Sugammadex contains eight identical hydroxyl chains designed specifically to encapsulate rocuronium; however, it is also able to bind vecuronium and pancuronium with less affinity. Sugammadex binds free intravascular rocuronium, leading to a concentration gradient which shifts peripherally-acting rocuronium centrally. Due to this action, rocuronium is rendered incapable to bind to the acetylcholine receptor at the neuromuscular junction. Higher doses of sugammadex are better able to lower free rocuronium concentration than lower doses. It does not inhibit acetylcholinesterase-like traditional reversal agents, such as neostigmine; therefore, use of an antimuscarinic agent such as glycopyrrolate is unnecessary.
Administration of Sugammadex from 2 mg/kg to 16 mg/kg demonstrates a linear and dose-dependent pharmacokinetic relationship, with an elimination half-life of 100 to 150 minutes and 100% rapid renal clearance. Dosing is dependent on the stage of neuromuscular blockade: 2 mg/kg for reversal of moderate neuromuscular blockade (one to two twitches from TOF stimulation), 4 mg/kg for deep blockade (after obtaining one to two post-tetanic counts), and 16 mg/kg for immediate reversal following 1.2 mg/kg dose of rocuronium. Studies have shown that recovery from a 2 or 4 mg/kg dose of sugammadex was significantly faster than with neostigmine, allowing the ability to speed recovery from blockade to TOF of 0.9 in an average of 3 minutes. Sugammadex should be dosed according to actual body weight. For obese patients, the use of ideal body weight dosing is likely not enough for the full reversal from rocuronium.
A patient can be given medication for paralysis after sugammadex administration. First, a depolarizing neuromuscular blocking agent such as succinylcholine can be given instead of a non-depolarizing agent to circumvent the effects of sugammadex. Second, a benzylisoquinoline non-depolarizing agent can be given instead of a steroidal agent, such as mivacurium, atracurium, or cisatracurium. Finally, the second dose of a steroidal non-depolarizing agent such as rocuronium can be given, depending on the time since sugammadex administration. Per the product label, a minimum waiting time of 5 minutes is needed for a 1.2 mg/kg dose of rocuronium, while a 4-hour wait time is needed for a 0.6 mg/kg dose of rocuronium. However, patients receiving a 1.2 mg/kg dose of rocuronium within 30 minutes of reversal are likely to experience delayed onset and shortened duration of neuromuscular blockade. For those receiving a 16 mg/kg dose, a minimum wait time of 24 hours is likely needed.
Bradycardia has been noted for patients, with some leading to cardiac arrest. Anticholinergics can be administered to counteract marked bradycardia.
Patients under light anesthesia may start to cough or move due to rapid recovery of neuromuscular function. One case of bronchospasm had been noted in clinical trials.
Some studies have demonstrated QT prolongation, though larger studies have shown a good safety profile.
Allergic reactions are possible with sugammadex with known case reports, though much less common than neuromuscular blocking drugs themselves.
Reoccurance of neuromuscular blockade is possible with an insufficient reversal with sugammadex. At that point, a further dose of medication should be administered for complete reversal of blockade.
Clinical trials looking at patients receiving 2 mg/kg, 4 mg/kg, and 16 mg/kg dosing of sugammadex demonstrated adverse effects at a higher rate than those receiving placebo. These adverse effects, in greater than 10% of patients, include pain, nausea, vomiting, headache, and hypotension.
Sugammadex is contraindicated for patients who have a known hypersensitivity, which ranges from isolated skin reactions to anaphylaxis. Anaphylaxis occurred in 0.3% of healthy volunteers in a study looking at hypersensitivity reactions. The incidence of hypersensitivity in patients with given doses of placebo, 4 mg/kg sugammadex, or 16 mg/kg sugammadex was 1%, 7%, and 9%, respectively.
Volunteers receiving 4 to 16 mg/kg dosages demonstrated prolonged aPTT, PT, and INR of up to 25% for 1 hour. Patients who completed major orthopedic surgery while on heparin or low molecular weight heparin for prophylaxis demonstrated an increase in aPTT of 5.5% and an increase in PT of 3.0% after 4 mg/kg sugammadex. While not found to be clinically relevant in volunteers, patients with pre-existing bleeding issues would need to have risks and benefits weighed prior to administration, including patients with medications that increase bleeding, hereditary disorders, or other causes of anticoagulation.
Patients with high renal dysfunction or on dialysis should not receive sugammadex due to its 100% renal elimination. Patients with renal failure should be monitored closely if the decision to give sugammadex is made. Rocuronium changes from a hepatic to the renal pathway of elimination when sugammadex is administered. The use of this medication is not recommended for patients with a creatinine clearance less than 30 mL/min or needing dialysis.
For children, adult dosing appears to be effective with a faster onset time, though little information is available. In a study of juvenile rats, sugammadex concentration was higher in bone deposition compared to adults after a single dose.
In contrast, reversal in patients older than 65 years old have shown to be prolonged, though co-morbidities may play a role in circulation of drug. A study of geriatric patients demonstrated a median time to recovery of TOF of 2.2 minutes in 18 to 64 year-olds, 2.5 minutes in 65 to 74 year-olds, and 3.6 minutes in patients older than 75. In addition, the incidence of renal dysfunction is higher in the elderly, which should be taken into consideration.
The use of sugammadex in breastfeeding patients is safe at this time. While it is not known if the drug is secreted into human breast milk, the likelihood of effects on infant is low. Sugammadex was present in rat milk in one study, with maximum drug level occurring at 30 minutes.
There is very little information regarding the use of sugammadex in patients who are pregnant. In animal studies, while no signs of teratogenicity were noted, there was a higher incidence of reduced fetal body weights and incomplete ossification of the sternebra. There was also an increase in postnatal loss in those studies.
Patients taking hormonal birth control should consider nonhormonal alternatives, as sugammadex might affect progesterone efficacy by binding to progestrogen. A single dose of sugammadex is similar to missing a dose of birth control containing estrogen or progesterone. These patients should use an additional, non-hormonal alternative for the following 7 days.
Patients who take the medications toremifene or fusidic acid should be monitored for possible prolonged neuromuscular blockade. Toremifene has a high affinity for sugammadex, leading to possible displacement of rocuronium or vecuronium from the sugammadex molecule.
Sugammadex is a modified gamma-cyclodextrin that is used to reverse steroidal nondepolarizing neuromuscular blocking drugs rocuronium and vecuronium. The agent is primarily used by an anesthesiologist, anesthesia nurses and an intensivist. Anyone who uses Sugammadex should be familiar with its indications and contraindications. In addition, one also has the familiar with the adverse effects and know how to manage them. A relatively common complication is hypotension and bradycardia; hence resuscitative equipment and anticholinergics must be available in the room. Sugammadex is otherwise relatively safe as long as it is utilized in a monitored setting like the operating room and ICU.
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