Sugammadex: novos questionamentos sobre a reversão

Abstract

Sugammadex: new questions on reversalRecently released in Brazil, sugammadex is a modified γ-cyclodextrin, which is showing favorable results regarding reversal of motor blockade, particularly by rocuronium. One of the main advantages of this agent over neostigmine is the reversal of relaxation when the patient is deeply curarized. However, the use of sugammadex in such conditions of deep blockade has shown a phenomenon not previously seen: train-of-four (TOF) recovery before complete recovery of single twitch (T1), with a difference up to five minutes between the two types of neurostimulation 1 . The concept of a satisfactory recovery includes only the return of TOF > 0.9 or, according to current guidelines, about 1.0 2,3 .Neuromuscular transmission (NMT) monitoring is different from other methods used in anesthesia, such as pulse oximetry, because it requires the interpretation of data from the peripheral nerve stimulator.For a better understanding, the NMT phenomena can be divided into three distinct parts: pre-synaptic processes; those related to the synaptic cleft and basement membrane; and post-synaptic or muscular. In the first, the greatest emphasis is on the alpha motor neurons in which neuronal nicotinic receptors can be identified 4 , as well as voltage-gated calcium and potassium channels, which are fundamental structures to control the entry of calcium into neuron. These receptors have characteristics that distinguish them from muscle receptors, such as the presence of only two types of subunits, α2-10 and β2-4, and the lack of safety margin 4-8 . This last characteristic is related to the additional release of acetylcholine in the presence of high-intensity stimuli, by a positive feedback mechanism from stimulation of α3β2 nicotinic receptor.When the neuronal receptor is occupied by a non-depolarizing neuromuscular blocker (NMB), the positive feedback mechanism and release of additional acetylcholine do not occur; and, in the presence of a high-intensity stimulus, the muscle does not maintain an intense contraction, i.e., shows fatigue. Other mechanisms, besides the blockade of neuronal nicotinic receptors, seem to be involved with the development of fatigue, as shown in muscle-phrenic nerve preparation. Among them, there are the facilitator action of type 1 muscarinic receptors (M1) and/or inhibitory action of type 2 (M2) 9 . In clinical monitoring this fatigue is characterized by TOF < 0.9 2,10,11 .Physiologically, the acetylcholine molecules not destroyed in the synaptic cleft by acetylcholinesterase arrive at the muscular nicotinic receptor and occupy it triggering the opening of the receptor central pore, which is represented by M2-M4 chains located in the transmembrane portion of the sarcolemma 4,8 . Hydrated sodium molecules enter through this pore generating an action potential. The electric potential stimulates the sodium dependent voltage-gated receptors juxtaposed to muscular nicotinic receptors, which will allow the additional entry of sodium, increasing the action potential. This membr...