Implementation of a quality improvement initiative substantially reduced excessive use of neostigmine while improving train-of-four–guided neostigmine administration. Over a six-month period, the initiative led to a decrease in the mean dose of intraoperative neostigmine from 2.9 to 2.5 mg, researchers reported.
“Preliminary data have shown that these interventions led to a statistically significant reduction in the average neostigmine dose that was administered,” said Hovig V. Chitilian, MD, of the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital (MGH), Harvard Medical School, in Boston. “There was also significant improvement in train-of-four documentation prior to the administration of neostigmine.”
As Dr. Chitilian’s group reported at the 2016 annual meeting of the International Anesthesia Research Society (abstract S-230), although debate remains about what constitutes adequate reversal, residual neuromuscular blockade, defined as a train-of-four ratio less than 0.9, is a persistent issue, with a reported incidence between 20% and 50%.
Regardless of the ratio applied, Dr. Chitilian said, optimal reversal requires neostigmine administration guided by train-of-four readings, as excessive doses of neostigmine given in the absence of adequate twitches can lead to depolarizing neuromuscular blockade.
In addition, a recent study has shown an association between high doses of neuromuscular blocking agents and an increased risk for postoperative respiratory complications (Anesthesiology 2015;122:1201-1213). This study also showed that neostigmine was associated with a dose-dependent increase in the risk for respiratory complications. Doses less than 60 mcg/kg, guided by train-of-four monitoring, were associated with reduced respiratory complications.
Quality Improvement Initiative
In order to provide more guidance regarding appropriate dosing of neostigmine for neuromuscular blockade or reversal and to encourage train-of-four monitoring intraoperatively, Dr. Chitilian and his colleagues devised a three-part quality improvement project. Instituted at MGH from April 1 to Sept. 1, 2015, the initiative consisted of:
department-wide education to define the incidence and consequences of residual neuromuscular blockade and unwarranted use of neostigmine, which included an online repository of relevant data and a neostigmine reversal guide (Table);
an incentivized, Anesthesia Information Management System–based quality improvement metric to encourage train-of-four documentation before the administration of neostigmine (a financial bonus was tied to 75% departmental compliance with the metric); and
a change in the available dose of neostigmine in anesthesia carts from 5-mg vials to 3-mg prefilled syringes.
Table. Neostigmine Reversal Guide
Type of Monitoring Neostigmine Dose
Qualitative Quantitative Weight-Based 70-kg Patient
No twitch No twitch Wait Wait
1 twitch 1 twitch Wait Wait
2-3 twitches 2-3 twitches Approx. 50 mcg/kg 3-4 mg
4 twitches with fade TOF ratio (<0.4) Approx. 40 mcg/kg 2-3 mg
4 twitches without fade TOF ratio (0.4-0.9) 15-25 mcg/kg 1-2 mg
TOF ratio (>0.9) None None
Risk Factors for Residual Postoperative Paralysis
High total dose of neuromuscular blockade (>1.5 mg/kg rocuronium; >0.4 mg/kg cisatracurium)
High-dose neostigmine reversal (>60 mcg/kg)
TOF, train of four Based on Kopman AF, et al. Anaesthesia. 2009;S1:22-30.
During the study period, 14,135 anesthetics included the administration of both neuromuscular blockade and neostigmine. When compared with the prestudy period, Dr. Chitilian reported that the percentage of cases receiving both neuromuscular blockade and subsequent neostigmine reversal intraoperatively did not differ after implementation of the initiative (29.8% vs. 29.4%; P=0.370).
However, following the initiative, there was a significant decrease in the mean total intraoperative dose of neostigmine, from 2.9 to 2.5 mg (P<0.001). The upper adjacent value of the total neostigmine dose also decreased from 7 to 4.5 mg.
Furthermore, Dr. Chitilian said, preliminary data showed a significant increase in the documentation rate of the train-of-four monitoring before the administration of neostigmine, from 60% to 75% of cases (P<0.001).
Because the intervention was made as a bundle, Dr. Chitilian acknowledged the difficulty of determining which component had the greatest effect; nevertheless, the researchers were impressed by the potential effect of modifying the available dose of neostigmine from 5-mg vials to 3-mg prefilled syringes.
Effect on Respiratory Complications?
“We noticed that a small change in the environment in which the anesthetic is practiced—that is, the quantity of drug that is available—might translate into a measurable change in practice,” Dr. Chitilian said. “If that turns out to be a major component, then it illustrates a fairly easy way to introduce behavioral change in practice, which is generally hard to do.”
Vital to the initiative’s success, said Dr. Chitilian, was the “interest and investment of a core group of people, support from the department, and the guidance of Matthias Eikermann, MD, PhD [clinical director of the Critical Care Division at MGH], and Aalok Agarwala, MD, associate director of anesthesia quality and safety at MGH.”
The study is ongoing, as researchers look to determine whether the intervention translated into a clinically significant effect in terms of respiratory complications. An initial unadjusted analysis revealed that the proportion of patients with respiratory complications was significantly lower after the initiative (5.7% vs. 8.7%; P<0.001).
“We need to develop a model to show that the patient populations we’re studying are effectively similar in terms of comorbidities,” Dr. Chitilian said. “Once we do that, we can see if there’s been a change in respiratory complications as a result of the intervention.”
Patricia Fogarty-Mack, MD, chair of quality and patient safety, director of non-operating room anesthesiology and associate professor of clinical anesthesiology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, in New York City, said this study documents “the importance of encouraging a substantive shift in the paradigm of reversal of neuromuscular blockade to a more precise, patient-centered approach.
“Taken as a whole,” said Dr. Fogarty-Mack, “these changes should be relatively easy to implement in most practices. Although some may say that a decrease in the average dose of neostigmine from 2.9 mg to 2.5 mg is statistically significant but not clinically relevant, I believe that a 13% reduction in average dose is important.
“More important than the dose reduction, however,” Dr. Fogarty-Mack added, “is the significant reduction in respiratory complications demonstrated. This is the true indicator of how … giving the patients the ‘right dose’ of medicine at the ‘right time’ really does improve the quality of patient care.”