The most clinically relevant common side effects (>2%) of sugammadex are due to the fast recovery of the muscle function during balanced anesthesia, which might unmask a too light anesthesia. In such cases, the patient might cough, move, grimace, or suckle on of the endotracheal tube.10
QT-Prolongation has been a concern since there have been reports of possible QT prolongation19
and one case of atrioventricular block after sugammadex.20
Several larger studies, however, have proven the safety of the drug,92
so that other factors during the administration of general anesthesia may have been a trigger in the reported cases.
As with all drugs, allergic reactions towards sugammadex are of concern. Cyclodextrins are ubiquitous molecules; therefore, an allergic predisposition is possible. This has been confirmed by several case reports of allergic reactions in patients who had received sugammadex for the first time.96
Reviews of both the published approval studies100
and of retrospective data from a single center in Japan over a period of 1 year97
show an incidence below 1%.
Of clinical concern is the possible reoccurrence of neuromuscular block. In 2% of the patients in the Phase I–III trials, neuromuscular block deepened again after it had initially recovered.9
However, all patients with reoccurrence had not received the adequate dose of sugammadex, ie, they had received less than the recommended dose. In these patients, the redistribution of rocuronium from the peripheral compartment to the central (intravascular) compartment led to rocuronium plasma levels that were not adequately hepatically metabolized, nor encapsulated by free sugammadex, leading in turn, to a second redistribution into the effect compartment (neuromuscular junction). The reason that a small shift of rocuronium back into the effect compartment can lead to reoccurrence of neuromuscular block lies in the physiologic margin of safety of the neuromuscular transmission: A neuromuscular block only becomes evident when over 85% of acetylcholine receptors are occupied by the muscle relaxant;101
in other words, full muscle contraction, ie, a TOF ratio of 100% can be achieved even though 75% of acetylcholine receptors are still occupied. Therefore, a small recurring dose of rocuronium is able to occupy enough acetylcholine receptors to reestablish a certain degree of neuromuscular block. In an unlikely case of reoccurrence of neuromuscular block, the anesthesiologist cannot wait to see what the deepest level of block during this event will be. Consequently a high and safe dose should be given. There have not been studies looking at such a scenario to date; for purely safety reasons, the manufacturer recommends 4 mg/kg sugammadex.10
An allergy to sugammadex is the only absolute contraindication. Additional diligence is necessary for patients with (1) bleeding disorders, (2) impaired renal function, and (3) patients using toremifene or fusidic acid.10
Phase I studies in volunteers using doses of 4 mg/kg up to 16 mg/kg showed that sugammadex led to prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT) or international normalized ratio (INR). These effects, however, were limited in time (below 30 minutes) and were not found to be clinical relevant. If the risk of bleeding is increased (either by hereditary factor deficiencies, coagulopathy, or use of medication), the possible additional anticoagulatory effects of sugammadex might become clinically relevant. Multicenter trials that will specifically look at bleeding complication after the use of sugammadex are currently under investigation. As of today, from a clinical perspective, the benefits of giving sugammadex have to be individually weighted against the possible risk of bleeding in such patients.10
Due to its renal elimination pathway, sugammadex should not be used in patients with highly impaired renal function, ie, creatinine clearance below 30 mL/min, or in patients requiring dialysis.10
Sugammadex is a cyclodextrin specifically designed to encapsulate rocuronium. Therefore drug interactions with other molecules seem to be rare. However, a potential change in efficacy could not be excluded for toremifene (estrogen receptor modulator) and fusidic acid (bacteriostatic antibiotic).102
Patients who receive these drugs might show a delayed recovery from neuromuscular block when receiving sugammadex. In addition, sugammadex might affect the efficacy of progesterone. Therefore, one bolus administration of sugammadex has to be considered as equivalent to one missed dose of hormonal contraceptives. It is suggested to use either a nonhormonal contraceptive method or to refer to the package leaflet of the contraceptive used and follow the directions for a missed dose.10
Multiple doses of sugammadex
If a patient has to undergo a reoperation after receiving sugammadex, three options to manage the neuromuscular block are available:
- the use of succinylcholine;
- the use of a benzylisoquinoline muscle relaxant (atracurium, cisatracurium, or mivacurium); or
- a second use of rocuronium.
There is an ongoing discussion which is the best option.103
Some data suggest that 5 minutes after the administration for sugammadex, rocuronium can be used again but may have a slower onset and shorter duration time. Due to the high elimination from the body, this is improved 25 minutes after sugammadex has been administered.105
The recommended doses for a readministration after sugammadex can be found in . The onset of relaxation might be prolonged to up to 4 minutes and the duration of action reduced to 15 minutes.10
Neuromuscular monitoring is, in every case, essential to adequately assess the neuromuscular block of the individual patient.
Dose recommendations for rocuronium after sugammadex use