Neuromuscular Block Clinical Trial
Official title:
Efficacy of Sugammadex for the Reversal of Moderate and Deep Rocuronium Induced Neuromuscular Block in Patients Pretreated With Magnesium Sulphate
Sugammadex is a new reversal agent for neuromuscular blockers (curare). It encapsulates the curare molecule and terminates immediately its action. The recommended dose is 2 mg/kg for a slight neuromuscular block and 4 mg/kg for a profound neuromuscular block. Magnesium sulphate is frequently used in perioperative medicine and it is known to reinforce the neuromuscular block induced for instance by rocuronium. The researchers want to investigate, whether higher doses of sugammadex must be given to antagonize the neuromuscular block induced by rocuronium in patients who received magnesium sulphate.
Neuromuscular blocking agents (NMBAs) are frequently used in anaesthesia and intensive care
medicine for tracheal intubation, artificial ventilation, and continued muscle relaxation
during surgical interventions. Postoperative residual curarisation is associated with an
increased risk of postoperative complications and morbidity. Consequently, adequate reversal
of neuromuscular block after surgery is of great importance.
Cholinesterase inhibitors have been widely used as reversal agents. They increase the amount
of acetycholine at the neuromuscular junction, which then competes with the NMBA to restore
muscle function. Cholinesterase inhibitors have, however, a number of limitations. They
antagonise the neuromuscular block slowly and are only effective when partial spontaneous
recovery has already occurred. These agents are also associated with a relatively high
incidence of cholinergic adverse reactions, including bradycardia, arrhythmia, salivation,
and bronchoconstriction.
Sugammadex, a modified gamma cyclodextrin, is a selective binding agent specifically
designed to encapsulate steroidal NMBAs such as rocuronium. It causes a rapid and complete
reversal of neuromuscular blockade by preventing directly rocuronium to react on the
neuromuscular receptor.
Dose-finding studies have suggested that sugammadex 2 mg kg-1 was needed for the reversal of
a moderate neuromuscular block (reappearance of T2), and that doses ≥4 mg kg-1 were needed
for the reversal of a profound block (1 to 2 post-tetanic counts). The median time for the
recovery of a moderate neuromuscular block to a T4/T1 ratio of 0.9 (which is considered
clinically safe) is around two minutes, and of a profound neuromuscular block is about three
minutes.
Magnesium is sometimes used in perioperative medicine, for instance, to prevent seizures in
parturients with pre-eclampsia. Magnesium has an impact on neuromuscular transmission. It
reduces the amount of acetylcholine that is released at the motor nerve terminal, by
decreasing the calcium conductance of presynaptic voltage-dependent calcium channels. After
pre-treatment with a clinically relevant dose of magnesium sulphate (MgSO4), an increased
speed of onset and a prolongation of the recovery period of the neuromuscular blockade have
been observed with standard intubation doses of atracurium, vecuronium, and rocuronium. With
rocuronium, for instance, the investigators recorded a shortening of the speed of onset of
the neuromuscular block by about 35% but at the expense of a prolongation of the recovery
period by about 25%. It has been shown that the interaction between magnesium and rocuronium
may become relevant in specific clinical situations.
The clinically relevant interaction between MgSO4 and rocuronium begs the question as to
whether in a patient who has received MgSO4, the efficacy of sugammadex to reverse a
rocuronium-induced block may be affected. Indeed, animal studies have indicated that
significantly higher doses of sugammadex might be needed to reverse a rocuronium-induced
neuromuscular block after magnesium pretreatment.
The aim of this study is to test the hypothesis that the established doses of sugammadex for
the fast and safe reversal of a moderate and a profound rocuronium-induced neuromuscular
block are inadequate in patients who have received MgSO4. The investigators hypothesize that
in subjects who received magnesium pretreatment, the time to reverse a moderate and a deep
neuromuscular block (induced by a single intubation dose of rocuronium) with standard doses
of sugammadex (2 and 4 mg kg-1, respectively) is prolonged by ≥ 50% and that the dose
response curves will be displaced to the right (i.e. higher doses of sugammedex will be
necessary to achieve the same speed of action as in patients who are not exposed to
magnesium.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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