Sugammadex: a selective relaxant binding agent for reversal of neuromuscular block.

Neostigmine, the currently used agent for reversal of neuromuscular block, has several drawbacks, such as a slow onset of peak effect, inability to reverse deep block and the occurrence of widespread muscarinic effects. Sugammadex is a new class of reversal agent that acts by encapsulating the molecules of the relaxants rocuronium and vecuronium, for which it is a specific antagonist. Clinical trials in over 2000 subjects have shown it to be effective for reversal of block by these two relaxants even from deep levels, in doses of 2.0-4.0 mg/kg. Sugammadex can also reverse an intense (profound) high-dose rocuronium block, but the dose required in this situation is 16.0 mg/kg. The agent has been found to be safe so far, with few side effects.

Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients.

BACKGROUND: Sugammadex reverses neuromuscular blockade by chemical encapsulation of rocuronium. This phase IIIA study explored efficacy and safety of sugammadex in infants (28 days to 23 months), children (2-11 yr), adolescents (12-17 yr), and adults (18-65 yr). METHODS: Anesthetized patients (American Society of Anesthesiologists class 1-2) received 0.6 mg/kg rocuronium and were randomized to receive sugammadex (0.5, 1.0, 2.0, or 4.0 mg/kg) or placebo at reappearance of T2. Neuromuscular monitoring was performed using acceleromyography. Primary endpoint was time from sugammadex/placebo administration to recovery of the train-of-four ratio to 0.9. Adverse events and electrocardiograms were recorded, and blood samples were collected for safety and determination of sugammadex and rocuronium plasma concentrations. RESULTS: A dose-response relation was demonstrated in children (n = 22), adolescents (n = 28), and adults (n = 26), but not infants because of the small sample size (n = 8). After placebo, median recovery time of train-of-four to 0.9 was 21.0, 19.0, 23.4, and 28.5 min in infants, children, adolescents, and adults, respectively. After 2.0 mg/kg sugammadex train-of-four 0.9 was attained in 0.6, 1.2, 1.1, and 1.2 min, respectively. The sugammadex plasma concentrations were similar for the children, adolescent, and adult age groups across the dose range. Sugammadex was well tolerated: No reoccurrence of blockade, inadequate reversal, significant QT prolongation, or other abnormalities were observed. CONCLUSIONS: Sugammadex is a new reversal agent that rapidly, effectively, safely, and with similar recovery times reverses rocuronium-induced neuromuscular blockade in children, adolescents, adults, and the small number of infants studied.

Protection of cardiomyocyte function by propofol during simulated ischemia is associated with a direct action to reduce pro-oxidant activity.

To demonstrate a direct protective effect of propofol on myocardial contractile performance during an ischemic episode and investigate underlying mechanisms, isolated adult rat ventricular cardiomyocytes were subjected for 2 h to (i) ischemic medium containing 2-deoxyglucose (20 mM), gassed with 100% N(2) at pH 6.4, (ii) normal medium with 95% O(2)/5% CO(2) at pH 7.4 or (iii) normal medium with addition of H(2)O(2) (50 microM). Propofol under normal conditions decreased the peak amplitude of electrically stimulated contraction of cardiomyocytes from a basal value of 6.5+/-0.37 microm to a maximum attenuation ( approximately 37%) at 0.44 to 56 microM. Under ischemic conditions, the contraction amplitude at baseline was 2.8+/-0.34 microm, but propofol, despite having a cardiodepressant effect per se, stimulated contraction, such that at >or=0.44 microM, normal and ischemic values in the presence of propofol were similar. Comparably, pro-oxidant (H(2)O(2))-induced attenuation of cell shortening was reversed by propofol (0.5 microM) to the level of contractile activity produced by the anaesthetic alone. The protective effect against ischemia-induced injury was not reflected in an improved ATP/ADP ratio nor was it mediated through diltiazem-sensitive L-type Ca(2+) channels. Propofol (0.5 microM) did, however, attenuate the ischemia- and H(2)O(2)-induced increases in the membrane lipid hydroperoxides, MDA (by 83% and 30%) and 4-HNE (by 47% and 69%). It is concluded that propofol, at clinically relevant concentrations, can counteract the effects of increased production of free radical compounds by cardiomyocytes subjected to oxidant stress and improve contractile performance.