Author: Michael Vlessides
Management of neuromuscular block with rocuronium and its reversal with neostigmine and sugammadex according to a protocol is associated with a very low incidence of postoperative residual neuromuscular blockade, in a new study.
The researchers reported that neostigmine played an important role in the protocol, and resulted in significant cost savings compared with sugammadex alone for reversal.
“Instead of continuing research that’s been going on for decades examining risk factors for residual paralysis and describing what doesn’t work, we have switched gears at our hospital. We now do research on trying to figure [out] what does work,” said Stephan Thilen, MD, MS, an associate professor of anesthesiology and pain medicine at the University of Washington, in Seattle.
“We are designing protocols that we consider to be evidence-based,” Dr. Thilen continued. “Then we enroll patients to be prospectively managed by those protocols and we measure the incidence of residual paralysis.”
In a previous publication, Dr. Thilen and his colleagues found that the incidence of severe postoperative residual neuromuscular block was significantly reduced following introduction of a similar protocol in 78 patients undergoing abdominal surgery (Br J Anaesth 2018;121:367-377). However, that effort preceded FDA approval of sugammadex, prompting the researchers to revise their protocol.
The current protocol calls for an intubating rocuronium dose of 0.6 mg/kg, but with several possible adjustments, described below.
Dosing: “The intubating dose should not be the same for all patients,” Dr. Thilen told Anesthesiology News. “Muscle relaxants should be given based on ideal body weight, not actual body weight. It has been well reported that high BMI [body mass index] is a risk factor for residual paralysis.” The protocol considers actual body weight and ideal body weight to be the same in patients with a BMI less than 25 kg/m2. If the patient’s BMI is more than 25, then ideal body weight should be used instead.
Age: The protocol reduces the dose for the patient by 1% for each year over 55 years of age.
Sex: The protocol adjusts the intubating rocuronium dose based on sex. “It’s been well described that females need less than men do, so we give a 15% lower dose to female patients,” he said.
Maximal dosing: Incremental dosing calls for a maximum dose that is 25% of the induction dose, with no limit on the number of times clinicians can redose patients. “The idea here is to not be caught with a deeper block than you want toward the end of the procedure,” Dr. Thilen explained.
Monitoring: Interestingly, the protocol only calls for intraoperative monitoring with subjective monitoring using peripheral nerve stimulation, which is recommended at the adductor pollicis.
Reversal choice: The protocol calls for pre-reversal assessment, which is obtained by manual assessment of the adductor pollicis response. The results of this assessment then determine the reversal choice and dosage, as follows:
- Train-of-four (TOF) count of 4 with no fade: neostigmine 30 mcg/kg, or 15 mcg/kg if the fade is absent for more than 30 minutes;
- TOF count 1 to 4 with fade: sugammadex 2 mg/kg based on actual body weight; or
- TOF count 0 and post-tetanic count of 1 or higher: sugammadex 4 mg/kg based on actual body weight.
“With respect to timing, we always wait at least 10 minutes after giving neostigmine before extubating, and three minutes after sugammadex, and we measure the train-of-four ratio at the time of extubation,” Dr. Thilen said.
Testing the Protocol
To help determine the efficacy of the novel protocol, Dr. Thilen and his colleagues studied 180 adult patients (mean age, 47±16 years; 44.4% women), who were scheduled for elective orthopedic or abdominal surgery with the anticipated use of rocuronium.
Among the 155 orthopedic cases, 94 were reversed with neostigmine and 61 with sugammadex. Among the 25 abdominal cases, eight were reversed with neostigmine and 17 with sugammadex.
In total, the study found that the incidence of postoperative residual neuromuscular blockade on arrival to the PACU was 2.9% (95% CI, 0.3%-5.4%).
“We ended up with very good results,” said Dr. Thilen, who originally reported the findings at the 2019 annual meeting of the International Anesthesia Research Society (abstract E23).
The final part of the study examined cost. It found that the total acquisition cost for all reversal drugs used in the trial was $5,208.
“If we had given them all sugammadex, our cost would have been almost $10,000 [$9,968],” Dr. Thilen noted. “If we extrapolate that to a national sample, assuming 30 million patients undergo reversal from neuromuscular blockade each year, then the savings could be close to $1 billion, compared to simply giving everyone sugammadex.”
Adding Objective Monitoring
The researchers were encouraged that their protocol and subsequent study helped demonstrate the place that neostigmine can have in reversing neuromuscular blockade. Future research, they added, will implement the protocol in all surgical patients and add objective monitoring.
“We would expect even better results when adding also objective monitoring to our next protocol,” Dr. Thilen said. “However, we wanted to conduct this study before objective monitoring becomes the standard at our institution.
“Then we’ll compare the outcomes between our protocol and sugammadex for all patients,” he said. “If they’re equal, then we have found a significant cost savings approach, because there is no convincing evidence that reversal with sugammadex is safer than reversal with neostigmine, as long as residual paralysis is prevented at the time of extubation.”
For Sorin J. Brull, MD, the novel protocol is well thought out. “The results, an incidence of residual neuromuscular block of 2.9%, are significantly better than the current routine clinical results—e.g., 64.7% in the RECITE-US trial—and the authors are to be congratulated for undertaking this important patient safety trial,” said Dr. Brull, a professor of anesthesiology and perioperative medicine at Mayo Clinic in Jacksonville, Fla., who cited recently published results (J Clin Anesth 2019;55:33-41). “However, are we as clinicians and patient safety advocates prepared to accept a 2.9% incidence of residual neuromuscular block, a totally preventable complication?”
Instead, Dr. Brull advocated for more objective monitoring, which he said could eliminate postoperative residual neuromuscular blockade. “We could accomplish this regardless of the pharmacologic antagonist—neostigmine, pyridostigmine or sugammadex—since we would only extubate our patients’ tracheas once the TOF ratio was greater than 0.90, a recovery level that cannot be assured with subjective (qualitative) evaluation,” he commented.
“The cost associated with objective monitoring would likely be minimal beyond the initial investment in equipment,” Dr. Brull said, “and may include the cost of disposables, similar to pulse oximetry and depth of anesthesia monitoring. Based on historical cost experience, a single dose of saved sugammadex administration ($90) would pay for five to 10 patients undergoing quantitative monitoring. Do most clinicians feel this is not a worthwhile investment in our patients’ safety?”