Sugammadex, a gamma cyclodextrin discovered in 2007, provides a safe and effective alternative to drugs currently used in surgery by anesthesiologists. A problem in the current practice of anesthesia is the use of Succinylcholine, a neuromuscular blocking agent used for the cessation of the patient's skeletal muscle movement. Succinylcholine is used due to its unique fast onset and short duration, ideal for short procedures, difficult intubation scenarios, and rapid sequence intubation. However, it is used cautiously due to several risks such as causing myalgia, hyperkalemia, fasciculations, and increasing intracranial, intragastric, and intraocular pressure. Sugammadex provides a safer alternative to Succinylcholine because it allows immediate reversal of a neuromuscular blockade through a different mechanism, which does not lead to harmful adverse effects. Sugammadex works by encapsulating its target muscle relaxant, Rocuronium. Rocuronium is a relatively safer drug than Succinylcholine with a similar time of onset, but a very long duration of action. Since Sugammadex is able to immediately reverse the effects of Rocuronium, this combination of Rocuronium and Sugammadex provides the same desired effect as Succinylcholine but without the harmful side effects. The current most widely used reversal agent for muscle relaxation is Neostigmine. The problems with Neostigmine are that it can lead to residual paralysis and recurarisation if under dosed. It also produces unwanted cholinergic side effects that lead to cardiovascular instability. Due to this, the medical community is in need for a better reversal agent that can both quickly and completely reverse muscle paralysis without the need to manage unwanted side effects. Sugammadex is able to address both the problems of Succinylcholine and Neostigmine. Studies have shown Sugammadex to provide a faster, safer, and more predictable reversal of Rocuronium - induced neuromuscular blockade than Neostigmine. Sugammadex has shown to also achieve faster recovery from Rocuronium - induced muscle paralysis than the fast spontaneous recovery of Succinylcholine. With no serious adverse effects observed in these studies, the data supports the use of Sugammadex and its potential to replace the current standards of practice with Succinylcholine and Neostigmine. Furthermore, high dosage of Sugammadex has shown to be capable of immediately reversing profound neuromuscular blockades, an ability that no reversal drug currently in the market possesses. This enables the anesthesiologist to provide optimal muscle relaxation for the surgeon throughout the operation without the concern of being unable to reverse the patient in a timely manner. Studies on multiple patient population groups do not show any serious adverse effects are linked to using Sugammadex. There have been incidences of drug induced QTc prolongation in cardiac patients, but its cause was not determined to be related solely with Sugammadex. Sugammadex has shown to be the safer reversal agent compared to Neostigmine in cardiac, pulmonary, and renal patients. One problem that prevents the routine use of Sugammadex is its cost. The cost is significantly higher than Neostigmine. This cost is justified, however, due to staff costs saved from a faster patient recovery and shorter stay in the hospital. Therefore, while Sugammadex is definitely warranted over Succinylcholine due to its safety profile, its use over Neostigmine is dependent on each healthcare facility. While Sugammadex is currently under review by the Food and Drug Administration, it will evolve the practice of anesthesia if allowed into the United States market.

La nétose du polynucléaire neutrophile (PN) correspond à la libération de filaments d’ADN recouverts de protéines appelés Neutrophil Extracellular Trap (NETs). Outre leur rôle anti-infectieux, les NETs représentent des acteurs émergents de nombreuses pathologies inflammatoires et nous avons souhaité évaluer leur implication au cours de réactions allergiques.Au cours d’une étude clinique multicentrique notre équipe a mis en évidence un mécanisme alternatif de l’anaphylaxie aux curares, impliquant les PN. La phase aiguë de ces réactions s’accompagne d’une libération de NETs dont la concentration est corrélée avec la sévérité et avec une diminution de l’expression des récepteurs activateurs des IgG à la surface des PN (FcγRs) ; ceci suggère un rôle des complexes immuns (CI) IgG/curares dans la formation des NETs au cours de ces réactions anaphylactiques.Pour confirmer cette hypothèse, la capacité d’activation de la nétose par les CI IgG a été étudiée, via la mise au point d’un modèle de stimulation in vitro des PN humains purifiés.Ce travail montre que 2 récepteurs aux IgG du PN (FcγRIIa et FcγRIIIB) contribuent à la libération de NETs en réponse à différents types de CI.En parallèle, la formation des NETs a été explorée dans un modèle de réaction allergique chronique, l’asthme. Au niveau systémique, la concentration de NETs est associée à la présence d’un asthme sévère mal contrôlé et d’une obstruction bronchique peu réversible. Inversement, la concentration de NETs dans le lavage broncho-alvéolaire est plus élevée au cours de l’asthme modéré et semble traduire un recrutement pulmonaire et une activation des PN en réponse à une colonisation microbienne.Au total nous montrons que les NETs sont libérés au cours des deux modèles de réactions allergiques choisis, aiguë (anaphylaxie aux curares) et chronique (asthme) et qu’ils pourraient représenter des biomarqueurs de sévérité. Des travaux complémentaires sont nécessaires pour déterminer dans quelle mesure les NETs contribuent à la physiopathologie des allergies. / Neutrophil netosis consists in the release of extracellular DNA filaments bound to granular proteins, called Neutrophil extracellular traps (NETs). In addition to their anti-infectious role, NETs are emerging actors of many inflammatory diseases and we decided to investigate their involvement during allergy.In a multicenter clinical study, our team highlighted an alternative mechanism of anaphylaxis to neuromuscular blocking agents (NMBA) involving neutrophils (PN). The acute phase of these reactions is characterized by NETs release which level is correlated with severity and with a decrease in IgG activating receptors (FcγRs) expression on PN; this suggests a role of immune complexes (IC) IgG / NMBA in NETs formation during these anaphylactic reactionsTo confirm this hypothesis, the ability of IgG ICs to activate netosis was studied through the development of an in vitro stimulation model of purified human PNs.This work shows that two PN IgG receptors (FcγRIIa and FcγRIIIB) contribute to NET release upon cellular activation by different ICsIn parallel, NETs formation has been explored in a model of chronic allergic reactions, asthma. At systemic level, NETs levels are associated with severe and poorly controlled asthma as well with the presence of low reversible bronchial obstruction. Conversely, NETs levels in bronchoalveolar lavage are higher in moderate asthma and appear to reflect pulmonary recruitment and activation of PN in response to microbial colonization.Taking together these results show that NETs are released during the two selected models of allergic reactions : acute (NMBA anaphylaxis) and chronic (asthma) and could be used as biomarkers of severity. Furthers works are needed to determine to what extent NETs contribute to the pathophysiology of allergy.