyte retrieval, fertilizationroutines were applied according to local procedures. No morethan three embryos were replaced. In all, 585 subjects receivedrecombinant FSH and 396 urinary FSH. Significantly more oocyteswere retrieved after recombinant FSH treatment (mean adjustedfor centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancyrates per attempt and transfer in the recombinant FSH groupwere 22.17 and 25.97% respectively, and in the urinary FSH group,18.22 and 22.02% respectively (not significant). Ongoing pregnancyrates including pregnancies resulting from frozen-thawed embryocycles were 25.7% for recombinant and 20.4% for urinary FSH(P = 0.05). Compared to urinary FSH, the total dose of FSH wassignificantly lower with recombinant FSH (2138 versus 2385 IU,P < 0.0001) in a significantly shorter treatment period (10.7versus 11.3 days, P < 0.0001). No clinically relevant differencesbetween recombinant and urinary FSH were seen with respect tosafety variables. It is concluded that recombinant FSH (Puregon)is more effective than urinary FSH in inducing multifolliculardevelopment and achieving an ongoing pregnancy.     

Functional consequences of inhibition of nucleotide breakdown in rat vas deferens: a study with Evans blue

The effect of Evans blue on nucleotide breakdown, nucleotide-evoked contractions and electrically evoked contractions, overflow of ATP and overflow of tritium (after labelling with [³H]-noradrenaline) was studied in rat vas deferens. Pieces of vas deferens degraded 83 to 85% of added ATP, ADP and 2-methylthio ATP (all 100 M) over 30 min. Evans blue (100 M) reduced this degradation to 22 to 26%. Nucleotides elicited contraction with potency declining in the order , \-methylene ATP > 2-methylthio ATP > ATP > ADP. Evans blue (100 M) shifted the concentration-response curve of , \-methylene ATP to the right and increased the maximum. Concentration-response curves of ATP, ADP and 2-methylthio ATP, in contrast, were shifted to the left and responses were much potentiated. In the presence of Evans blue, the rank order of potency was ATP > 2-methylthio ATP > , \-methylene ATP > ADP. Electrical field stimulation (100 pulses at 10 Hz) elicited contraction and an overflow of tritium and ATP. Evans blue (100 M) did not alter the contraction and the evoked overflow of tritium but increased 24-fold the evoked overflow of ATP. The results indicate that Evans blue may serve as an — albeit impure — ecto-nucleotidase inhibitor in functional experiments. Such experiments demonstrate that the low potency of ATP (and also ADP and 2-methylthio ATP) in eliciting contraction, and the small size of the overflow of ATP upon sympathetic nerve stimulation, are due to rapid breakdown.